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Ravi Raghavan

Publications and source records attributed to Ravi Raghavan.

8 recordsLinked to original sources
PubMed2026

High-grade astrocytoma with piloid features: a clinical and genomic analysis of prognostic factors using a large cohort.

BACKGROUND: High-grade astrocytoma with piloid features (HGAP) is a recently defined tumor type that is not well-understood. Prognostic factors of clinical outcomes are not well-established. METHODS: Methylation profiling was performed on tumor samples, many at the National Cancer Institute (NCI) Laboratory of Pathology, and others from publicly available sources. Methylation classifier scores of ≥ 0.90 to the HGAP class on the NCI-Bethesda classifier version 3 were included. Clinical features were collected from the medical record. Survival analyses were performed using the Kaplan-Meier and Cox-proportional hazards methods. RESULTS: The cohort comprised 421 patients. There were high rates of ATRX alteration (62%), CDKN2A/B homozygous loss (78%) and MGMT promoter methylation (53%). MAPK alterations were identified in 74% of evaluable samples. The median age was 46 years, and posterior fossa location was predominant (52%). The median overall survival (OS) was 88 months. Older age (p = 0.01) and the presence of an ATRX alteration (p = 0.04) were found to be negative prognostic factors. The presence of cystic features on magnetic resonance imaging (MRI) was found to be favorably prognostic (p = 0.01). Factors that were not significantly associated with prognosis included histologic high-grade features, CDKN2A/B homozygous deletion, MGMT promoter methylation, extent of resection, and presence of NF1 syndrome. CONCLUSIONS: This large cohort establishes relative frequencies of several important markers. Additionally, older age, the presence of an ATRX alteration, and cystic features on MRI were found to be prognostic. Our work may aid in optimizing treatment regimens for patients with this tumor type.

ATRX alteration↗
PubMed2004

Alpha-synuclein expression in the developing human brain.

Alpha (alpha)-synuclein is a presynaptic protein, abnormal expression of which has been associated with neurodegenerative and neoplastic diseases. It is abundant in the developing vertebrate central nervous system (CNS), but less is known about its developmental expression in the human CNS. Immunohistochemical expression of alpha-synuclein was studied in 39 fetal, perinatal, pediatric, and adolescent brains. Perikaryal expression of alpha-synuclein is observed as early as 11-wk gestation in the cortical plate. Several discrete neuronal groups in the hippocampus, basal ganglia, and brain stem express perikaryal alpha-synuclein by 20-wk gestation, persisting through the first few years of life. In the cerebellum, alpha-synuclein is present by 21-wk gestation and persists into adult life as a coarse granular neuropil reaction product in the internal granular layer, and as a diffuse neuropil "blush" in the molecular layer. The germinal matrix, glia, endothelial cells, external granular layer, Pukinje cells, and dentate neurons are consistently negative for alpha-synuclein. We conclude that alpha-synuclein is expressed very early in human gestation, and that its distribution and temporal sequence of expression varies in discrete neuronal groups. Perikaryal alpha-synuclein starts disappearing from the neuronal cytosol in early childhood, and only the neuropil retains immunoreactivity into adulthood. The reappearance of alpha-synuclein in the adult neuronal cytosol in certain disease processes may represent reemergence of cues from an earlier developmental stage as part of a stress response.

Adolescent↗
PubMed2003

Pediatric oligodendrogliomas: a study of molecular alterations on 1p and 19q using fluorescence in situ hybridization.

Oligodendrogliomas (OGs) are rare in children and have not been well characterized from a molecular viewpoint. In adults, losses on chromosomes 1p and/or 19q are common in "oligodendroglial" neoplasms and are highly associated with chemosensitivity and greater length of survival, especially in the anaplastic category. We have analyzed the 1p/19q status of pediatric OGs and compared it with similar alterations in adult OGs. Paraffin sections from 26 pediatric OGs (21 WHO Grade II OGs: 2 anaplastic oligodendrogliomas [AOGs]: and 3 mixed oligo-astrocytomas [MOA]) were retrieved. Fluorescence in situ hybridization (FISH) was performed using probes spanning the 1p32 and 19q13 regions. In tumors from children 0 to 9 years of age (n = 15), none had any deletions on 1p or 19q, but 2 had polysomies for 1p and/or 19q. All are alive and 4 have had recurrences. In tumors from children > 9 years, losses were identified on chromosomes 1p (5/11; 45%) and/or 19q (3/11; 27%), but to a much lesser extent than that observed in adult OGs. Tumors from 6 older patients also had polysomies for 1p and/or 19q. Although the majority of the older children are alive, 4 had recurrences. Curiously, 2 of the older children with AOGs had combined losses and polysomies on 1p and 19q, but responded poorly to treatment and died within a year. We conclude that alterations on 1p or 19q are infrequent in pediatric compared to adult OGs and are virtually absent in OGs presenting in the first decade of life. Compared to adults therefore, different genetic pathways are likely involved in the pathogenesis of most pediatric OGs. Genomic screening on a larger series is clearly indicated to delineate the unique molecular characteristics of these rare pediatric tumors.

Adolescent↗
PubMed2002

Innate differences between simian-human immunodeficiency virus (SHIV)(KU-2)-infected rhesus and pig-tailed macaques in development of neurological disease.

Neurological disease associated with HIV infection results from either primary replication of the virus or a combination of virus infection and replication of opportunistic pathogens in the CNS. Recent studies indicate that the primary infection is mediated mainly by viruses that utilize CCR5 as the coreceptor; it is not known whether the syndrome can be mediated by viruses that use the CXCR4 coreceptor. The macaque model of the disease using simian immunodeficiency virus (SIV) has confirmed that CCR5-using viruses such as SIV(mac)251 can cause primary disease in the CNS. In this report we have examined the role of simian-human immunodeficiency virus (SHIV)(KU-2), a CXCR4 virus which replicates productively in rhesus macrophages, in causing CNS disease. A survey of archival brain tissues from SHIV(KU-2)-infected rhesus and pig-tailed macaques that succumbed to AIDS showed productive viral replication in the CNS of 10 of 14 rhesus animals. Eight of these 10 had additional infections with opportunistic pathogens. In contrast, 21 of 22 pig-tailed macaques had no evidence of productive viral infection in the brain. In an earlier study we had shown that inoculation of SHIV-infected rhesus macaques with eggs of Schistosoma mansoni, a potent inducer of IL-4, resulted in enhanced replication of the virus in tissue macrophages. In the present study, we compared the replication of the virus in macrophages from normal rhesus and pig-tailed macaques and determined further whether exogenous IL-4 could cause enhancement of virus replication in these cells. These studies showed that the virus replicated productively in rhesus macrophages, and this was enhanced significantly after recombinant macaque IL-4 was added to the medium. IL-4 also caused enhancement of virus production in macrophages isolated from virus-infected animals. In contrast, the virus replicated only minimally in pig-tailed macaque macrophages and supplemental IL-4 had negligible effects. The data thus suggested that failure of pig-tailed macaques to develop encephalitis was due to the innate resistance of macrophages from this species of macaque to support replication of SHIV(KU-2). The ability of the virus to replicate in the brains of rhesus macaques was dependent on coinfection in the brain with opportunistic pathogens which presumably induced both macrophages and IL-4 in the CNS microenvironment. A supportive role for IL-4 in the CNS disease was suggested by the presence of IL-4 RNA in the encephalitic brains of rhesus macaques and reduced levels of this cytokine in the brains from pig-tailed macaques.

Acquired Immunodeficiency Syndrome↗