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Biomedical subjects

C A Wiley

Publications and source records attributed to C A Wiley.

At least 109 records · Page 6Linked to original sources
PubMed1992

Relationship of cerebrospinal fluid immune activation associated factors to HIV encephalitis.

OBJECTIVES AND DESIGN: Because macrophages are the predominant immune cell and the predominant infected cell in the brains of patients with HIV encephalitis, we studied macrophage and immune activation-associated factors in the cerebrospinal fluid (CSF) from 39 autopsied AIDS cases for whom complete neuropathologic evaluation of the brain was available. RESULTS: CSF HIV p24 antigen was present in less than one-third of cases (11 out of 39). Less than half of the autopsies with moderate to severe parenchymal infection by HIV had high levels of CSF p24, although all autopsies with elevated levels of HIV p24 had moderate to severe HIV encephalitis. Elevated levels of cytokines, beta 2-microglobulin, neopterin, and quinolinic acid were observed. CONCLUSIONS: Although many of the CSF findings showed a strong correlation with each other, none showed a strong correlation with the severity of HIV infection of the brain itself. The absence of a close association between CSF abnormalities and HIV encephalitis could reflect the abundance of complicating opportunistic infections in these terminally ill patients or the inadequacy of CSF as a marker of basal ganglia involvement in HIV encephalitis. These findings complicate interpretation of clinical studies of CSF in patients with AIDS where neuropathologic evaluation is unavailable.

AIDS Dementia Complex↗
PubMed1992

Expression of major histocompatibility complex antigens in the brains of patients with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is caused by JC virus (JCV) infection of the central nervous system (CNS) in immunosuppressed patients. The immunopathogenesis of this chronic encephalitis is unknown. Because major histocompatibility (MHC) class I and class II antigens are important in modulating the immune response and viral clearance, we examined the tissue expression of MHC molecules in relation to CNS damage and presence of virus. By immunocytochemical staining, both MHC class I and class II antigens were expressed at high levels within PML lesions. Beta-2 microglobulin (beta-2m) was present on endothelial cells and JCV-infected oligodendroglia within the lesions. Also, many astrocytes with bizarre morphology expressed MHC class I antigens. In histologically normal regions of PML brains expression of beta-2m was noted only on endothelial cells. Expression of MHC class II also was focused within demyelinating lesions and was restricted to macrophages/microglia and occasional endothelial cells. When compared to other viral encephalitides (e.g. human immunodeficiency virus) these findings suggest that intra-CNS immune response to JCV is appropriate for antigenic presentation; however, the absence of responsive systemic T-cells may lead to chronic viral infection with progressive neuropathology.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Selective neuronal vulnerability in HIV encephalitis.

Recent studies of human immunodeficiency virus type 1 (HIV-1) encephalitis have shown that in addition to well established white matter damage, the neocortex shows thinning, loss of large neurons and dendritic damage. In order to identify neuronal populations affected in HIV encephalitis and to determine how neuronal damage relates to the severity of HIV infection within the nervous system, we quantified parvalbumin (PV+) and neurofilament (NF+) immunoreactive neurons in the frontal cortex and hippocampus. We found that in the neocortex, the density of NF+ and PV+ neurons was independent of severity of HIV encephalitis, and therefore changes in these neuronal subsets did not account for previously reported neuronal loss. However, neuritic processes of PV+ neurons were fragmented, atrophic and in some cases distended. In contrast to the frontal cortex, there was a trend toward decreased density of PV+ neurons in the hippocampus which only reached significance in the CA3 layer where there was a 50-90% decrease in PV+ neurons. This decrease was closely correlated with the severity of HIV encephalitis. Double-label immunocytochemical analysis confirmed neuritic damage to interneurons. These results suggest that HIV encephalitis differentially involves specific subpopulations of neurons. Since direct HIV infection of neuronal cells was not detected, damage to PV+ cells and fibers may be indirectly mediated by cytokines released by HIV-infected microglia.

AIDS Dementia Complex↗
PubMed1992

Early viral brain invasion in iatrogenic human immunodeficiency virus infection.

