Neuropathology of the Brain in Hiv Infection

Lantos, Peter L.; Scholtz, Carl L.; McLaughlin, James E.; Berry, C. L.; Tighe, J. R.

doi:10.1016/s0140-6736(89)91316-0

Cited by 67 publications

(20 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For each miRNA, a list of all targets present on the array is generated (m); from that list of targets, the number k targets are found to be significantly dysregulated within each of the four windows. Using cumulative hypergeometric distribution from SPSS software [41], we calculated the probability that k targets would be dysregulated from a list of size n genes, given that there are m targets on the gene array of the population N genes. (Using the function: P = 1-cdst.hypergeo(k,n,N,m) in SPSS).…”

Section: Resultsmentioning

confidence: 99%

Evidence for Alteration of Gene Regulatory Networks through MicroRNAs of the HIV-Infected Brain: Novel Analysis of Retrospective Cases

et al. 2010

View full text Add to dashboard Cite

HIV infection disturbs the central nervous system (CNS) through inflammation and glial activation. Evidence suggests roles for microRNA (miRNA) in host defense and neuronal homeostasis, though little is known about miRNAs' role in HIV CNS infection. MiRNAs are non-coding RNAs that regulate gene translation through post-transcriptional mechanisms. Messenger-RNA profiling alone is insufficient to elucidate the dynamic dance of molecular expression of the genome. We sought to clarify RNA alterations in the frontal cortex (FC) of HIV-infected individuals and those concurrently infected and diagnosed with major depressive disorder (MDD). This report is the first published study of large-scale miRNA profiling from human HIV-infected FC. The goals of this study were to: 1. Identify changes in miRNA expression that occurred in the frontal cortex (FC) of HIV individuals, 2. Determine whether miRNA expression profiles of the FC could differentiate HIV from HIV/MDD, and 3. Adapt a method to meaningfully integrate gene expression data and miRNA expression data in clinical samples. We isolated RNA from the FC (n = 3) of three separate groups (uninfected controls, HIV, and HIV/MDD) and then pooled the RNA within each group for use in large-scale miRNA profiling. RNA from HIV and HIV/MDD patients (n = 4 per group) were also used for non-pooled mRNA analysis on Affymetrix U133 Plus 2.0 arrays. We then utilized a method for integrating the two datasets in a Target Bias Analysis. We found miRNAs of three types: A) Those with many dysregulated mRNA targets of less stringent statistical significance, B) Fewer dysregulated target-genes of highly stringent statistical significance, and C) unclear bias. In HIV/MDD, more miRNAs were downregulated than in HIV alone. Specific miRNA families at targeted chromosomal loci were dysregulated. The dysregulated miRNAs clustered on Chromosomes 14, 17, 19, and X. A small subset of dysregulated genes had many 3′ untranslated region (3′UTR) target-sites for dysregulated miRNAs. We provide evidence that certain miRNAs serve as key elements in gene regulatory networks in HIV-infected FC and may be implicated in neurobehavioral disorder. Finally, our data indicates that some genes may serve as hubs of miRNA activity.

show abstract

Section: Resultsmentioning

confidence: 99%

Evidence for Alteration of Gene Regulatory Networks through MicroRNAs of the HIV-Infected Brain: Novel Analysis of Retrospective Cases

et al. 2010

View full text Add to dashboard Cite

show abstract

“…At least 10% of all patients with AIDS present initially with neurological complaints, and more than one third will manifest a clinically apparent neurological disorder sometime during the course of their disease [17]. On autopsy series, evidence of significant neuropathologic abnormalities has been shown in 75-90% of patients with AIDS, and usually more than one disease process was present [18]. The CNS infections in the AIDS population share some atypical clinical and imaging characteristics, different from the corresponding picture in individuals with normal immune status.…”

