Guidelines for the management of obstructive hydrocephalus from suprasellar-prepontine arachnoid cysts using endoscopic third ventriculocystocisternostomy.

Intracranial endoscopy has emerged as an innovative surgical tool for various intracranial procedures, but its use remains limited to neurosurgeons trained in this minimally invasive technique. Complex, skull base arachnoid cysts represent one entity that is challenging to treat because of adjacent critical neurovascular structures; however, the advent of intracranial endoscopic techniques has revolutionized treatment. Arachnoid cysts located in the suprasellar-prepontine skull base region can cause obstructive hydrocephalus or symptomatic mass effect and require urgent decompression. These patients may present with nonfocal symptoms that can quickly lead to a life-threatening condition if not accurately diagnosed and treated. The authors present a summary of the world literature of suprasellar-prepontine arachnoid cysts (SPACs) to ascertain clinical presentations and provide class III evidentiary treatment guidelines for this uniquely challenging type of arachnoid cyst. Urgent endoscopic third ventriculostomy results in normalization of intracranial pressure, return of normal CSF flow, and relief of symptoms.

Major and minor music compared to excited and subdued speech.

The affective impact of music arises from a variety of factors, including intensity, tempo, rhythm, and tonal relationships. The emotional coloring evoked by intensity, tempo, and rhythm appears to arise from association with the characteristics of human behavior in the corresponding condition; however, how and why particular tonal relationships in music convey distinct emotional effects are not clear. The hypothesis examined here is that major and minor tone collections elicit different affective reactions because their spectra are similar to the spectra of voiced speech uttered in different emotional states. To evaluate this possibility the spectra of the intervals that distinguish major and minor music were compared to the spectra of voiced segments in excited and subdued speech using fundamental frequency and frequency ratios as measures. Consistent with the hypothesis, the spectra of major intervals are more similar to spectra found in excited speech, whereas the spectra of particular minor intervals are more similar to the spectra of subdued speech. These results suggest that the characteristic affective impact of major and minor tone collections arises from associations routinely made between particular musical intervals and voiced speech.

Cryptococcal meningitis in patients with glioma: a report of two cases.

OBJECTIVE AND IMPORTANCE: We describe two patients with high-grade glioma undergoing treatment with corticosteroids and chemotherapy who presented with cryptococcal meningitis and sepsis. This report of two cases highlights the importance of examining the efficacy of prophylactic antibiotic and/or antifungal regimens in this patient population due to their increased risk of opportunistic infections. CLINICAL PRESENTATION: A 73-year-old man with a history of glioblastoma multiforme (GBM), on dexamethasone and status post radiation therapy and two cycles of temozolamide, presented with decreased level of consciousness for 24 h and was found to have cerebrospinal fluid (CSF) and blood cultures positive for Cryptococcus neoformans. A 33-year-old man with a history of anaplastic astrocytoma, on dexamethasone and status post radiation therapy, four cycles of temozolomide and two cycles of Lomustine (CCNU), presented with headache, dizziness and photophobia and was found to have CSF and blood cultures positive for Cryptococcus neoformans. INTERVENTION: Both patients were treated with an initial regimen of amphotericin B and flucytosine for a minimum of two weeks and switched to fluconazole for 6 months to 1 year of treatment. CONCLUSION: Patients with high-grade glioma treated with long-term corticosteroid therapy and chemotherapy are at increased risk of developing opportunistic infections. The two patients reported here developed cryptococcal meningitis and sepsis. Prophylactic regimens with either fluconazole or itraconazole currently exist that effectively decrease the incidence of both cryptococcal infections. Further investigations into the risk:benefit ratio of primary prophylactic therapy in this patient population may prove beneficial.

Chromosome-wide identification of novel imprinted genes using microarrays and uniparental disomies.

Genomic imprinting refers to a specialized form of epigenetic gene regulation whereby the expression of a given allele is dictated by parental origin. Defining the extent and distribution of imprinting across genomes will be crucial for understanding the roles played by imprinting in normal mammalian growth and development. Using mice carrying uniparental disomies or duplications, microarray screening and stringent bioinformatics, we have developed the first large-scale tissue-specific screen for imprinted gene detection. We quantify the stringency of our methodology and relate it to previous non-tissue-specific large-scale studies. We report the identification in mouse of four brain-specific novel paternally expressed transcripts and an additional three genes that show maternal expression in the placenta. The regions of conserved linkage in the human genome are associated with the Prader-Willi Syndrome (PWS) and Beckwith-Wiedemann Syndrome (BWS) where imprinting is known to be a contributing factor. We conclude that large-scale systematic analyses of this genre are necessary for the full impact of genomic imprinting on mammalian gene expression and phenotype to be elucidated.

