bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a New Genetic Model for Absence Epilepsy: Spike-Wave Seizures in C3H/He and Backcross Mice
Authors: Frankel Wayne N. , Beyer Barbara , Maxwell Christina R. , Pretel Stephanie , Letts Verity A. , Siegel Steven J.
Published: March 2005

To characterize the genetic basis of spike-wave discharges (SWDs) detected by electroencephalography (EEG) in C3H/He mice, substrains of C3H mice were evaluated by EEG and sensitivity to ethosuximide. Crosses with the SWD-negative strain C57BL/6J were performed to map the underlying gene(s). C3H/He substrains exhibited a modest incidence (average of 19 SWDs per hour) of 7-8 Hz SWDs when at rest, compared with the C3HeB/Fe subline (four SWDs per hour). In the mapping backcross, however, many mice showed a very high incidence (50-220 SWDs per hour) throughout the recording period. SWDs were first detected at 3.5 weeks of age, were associated with behavioral arrest, were suppressed by ethosuximide, and were strongest in the cerebral cortex and thalamus. The major C3H determinant of SWDs,spkw1(spike-wave 1), mapped to chromosome (Chr 9), and together with a C57BL/6J determinant on Chr 8,spkw2, accounted for more than one-half of the phenotypic variation in the backcross mice. The modest SWD incidence in C3H/He mice and the high incidence in backcrosses implies that SWD could be a confounding variable for other behaviors. Because C3H/He mice have no other brain abnormalities, they are an attractive alternative for studying idiopathic absence epilepsy.
Relationship between Membrane Phosphatidylinositol-4,5-Bisphosphate and Receptor-Mediated Inhibition of Native Neuronal M Channels
Authors: Winks Joanna S. , Hughes Simon , Filippov Alexander K. , Tatulian Lucine , Abogadie Fe C. , Brown David A. , Marsh Stephen J.
Published: March 2005

The relationship between receptor-induced membrane phosphatidylinositol-4′5′-bisphosphate (PIP2) hydrolysis and M-current inhibition was assessed in single-dissociated rat sympathetic neurons by simultaneous or parallel recording of membrane current and membrane-to-cytosol translocation of the fluorescent PIP2/inositol 1,4,5-trisphosphate (IP3)-binding peptide green fluorescent protein-tagged pleckstrin homology domain of phospholipase C (GFP-PLCδ-PH). The muscarinic receptor agonist oxotremorine-M produced parallel time- and concentration-dependent M-current inhibition and GFP-PLCδ-PH translocation; bradykinin also produced parallel time-dependent inhibition and translocation. Phosphatidylinositol-4-phosphate-5-kinase (PI5-K) overexpression reduced both M-current inhibition and GFP-PLCδ-PH translocation by both oxotremorine-M and bradykinin. These effects were partly reversed by wortmannin, which inhibits phosphatidylinositol-4-kinase (PI4-K). PI5-K overexpression also reduced the inhibitory action of oxotremorine-M on PIP2-gated G-protein-gated inward rectifier (Kir3.1/3.2) channels; bradykinin did not inhibit these channels. Overexpression of neuronal calcium sensor-1 protein (NCS-1), which increases PI4-K activity, did not affect responses to oxotremorine-M but reduced both fluorescence translocation and M-current inhibition by bradykinin. Using an intracellular IP3membrane fluorescence-displacement assay, initial mean concentrations of membrane [PIP2] were estimated at 261 μm(95% confidence limit; 192-381 μm), rising to 693 μm(417-1153 μm) in neurons overexpressing PI5-K. Changes in membrane [PIP2] during application of oxotremorine-M were calculated from fluorescence data. The results, taken in conjunction with previous data for KCNQ2/3 (Kv7.2/Kv7.3) channel gating by PIP2(Zhang et al., 2003), accorded with the hypothesis that the inhibitory action of oxotremorine-M on M current resulted from depletion of PIP2. The effects of bradykinin require additional components of action, which might involve IP3-induced Ca2+release and consequent M-channel inhibition (as proposed previously) and stimulation of PIP2synthesis by Ca2+-dependent activation of NCS-1.
A Dissociation of Encoding and Retrieval Processes in the Human Hippocampus
Authors: Eldridge Laura L. , Engel Stephen A. , Zeineh Michael M. , Bookheimer Susan Y. , Knowlton Barbara J.
Published: March 2005

The hippocampal formation performs two related but distinct memory functions: encoding of novel information and retrieval of episodes. Little evidence, however, resolves how these two processes are implemented within the same anatomical structure. Here we use high-resolution functional magnetic resonance imaging to show that distinct subregions of the hippocampus are differentially involved in encoding and retrieval. We found that regions early in the hippocampal circuit (dentate gyrus and CA fields 2 and 3) were selectively active during episodic memory formation, whereas a region later in the circuit (the subiculum) was active during the recollection of the learning episode. Different components of the hippocampal circuit likely contribute to different degrees to the two basic memory functions.
A GIT1/PIX/Rac/PAK Signaling Module Regulates Spine Morphogenesis and Synapse Formation through MLC
Authors: Zhang Huaye , Webb Donna J. , Asmussen Hannelore , Niu Shuang , Horwitz Alan F.
Published: March 2005