We report a 68-year-old man who received an IV inoculation of WBCs for an indium radionuclide scan containing 600 to 700 tissue culture infectious doses of human immunodeficiency virus type 1 (HIV-1) from an HIV-1-infected individual. The recipient immediately received zidovudine, then was switched to dideoxyinosine and interferon-alpha, but died of hepatorenal syndrome and hepatic encephalopathy 15 days later. HIV-1 cultures were positive from the recipient's blood on day 14 but not days 0, 1, and 8. At autopsy, cultures of parietal lobe isolated HIV-1. HIV-1 nucleic acid was present in several brain areas, but not in several other organs, by two independent laboratories using the polymerase chain reaction. The brain showed mild perivascular cuffing and a mild lymphocytic meningitis, but there was no evidence of glial nodules, giant cells, or white matter abnormalities. HIV-1 pg41 viral antigen was seen by immunoperoxidase staining in rare infiltrating cells within perivascular and subpial spaces. Thus, HIV-1 was isolated from brain 15 days after mistaken HIV-1 inoculation and 1 day after virus was first recovered from blood.

Aged↗
PubMed1992

Development of spongiform encephalopathy in retroviral infected mice.

The Cas-Br-E strain of murine leukemia virus is a neurovirulent retrovirus that induces progressive noninflammatory degeneration of the central nervous system (CNS). The molecular clone pNE-8 retains pathogenic properties of Cas-Br-E. The neurotropic determinants are known; however, the mechanism of neuropathogenesis is unknown. We examined the temporal development of disease after infection of SWR/J mice with pNE-8 virus. Development of CNS lesions, cellular targets of viral replication, accumulation of ubiquitinated proteins and integrity of blood-brain barrier were determined in mice infected with pNE-8 virus; and compared with uninfected, sham-infected, and nonneuropathogenic virus-infected mice. During 24 weeks of pNE-8 infection, noninflammatory spongiform lesions developed initially in the lumbar spinal cord and progressed to involve the brainstem and deep cerebellar nuclei. Virions and viral antigens accumulated for 18 weeks postinfection and then declined. Major sites of viral infection outside the CNS were splenic megakaryocytes, and skeletal muscle. Cellular targets of viral replication in the CNS included neurons, oligodendrocytes, and capillary endothelium. No astrocytic infection was observed; however, a reactive gliosis marked the development of clinical symptoms and histopathology. Spongiform lesions began as swelling of perivascular astrocytic processes. Intramyelinic vacuoles with splitting of myelin at major dense lines were prominent around dystrophic axons at later time points. Dendritic processes showed vacuolization and local degeneration. Viral particles were most commonly observed in extracellular spaces and within rough endoplasmic reticulum of neurons, oligodendrocytes, and splenic megakaryocytes. Infected megakaryocytes and regions of spleen containing viral aggregates showed accumulation of ubiquitinated proteins. Areas of histopathology in the CNS showed accumulation of ubiquitinated proteins but unlike spleen, viral proteins were not highly ubiquitinated. Disruption of the blood brain barrier was only evident at late stages of infection. In conclusion, the neuropathogenic damage associated with pNE-8 infection appears to be tightly associated with direct viral infection of oligodendroglia and neurons.

Animals↗
PubMed1992

Role of HIV and CMV in the pathogenesis of retinitis and retinal vasculopathy in AIDS patients.

Cotton-wool spots and cytomegalovirus (CMV) retinitis are seen frequently in AIDS patients. Human immunodeficiency virus (HIV) infection of the retina has been proposed as a mechanism for the high incidence of retinal pathology. An autopsy study of the eyes from 25 consecutive cases of AIDS was performed using gross examination, light microscopy, trypsin digestion of retinal vasculatures, and immunohistochemistry to evaluate the possible role of HIV, as well as CMV, in the pathogenesis of retinitis and retinal vasculopathy. Brain tissue was studied in the first 20 of these cases to evaluate any correlation between retinal and central nervous system pathology. CMV retinitis was observed in 15 cases (60%). Cotton-wool spots were seen in nine cases (36%). CMV encephalitis was detected in four cases, whereas HIV encephalitis was noted in five cases. We were unable to demonstrate a correlation between CMV retinitis and CMV encephalitis. However, the number of cases studied was small, and the frequency of CMV encephalitis was low. On the other hand, bilateral CMV retinitis demonstrated a correlation to HIV encephalitis (P less than 0.005, Fisher's exact test). HIV infection of the retina was not detected by typical morphologic changes or immunohistochemistry. Immunohistochemistry localized CMV infection solely to areas of active retinitis. These findings suggest that bilateral CMV may serve as a marker of HIV encephalitis, possibly indicating a severely immunodepressed state.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1992

Malignant phyllodes tumor of the prostate. A case report with immunohistochemical and ultrastructural studies.

