Acanthamoeba meningoencephalitis in a patient with AIDS.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
C A Wiley
Publications and source records attributed to C A Wiley.
Implications of the neuropathology of HIV encephalitis for the pathogenesis of Alzheimer disease.
The strong familial association of Alzheimer disease (AD), the difficulty in transmitting the disease to animals, the mapping of the amyloid gene to human chromosome 21, and the non-inflammatory neuropathology have all been considered evidence against a viral etiology for this disease. However, unconventional slow viral infections share some of these traits with AD and yet they are caused by retroviruses or suspected viruses. The recent discovery of 2 human retroviruses causing central nervous system pathology similar to spongiform encephalopathies should prompt renewed search for retroviral causes of human neurodegenerative diseases.
Acquired Immunodeficiency Syndrome↗
Acute ascending necrotizing myelopathy caused by herpes simplex virus type 2.
A 57-year-old diabetic man died of a rapidly ascending necrotizing myelitis. Autopsy results proved that the etiologic agent was herpes simplex virus type 2 (HSV2). The clinical findings, autopsy immunohistopathology, and electron-microscopy suggest that either primary HSV2 infection or reactivation of HSV2 infection within dorsal root ganglia was followed by spread to the spinal cord. Viral infection of the CNS occurred by direct extension and led to death by involvement of the brainstem. Although there is only one previous report of HSV2 myelitis in the literature, our findings suggest that HSV2 might be a more common etiologic agent of necrotizing myelitis. Because CSF cultures are usually negative, viral inclusions are not usually seen, and morphologically identifiable virions are exquisitely rare, previous cases were probably descriptively diagnosed as acute ascending necrotizing myelitis without etiologic identification.
Brain↗
Immuno-gold localization of prion filaments in scrapie-infected hamster brains.
The brains of scrapie-infected hamsters have been examined for the presence of structures antigenically related to the prion protein (PrP 27-30). Glutaraldehyde-perfused hamster brains, 72 days postinfection, were immunostained using rabbit monospecific antisera raised against synthetic peptides corresponding to the N-terminal 13 or 15 amino acids of PrP 27-30, and using rabbit antisera raised against infectious prions or PrP 27-30 purified from scrapie-infected hamster brains. Antisera to the synthetic peptides stained extracellular filaments in agreement with previous immunoperoxidase studies which used affinity-purified PrP 27-30 antibodies; in addition to subependymal and subpial localization, we show ventricular and perivascular staining. Using a colloidal gold-secondary antibody technique, we have demonstrated that the antibodies labeled filaments measuring 7 to 17 nm in diameter. Whereas most of the periventricular and perivascular filaments appeared extracellular, some appeared to be within processes intimately associated with ependymal cells, degenerating membranes of astrocytes, and neurites.
Amino Acid Sequence↗
The effect of carbon dioxide laser irradiation on cranial bone healing. An experimental study.
An experimental study on the effects of carbon dioxide laser irradiation osteotomy of the calvarium of 4-week old rabbits was compared with tht of an osteotomy performed with a high speed drill. Histological studies of calvarium cross sections were performed at 2, 4 and 6 weeks following the osteotomies. As early as 2 weeks following high speed drill osteotomy connective tissue bridged the bone edges. By 4 weeks this bridge was thickened and endowed with numerous vessels. At 6 weeks numerous osteoblasts lined the bone edge and connective tissue bridge. Following laser osteotomy the carbonized edges interrupted the connective tissue from bridging the bone edges at 2, 4 and 6 weeks. By 6 weeks following the laser osteotomy connective tissue had grown past the carbonized residue and the healing process proceeded with osteoblast proliferation from points beyond the carbonized residue. The significance of these findings in reference to the reossification process following osteotomies for craniosynostosis and craniofacial surgery, is discussed.
Animals↗
Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients.
Dysfunction of the central nervous system (CNS) is a prominent feature of the acquired immune deficiency syndrome (AIDS). Many of these patients have a subacute encephalitis consistent with a viral infection of the CNS. We studied the brains of 12 AIDS patients using in situ hybridization to identify human immunodeficiency virus [HIV, referred to by others as human T-cell lymphotropic virus type III (HTLV-III), lymphadenopathy-associated virus (LAV), AIDS-associated retrovirus (ARV)] nucleic acid sequences and immunocytochemistry to identify viral and cellular proteins. Nine patients had significant HIV infection in the CNS. In all examined brains, the white matter was more severely involved than the grey matter. In most cases the infection was restricted to capillary endothelial cells, mononuclear inflammatory cells, and giant cells. In a single case with severe CNS involvement, a low-level infection was seen in some astrocytes and neurons. These results suggest that CNS dysfunction is due to indirect effects rather than neuronal or glial infection.