Three of seven recently identified genes mutated in nonsyndromic mental retardation are involved in Rho family signaling. Two of the gene products, α-p-21-activated kinase (PAK) interacting exchange factor (αPIX) and PAK3, form a complex with the synaptic adaptor protein G-protein-coupled receptor kinase-interacting protein 1 (GIT1). Using an RNA interference approach, we show that GIT1 is critical for spine and synapse formation. We also show that Rac is locally activated in dendritic spines using fluorescence resonance energy transfer. This local activation of Rac is regulated by PIX, a Rac guanine nucleotide exchange factor. PAK1 and PAK3 serve as downstream effectors of Rac in regulating spine and synapse formation. Active PAK promotes the formation of spines and dendritic protrusions, which correlates with an increase in the number of excitatory synapses. These effects are dependent on the kinase activity of PAK, and PAK functions through phosphorylating myosin II regulatory light chain (MLC). Activated MLC causes an increase in dendritic spine and synapse formation, whereas inhibiting myosin ATPase activity results in decreased spine and synapse formation. Finally, both activated PAK and activated MLC can rescue the defects of GIT1 knockdown, suggesting that PAK and MLC are downstream of GIT1 in regulating spine and synapse formation. Our results point to a signaling complex, consisting of GIT1, PIX, Rac, and PAK, that plays an essential role in the regulation of dendritic spine and synapse formation and provides a potential mechanism by which αPIX and PAK3 mutations affect cognitive functions in mental retardation.
Microanatomy of Axon/Glial Signaling during Wallerian Degeneration
Authors: Guertin Amy D. , Zhang Dan P. , Mak Kimberley S. , Alberta John A. , Kim Haesun A.
Published: March 2005

How do myelinated axons signal to the nuclei of cells that enwrap them? The cell bodies of oligodendrocytes and Schwann cells are segregated from axons by multiple layers of bimolecular lipid leaflet and myelin proteins. Conventional signal transduction strategies would seem inadequate to the challenge without special adaptations. Wallerian degeneration provides a model to study axon-to-Schwann cell signaling in the context of nerve injury. We show a hitherto undetected rapid, but transient, activation of the receptor tyrosine kinase erbB2 in myelinating Schwann cells after sciatic nerve axotomy. Deconvolving microscopy using phosphorylation state-specific antibodies shows that erbB2 activation emanates from within the microvilli of Schwann cells, in direct contact with the axons they enwrap. To define the functional role of this transient activation, we used a small molecule antagonist of erbB2 activation (PKI166). The response of myelinating Schwann cells to axotomy is inhibited by PKI166in vivo. Using neuron/Schwann cell cocultures prepared in compartmentalized cell culture chambers, we show that even transient activation of erbB2 is sufficient to initiate Schwann cell demyelination and that the initiating functions of erbB2 are localized to Schwann cells.
Neuronal Mechanisms of Repetition Priming in Occipitotemporal Cortex: Spatiotemporal Evidence from Functional Magnetic Resonance Imaging and Electroencephalography
Authors: Fiebach Christian J. , Gruber Thomas , Supp Gernot G.
Published: March 2005

Repeated stimulus presentation (priming) is generally associated with a reduction in neuronal firing, macroscopically mirrored by a decrease in oscillatory electrophysiological markers as well as reduced hemodynamic responses. However, these repetition effects seem to be dependent on stimulus familiarity. We investigate the spatiotemporal correlates of repetition priming in cortical word-recognition networks and their modulation by stimulus familiarity (i.e., words vs pseudowords). Event-related functional magnetic resonance imaging results show reduced activation for repeated words in occipitotemporal cortical regions. Electroencephalogram recordings reveal a significant reduction of induced gamma-band responses (GBRs) between 200 and 350 ms after stimulus onset, accompanied by a decrease in phase synchrony between electrode positions. Pseudoword repetition, in contrast, leads to an activation increase in the same areas, to increased GBRs, and to an increased phase coupling. This spatiotemporal repetition by stimulus type interaction suggests that qualitatively distinct mechanisms are recruited during repetition priming of familiar and unfamiliar stimuli. Repetition of familiar stimuli leads to a “sharpening” of extrastriate object representations, whereas the repetition of unfamiliar stimuli results in the “formation” of a novel cortical network by means of synchronized oscillatory activity. In addition to isolating these mechanisms, the present study provides the first evidence for a possible link between induced electrophysiological and hemodynamic measures of brain activity.
Brain-Derived Neurotrophic Factor Enhances GABA Release Probability and Nonuniform Distribution of N- and P/Q-Type Channels on Release Sites of Hippocampal Inhibitory Synapses
Authors: Baldelli Pietro , Hernandez-Guijo Jesus-Miguel , Carabelli Valentina , Carbone Emilio
Published: March 2005

