Prevalence of hepatitis B and C in patients with meningiomas and glioblastoma multiforme.

The prevalence of hepatitis B and C in patients with glioblastoma multiforme or meningiomas has not been described. These infections are known to modulate the activity of the immune system, which potentially influences the development and course of cancer. We hypothesized that chronic hepatitis infection, which activates the immune system, decreases the risk of brain tumors, particularly those that are highly malignant. We performed a retrospective study to examine the prevalence of hepatitis B and C in patients with meningiomas and glioblastomas. The combined prevalence of hepatitis B and C in the USA from 1999-2008 was 5.7%. The prevalence of hepatitis B and C in patients with meningiomas was 2.4%; while among glioblastoma patients, the prevalence of hepatitis B and C was 1.38%. The odds ratio of having hepatitis B or C with glioblastoma versus meningiomas was 0.56, with a confidence interval of 0.19-1.6 and a P-value of 0.29. Compared with historical controls, the prevalence of hepatitis B and C in meningioma and glioblastoma patients was decreased. However, this difference may be attributed to the retrospective nature of our data and the natural history of hepatitis B and C infections. The prevalence of these viral infections was not statistically different in patients with meningiomas and glioblastomas. This suggests that hepatitis B and C primarily influence slow-growing, benign tumors and more aggressive cancers equally, if at all. To definitively test our hypothesis, future studies in which data are prospectively gathered are likely to be required.

Transoral Surgical Approach for Retropharyngeal Node Involvement in I-131-Negative 18-fluoro-2-deoxyglucose Positron Emission Tomography-Positive Recurrent Thyroid Cancer.

Transoral pharyngotomy is a viable minimally invasive approach for resection of metastatic thyroid cancer in retropharyngeal lymph nodes in highly select patients. A few authors have already reported on its safe application with excellent outcomes. We herein describe a case where the technique is assisted with the Omniguide CO(2) laser system to safely access and remove a metastatic node in the retropharyngeal space of a 24 year-old Caucasian woman. Furthermore, her disease was I-131-negative and positron emission tomography-positive, demonstrating the technique is still feasible in this dedifferentiated cancer state.

Inverse temporal contributions of the dorsal hippocampus and medial prefrontal cortex to the expression of long-term fear memories.

Retrograde amnesia following disruptions of hippocampal function is often temporally graded, with recent memories being more impaired. Evidence supports the existence of one or more neocortical long-term memory storage/retrieval site(s). Neurotoxic lesions of the medial prefrontal cortex (mPFC) or the dorsal hippocampus (DH) were made 1 day or 200 days following trace fear conditioning. Recently encoded trace fear memories were most disrupted by DH lesions, while remotely encoded trace and contextual memories were most disrupted by mPFC lesions. These data strongly support the consolidation theory of hippocampus function and implicate the mPFC as a site of long-term memory storage/retrieval.

Dorsal hippocampus involvement in delay fear conditioning depends upon the strength of the tone-footshock association.

The hippocampus is important for the formation of spatial, contextual, and episodic memories. For instance, lesions of the dorsal hippocampus (DH) produce demonstrable deficits in contextual fear conditioning. By contrast, it is generally agreed that the DH is not important for conditioning to a discrete cue (such as a tone or light) that is paired with footshock in a temporally contiguous fashion (delay conditioning). There are, however, some reports of hippocampus involvement in delay conditioning. The present series of experiments was designed to assess the conditions under which the hippocampus-dependent component of delay fear conditioning performance may be revealed. Here, we manipulated the number of conditioning trials and the intensity of the footshock in order to vary the strength of conditioning. The results indicate that the DH contributes to freezing performance to a delay conditioned tone when the conditioning parameters are relatively weak (few trials or low footshock intensity), but not when strong parameters are used. The results are discussed in terms of two parallel memory systems: a direct tone-footshock association that is independent of the hippocampus and a hippocampus-dependent memory for the conditioning session.

Dorsal hippocampus NMDA receptors differentially mediate trace and contextual fear conditioning.

The dorsal hippocampus (DH) is critically involved in the acquisition and expression of trace and contextual fear conditioning. NMDA/glutamate receptor-mediated transmission is thought to be one mechanism mediating the plastic changes that support long-term memories in the DH. However, their precise involvement in acquisition and expression processes has not been defined. To examine this issue, the NMDA receptor antagonist, D,L-2-amino-5-phosphonovaleric acid (APV; 10 microg/microl; 0.5 microl), was infused into the DH prior to conditioning and/or testing, using a trace fear conditioning procedure. All rats were tested for freezing to both tone and context in separate, counterbalanced sessions. The three sessions (1 training and 2 test) were separated by approximately 24 h. Using this design, it was possible to assess the role for DH NMDA receptors in the acquisition versus expression of trace and contextual fear conditioning. APV disrupted acquisition, but not expression, of contextual fear conditioning. By contrast, APV attenuated both acquisition and expression of trace fear memories. Thus, DH NMDA receptors appear to contribute to retrieval of some, but not all, fear memories.

Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain.

Catechol-O-methyltransferase (COMT) is a key enzyme in the elimination of dopamine in the prefrontal cortex of the human brain. Genetic variation in the COMT gene (MIM 116790) has been associated with altered prefrontal cortex function and higher risk for schizophrenia, but the specific alleles and their functional implications have been controversial. We analyzed the effects of several single-nucleotide polymorphisms (SNPs) within COMT on mRNA expression levels (using reverse-transcriptase polymerase chain reaction analysis), protein levels (using Western blot analysis), and enzyme activity (using catechol methylation) in a large sample (n = 108) of postmortem human prefrontal cortex tissue, which predominantly expresses the -membrane-bound isoform. A common coding SNP, Val158Met (rs4680), significantly affected protein abundance and enzyme activity but not mRNA expression levels, suggesting that differences in protein integrity account for the difference in enzyme activity between alleles. A SNP in intron 1 (rs737865) and a SNP in the 3' flanking region (rs165599)--both of which have been reported to contribute to allelic expression differences and to be associated with schizophrenia as part of a haplotype with Val--had no effect on mRNA expression levels, protein immunoreactivity, or enzyme activity. In lymphocytes from 47 subjects, we confirmed a similar effect on enzyme activity in samples with the Val/Met genotype but no effect in samples with the intron 1 or 3' SNPs. Separate analyses revealed that the subject's sex, as well as the presence of a SNP in the P2 promoter region (rs2097603), had small effects on COMT enzyme activity. Using site-directed mutagenesis of mouse COMT cDNA, followed by in vitro translation, we found that the conversion of Leu at the homologous position into Met or Val progressively and significantly diminished enzyme activity. Thus, although we cannot exclude a more complex genetic basis for functional effects of COMT, Val is a predominant factor that determines higher COMT activity in the prefrontal cortex, which presumably leads to lower synaptic dopamine levels and relatively deleterious prefrontal function.