bluuebunny/crossref_metadata_2025 huggingface dataset:
The counter-rotating core of a swirling turbulent jet issued from a rotating pipe flow
Authors: Facciolo Luca , Alfredsson P. Henrik
Published: July 2004

Axially rotating turbulent pipe flow is an example where rotation strongly affects the turbulence and thereby the Reynolds stresses and mean flow properties. The present Letter reports new measurements where a rotating pipe flow is used to establish a swirling jet. The measurements in the jet show that at some distance downstream (approximately 6 nozzle diameters) the central part of the jet starts to rotate in the opposite direction as compared to the rotation of the pipe. This effect is explained by the influence of the cross flow Reynolds stress originating in the pipe flow.
The effects of a counter-current interstitial flow on a discharging hourglass
Authors: Muite B. K. , Hunt M. L. , Joseph G. G.
Published: July 2004

This work experimentally investigates the effects of an interstitial fluid on the discharge of granular material within an hourglass. The experiments include observations of the flow patterns, measurements of the discharge rates, and pressure variations for a range of different fluid viscosities, particle densities and diameters, and hourglass geometries. The results are classified into three regimes: (i) granular flows with negligible interstitial fluid effects; (ii) flows affected by the presence of the interstitial fluid; and (iii) a no-flow region in which particles arch across the orifice and do not discharge. Within the fluid-affected region, the flows were visually classified as lubricated and air-coupled flows, oscillatory flows, channeling flows in which the flow preferentially rises along the sidewalls, and fluidized flows in which the upward flow suspends the particles. The discharge rates depends on the Archimedes number, the ratio of the effective hopper diameter to the particle diameter, and hourglass geometry. The hopper-discharge experiments, as well as experiments found in the literature, demonstrate that the presence of the interstitial fluid is important when the nondimensional ratio (N) of the single-particle terminal velocity to the hopper discharge velocity is less than 10. Flow ceased in all experiments in which the particle diameter was greater than 25% of the effective hopper diameter regardless of the interstitial fluid.
In vivo
identification of genes that modify ether-a-go-go-related gene activity in
Caenorhabditis elegans
may also affect human cardiac arrhythmia
Authors: Petersen Christina I. , McFarland Toni R. , Stepanovic Svetlana Z. , Yang Ping , Reiner David J. , Hayashi Kenshi , George Alfred L. , Roden Dan M. , Thomas James H. , Balser Jeffrey R.
Published: July 2004

Human ether-a-go-go-related gene (HERG) encodes the pore-forming subunit of I
Kr
, a cardiac K
+
channel. Although many commonly used drugs block I
Kr
, in certain individuals, this action evokes a paradoxical life-threatening cardiac rhythm disturbance, known as the acquired long QT syndrome (aLQTS). Although aLQTS has become the leading cause of drug withdrawal by the U.S. Food and Drug Administration, DNA sequencing in aLQTS patients has revealed HERG mutations only in rare cases, suggesting that unknown HERG modulators are often responsible. By using the worm
Caenorhabditis elegans
, we have developed
in vivo
behavioral assays that identify candidate modulators of
unc-103
, the worm HERG orthologue. By using RNA-interference methods, we have shown that worm homologues of two HERG-interacting proteins, Hyperkinetic and K channel regulator 1 (KCR1), modify
unc-103
function. Examination of the human KCR1 sequence in patients with drug-induced cardiac repolarization defects revealed a sequence variation (the substitution of isoleucine 447 by valine, I447V) that occurs at a reduced frequency (1.1%) relative to a matched control population (7.0%), suggesting that I447V may be an allele for reduced aLQTS susceptibility. This clinical result is supported by
in vitro
studies of HERG dofetilide sensitivity by using coexpression of HERG with wild-type and I447V KCR1 cDNAs. Our studies demonstrate the feasibility of using
C. elegans
to assay and potentially identify aLQTS candidate genes.
Persistent tetrodotoxin-sensitive sodium current resulting from U-to-C RNA editing of an insect sodium channel
Authors: Liu Zhiqi , Song Weizhong , Dong Ke
Published: July 2004

The persistent tetrodotoxin (TTX)-sensitive sodium current, detected in neurons of many regions of mammalian brains, is associated with many essential neuronal activities, including boosting of excitatory synaptic inputs, acceleration of firing rates, and promotion of oscillatory neuronal activities. However, the origin and molecular basis of the persistent current have remained controversial for decades. Here, we provide direct evidence that U-to-C RNA editing of an insect sodium channel transcript generates a sodium channel with a persistent current. We detected a persistent TTX-sensitive current in a splice variant of the cockroach sodium channel gene