Acquired Immunodeficiency Syndrome↗
Localization of cytomegalovirus proteins and genome during fulminant central nervous system infection in an AIDS patient.
Approximately one-half of autopsied acquired immune deficiency syndrome (AIDS) patients demonstrate probable human cytomegalovirus (CMV) infection of the central nervous system (CNS). Because CMV in brain tissue or cerebrospinal fluid is difficult to culture, we used antisera, and radioactive probes to diagnose CMV infection in the brain of an autopsied AIDS patient, who died of a fulminant CNS and systemic infection with CMV, suggesting a complete seeding of the ependymal regions possibly followed by a uniform ventriculofugal spread of the virus deep into the parenchyma. Cytomegalic cells were observed in optic nerve, retina, ependymal and subependymal regions of the brain and in the motor (but not sensory) root-CNS junctions. Immunocytochemistry demonstrated viral antigen predominantly in cytomegalic cells, which also stained positively for glial fibrillary acidic protein, S-100, or neuron-specific enolase, but not a common leukocyte antigen. Virions were visible in these cells examined by electron microscopy. No viral replication was observed in pineocytes, pituicytes or the choroid plexus. Morphologically normal cells that were CMV antigen-negative proved to be infected after in situ hybridization with well-defined human CMV DNA fragments. Hence, morphologically normal glia and neurons show restricted replication of CMV, indicating that such cells may be latently infected.
Acquired Immunodeficiency Syndrome↗
Autonomic nerves in experimental allergic neuritis in the rat.
After experimental allergic neuritis (EAN) was induced in 16 male Lewis rats with bovine peripheral myelin and adjuvants, peripheral nerves were examined morphologically at intervals of 12-21 days post inoculation (dpi). Signs of motor involvement were present in ten rats and were first elicited 12 dpi. They ranged from tail droop to complete lower limb paralysis. Autonomic nervous system (ANS) involvement was studied by contrasting morphological findings in the cervical sympathetic nerves (CSN), which are poorly myelinated and vagal nerves (VN) which contain numerous myelinated fibers in the endoneurium. Edema, perivenular infiltrates, and demyelination appeared in the VN of seven of nine neurologically affected rats, while the CSN showed edema and infiltrates in only one rat. ELISA assays were negative for anti-galactocerebroside antibody, and electron microscopy failed to show abnormalities of Schwann cells.
Animals↗
Enzyme-linked immunosorbent assay for detection of specific antibodies to Ureaplasma urealyticum serotypes.
Optimal conditions of a micro-enzyme-linked immunosorbent assay system for the detection of immunoglobulin G antibodies to Ureaplasma urealyticum were established with rabbit antisera. Initially, the antisera, raised against eight U. urealyticum serotypes grown on medium containing horse serum, displayed nonspecific reactions with our enzyme-linked immunosorbent assay antigens. Substitution of fetal bovine serum in the medium eliminated this nonspecificity. The assay was then serotype-specific for the original eight U. urealyticum serotypes. The prominent homologous reaction was easily differentiated from the heterologous reactions. A one-way cross-reaction was observed with serotype 2 antiserum and serotype 5 antigen. The results were reproducible and could be obtained in 4 h with only 10 microliters of serum for eight serotypes. Optimal antigen concentrations for the U. urealyticum serotypes ranged from 0.40 to 1.60 micrograms/ml. Our results indicated that enzyme-linked immunosorbent assay has the potential for the detection of antibodies to specific serotypes of U. urealyticum.
Animals↗
Rows of dimeric-particles within the axolemma and juxtaposed particles within glia, incorporated into a new model for the paranodal glial-axonal junction at the node of Ranvier.