Long-lasting exposures to brain-derived neurotrophic factor (BDNF) accelerate the functional maturation of GABAergic transmission in embryonic hippocampal neurons, but the molecular bases of this phenomenon are still debated. Evidence in favor of a postsynaptic site of action has been accumulated, but most of the data support a presynaptic site effect. A crucial issue is whether the enhancement of evoked IPSCs (eIPSCs) induced by BDNF is attributable to an increase in any of the elementary parameters controlling neurosecretion, namely the probability of release, the number of release sites, the readily releasable pool (RRP), and the quantal size. Here, using peak-scaled variance analysis of miniature IPSCs, multiple probability fluctuation analysis, and cumulative amplitude analysis of action potential-evoked postsynaptic currents, we show that BDNF increases release probability and vesicle replenishment with little or no effect on the quantal size, the number of release sites, the RRP, and the Ca2+dependence of eIPSCs. BDNF treatment changes markedly the distribution of Ca2+channels controlling neurotransmitter release. It enhances markedly the contribution of N- and P/Q-type channels, which summed to >100% (“supra-additivity”), and deletes the contribution of R-type channels. BDNF accelerates the switch of presynaptic Ca2+channel distribution from “segregated” to “nonuniform” distribution. This maturation effect was accompanied by an uncovered increased control of N-type channels on paired-pulse depression, otherwise dominated by P/Q-type channels in untreated neurons. Nevertheless, BDNF preserved the fast recovery from depression associated with N-type channels. These novel presynaptic BDNF actions derive mostly from an enhanced overlapping and better colocalization of N- and P/Q-type channels to vesicle release sites.
Adaptivity of Tuning Functions in a Generic Recurrent Network Model of a Cortical Hypercolumn
Authors: Schwabe Lars , Obermayer Klaus
Published: March 2005

The representation of orientation information in the adult visual cortex is plastic as exemplified by phenomena such as perceptual learning or attention. Although these phenomena operate on different time scales and give rise to different changes in the response properties of neurons, both lead to an improvement in visual discrimination or detection tasks. If, however, optimal performance is indeed the goal, the question arises as to why the changes in neuronal response properties are so different. Here, we hypothesize that these differences arise naturally if optimal performance is achieved by means of different mechanisms. To evaluate this hypothesis, we set up a recurrent network model of a visual cortical hypercolumn and asked how each of four different parameter sets (strength of afferent and recurrent synapses, neuronal gains, and additive background inputs) must be changed to optimally improve the encoding accuracy of a particular set of visual stimuli. We find that the predicted changes in the population responses and the tuning functions were different for each set of parameters, hence were strongly dependent on the plasticity mechanism that was operative. An optimal change in the strength of the recurrent connections, for example, led to changes in the response properties that are similar to the changes observed in perceptual learning experiments. An optimal change in the neuronal gains led to changes mimicking neural effects of attention. Assuming the validity of the optimal encoding hypothesis, these model predictions can be used to disentangle the mechanisms of perceptual learning, attention, and other adaptation phenomena.
Dissociable Retrosplenial and Hippocampal Contributions to Successful Formation of Survey Representations
Authors: Wolbers Thomas , Büchel Christian
Published: March 2005

During everyday navigation, humans encounter complex environments predominantly from a first-person perspective. Behavioral evidence suggests that these perceptual experiences can be used not only to acquire route knowledge but also to directly assemble map-like survey representations. Most studies of human navigation focus on the retrieval of previously learned environments, and the neural foundations of integrating sequential views into a coherent representation are not yet fully understood. We therefore used our recently introduced virtual-reality paradigm, which provides accuracy and reaction-time measurements precisely indicating the emergence of survey knowledge, and functional magnetic resonance imaging while participants repeatedly encoded a complex environment from a first-person ground-level perspective. Before the experiment, we gave specific instructions to induce survey learning, which, based on the clear evidence for emerging survey knowledge in the behavioral data from 11 participants, proved successful. Neuroimaging data revealed increasing activation across sessions only in bilateral retrosplenial cortices, thus paralleling behavioral measures of map expertise. In contrast, hippocampal activation did not follow absolute performance but rather reflected the amount of knowledge acquired in a given session. In other words, hippocampal activation was most prominent during the initial learning phase and decayed after performance had approached ceiling level. We therefore conclude that, during navigational learning, retrosplenial areas mainly serve to integrate egocentric spatial information with cues about self-motion, whereas the hippocampus is needed to incorporate new information into an emerging memory representation.
High-Frequency γ-Band Activity in the Basal Temporal Cortex during Picture-Naming and Lexical-Decision Tasks
Authors: Tanji Kazuyo , Suzuki Kyoko , Delorme Arnaud , Shamoto Hiroshi , Nakasato Nobukazu
Published: March 2005

γ-Band activity (GBA) in electroencephalograms (EEGs) has been shown to reflect various cognitive processes. GBA has typically been recorded in the 30-60 Hz range in scalp EEGs. Recently, task-related “high GBA” (HGBA) with frequencies up to 100 Hz has been observed in studies with invasive electrocorticograms (ECoGs). In the present study, we recorded ECoGs from the bilateral basal temporal cortices in a patient with epilepsy and evaluated the task-related HGBA (most prominently in the 80-120 Hz range) accompanying picture-naming and lexical-decision tasks. We examined picture naming using two categories (line drawings of animals and tools). The lexical-decision task was performed using words and pseudowords of two distinct Japanese writing forms, kanji (morphograms) and kana (syllabograms). Task-related HGBA was observed bilaterally during the naming task. Recordings from some electrodes revealed significant differences in HGBA between animal and tool pictures. In contrast to the naming task, there was apparent left dominance in the lexical-decision task. Furthermore, significant differences in HGBA were observed between the Japanese kanji and kana words and between the kanji words and kanji pseudowords. A number of differences in the HGBA observed in the recordings from the basal temporal area were consistent with previous findings from neuroimaging and patient studies and suggest that HGBA is a good correlate of visual cognitive functions.
Chronic Antidepressants Reduce Depolarization-Evoked Glutamate Release and Protein Interactions Favoring Formation of SNARE Complex in Hippocampus
Authors: Bonanno Giambattista , Giambelli Roberto , Raiteri Luca , Tiraboschi Ettore , Zappettini Simona , Musazzi Laura , Raiteri Maurizio , Racagni Giorgio , Popoli Maurizio
Published: March 2005