BgNa
v

(formerly

para
CSMA

). Site-directed mutagenesis experiments revealed that an F-to-S change at the C-terminal domain of this variant was responsible for the persistent current. We demonstrated that this F-to-S change was the result of a U-to-C RNA editing event, which also occurred in the
Drosophila para
sodium channel transcript. Our work provides direct support for the hypothesis that posttranscriptional modification of a conventional transient sodium channel produces a persistent TTX-sensitive sodium channel.
Pauling and Corey's α-pleated sheet structure may define the prefibrillar amyloidogenic intermediate in amyloid disease
Authors: Armen Roger S. , DeMarco Mari L. , Alonso Darwin O. V. , Daggett Valerie
Published: July 2004

Transthyretin, β2-microglobulin, lysozyme, and the prion protein are four of the best-characterized proteins implicated in amyloid disease. Upon partial acid denaturation, these proteins undergo conformational change into an amyloidogenic intermediate that can self-assemble into amyloid fibrils. Many experiments have shown that pH-mediated changes in structure are required for the formation of the amyloidogeneic intermediate, but it has proved impossible to characterize these conformational changes at high resolution using experimental means. To probe these conformational changes at atomic resolution, we have performed molecular dynamics simulations of these proteins at neutral and low pH. In low-pH simulations of all four proteins, we observe the formation of α-pleated sheet secondary structure, which was first proposed by L. Pauling and R. B. Corey [(1951)Proc. Natl. Acad. Sci. USA37, 251–256]. In all β-sheet proteins, transthyretin and β2-microglobulin, α-pleated sheet structure formed over the strands that are highly protected in hydrogen-exchange experiments probing amyloidogenic conditions. In lysozyme and the prion protein, α-sheets formed in the specific regions of the protein implicated in the amyloidogenic conversion. We propose that the formation of α-pleated sheet structure may be a common conformational transition in amyloidosis.
Twisting macromolecular chains: Self-assembly of a chiral supermolecule from nonchiral polythiophene polyanions and random-coil synthetic peptides
Authors: Nilsson K. Peter R. , Rydberg Johan , Baltzer Lars , Inganäs Olle
Published: July 2004

The self-assembly of a negatively charged conjugated polythiophene derivative and a positively charged synthetic peptide will create a chiral, well ordered supermolecule. This supermolecule has the three-dimensional ordered structure of a biomolecule and the electronic properties of a conjugated polymer. The molecular complex being formed clearly affects the conformation of the polymer backbone. A main-chain chirality, such as a predominantly one-handed helical structure induced by the acid–base complexation between the conjugated polymer and the synthetic peptide, is seen. The alteration of the polymer backbone influences the optical properties of the polymer, seen as changes in the absorption, emission, and Raman spectra of the polymer. The complexation of the polythiophene and the synthetic peptide also induce a change from random-coil to helical structure of the synthetic peptide. The supermolecule described in this article may be used in a wide range of applications such as biomolecular devices, artificial enzymes, and biosensors.
Distinct stoichiometry of BK
Ca
channel tetramer phosphorylation specifies channel activation and inhibition by cAMP-dependent protein kinase
Authors: Tian Lijun , Coghill Lorraine S. , McClafferty Heather , MacDonald Stephen H.-F. , Antoni Ferenc A. , Ruth Peter , Knaus Hans-Guenther , Shipston Michael J.
Published: July 2004

Large conductance voltage- and calcium-activated potassium (BK
Ca
) channels are important signaling molecules that are regulated by multiple protein kinases and protein phosphatases at multiple sites. The pore-forming α-subunits, derived from a single gene that undergoes extensive alternative pre-mRNA splicing, assemble as tetramers. Although consensus phosphorylation sites have been identified within the C-terminal domain of α-subunits, it is not known whether phosphorylation of all or single α-subunits within the tetramer is required for functional regulation of the channel. Here, we have exploited a strategy to study single-ion channels in which both the α-subunit splice-variant composition is defined and the number of consensus phosphorylation sites available within each tetramer is known. We have used this approach to demonstrate that cAMP-dependent protein kinase (PKA) phosphorylation of the conserved C-terminal PKA consensus site (S899) in all four α-subunits is required for channel activation. In contrast, inhibition of BK
Ca
channel activity requires phosphorylation of only a single α-subunit at a splice insert (STREX)-specific PKA consensus site (S4
STREX
). Thus, distinct modes of BK
Ca
channel regulation by PKA phosphorylation exist: an “all-or-nothing” rule for activation and a “single-subunit” rule for inhibition. This essentially digital regulation has important implications for the combinatorial and conditional regulation of BK
Ca
channels by reversible protein phosphorylation.
N-acetylation of hypothalamic α-melanocyte-stimulating hormone and regulation by leptin
Authors: Guo Li , Münzberg Heike , Stuart Ronald C. , Nillni Eduardo A. , Bjørbæk Christian
Published: July 2004