Phyllodes tumor of the prostate is a rare neoplasm with cellular or sarcomatoid stroma and hyperplastic glands. This lesion shares many histologic features with cystosarcoma phyllodes of the breast. Although a malignant variant of phyllodes tumor of the prostate has been described, the majority of cases have been clinically benign. We report an unusual case of phyllodes tumor of the prostate in which the stromal component underwent malignant degeneration, a finding not previously described (to our knowledge). Immunohistochemical and ultrastructural studies demonstrated smooth-muscle differentiation of the stromal cells.

Aged↗
PubMed1992

Cortical dendritic pathology in human immunodeficiency virus encephalitis.

Previous neuropathological and morphometric studies of the cerebral cortex of patients with human immunodeficiency virus encephalitis (HIVE) have shown a decrease in the population of large neurons, moderate loss in synaptophysin immunoreactivity, and pathological changes in dendrites. To further characterize and quantify alterations in the dendritic tree of neocortical pyramidal neurons, we performed a modified Golgi impregnation technique on Formalin fixed blocks from the frontal cortex of 5 HIVE cases, 5 human immunodeficiency virus seropositive control cases without encephalitis, and 5 human immunodeficiency virus seronegative controls. Apical dendrites of HIVE cases were dilated, vacuolated, and tortuous with decreased length and branching. Basal and oblique dendrites also showed these alterations, but to a lesser extent. Some dendrites presented lacunae and filopodia consistent with remodeling. Computer aided quantification of HIVE cases showed a 40-60% decrease in spine density throughout the entire length of dendrites. Laser confocal imaging of Golgi impregnated sections displayed aberrant spines in regions of abnormal second order dendritic branches. These observations support the role of primary dendritic damage in HIVE in contrast to other neurodegenerative disorders where the primary pathology is presynaptic.

AIDS Dementia Complex↗
PubMed1992

Lack of retinal toxicity of the anticytomegalovirus drug (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine.

The drug (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC) is an antiherpesvirus group compound with a higher potency and longer duration of action against human cytomegalovirus (CMV) than ganciclovir or foscarnet. Twenty eyes of ten New Zealand white rabbits received 0.1-ml injections of either normal saline or HPMPC at doses of 10, 50, 100, 300, or 1000 micrograms. The animals were killed on days 14 and 28. Toxicity was assessed by indirect ophthalmoscopy, electroretinography (ERG), and light and electron microscopy. Both a- and b-wave ERG findings and indirect ophthalmoscopic appearance of retinas in all groups were normal. Light and electron microscopy of perfusion-fixed retinal tissue revealed no morphologic changes at doses of 100 micrograms or lower. The pharmacokinetics of eight rabbits injected intravitreally with 100 micrograms of HPMPC showed a 24.4-hr half-life for the drug. These results indicate that HPMPC is not toxic to the rabbit retina at 500-1000-fold the dose that is effective in suppressing CMV infections. Doses of 100 micrograms also were injected into the vitreous of monkey eyes. Intravitreal injections of HPMPC may be efficacious in inhibiting CMV retinitis for longer dosing intervals than can be used with other anti-CMV compounds.

Animals↗
PubMed1991

Neocortical damage during HIV infection.

Clinical and pathological evidence of subcortical central nervous system (CNS) damage is observed commonly in patients with human immunodeficiency virus (HIV) encephalitis. Whether other CNS regions are also affected has not been well studied. We report neocortical damage in patients with HIV encephalitis. Using quantitative techniques, we demonstrate statistically significant thinning of the neocortex, with a loss of large cortical neurons. Qualitative and quantitative assessments of neocortical neuropil reveal a loss of synaptic density and vacuolation of dendritic processes. Failure to demonstrate an association of these changes with the presence of HIV antigens suggests that neocortical damage may be an indirect effect of HIV infection of the CNS.