Glutamate neurotransmission was recently implicated in the action of stress and in antidepressant mechanisms. We report that chronic (not acute) treatment with three antidepressants with different primary mechanisms (fluoxetine, reboxetine, and desipramine) markedly reduced depolarization-evoked release of glutamate, stimulated by 15 or 25 mmKCl, but not release of GABA. Endogenous glutamate and GABA release was measured in superfused synaptosomes, freshly prepared from hippocampus of drug-treated rats. Interestingly, treatment with the three drugs only barely changed the release of glutamate (and of GABA) induced by ionomycin. In synaptic membranes of chronically treated rats we found a marked reduction in the protein-protein interaction between syntaxin 1 and Thr286-phosphorylated αCaM kinase II (α-calcium/calmodulin-dependent protein kinase II) (an interaction previously proposed to promote neurotransmitter release) and a marked increase in the interaction between syntaxin 1 and Munc-18 (an interaction proposed to reduce neurotransmitter release). Furthermore, we found a selective reduction in the expression level of the three proteins forming the core SNARE (solubleN-ethylmaleimide-sensitive factor attachment protein receptor) complex. These findings suggest that antidepressants work by stabilizing glutamate neurotransmission in the hippocampus and that they may represent a useful tool for the study of relationship between functional and molecular processes in nerve terminals.
Decisions under Uncertainty: Probabilistic Context Influences Activation of Prefrontal and Parietal Cortices
Authors: Huettel Scott A. , Song Allen W. , McCarthy Gregory
Published: March 2005

Many decisions are made under uncertainty; that is, with limited information about their potential consequences. Previous neuroimaging studies of decision making have implicated regions of the medial frontal lobe in processes related to the resolution of uncertainty. However, a different set of regions in dorsal prefrontal and posterior parietal cortices has been reported to be critical for selection of actions to unexpected or unpredicted stimuli within a sequence. In the current study, we induced uncertainty using a novel task that required subjects to base their decisions on a binary sequence of eight stimuli so that uncertainty changed dynamically over time (from 20 to 50%), depending on which stimuli were presented. Activation within prefrontal, parietal, and insular cortices increased with increasing uncertainty. In contrast, within medial frontal regions, as well as motor and visual cortices, activation did not increase with increasing uncertainty. We conclude that the brain response to uncertainty depends on the demands of the experimental task. When uncertainty depends on learned associations between stimuli and responses, as in previous studies, it modulates activation in the medial frontal lobes. However, when uncertainty develops over short time scales as information is accumulated toward a decision, dorsal prefrontal and posterior parietal contributions are critical for its resolution. The distinction between neural mechanisms subserving different forms of uncertainty resolution provides an important constraint for neuroeconomic models of decision making.
Step-Response Analysis of Chemotaxis inCaenorhabditis elegans
Authors: Miller Adam C. , Thiele Tod R. , Faumont Serge , Moravec Marin L. , Lockery Shawn R.
Published: March 2005

The sensorimotor transformation underlyingCaenorhabditis eleganschemotaxis has been difficult to measure directly under normal assay conditions. Thus, key features of this transformation remain obscure, such as its time course and dependence on stimulus amplitude. Here, we present a comprehensive characterization of the transformation as obtained by inducing stepwise temporal changes in attractant concentration within the substrate as the worm crawls across it. We found that the step response is complex, with multiple phases and a nonlinear dependence on the sign and amplitude of the stimulus. Nevertheless, the step response could be reduced to a simple kinetic model that predicted the results of chemotaxis assays. Analysis of the model showed that chemotaxis results from the combined effects of approach and avoidance responses to concentration increases and decreases, respectively. Surprisingly, ablation of the ASE chemosensory neurons, known to be necessary for chemotaxis in chemical gradient assays, eliminated avoidance responses but left approach responses intact. These results indicate that the transformation can be dissected into components to which identified neurons can be assigned.
Adherens Junctions in Myelinating Schwann Cells Stabilize Schmidt-Lanterman Incisures via Recruitment of p120 Catenin to E-Cadherin
Authors: Tricaud Nicolas , Perrin-Tricaud Claire , Brusés Juan L. , Rutishauser Urs
Published: March 2005

Schwann cell myelin contains highly compacted layers of membrane as well as noncompacted regions with a visible cytoplasm. One of these cytoplasmic compartments is the Schmidt-Lanterman incisure, which spirals through the compacted layers and is believed to help sustain the growth and function of compact myelin. Incisures contain adherens junctions (AJs), the key components of which are E-cadherin, its cytoplasmic partners called catenins, and F-actin. To explorein vivothe role of cadherin and catenins in incisures, E-cadherin mutant proteins that completely replace endogenous cadherin have been delivered to the cells using adenovirus. When the introduced cadherin lacked its extracellular domain, association of p120 catenin (p120ctn) with the cadherin did not occur, and incisures disappeared. Remarkably, the additional replacement of two phosphorylatable tyrosines by phenylalanine in the cytoplasmic tail of the mutant cadherin restored both p120ctn binding and incisure architecture, indicating that p120ctn recruitment is critical for incisures maintenance and might be regulated by phosphorylations. In addition, the ability of the p120ctn/cadherin complex to support incisures was blocked by mutation of the Rho GTPase regulatory region of the p120ctn, and downregulation of Rac1 activity at the junction reversed this inhibition. Because Rho GTPases regulate the state of the actin filaments, these findings suggest that one role of p120ctn in incisures is to organize the cytoskeleton at the AJ. Finally, developmental studies of Schwann cells demonstrated that p120ctn recruitment from the cytoplasm to the AJ occurs before the appearance of Rac1 GTPase and F-actin at the junction.
Monosynaptic Connections between Pairs of Spiny Stellate Cells in Layer 4 and Pyramidal Cells in Layer 5A Indicate That Lemniscal and Paralemniscal Afferent Pathways Converge in the Infragranular Somatosensory Cortex
Authors: Feldmeyer Dirk , Roth Arnd , Sakmann Bert
Published: March 2005

