Familial hemiplegic migraine and autosomal dominant arteriopathy with leukoencephalopathy (CADASIL)

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently described familial cerebrovascular disorder shown to map to chromosome 19q12. Familial hemiplegic migraine has also been shown in some families to map close to the CADASIL locus. The fully developed CADASIL phenotype consists of recurrent strokes developing in the fourth decade, progressing to a pseudobulbar palsy, spastic quadriparesis, and subcortical dementia. In an Irish family 15 members were fully investigated by magnetic resonance scanning; 10 had typical magnetic resonance features of CADASIL. Five members of this family had familial hemiplegic migraine and 4 of these had magnetic resonance evidence of CADASIL. Two other members had migraine with and without aura as a presenting clinical symptom of CADASIL. This disorder has been shown by linkage analysis to map to the CADASIL locus at chromosome 19. The phenotype at presentation of CADASIL in this family was variable and age related and included familial hemiplegic migraine, migraine with and without aura, transient ischemic attacks, strokes, and spinal cord infarction. This family study increases our understanding of the spectrum of clinical manifestations of this underrecognized familial cerebrovascular disorder.     

Sevoflurane versus Halothane: Postoperative Maladaptive Behavioral Changes: A Randomized, Controlled Trial

Background: The authors conducted a double-blind, randomized, controlled trial to determine whether the use of sevoflurane in children undergoing anesthesia and surgery results in a higher incidence of postoperative maladaptive behavioral changes as compared with halothane.

Methods: Children and their parents (n = 102) were randomly assigned to either a halothane group (n = 50) or a sevoflurane group (n = 52). The intraoperative anesthetic protocol was strictly controlled, and the postoperative analgesic consumption and pain levels were recorded. The effect of the group assignment on emergence status and maladaptive postoperative behavioral changes was assessed both by validated psychological measures and physiologic instruments (actigraphy) on postoperative days 1-7. Anxiety of the parent and child was also assessed, as was the child's postoperative recovery (Recovery Inventory).

Results: There were no group differences in preoperative state anxiety, postoperative analgesic requirements, postoperative pain, or the incidence of emergence delirium (P = not significant). Two-way repeated-measures analysis of variance showed no group differences in the incidence of postoperative maladaptive behaviors (F4,72 = 0.60, P = 0.701) or actigraphic variables such as percent sleep, number of night awakenings, and night awakenings that lasted for more than 5 min (P = not significant).     

Decreased diet-induced thermogenesis in gluteal-femoral obesity

Resting metabolic rate (RMR) and diet-induced thermogenesis (DIT), induced by 100 g glucose given orally, were measured in two groups of obese women, characterized by the abdominal or gluteal-femoral type of obesity. No difference in RMR was found between the two groups. Obese women with an abdominal fat mass distribution have a higher and more prolonged DIT in comparison with gluteal-femoral obese women. This finding may help explain why women with upper body obesity are more able to lose weight than women with lower body obesity.     

Role of endogenous cannabinoids in synaptic signaling

Research of cannabinoid actions was boosted in the 1990s by remarkable discoveries including identification of endogenous compounds with cannabimimetic activity (endocannabinoids) and the cloning of their molecular targets, the CB1 and CB2 receptors. Although the existence of an endogenous cannabinoid signaling system has been established for a decade, its physiological roles have just begun to unfold. In addition, the behavioral effects of exogenous cannabinoids such as delta-9-tetrahydrocannabinol, the major active compound of hashish and marijuana, await explanation at the cellular and network levels. Recent physiological, pharmacological, and high-resolution anatomical studies provided evidence that the major physiological effect of cannabinoids is the regulation of neurotransmitter release via activation of presynaptic CB1 receptors located on distinct types of axon terminals throughout the brain. Subsequent discoveries shed light on the functional consequences of this localization by demonstrating the involvement of endocannabinoids in retrograde signaling at GABAergic and glutamatergic synapses. In this review, we aim to synthesize recent progress in our understanding of the physiological roles of endocannabinoids in the brain. First, the synthetic pathways of endocannabinoids are discussed, along with the putative mechanisms of their release, uptake, and degradation. The fine-grain anatomical distribution of the neuronal cannabinoid receptor CB1 is described in most brain areas, emphasizing its general presynaptic localization and role in controlling neurotransmitter release. Finally, the possible functions of endocannabinoids as retrograde synaptic signal molecules are discussed in relation to synaptic plasticity and network activity patterns.     

