Faculty Bibliography

Unlike peripheral lower extremity vascular disease, upper extremity vascular disease is relatively uncommon. While atherosclerosis and embolic disease are the most common causes of upper extremity ischemia, a wide variety of systemic diseases and anatomic abnormalities can affect the upper extremity. Upper extremity ischemia poses a significant diagnostic and therapeutic challenge for both clinicians and radiologists. Although history and physical examination remain the mainstays of diagnosis, imaging can be vital in confirming suspected disease and guiding treatment planning. Digital subtraction angiography is often the preferred method for detection of upper extremity vascular disease, particularly for characterization of complex arteriovenous anatomy such as in vascular malformations and for evaluation of dialysis fistulas and grafts. However, this modality is invasive, requires iodinated contrast agents and radiation, and may fail to demonstrate significant extraluminal disease. More recently, magnetic resonance (MR) angiography techniques have made important advances, permitting higher temporal and spatial resolution that is preferable for diagnosing upper extremity vascular disorders. In this review, the authors present an overview of upper extremity MR angiography techniques and protocols, revisit the often variable vascular anatomy of the arm and hand, and offer examples of various pathologic entities diagnosed with MR angiography. Finally, several imaging pitfalls that one must be aware of for accurate diagnosis are illustrated and reviewed

Gangliosides are a subfamily of complex glycosphingolipids (GSLs) with important roles in many biological processes. In this study, we report the cDNA cloning, functional characterization, and the spatial and temporal expression of Xlcgt and Xlgd3 synthase during Xenopus laevis development. Xlcgt was expressed both maternally and zigotically persisting at least until stage 35. Maternal Xlgd3 synthase mRNA could not be detected and showed a steady-state expression from gastrula to late tailbud stage. Xlcgt is mainly present in involuted paraxial mesoderm, neural folds, and their derivatives. Xlgd3 synthase transcripts were detected in the dorsal blastoporal lip, in the presumptive neuroectoderm, and later in the head region, branchial arches, otic and optic primordia. We determined the effect of glycosphingolipid depletion with 1-phenyl-2-palmitoyl-3-morpholino-1-propanol (PPMP) in mesodermal layer. PPMP-injected embryos showed altered expression domains in the mesodermal markers. Our results suggest that GSL are involved in convergent-extension movements during early development in Xenopus

Reports an error in 'MuSK controls where motor axons grow and form synapses' by Natalie Kim and Steven J. Burden (Nature Neuroscience, 2008[Jan], Vol 11[1], 19-27). In the version of this article initially published online, several items were omitted from the text. These errors have been corrected in the HTML and PDF versions of the article. (The following abstract of the original article appeared in record 2008-05455-009). Motor axons approach muscles that are regionally prespecialized, as acetylcholine receptors are clustered in the central region of muscle before and independently of innervation. This muscle prepattern requires MuSK, a receptor tyrosine kinase that is essential for synapse formation. It is not known how muscle prepatterning is established, and whether motor axons recognize this prepattern. Here we show that expression of Musk is prepatterned in muscle and that early Musk expression in developing myotubes is sufficient to establish muscle prepatterning. We further show that ectopic Musk expression promotes ectopic synapse formation, indicating that muscle prepatterning normally has an instructive role in directing where synapses will form. In addition, ectopic Musk expression stimulates synapse formation in the absence of Agrin and rescues the lethality of Agrn mutant mice, demonstrating that the postsynaptic cell, and MuSK in particular, has a potent role in regulating the formation of synapses. (PsycINFO Database Record (c) 2008 APA, all rights reserved)

Motor axons approach muscles that are regionally prespecialized, as acetylcholine receptors are clustered in the central region of muscle before and independently of innervation. This muscle prepattern requires MuSK, a receptor tyrosine kinase that is essential for synapse formation. It is not known how muscle prepatterning is established, and whether motor axons recognize this prepattern. Here we show that expression of Musk is prepatterned in muscle and that early Musk expression in developing myotubes is sufficient to establish muscle prepatterning. We further show that ectopic Musk expression promotes ectopic synapse formation, indicating that muscle prepatterning normally has an instructive role in directing where synapses will form. In addition, ectopic Musk expression stimulates synapse formation in the absence of Agrin and rescues the lethality of Agrn mutant mice, demonstrating that the postsynaptic cell, and MuSK in particular, has a potent role in regulating the formation of synapses

Time invariant description of synaptic connectivity in cortical circuits may be precluded by the ongoing growth and retraction of dendritic spines accompanied by the formation and elimination of synapses. On the other hand, the spatial arrangement of axonal and dendritic branches appears stable. This suggests that an invariant description of connectivity can be cast in terms of potential synapses, which are locations in the neuropil where an axon branch of one neuron is proximal to a dendritic branch of another neuron. In this paper, we attempt to reconstruct the potential connectivity in local cortical circuits of the cat primary visual cortex (V1). Based on multiple single-neuron reconstructions of axonal and dendritic arbors in 3 dimensions, we evaluate the expected number of potential synapses and the probability of potential connectivity among excitatory (pyramidal and spiny stellate) neurons and inhibitory basket cells. The results provide a quantitative description of structural organization of local cortical circuits. For excitatory neurons from different cortical layers, we compute local domains, which contain their potentially pre- and postsynaptic excitatory partners. These domains have columnar shapes with laminar specific radii and are roughly of the size of the ocular dominance column. Therefore, connections between most excitatory neurons in the ocular dominance column can be implemented by local synaptogenesis. Structural connectivity involving inhibitory basket cells is generally weaker than excitatory connectivity. Here, only nearby neurons are capable of establishing more than one potential synapse, implying that within the ocular dominance column these connections have more limited potential for circuit remodeling.