Monosynaptic interlaminar connections between spiny stellate cells in layer 4 (L4), the main cortical recipient layer for thalamic projections, and pyramidal cells in layer 5A (L5A), one of the main cortical output layers, were examined anatomically and functionally by paired recordings in acute brain slices. The somata of pairs forming interlaminar L4-to-L5A connections were located predominantly close to or directly under the barrel-septum wall in layer 4. Superposition of spiny stellate axon arbors and L5A pyramidal cell dendritic arbors suggested an innervation domain underneath an L4 barrel wall. Functionally, the L4-to-L5A connections were of high reliability and relatively low efficacy, with a unitary EPSP amplitude of 0.6 mV, and the connectivity was moderately high (one in seven pairs tested was connected). The EPSP amplitude was weakly depressing (paired-pulse ratio of ≈0.8) during repetitive presynaptic action potentials at 10 Hz. The existence of monosynaptic L4-to-L5A connections indicates that the specific “lemniscal” thalamic input from the ventro-basal nucleus of the thalamus to the cortex and the more unspecific “paralemniscal” afferent thalamic projections from the posterior medial nucleus of the thalamus merge already at an initial stage of cortical signal processing. These monosynaptic connections establish a monosynaptic coupling of the input to the cortex and its output, thereby effectively bypassing the supragranular layers.
Routine Preoperative Insertion of IABP in High-Risk Off-Pump Coronary Artery Bypass Grafting
Authors: Vohra Hunaid A. , Briffa Norman P.
Published: March 2005

The beneficial effects of intraaortic balloon pump (IABP) in coronary artery bypass graft surgery with cardiopulmonary bypass have been reported. However, whether preoperative insertion of IABP in high-risk off-pump coronary artery bypass grafting (OPCAB) has any beneficial effects remains to be established. We report our experience of preoperative insertion of IABP in OPCAB.
An Approach to LVAD Explantation during Heart Transplantation
Authors: Moazami Nader , Pasque Michael K.
Published: March 2005

Reoperations during ventricular assist device (VAD) explantation and subsequent heart transplantation are difficult procedures because of dense adhesions, obliterated planes of dissection, and proximity of the right ventricle to the sternum. We present our approach for left VAD explantation to minimize potential complications that may occur during this procedure.
Transmyocardial Laser Revascularization as Sole Reoperative Therapy following Late Anginal Recurrence: Case Report
Authors: Samuels Louis E. , Holmes Elena C. , Janzer Sean
Published: March 2005

A case of recurrent angina 3 years following sole therapy transmyocardial laser revascularization (TMR) is described. Repeat sole therapy TMR with the Holmium:YAG system was performed and resulted in complete and immediate angina relief. Repeat TMR should be considered in patients with angina recurrence who underwent primary TMR.
Initial Report of Off-Pump Coronary Artery Bypass Surgery as Sole Therapy for Moderate Ischemic Mitral Regurgitation: Operative and Intermediate-Term Outcome
Authors: Harris Kevin M. , Reddy Avinash , Aepplii Dorothee , Wilson Betsy , Emery Robert W.
Published: March 2005

Background: Patients undergoing on-pump coronary artery bypass surgery (CAB) with coexistent moderate ischemic mitral regurgitation (IMR) have a significant mortality rate compared to patients without MR. The mortality rate is elevated both perioperatively (0%-12% mortality), as well as over a 1- and 2-year postoperative period (15%-25%). It is thought that some patients are best served by off-pump CAB (OPCAB); however, outcomes have not been reported for such patients with coexistent moderate IMR. Methods: We reviewed the independent database of patients undergoing OPCAB between 1995 and 2002 to find 989 patients, 17 (1.7%) of whom had moderate or moderately severe MR. Patients were contacted and clinical and echocardiographic data were obtained. Results: The patient group consisted of 11 men and 6 women (age, 65 15 years). The study group had a PA pressure of 52 14, creatinine of 1.6 0.7, and left ventricular ejection fraction of 43 18. Nine patients (53%) had advanced New York Heart Association (class III-IV) heart failure. Mortality rates perioperatively and at 1, 2, and 3 years were 0%, 6.25% (1/16), 12.5% (2/16), and 38% (4/8), respectively. At the time of this report, no patient had returned for a reparative procedure. Conclusion: In patients felt to be best served by OPCAB with ischemic MR, operative and intermediate mortality rates are remarkably similar to those previously reported for on-pump series. These data underscore the continued need to understand which patients undergoing CAB require mitral valve problems to be addressed at the time of surgery.
Closure of Secundum Atrial Septal Defect with Autologous Right Atrial Patch: Case Report
Authors: Dar�in Osman Tansel , Kunt Alper Sami , Andac Mehmet Halit
Published: March 2005