AIDS Dementia Complex↗
PubMed1991

Expression of major histocompatibility complex and HIV antigens within the brains of AIDS patients.

HIV establishes a chronic infection in the central nervous system (CNS) of AIDS patients. The immunopathogenesis of this chronic encephalitis is unknown. Because of the importance of major histocompatibility (MHC) class I and class II antigens in modulating the immune response, we examined the tissue expression of MHC molecules in relation to CNS damage and expression of viral antigens. By immunocytochemical staining we found that beta 2-microglobulin (beta 2M) expression is elevated in all cases with signs of viral encephalitis. beta 2M was expressed at high levels on endothelial cells, macrophages and possible oligodendroglia within regions of histopathology. In histologically normal regions elevated expression of beta 2M was noted only on endothelial cells. MHC class II expression was elevated only in the HIV encephalitis cases, and was restricted to macrophages/microglia and occasional endothelial cells. When compared with other viral encephalitides these findings suggest that the intra-CNS immune response to HIV is appropriate for viral presentation; however, the absence of responsive systemic T cells may lead to chronic viral infection.

AIDS Dementia Complex↗
PubMed1991

Pathogenesis of HIV encephalitis.

A wide spectrum of infectious agents attack the central nervous system (CNS) of acquired immunodeficiency syndrome (AIDS) patients. Human immunodeficiency virus (HIV) itself, infects the CNS of a subgroup of these patients. The mechanism behind why HIV enters the CNS is unclear. We have observed an interesting association between HIV and opportunistic viral infections that may explain why HIV enters the brain. Infection of the CNS by opportunistic agents results in recruitment of latently HIV-infected monocytes. Upon differentiation into macrophages these cells produce abundant HIV. Latent HIV-infection of monocytes/macrophages provides a unique opportunity for cooperativity between opportunistic infections and HIV in mediating CNS damage.

AIDS Dementia Complex↗
PubMed1991

Immunopathogenesis of HIV encephalitis.

HIV infection leads to severe immunosuppression and in a sub-population of patients, encephalitis. Whether systemic immunosuppression is required for CNS infection is still unclear. However, latent infection of monocytes/macrophages is an important mechanism by which HIV escapes immune surveillance and enters the CNS. Unlike other viral encephalitides, HIV predominantly infects macrophages/microglia and not neurons and glia. These cells produce retroviral proteins and cytokines which may be neurotoxic. Despite significant MHC expression within the CNS, there is a limited infiltration of immune cells, possibly due to a defect in systemic immunity. Anti-retroviral therapy by decreasing viral replication and reversing immunosuppression, may arrest nervous system damage.

Cell Movement↗
PubMed1991

Absence of association of HTLV-I infection with type 1 neurofibromatosis in the United States or Japan.

An HTLV-I tax transgenic mouse model develops a syndrome with similarities to type 1 neurofibromatosis (NF-1). To investigate possible associations between this human retrovirus and NF-1, we have analyzed 67 neurofibromas from Japan (where HTLV-I infection is endemic) and compared them with 21 cases from the United States. We were not able to identify virus in tumor tissue in either group. This suggests that HTLV-I infection is not commonly associated with NF-1.

Amino Acid Sequence↗
PubMed1991

HTLV-I-associated myelopathy: clinicopathologic correlation with localization of provirus to spinal cord.

A 49-year-old South African man developed a rapidly progressive myelopathy 14 months after blood transfusion and died 1 year after the onset of symptoms. Detailed pathologic examination of the spinal cord was consistent with the diagnosis of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although no HTLV-I viral particles, antigens, or nucleic acids were detected in situ, polymerase chain reaction assays revealed HTLV-I proviral DNA in cervical, thoracic, and lumbar levels of the spinal cord, with the greatest amount being detected at the thoracic level. These findings suggest that the pathogenesis of HAM/TSP depends on direct infection of neural or immune elements within the spinal cord.

DNA, Viral↗