The central melanocortin system is critical in the regulation of appetite and body weight, and leptin exerts its anorexigenic actions partly by increasing hypothalamic proopiomelanocortin (POMC) expression. The POMC-derived peptide α-melanocyte-stimulating hormone (αMSH) is a melanocortin 4 receptor agonist, and its potency in reducing energy intake is strongly increased by N-acetylation. The reason for the higher biological activity of N-acetylated αMSH (Act-αMSH) compared with that of N-desacetylated αMSH (Des-αMSH) is unclear, and regulation of acetylation by leptin has not been investigated. We show here that total hypothalamic αMSH levels are decreased in leptin-deficient
ob
/
ob
mice and increased in leptin-treated
ob
/
ob
and C57BL/6J mice. The increase in total αMSH occurred as soon as 3 h after leptin injection and was entirely due to an increase in Act-αMSH. Consistent with this observation, leptin rapidly induced the enzymatic activity of a
N
-acetyltransferase in the hypothalamus of mice. In 293T cells expressing the melanocortin 4 receptor, Act-αMSH is far more potent than Des-αMSH in stimulating cAMP accumulation, an effect caused by a dramatically increased stability of Act-αMSH. Moreover, Des-αMSH is rapidly degraded in the hypothalamus after intracerebroventricular injection in rats and was less potent in inhibiting energy intake. The results suggest that leptin activates a
N
-acetyltransferase in POMC neurons, leading to increased hypothalamic levels of Act-αMSH. Due to its increased stability, this posttranslational modification of αMSH may play a critical role in leptin action via the central melanocortin pathway.
The inhibitory effect of anandamide on luteinizing hormone-releasing hormone secretion is reversed by estrogen
Authors: Scorticati Camila , Fernández-Solari Javier , De Laurentiis Andrea , Mohn Claudia , Prestifilippo Juan P. , Lasaga Mercedes , Seilicovich Adriana , Billi Silvia , Franchi Ana , McCann Samuel M. , Rettori Valeria
Published: July 2004

Because Δ-9-tetrahydrocannabinol (THC) inhibited luteinizing hormone-releasing hormone (LHRH) in male rats, we hypothesized that the endocannabinoid, anandamide (AEA), would act similarly. AEA microinjected intracerebroventricularly (i.c.v.) decreased plasma luteinizing hormone (LH) at 30 min in comparison to values in controls (P< 0.001). The cannabinoid receptor 1 (CB1-r)-specific antagonist, [N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P< 0.01). AEA (10-9M) decreased LHRH release from medial basal hypothalami incubatedin vitro. These results support the concept that endogenous AEA inhibits LHRH followed by decreased LH release in male rats. In ovariectomized (OVX) female rats, AEA i.c.v. also inhibited LH release, but in this case AM251 had an even greater inhibitory effect than AEA.In vitro, AEA had no effect on LHRH in OVX rats. It seems that endogenous AEA inhibits LHRH followed by decreased LH release in OVX rats but that AM251 has an inhibitory action in this case. In striking contrast, in OVX, estrogen-primed (OVX-E) rats, AEA i.c.v. instead of decreasing LH, increased its release. This effect was completely blocked by previous injection of AM251. When medial basal hypothalami of OVX-E rats were incubated, AEA increased LHRH release. The synthesized AEA was higher in OVX-E rats than in OVX and males, indicating that estrogen modifies endocannabinoid levels and effects. The results are interpreted to mean that sex steroids have profound effects to modify the response to AEA. It inhibits LHRH and consequently diminishes LH release in males and OVX females, but stimulates LHRH followed by increased LH release in OVX-E-primed rats.
MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias
Authors: Calin George Adrian , Liu Chang-Gong , Sevignani Cinzia , Ferracin Manuela , Felli Nadia , Dumitru Calin Dan , Shimizu Masayoshi , Cimmino Amelia , Zupo Simona , Dono Mariella , Dell'Aquila Marie L. , Alder Hansjuerg , Rassenti Laura , Kipps Thomas J. , Bullrich Florencia , Negrini Massimo , Croce Carlo M.
Published: July 2004