Background: Although various synthetic materials and pericardium have been used for atrial septal defect (ASD) closure, investigators are continuing to search for an ideal material for this procedure. We report and evaluate a case in which autologous right atrial wall tissue was used for ASD closure. Case: In this case, we closed a secundum ASD of a 22-year-old woman who also had right atrial enlargement due to the defect. After establishing standard bicaval cannulation and total cardiopulmonary bypass, we opened the right atrium with an oblique incision in a superior position to a standard incision. After examining the secundum ASD, we created a flap on the inferior rim of the atrial wall. A stay suture was stitched between the tip of the flap and the superior rim of the defect, and suturing was continued in a clockwise direction thereafter. Considering the size and shape of the defect, we incised the inferior attachment of the flap, and suturing was completed. Remnants of the flap on the inferior rim were resected, and the right atrium was closed in a similar fashion. Results: During an echocardiographic examination, neither a residual shunt nor perigraft thrombosis was seen on the interatrial septum. The patient was discharged with complete recovery. Conclusion: Autologous right atrial patch is an ideal material for ASD closure, especially in patients having a large right atrium. A complete coaptation was achieved because of the muscular nature of the right atrial tissue and its thickness, which is a closer match to the atrial septum than other materials.
A Multipurpose Arterial Graft Holder for Coronary Artery Bypass Grafting
Authors: Watanabe Go , Yasuda Tamotsu , Tomita Shigeyuki
Published: March 2005

A multipurpose arterial graft holder designed for use during coronary artery bypass grafting is described. This new holder is atraumatic and holds the arterial grafts and saphenous vein graft securely during anastomosis. The use of this instrument facilitates the use of multiple arterial grafts for coronary artery bypass grafting.
Role of reflective (metallic) support on microwave heating
Authors: Basak Tanmay
Published: March 2005

A detailed analysis has been carried out to assess the role of reflective support on microwave heating of one‐dimensional (1‐D) slabs and 2‐D cylinders for water and oil samples. The reflective supports are placed at the unexposed face for 1‐D slabs, and the supports are the annular cylinders with specific radii for 2‐D cylinders. A preliminary analysis on microwave heating of samples has been shown via average power within a sample vs sample dimension diagram for various regimes. For 1‐D water samples, the regime I corresponds to local maxima in average power for samples with supports, and regime II corresponds to maxima in power for samples without supports. For 1‐D oil samples, the greater average power with supports during regimes I and II is observed. The enhanced power absorption is observed due to greater stationary field intensities, and the greater heating rates are due to the enhanced power deposition in samples with supports for specific regimes. For 2‐D water samples, the reflective supports are found to be attractive for specific aspects ratios and power absorption can be enhanced by several magnitudes for thicker cylinder radii. The power absorption is found to be generally decreased due to supports for 2‐D oil samples. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Introduction to this issue of American Journal of Medical Genetics
Authors: Toriello Helga V. , Finnell Richard
Published: March 2005

This is an introduction to this issue of “Seminars” which is an offshoot of the proceedings of the third International Neural Tube Defects Symposium, held in 2003. This was an interdisciplinary meeting with the common emphasis on neural tube defects research. © 2005 Wiley‐Liss, Inc.
Role of Folbp1 in the regional regulation of apoptosis and cell proliferation in the developing neural tube and craniofacies
Authors: Tang Louisa S. , Santillano Daniel R. , Wlodarczyk Bogdan J. , Miranda Rajesh C. , Finnell Richard H.
Published: March 2005

Folic acid is essential for many cellular reactions, including synthesis of nucleotides and regulation of cell cycle. Folic acid‐binding protein one (Folbp1), a membrane‐bounded protein, is the primary mediator of folic acid transport. Mice deficient in Folbp1 gene die in utero with multiple malformations, including severe exencephaly and craniofacial defects. Fusion of the neural tube and craniofacies require precisely regulated interactions of apoptosis, cell proliferation, and differentiation. To understand the role of Folbp1 in regulating the fusions of these primordia, levels of dead and proliferating precursor cells from Folbp1 embryos were quantified before the fusion processes. Massive apoptosis was detected in the Folbp1−/− defective tissues, with Bax and activated caspase‐3 distributed evenly across the apico‐basal axis of the lateral neural plate. 5‐Bromodeoxyuridine (BrdU) and PCNA labeling assays revealed a reduced cell proliferation as well. However, telomerase activity was unaltered, arguing against telomere shortening and consequently, chromosomal instability, as the cause of the apoptosis. Notably, Islet‐1 and 2H3 immunohistochemistry demonstrated the presence of differentiating neuronal cells, albeit in decreased numbers. Interestingly, Folbp1−/− embryos also elaborated novel neural structures that sprouted orthogonally from the embryonic neuraxis. Assays on the defective craniofacies exhibited similar phenomena, suggesting the neural crest precursor population that gives rise to both these structures is selectively vulnerable to Folbp1 inactivation. The results demonstrate a prominent role of Folbp1 in the regional regulation of apoptosis and cell proliferation that underlies the aberrant neural tube and craniofacial defects. © 2005 Wiley‐Liss, Inc.
Current perspectives on the causes of neural tube defects resulting from diabetic pregnancy
Authors: Loeken Mary R.
Published: March 2005