Using freeze-fracture techniques, we have analyzed the glial-axonal junction (GAJ) between Schwann cells and axons in the peripheral nervous system, and between oligodendrocytes and axons in the central nervous system of the rat. We have identified a new set of dimeric-particles arranged in circumferential rows within the protoplasmic fracture faces (P-faces) of the paranodal axolemma in the region of glial-axonal juxtaposition. These particles, 260 A in length, composed of two 115-A subunits, are observed in both aldehyde-fixed and nonfixed preparations. The rows of dimeric-particles within the axonal P-face are associated with complementary rows of pits within the external fracture face (E-face) of the paranodal axolemma. These axonal particles are positioned between rows of 160-A particles that occur in both fracture faces of the glial loops in the same region. We observed, in addition to these previously described 160-A particles, a new set of 75-A glial particles within the glial P-faces of the GAJ. These 75-A particles form rows that are centered between the rows of 160-A particles and are therefore superimposed over the rows of dimeric-particles within the paranodal axolemma. Our new findings are interpreted with respect to methods of specimen preparation as well as to a potential role for the paranodal organ in saltatory conduction. We conclude that this particle-rich junction between axon and glia could potentially provide an intricate mechanism for ion exchange between these two cell types.
Animals↗
Observations on the human corpus luteum: histochemical changes during development and involution.
Morphologic studies of the developing, gestational, and involuting corpus luteum show that rapid structural changes occur and that involution is not associated with an appropriate inflammatory response. Histochemical techniques were used to demonstrate several patterns of enzyme activity. The luteunized granulosa cells stained with increasing intensity for lactic dehydrogenase, succinic dehydrogenase, cytochrome oxidase, glucose-6-phosphatase, and 3 beta-hydroxysteroid dehydrogenase, but reactivity for these enzymes dropped markedly with early involution, and staining was never conspicuous in the organizing cavity. Reactions for acid phosphatase, glucosaminidase, galactosidase, glucuronidase, and nonspecific esterase were also present in the developing corpus luteum, but staining decreased more slowly during involution and was prominent in the occasional macrophages in the granulosa and the granulation tissue in the cavity. Staining was moderately intense for all of the enzymes in the corpus luteum of pregnancy. The decrease in activity for these metabolic enzymes confirms the histologic impression of degeneration, but the loss of staining for lysosomal enzymes was more rapid than expected. The latter finding complicates the hypothesis of involution of involution of the corpus luteum as an example of programmed cell death.
Corpus Luteum↗
In situ nucleic acid hybridization.
Nucleic acid hybridization is a recently developed laboratory technique that allows identification of the genetic material in tissue specimens. The role of the nucleic acids DNA and RNA in cellular function and disease is reviewed, followed by discussion of nucleic acid detection techniques. Earlier methods used to detect nucleic acids were slow and time-consuming. Current in situ detection techniques allow rapid characterization of pathogenic organisms in tissue sections and localization of the pathologic genetic material to specific cellular regions. This technology has been useful in the understanding of viral ocular diseases including herpes keratitis and cytomegalovirus retinitis and also has great potential in the understanding of the pathogenesis of human cancers, genetic disorders and endocrine and immunologic diseases.
DNA↗
Immunoelectron microscopy of Alzheimer and Pick brain tissue labelled with the monoclonal antibody Alz-50.
Previous studies have shown that Alzheimer and Pick brains contain abnormally elevated amounts of a 68 Kd protein detected by the monoclonal antibody Alz-50. We have used immunoperoxidase and immunological techniques to localize Alz-50-reactive epitopes in sections from Alzheimer and Pick brains at the ultrastructural level. Detectable immunoreactivity was restricted to the paired helical filaments of Alzheimer neurofibrillary tangles and to the paired helical and straight filaments of Pick bodies. In Alzheimer tissue, the antibody also labelled scattered neuronal paired helical filaments that were not aggregated into neurofibrillary tangles. Amorphous components of Pick bodies and other constituents in the Alzheimer and Pick brain tissue were not immunostained.
Aged↗
Neuron-enriched second trimester human cultures: growth factor response and in vivo graft survival.
Grafts of first trimester fetal tissue show limited survival and integration in the adult CNS. Alternative grafting strategies have been sought for treatment of neurodegenerative disease. We have developed cultures of human second trimester fetal tissues to study neuronal differentiation. Grafted into the SCID mouse striatum, aggregates of these cultures formed neuron-rich xenografts for at least 8 months. We examined the influence of various neurotrophic factors, including basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), transforming growth factor-beta 1 (TGF-beta1), and hepatocyte growth factor (HGF), on the growth and differentiation of neuronal and glial cell populations. BDNF promoted the survival and differentiation of second trimester neurons whereas bFGF exhibited a strong proliferative effect on precursors and the astroglial population. Our data suggest that second trimester human fetal cultures contain neuroprogenitor cells that can be directed to the neuronal lineage. This process may be amplified by treatment with BDNF, which we hypothesize could improve the long-term in vivo survival of neuron-enriched grafts.
