In malignant tumours, ferumoxtran may show areas of enhancement, even with a 0.15 T intraoperative MR, that do not enhance with gadolinium. Ferumoxtran-enhancing lesions have persistent increased T1 signal intensity for 2-5 days, which may provide advantages over gadolinium for postoperative imaging. Histochemistry for iron shows uptake of ferumoxtran in reactive cells (astrocytes and macrophages) rather than tumour cells.

Interictal activity is a hallmark of epilepsy diagnostics and is linked to neuronal hypersynchrony. Little is known about perturbations in human epileptic neocortical microcircuits, and their role in generating pathological synchronies. To explore hyperexcitability of the human epileptic network, and its contribution to convulsive activity, we investigated an in vitro model of synchronous burst activity spontaneously occurring in postoperative tissue slices derived from patients with or without preoperative clinical and electrographic manifestations of epileptic activity. Human neocortical slices generated two types of synchronies. Interictal-like discharges (classified as epileptiform events) emerged only in epileptic samples, and were hypersynchronous bursts characterized by considerably elevated levels of excitation. Synchronous population activity was initiated in both epileptic and non-epileptic tissue, with a significantly lower degree of excitability and synchrony, and could not be linked to epilepsy. However, in pharmacoresistant epileptic tissue, a higher percentage of slices exhibited population activity, with higher local field potential gradient amplitudes. More intracellularly recorded neurons received depolarizing synaptic potentials, discharging more reliably during the events. Light and electron microscopic examinations showed slightly lower neuron densities and higher densities of excitatory synapses in the human epileptic neocortex. Our data suggest that human neocortical microcircuits retain their functionality and plasticity in vitro, and can generate two significantly different synchronies. We propose that population bursts might not be pathological events while interictal-like discharges may reflect the epileptogenicity of the human cortex. Our results show that hyperexcitability characterizes the human epileptic neocortical network, and that it is closely related to the emergence of synchronies.

Parathyroid hormone receptor 2 (PTH2R) and its ligand, tuberoinfundibular peptide of 39 residues (TIP39) constitute a neuromodulator system implicated in endocrine and nociceptive regulations. We now describe the presence and distribution of the PTH2R and TIP39 in the brain of primates using a range of tissues and ages from macaque and human brain. In situ hybridization histochemistry of TIP39 mRNA, studied in young macaque brain, due to its possible decline beyond late postnatal ages, was present only in the thalamic subparafascicular area and the pontine medial paralemniscal nucleus. In contrast in situ hybridization histochemistry in macaque identified high levels of PTH2R expression in the central amygdaloid nucleus, medial preoptic area, hypothalamic paraventricular and periventricular nuclei, medial geniculate, and the pontine tegmentum. PTH2R mRNA was also detected in several human brain areas by RT-PCR. The distribution of PTH2R-immunoreactive fibers in human, determined by immunocytochemistry, was similar to that in rodents including dense fiber networks in the medial preoptic area, hypothalamic paraventricular, periventricular and infundibular (arcuate) nuclei, lateral hypothalamic area, median eminence, thalamic paraventricular nucleus, periaqueductal gray, lateral parabrachial nucleus, nucleus of the solitary tract, sensory trigeminal nuclei, medullary dorsal reticular nucleus, and dorsal horn of the spinal cord. Co-localization suggested that PTH2R fibers are glutamatergic, and that TIP39 may directly influence hypophysiotropic somatostatin containing and indirectly influence corticotropin releasing-hormone containing neurons. The results demonstrate that TIP39 and the PTH2R are expressed in the brain *Authors for correspondence, proofs and reprint requests: Dr. Ted B. Usdin, Section on Fundamental Neuroscience, NIMH, Bethesda MD 20892-3728, Bldg 35/Rm1B-215. {35 Convent Dr MSC 3728 (U.S. mail)}, Tel.: 301-402-6976; fax.: +1-301-435-5465, e-mail address: E-mail: usdint@mail.nih.gov. Dr. Arpád Dobolyi, Laboratory of Neuromorphology, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest Hungary H-1094, Tüzoltó u. 58. Tel.: +36-1-215-6920/3634, fax.: +36-1-218-1612, email address: E-mail: dobolyi@ana.sote.hu. § These authors contributed equally to this work.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2010 August 4. Keywords tuberoinfundibular peptide; neuroendocrine modulator; primate hypothalamus; subparafascicular area; medial paralemnisc...

Primary central nervous system lymphomas (PCNSL) are aggressive non-Hodgkin lymphomas affecting the central nervous system (CNS). Although immunophenotyping studies suggested an uniform activated B-cell (ABC) origin, more recently a spectrum of ABC and germinal center B-cell (GC) cases has been proposed, with the molecular subtypes of PCNSL still being a matter of debate. With the emergence of novel therapies demonstrating different efficacy between the ABC and GC patient groups, precise assignment of molecular subtype is becoming indispensable. To determine the molecular subtype of 77 PCNSL and 17 secondary CNS lymphoma patients, we used the NanoString Lymphoma Subtyping Test (LST), a gene expression-based assay representing a more accurate technique of subtyping compared with standard immunohistochemical (IHC) algorithms. Mutational landscapes of 14 target genes were determined using ultra-deep next-generation sequencing. Using the LST-assay, a significantly lower proportion (80% vs 95%) of PCNSL cases displayed ABC phenotype compared with the IHC-based characterization. The most frequently mutated genes included MYD88, PIM1, and KMT2D. In summary, we successfully applied the LST-assay for molecular classification of PCNSL, reporting higher proportion of cases with GC phenotype compared with IHC analyses, leading to a more precise patient stratification potentially applicable in the diagnostic algorithm of PCNSL.