Section: Aids-related Infectionsmentioning

confidence: 99%

Cerebral infections

Karampekios

Hesselink

2004

Eur Radiol

View full text Add to dashboard Cite

Despite the development of many effective antibiotic therapies and the general improvement in hygiene and health care systems all over the world, the incidence of central nervous system (CNS) infection has increased significantly in the past 15 years. This can be attributed primarily to the acquired immunodeficiency syndrome (AIDS) epidemic and its devastating effect on the immune system and secondarily to various immunosuppressive agents that are being used in aggressive cancer treatment and in organ transplantations. The brain particularly is protected from infection by the calvarium, meninges and blood brain barrier. However, different types of pathogens, including bacteria, viruses, fungi and parasites, can reach the brain hematogenously or, less likely, by direct extension from an adjacent infected focus. The early detection and specific diagnosis of infection are of great importance, since brain infections are potentially treatable diseases. Imaging studies play a crucial role in the diagnostic process, along with the history (exposure to infectious agents), host factors (open head trauma, CSF leak, sinusitis, otitis, immune status), physical examination and laboratory analysis of CSF.

show abstract

“…23 Very few reports have described the presence of MNE, associated with CMV infection 3 or varicella encephalitis 5 after BMT. In our patients, MNE was noted in 10 of 49 patients with diffuse rod cell hyperplasia.…”

mentioning

confidence: 99%

Neuropathological findings after bone marrow transplantation: an autopsy study of 180 cases

Bleggi-Torres

Medeiros

Werner

et al. 2000

Bone Marrow Transplant

147

View full text Add to dashboard Cite

Summary:We prospectively evaluated the neuropathological complications of 180 patients who underwent autopsy studies following bone marrow transplantation (BMT) (177 allogeneic, three autologous). The most frequent underlying disorders included severe aplastic anemia (n = 55), chronic myelogenous leukemia (n = 53), acute myelogenous leukemia (n = 24) and Fanconi anemia (n = 16). There were 114 males and 66 females. Neuropathological findings were detected in 90.55% of the patients. The most frequent findings were subarachnoid hemorrhages (SAH) (n = 57), intraparenchymal hemorrhages (IHP) (n = 49), fungal infections (n = 16), Wernicke's encephalopathy (n = 10), microglial nodular encephalopathy (n = 10) and neurotoxoplasmosis (n = 8). In only 17 patients was the brain within normal limits. Survival time after BMT averaged 5.4 months and the majority of patients died in the first 3 months post BMT (n = 105). Central nervous system (CNS) pathology was the main cause of death in 17% of the patients (n = 31), with a predominance of IHP in this particular group. Furthermore, the survival time of these patients who died of CNS causes (96.3 days) was almost half of the survival time of those who died of extra-cerebral causes (177.8 days) (P = 0.0162). IHP (70.96 vs 27.22%) (P Ͻ 0.001), fungal infections (25.8 vs 8.88%) (P Ͻ 0.001) and toxoplasmosis (9.67 vs 4.44%) (P Ͻ 0.001) were significantly more frequent in the group of patients who died due to CNS causes than in the control group. The findings of this work provide a possible guide to the possible causes of neurological syndromes following BMT. Bone Marrow Transplantation (2000) 25, 301-307. Keywords: central nervous system; bone marrow transplantation; cerebrovascular disorders; infections Bone marrow transplantation (BMT) is used to treat several malignant diseases, severe aplastic anemia, immunodeficiencies and metabolic disorders.1,2 It allows use of potentially lethal doses of chemotherapy and/or irradiation to eradicate systemic malignancy or poorly functioning con-

show abstract

Neuropathology of the Brain in Hiv Infection

Cited by 67 publications

References 18 publications

Evidence for Alteration of Gene Regulatory Networks through MicroRNAs of the HIV-Infected Brain: Novel Analysis of Retrospective Cases

Evidence for Alteration of Gene Regulatory Networks through MicroRNAs of the HIV-Infected Brain: Novel Analysis of Retrospective Cases

Cerebral infections

Neuropathological findings after bone marrow transplantation: an autopsy study of 180 cases

Contact Info

Product

Resources

About