Agouti-related peptide-expressing neurons are mandatory for feeding

Multiple hormones controlling energy homeostasis regulate the expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus. Nevertheless, inactivation of the genes encoding NPY and/or AgRP has no impact on food intake in mice. Here we demonstrate that induced selective ablation of AgRP-expressing neurons in adult mice results in acute reduction of feeding, demonstrating direct evidence for a critical role of these neurons in the regulation of energy homeostasis.     

Ca2+ imaging of mouse neocortical interneurone dendrites: Ia-type K+ channels control action potential backpropagation

GABAergic interneurones are essential in cortical processing, yet the functional properties of their dendrites are still poorly understood. In this first study, we combined two-photon calcium imaging with whole-cell recording and anatomical reconstructions to examine the calcium dynamics during action potential (AP) backpropagation in three types of V1 supragranular interneurones: parvalbumin-positive fast spikers (FS), calretinin-positive irregular spikers (IS), and adapting cells (AD). Somatically generated APs actively backpropagated into the dendritic tree and evoked instantaneous calcium accumulations. Although voltage-gated calcium channels were expressed throughout the dendritic arbor, calcium signals during backpropagation of both single APs and AP trains were restricted to proximal dendrites. This spatial control of AP backpropagation was mediated by Ia-type potassium currents and could be mitigated by by previous synaptic activity. Further, we observed supralinear summation of calcium signals in synaptically activated dendritic compartments. Together, these findings indicate that in interneurons, dendritic AP propagation is synaptically regulated. We propose that interneurones have a perisomatic and a distal dendritic functional compartment, with different integrative functions.     

FGF-4 signaling is involved in mir-206 expression in developing somites of chicken embryos.

The microRNAs (miRNAs) are recently discovered short, noncoding RNAs, that regulate gene expression in metazoans. We have cloned short RNAs from chicken embryos and identified five new chicken miRNA genes. Genome analysis identified 17 new chicken miRNA genes based on sequence homology to previously characterized mouse miRNAs. Developmental Northern blots of chick embryos showed increased accumulation of most miRNAs analyzed from 1.5 days to 5 days except, the stem cell-specific mir-302, which was expressed at high levels at early stages and then declined. In situ analysis of mature miRNAs revealed the restricted expression of mir-124 in the central nervous system and of mir-206 in developing somites, in particular the developing myotome. In addition, we investigated how miR-206 expression is controlled during somite development using bead implants. These experiments demonstrate that fibroblast growth factor (FGF) -mediated signaling negatively regulates the initiation of mir-206 gene expression. This may be mediated through the effects of FGF on somite differentiation. These data provide the first demonstration that developmental signaling pathways affect miRNA expression. Thus far, miRNAs have not been studied extensively in chicken embryos, and our results show that this system can complement other model organisms to investigate the regulation of many other miRNAs.     

Germinal center and activated b-cell profiles separate Burkitt lymphoma and diffuse large B-cell lymphoma in AIDS and non-AIDS cases

Morphologic features of Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) overlap. No single phenotypic marker or molecular abnormality is pathognomonic. We tested a panel of 8 germinal center (GC) and activated B-cell (ABC) markers for their ability to separate BL and DLBCL. We diagnosed 16 BL and 39 DLBCL cases from 21 patients with AIDS and 34 without AIDS based on traditional morphologic criteria, Ki-67 proliferative index, and c-myc rearrangement (fluorescence in situ hybridization). After immunohistochemically staining tissue microarrays of BL and DLBCL for markers of GC (bcl-6, CD10, cyclin H) and ABC (MUM1, CD138, PAK1, CD44, bcl-2), we scored each case for the percentage of positive cells. Hierarchical clustering yielded 2 major clusters significantly associated with morphologic diagnosis (P < .001). For comparison, we plotted the sum of the GC scores and ABC scores for each case as x and y data points. This revealed a high-GC/low-ABC group and a low-GC/high-ABC group that were associated significantly with morphologic diagnosis (P < .001). Protein expression of multiple GC and ABC markers can separate BL and DLBCL.     

Histiocytic lesions involving the bone marrow

Histiocytic lesions involving the bone marrow include a number of reactive and neoplastic disorders. This article discusses the morphologic, immunophenotypic, and genotypic features of a variety of diseases associated with histiocytes and/or monocytes. Lysosomal storage disorders and hemophagocytic syndromes are often first diagnosed by bone marrow examination. Granulomas involving the bone marrow may also be the first indication of a systemic disorder. Apart from acute and chronic monocytic leukemias, the bone marrow is rarely involved by malignant histiocytic disorders, of which Langerhans cell histiocytosis is the most common.