Protein synthesis is required for the expression of enduring memories and long-lasting synaptic plasticity. During cellular proliferation and growth, S6 kinases (S6Ks) are activated and coordinate the synthesis of de novo proteins. We hypothesized that protein synthesis mediated by S6Ks is critical for the manifestation of learning, memory, and synaptic plasticity. We have tested this hypothesis with genetically engineered mice deficient for either S6K1 or S6K2. We have found that S6K1-deficient mice express an early-onset contextual fear memory deficit within one hour of training, a deficit in conditioned taste aversion (CTA), impaired Morris water maze acquisition, and hypoactive exploratory behavior. In contrast, S6K2-deficient mice exhibit decreased contextual fear memory seven days after training, a reduction in latent inhibition of CTA, and normal spatial learning in the Morris water maze. Surprisingly, neither S6K1- nor S6K2-deficient mice exhibited alterations in protein synthesis-dependent late-phase long-term potentiation (L-LTP). However, removal of S6K1, but not S6K2, compromised early-phase LTP expression. Furthermore, we observed that S6K1-deficient mice have elevated basal levels of Akt phosphorylation, which is further elevated following induction of L-LTP. Taken together, our findings demonstrate that removal of S6K1 leads to a distinct array of behavioral and synaptic plasticity phenotypes that are not mirrored by the removal of S6K2. Our observations suggest that neither gene by itself is required for L-LTP but instead may be required for other types of synaptic plasticity required for cognitive processing

The main psychoactive component of marijuana, Delta9-tetrahydrocannabinol (THC), acts in the CNS via type 1 cannabinoid receptors (CB1Rs). The behavioral consequences of THC or synthetic CB1R agonists include suppression of motor activity. One explanation for movement suppression might be inhibition of striatal dopamine (DA) release by CB1Rs, which are densely localized in motor striatum; however, data from previous studies are inconclusive. Here we examined the effect of CB1R activation on locally evoked DA release monitored with carbon-fiber microelectrodes and fast-scan cyclic voltammetry in striatal slices. Consistent with previous reports, DA release evoked by a single stimulus pulse was unaffected by WIN55,212-2, a cannabinoid receptor agonist. However, when DA release was evoked by a train of stimuli, WIN55,212-2 caused a significant decrease in evoked extracellular DA concentration ([DA]o), implicating the involvement of local striatal circuitry, with similar suppression seen in guinea pig, rat, and mouse striatum. Pulse-train evoked [DA]o was not altered by either AM251, an inverse CB1R agonist, or VCHSR1, a neutral antagonist, indicating the absence of DA release regulation by endogenous cannabinoids with the stimulation protocol used. However, both CB1R antagonists prevented and reversed suppression of evoked [DA]o by WIN55,212-2. The effect of WIN55,212-2 was also prevented by picrotoxin, a GABAA receptor antagonist, and by catalase, a metabolizing enzyme for hydrogen peroxide (H2O2). Furthermore, blockade of ATP-sensitive K+ (KATP) channels by tolbutamide or glybenclamide prevented the effect of WIN55,212-2 on DA release. Together, these data indicate that suppression of DA release by CB1R activation within striatum occurs via a novel nonsynaptic mechanism that involves GABA release inhibition, increased generation of the diffusible messenger H2O2, and activation of KATP channels to inhibit DA release. In addition, the findings suggest a possible physiological substrate for the motor effects of cannabinoid agonist administration

OBJECTIVE/HYPOTHESIS:: The role of fungal pathogens in the etiology of nasal polyposis remains unclear. The aim of this study was to determine whether there was a correlation between the presence of Alternaria-specific immunoglobulin (Ig)E antibodies, eosinophilic inflammation, and the development of nasal polyps. STUDY DESIGN:: Prospective study. METHODS:: Serum and nasal tissue homogenates from 21 patients with manifestations of chronic sinusitis with nasal polyps were compared with specimens from 13 chronic sinusitis patients without polyps and 8 healthy controls. The Phadia ImmunoCAP and enzyme-linked immunosorbent assay were used to quantify levels of total IgE and Alternaria-specific (IgE, IgG, and IgA) antibodies. Eosinophil cationic protein (ECP) and tryptase levels were measured in tissue homogenates, whereas the inflammatory response was evaluated using tissue eosinophil counts in tissue samples. RESULTS:: Serum analysis revealed no difference in the levels of total IgE and Alternaria-specific IgE, IgG, and IgA antibodies between the study groups. In contrast, the levels of Alternaria-specific IgE in tissue with polyps were significantly higher than in nonpolyp tissue. Increases in total tissue IgE paralleled increased levels of Alternaria-specific IgG and IgA antibodies in chronic sinusitis with nasal polyps as compared with control groups. A positive correlation was found between Alternaria-specific IgE and ECP in tissue. Increased mean levels of ECP corresponded to increased eosinophil counts in the group of patients with polyps. CONCLUSIONS:: Alternaria-specific IgE and eosinophilic inflammation in nasal tissue correlates with the incidence of nasal polyps irrespective of specific IgE antibodies in serum. Together, the correlation between the local immune responses and the eosinophilic inflammation in nasal polyps suggests a possible role of Alternaria in the pathogenesis of nasal polyposis