Animals↗
Abnormalities of the brain in AIDS patients: correlation of postmortem MR findings with neuropathology.
The ability of MR to detect CNS lesions in AIDS patients was evaluated by postmortem scanning of 10 formalin-fixed brains. Nine patients had premortem mental status changes and five had focal neurologic deficits. The brains were imaged and sectioned in corresponding planes. MR images showed atrophy in eight of the 10. All grossly identified lesions and areas of MR abnormality were histologically evaluated. Areas of infarction and necrosis associated with cytomegalovirus (CMV) or Toxoplasma gondii were seen as foci of increased signal intensity. Severe ventriculitis and focal gliosis were also visible by MR. Neither CT nor MR was able to detect diffuse CMV- or HIV-associated microglial nodules. Dementia without focal neurologic signs correlated best with the presence of diffuse microglial nodules at pathology. Our results demonstrate the usefulness of correlating postmortem MR imaging with neuropathology, and the relevance of postmortem findings to the interpretation of MR images in living patients.
Acquired Immunodeficiency Syndrome↗
Human immunodeficiency virus within the brains of children with AIDS.
Infants and children with symptomatic human immunodeficiency virus (HIV) infection frequently develop neurologic disease with symptoms and signs of acquired microcephaly, developmental delays, encephalopathy, pyramidal tract signs, and less often, movement disorders and ataxia. However, clinical courses vary and, based upon progression of neurologic findings, we have classified them into 2 broad categories; progressive (loss of previously acquired language and cognitive skills) and plateau (failure to acquire additional developmental skills). We have used immunocytochemistry to localize HIV within the brains of neurologically involved children with AIDS. Interestingly, the brains of those children with a progressive neurologic course showed readily detectable HIV antigen, while those with a plateau course showed little or no detectable HIV. These findings suggest that in children with symptomatic HIV infection, the progressive neurologic deterioration is due to continued presence of HIV within deep white matter and gray matter, while the plateau neurologic course is due to HIV induced damage followed by either limited penetration of virus into the central nervous system, or clearance of virus below detectable limits.
AIDS Dementia Complex↗
Herpes simplex virus brainstem encephalitis in an AIDS patient.
We report a case of a virulent, atypical herpes simplex infection in the brainstem of a patient with Acquired Immune Deficiency Syndrome (AIDS) which was characterized by demyelination and oligodendroglial tropism. At autopsy the brainstem showed demyelination. Immunocytochemistry, in situ hybridization, and electron microscopy confirmed the presence of herpes simplex virus (HSV). Viral cultures demonstrated HSV type 1. Neuroinvasiveness and neurovirulence were studied by intraperitoneal inoculation of susceptible mouse strains (A/J and Balb/cByJ) with different viral titers. The LD50 of the clinical isolate was 5 orders of magnitude greater than the LD50 of a laboratory HSV strain (HSV type 1 KOS). The brains of the mice inoculated with the clinical isolate showed brainstem and cerebellar demyelination.
AIDS-Related Opportunistic Infections↗
Brain HIV burden and length of survival after AIDS diagnosis.
Patients with AIDS in the late stages of disease can develop dementia. Previous studies have suggested HIV encephalitis is the pathological substrate of HIV-associated dementia. We hypothesized that patients who survive longer after the initial diagnosis of AIDS would have a higher brain HIV burden and consequently manifest dementia. We examined the relationship between length of survival after AIDS diagnosis and the presence of HIV encephalitis or HIV-associated dementia. We studied retrospectively the following parameters in 74 consecutive AIDS autopsies: length of survival after AIDS diagnosis, clinical diagnosis of dementia, and neuropathologic findings (including HIV burden assessment). Multinucleated giant cells (MNGC) were identified in 20% of the brains studied. HIV gp41 was detected by immunocytochemistry in 54%, approximately half of which had abundant HIV burden. Brains from all 4 patients who were clinically diagnosed with dementia and had no opportunistic neuropathologic changes contained MNGC and abundant HIV burden. Survival after AIDS diagnosis was significantly longer in patients with MNGC (p = 0.03) or abundant HIV burden (p = 0.02). A trend toward longer survival after AIDS diagnosis was apparent in patients with dementia, but did not reach statistical significance. These findings suggest that prolonged survival with immunosuppression may be a prerequisite for the development of HIV encephalitis.
AIDS Dementia Complex↗