Maternal diabetes increases the risk for neural tube, and other, structural defects. The mother may have either type 1 or type 2 diabetes, but the diabetes must be existing at the earliest stages of pregnancy, during which organogenesis occurs. Abnormally high glucose levels in maternal blood, which leads to increased glucose transport to the embryo, is responsible for the teratogenic effects of maternal diabetes. Consequently, expression of genes that control essential developmental processes is disturbed. In this review, some of the biochemical pathways by which excess glucose metabolism disturbs neural tube formation are discussed. Research from the author's laboratory has shown that expression of Pax3, a gene required for neural tube closure, is significantly reduced by maternal diabetes, and this is associated with significantly increased neural tube defects (NTD). Pax3 encodes a transcription factor that has recently been shown to inhibit p53‐dependent apoptosis. Evidence in support of this model, in which excess glucose metabolism inhibits expression of Pax3, thereby derepressing p53‐dependent apoptosis of neuroepithelium and leading to NTD will be discussed. © 2005 Wiley‐Liss, Inc.
Epidemiology of neural tube defects
Authors: Mitchell Laura E.
Published: March 2005

The epidemiological investigation of the common open neural tube defects (NTDs), anencephaly, and spina bifida, has a long history. The most significant finding from these past studies of NTDs was the identification of the protective effect of maternal, periconceptional supplementation with folic acid. Fortuitously, the association between folic acid and NTDs became widely accepted in the early 1990s, at a time when genetic association studies of complex traits were becoming increasingly feasible. The confluence of these events has had a major impact on the direction of epidemiological, NTD research. Association studies to evaluate genes that may influence the risk of NTDs through their role in folate‐related processes, or through other metabolic or developmental pathways are now commonplace. Moreover, the study of genetic as well as non‐genetic, factors that may influence NTD risk through effects on the nutrient status of the mother or embryo has emerged as a major research focus. Research efforts over the past decade indicate that gene–gene, gene–environment, and higher‐order interactions, as well as maternal genetic effects influence NTD risk, highlighting the complexity of the factors that underlie these conditions. The challenge for the future is to design studies that address these complexities, and are adequately powered to detect the factors or combination of factors that influence the development of NTDs. © 2005 Wiley‐Liss, Inc.
Synthesis and Benzodiazepine Receptor Affinity of Derivatives of the New Tricyclic Heteroaromatic System Pyrido[3′,2′:5,6]thiopyrano[4,3‐c]pyridazin‐3(2H,5H)‐one
Authors: Primofiore Giampaolo , Da Settimo Federico , Marini Anna Maria , Simorini Francesca , La Motta Concettina , Taliani Sabrina , Laneri Sonia , Trincavelli Letizia , Martini Claudia
Published: March 2005

Derivatives 7–13 of a new tricyclic heteroaromatic system, pyrido[3′,2′:5,6]thiopyrano[4,3‐c]pyridazin‐3(2H,5H)‐one, were prepared as potential ligands at the benzodiazepine receptor, in view of their structural analogy with potent ligands such as the pyrazoloquinolines of the CGS series II, and especially with the benzothiopyrano[4,3‐c]pyridazinones VI. They were obtained starting from the versatile ketones 2,3‐dihydrothiopyrano[2,3‐b]pyridin‐4(4H)‐one 1 and the corresponding 7‐methyl derivative 2, via condensation with glyoxylic acid, and reaction of the intermediate acid mixtures with hydrazine or substituted phenylhydrazines. When evaluated for their binding affinity at the benzo diazepine receptor in bovine cortical membranes, the target compounds 8–13 displayed an affinity in the micromolar/submicromolar order. A hypothesis is presented to rationalize these results.
An autonomously folding β‐hairpin derived from the human YAP65 WW domain: Attempts to define a minimum ligand‐binding motif
Authors: Espinosa Juan F. , Syud Faisal A. , Gellman Samuel H.
Published: March 2005

WW domains are broadly distributed among natural proteins; these modules play a role in bringing specific proteins together. The ligands recognized by WW domains are short segments rich in proline residues. We have tried to identify the minimum substructure within a WW domain that is required for ligand binding. WW domains typically comprise ca. 40 residues and fold to a three‐stranded β‐sheet. Structural data for several WW domain/ligand complexes suggest that most or all of the intermolecular contacts involve β‐strands 2 and 3. We have developed a 16‐residue peptide that folds to a β‐hairpin conformation that appears to mimic β‐strands 2 and 3 of the human YAP65 WW domain, but this peptide does not bind to known ligands. Thus, the minimum binding domain is larger than the latter two strands of the WW domain β‐sheet. © 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2005
Effects of excluded volume and polydispersity on solution properties of lentinan in 0.1 M NaOH solution
Authors: Zhang Xufeng , Xu Juan , Zhang Lina
Published: March 2005