A novel variant of Inpp5f is imprinted in brain, and its expression is correlated with differential methylation of an internal CpG island.

Using a tissue-specific microarray screen in combination with chromosome anomalies in the mouse, we identified a novel imprinted gene, Inpp5f_v2 on mouse chromosome 7. Characterization of this gene reveals a 3.2-kb transcript that is paternally expressed in the brain. Inpp5f_v2 is a variant of the related 4.7-kb transcript, Inpp5f, an inositol phosphatase gene that is biallelically expressed in the mouse. Inpp5f_v2 uses an alternative transcriptional start site within an intron of Inpp5f and thus has a unique alternative first exon. Whereas other imprinted transcripts have a unique first exon located within intron 1 of a longer transcript variant (such as at the Gnas and WT1 loci), Inpp5f_v2 is the first example of which we are aware in which the alternative first exon of an imprinted gene is embedded in a downstream intron (intron 15) of a transcript variant. The CpG island associated with the non-imprinted Inpp5f gene is hypomethylated on both alleles, a finding consistent with biallelic expression, whereas the CpG island present 5' of Inpp5f_v2 is differentially methylated on the maternal versus paternal alleles consistent with its imprinting status.

Microarray analysis of gene expression in human donor sclera.

PURPOSE: To develop gene expression profiles of human sclera to allow for the identification of novel, uncharacterized genes in this tissue-type, and to identify candidate genes for scleral disorders. METHODS: Total RNA was isolated from 6 donor sources of human sclerae, and reverse transcribed into cDNA using a T7-(dT) 24 primer. The resulting cDNA was in vitro transcribed to produce biotin-labeled cRNA, fragmented, and mixed with hybridization controls before a 16 h hybridization step with oligonucleotide probes on 6 Affymetrix U95A chips. The chips were scanned twice at 570 nM and the data collected using GeneChip software. Array analyses were carried out with Microarray Suite, version 5.0 (Affymetrix), using the expression analysis algorithm to run an absolute analysis after cell intensities were computed. All arrays were scaled to the same target intensity using all probe sets. Reverse-transcription polymerase chain reaction (RT-PCR) was performed to validate the microarray results. RESULTS: There were 3,751 genes with "present" calls assigned independently to all six human scleral samples. These genes could be clustered into 4 major categories; transcription (10%), metabolism (8.8%), cell growth and proliferation (5.4%), and extracellular matrix (2%). Many extracellular matrix proteins, such as collagens 6A3 and 10A1, thrombospondins 2 and 4, and dystroglycan have not previously been shown to be expressed in sclera. RT-PCR results confirmed scleral expression in 7 extracellular matrix genes examined. CONCLUSIONS: This study demonstrated the utility of gene microarray technology in identifying global patterns of scleral gene expression, and provides an extended list of genes expressed in human sclera. Identification of genes expressed in sclera contributes to our understanding of scleral biology, and potentially provides positional candidate genes for scleral disorders such as high myopia.

An Application of Molecular Genotyping in Mice.

Microsatellite markers are simple sequence repeats within the mammalian genome that can be used for identifying disease loci, mapping genes of interest as well as studying segregation patterns related to meiotic nondisjunction. Different strains of mice have variable CA repeat lengths and PCR based methods can be used to identify them, thus allowing for specific genotypes to be assigned. Molecular genotyping offers such identification at any developmental stage, which allows for a broad range of anomalies to be studied. We studied chromosomal segregation in relation to nondisjunction in early-gestation mouse embryos using molecular genotyping. Information on the parental origin as well as the number of chromosomes a given progeny carried was obtained in our analysis.

Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein.

Viruses have developed diverse non-immune strategies to counteract host-mediated mechanisms that confer resistance to infection. The Vif (virion infectivity factor) proteins are encoded by primate immunodeficiency viruses, most notably human immunodeficiency virus-1 (HIV-1). These proteins are potent regulators of virus infection and replication and are consequently essential for pathogenic infections in vivo. HIV-1 Vif seems to be required during the late stages of virus production for the suppression of an innate antiviral phenotype that resides in human T lymphocytes. Thus, in the absence of Vif, expression of this phenotype renders progeny virions non-infectious. Here, we describe a unique cellular gene, CEM15, whose transient or stable expression in cells that do not normally express CEM15 recreates this phenotype, but whose antiviral action is overcome by the presence of Vif. Because the Vif:CEM15 regulatory circuit is critical for HIV-1 replication, perturbing the circuit may be a promising target for future HIV/AIDS therapies.