Seven lentinan fractions of various weight‐average molecular weights (Mw), ranging from 1.45 × 105 to 1.13 × 106 g mol−1 were investigated by static light scattering and viscometry in 0.1M NaOH solution at 25°C. The intrinsic viscosity [η] − Mw and radius of gyration 〈s2〉 − Mw relationships for lentinan in 0.1M NaOH solution were found to be represented by [η] = 5.1 × 10−3M cm3 g−1 and 〈s2〉 = 2.3 × 10−1M nm, respectively. Focusing on the effects of the Mw polydispersity with the Schulz–Zimm distribution function, the data of Mw, 〈s2〉, and [η] was analyzed on the basis of the Yoshizaki–Nitta–Yamakawa theory for the unperturbed helical wormlike chain combined with the quasi‐two‐parameter (QTP) theory for excluded‐volume effects. The persistence length, molecular weight per unit contour length, and the excluded‐volume strength were determined roughly to be 6.2 nm, 980 nm−1, and 0.1, respectively. Compared with the theoretical value calculated by the Monte Carlo model, the persistence length is longer than that of the single (1 → 3)‐β‐D‐glucan chain. The results revealed that lentinan exists as single‐stranded flexible chains in 0.1M NaOH solution with a certain degree of expansion due to the electrostatic repulsion from the interaction between the OH− anions and lentinan molecules. © 2005 Wiley Periodicals, Inc. Biopolymers 78: 187–196, 2005
Supramolecular order following binding of the dichroic birefringent sulfonic dye Ponceau SS to collagen fibers
Authors: Vidal B. C. , Mello M. L. S.
Published: March 2005

The optical anisotropies (linear dichroism or LD and birefringence) of crystalline aggregates of the sulfonic azo‐dye Ponceau SS and of dye complexed with chicken tendon collagen fibers were investigated in order to assess their polarizing properties and similarity to liquid crystals. In some experiments, the staining was preceded by treatment with picric acid. Crystalline fibrous aggregates of the dye had a negative LD, and their electronic transitions were oriented perpendicular to the filamentary structures. The binding of Ponceau SS molecules to the collagen fibers altered the LD signal, with variations in the fiber orientation affecting the resulting dichroic ratios. The long axis of the rod‐like dye molecule was assumed to be bound in register, parallel to the collagen fiber. Picric acid did not affect the oriented binding of the azo dye to collagen fibers. There were differences in the optical anisotropy of Ponceau SS‐stained tendons from 21‐day‐old and 41‐day‐old chickens, indicating that Ponceau SS was able to distinguish between different ordered states of macromolecular aggregation in chicken tendon collagen fibers. In the presence of dichroic rod‐like azo‐dye molecules such as Ponceau SS, collagen also formed structures with a much higher degree of orientation. The presence of LD in the Ponceau SS‐collagen complex even in unpolarized light indicated that this complex can act as a polarizer. © 2005 Wiley Periodicals, Inc. Biopolymers 78: 121–128, 2005

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Vibrational infrared conformational studies of model peptides representing the semicrystalline domains of Bombyx mori silk fibroin
Authors: Taddei Paola , Monti Patrizia
Published: March 2005

The structural organization of Bombyx mori silk fibroin was investigated by infrared (IR) spectroscopy. To this aim, (AG)15 and other model peptides of varying chain length, containing tyrosine (Y), valine (V), and serine (S) in the basic (AG)n sequence were synthesized by the solid phase method and their spectroscopic properties were determined. Both the position and the relative content of Y, V, and S residues in the (AG)n model system appeared critical in determining the preferred conformation, i.e., silk I, silk II, and unordered structures. Curve fitting analysis in the amide I range showed that the model peptides with prevailing silk II structure displayed different β‐sheet content, which was dependent on the degree of interruption of the (AG)n sequence. In this regard, the bands at about 1000 and 980 cm−1, specifically assigned to the AG sequence of the B. mori silk fibroin chain, were identified as marker of the degree of interruption of the (AG)n sequence.

A stable silk I structure was observed only when the Y residue was located near the chain terminus, while a silk I → silk II conformational transition occurred when it was positioned in the central region of the peptide.

Analysis of the second‐derivative spectra in the amide I range allowed us to identify a band at 1639 cm−1 (4 → 1 hydrogen‐bonded type II β‐turns), which is characteristic of the silk I conformation. © 2005 Wiley Periodicals, Inc. Biopolymers 78: 249–258, 2005
Randomized clinical trial of pylorus-preserving duodenopancreatectomy versus classical Whipple resection—long term results
Authors: Seiler C A , Wagner M , Bachmann T , Redaelli C A , Schmied B , Uhl W , Friess H , Büchler M W
Published: March 2005

Background

It is not known whether pylorus-preserving duodenopancreatectomy is as effective as the classical Whipple procedure in the resection of pancreatic and periampullary tumours. A prospective randomized trial was undertaken to compare the results of the two procedures.

Methods

Clinical data, histological findings, short-term results, survival and quality of life of all patients having surgery for suspected pancreatic or periampullary cancer between June 1996 and September 2001 were analysed.

Results

Two hundred and fourteen patients were randomized to undergo either a standard or a pylorus-preserving Whipple resection. After exclusion of 84 patients on the basis of intraoperative findings, 130 patients (66 standard Whipple operation and 64 pylorus-preserving resection) were entered into the trial. Of these, 110 patients with proven adenocarcinoma (57 standard Whipple and 53 pylorus-preserving resection) were analysed for long-term survival and quality of life. There was no difference in perioperative morbidity. Long-term survival, quality of life and weight gain were identical after a median follow-up of 63·1 (range 4–93) months. At 6 months, capacity to work was better after the pylorus-preserving procedure (77 versus 56 per cent; P = 0·019).

Conclusion

Both procedures were equally effective for the treatment of pancreatic and periampullary cancer. Pylorus-preserving Whipple resection offers some minor advantages in the early postoperative period, but not in the long term.