Little is known about the expression levels or function of micro-RNAs (miRNAs) in normal and neoplastic cells, although it is becoming clear that miRNAs play important roles in the regulation of gene expression during development [Ambros, V. (2003)
Cell
113, 673–676; McManus, M. T. (2003)
Semin. Cancer Biol.
13, 253–258]. We now report the genomewide expression profiling of miRNAs in human B cell chronic lymphocytic leukemia (CLL) by using a microarray containing hundreds of human precursor and mature miRNA oligonucleotide probes. This approach allowed us to identify significant differences in miRNome expression between CLL samples and normal CD5+ B cells; data were confirmed by Northern blot analyses and real-time RT-PCR. At least two distinct clusters of CLL samples can be identified that were associated with the presence or absence of Zap-70 expression, a predictor of early disease progression. Two miRNA signatures were associated with the presence or absence of mutations in the expressed Ig variableregion genes or with deletions at 13q14, respectively. These data suggest that miRNA expression patterns have relevance to the biological and clinical behavior of this leukemia.
Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex
Authors: Kelly S. , Bliss T. M. , Shah A. K. , Sun G. H. , Ma M. , Foo W. C. , Masel J. , Yenari M. A. , Weissman I. L. , Uchida N. , Palmer T. , Steinberg G. K.
Published: July 2004

We characterize the survival, migration, and differentiation of human neurospheres derived from CNS stem cells transplanted into the ischemic cortex of rats 7 days after distal middle cerebral artery occlusion. Transplanted neurospheres survived robustly in naive and ischemic brains 4 wk posttransplant. Survival was influenced by proximity of the graft to the stroke lesion and was negatively correlated with the number of IB4-positive inflammatory cells. Targeted migration of the human cells was seen in ischemic animals, with many human cells migrating long distances (≈1.2 mm) predominantly toward the lesion; in naive rats, cells migrated radially from the injection site in smaller number and over shorter distances (0.2 mm). The majority of migrating cells in ischemic rats had a neuronal phenotype. Migrating cells between the graft and the lesion expressed the neuroblast marker doublecortin, whereas human cells at the lesion border expressed the immature neuronal marker β-tubulin, although a small percentage of cells at the lesion border also expressed glial fibrillary acid protein (GFAP). Thus, transplanted human CNS (hCNS)-derived neurospheres survived robustly in naive and ischemic brains, and the microenvironment influenced their migration and fate.
Total chemical synthesis of N-myristoylated HIV-1 matrix protein p17: Structural and mechanistic implications of p17 myristoylation
Authors: Wu Zhibin , Alexandratos Jerry , Ericksen Bryan , Lubkowski Jacek , Gallo Robert C. , Lu Wuyuan
Published: July 2004

The HIV-1 matrix protein p17, excised proteolytically from the N terminus of the Gag polyprotein, forms a protective shell attached to the inner surface of the plasma membrane of the virus. During the late stages of the HIV-1 replication cycle, the N-terminally myristoylated p17 domain targets the Gag polyprotein to the host-cell membrane for particle assembly. In the early stages of HIV-1 replication, however, some p17 molecules dissociate from the viral membrane to direct the preintegration complex to the host-cell nucleus. These two opposing targeting functions of p17 require that the protein be capable of reversible membrane interaction. It is postulated that a significant structural change in p17 triggered by proteolytic cleavage of the Gag polyprotein sequesters the N-terminal myristoyl group, resulting in a weaker membrane binding by the matrix protein than the Gag precursor. To test this “myristoyl switch” hypothesis, we obtained highly purified synthetic HIV-1 p17 of 131 amino acid residues and its N-myristoylated form in large quantity. Both forms of p17 were characterized by circular dichroism spectroscopy, protein chemical denaturation, and analytical centrifugal sedimentation. Our results indicate that although N-myristoylation causes no spectroscopically discernible conformational change in p17, it stabilizes the protein by 1 kcal/mol and promotes protein trimerization in solution. These findings support the premise that the myristoyl switch in p17 is triggered not by a structural change associated with proteolysis, but rather by the destabilization of oligomeric structures of membrane-bound p17 in the absence of downstream Gag subdomains.
School-milk intervention trial enhances growth and bone mineral accretion in Chinese girls aged 10–12 years in Beijing
Authors: DU Xueqin , Zhu Kun , Trube Angelika , Zhang Qian , Ma Guansheng , Hu Xiaoqi , Fraser David R. , Greenfield Heather
Published: July 2004

A 2-year milk intervention trial was carried out with 757 girls, aged 10 years, from nine primary schools in Beijing (April 1999 – March 2001). Schools were randomised into three groups: group 1, 238 girls consumed a carton of 330 ml milk fortified with Ca on school days over the study period; group 2, 260 girls received the same quantity of milk additionally fortified with 5 or 8 μg cholecalciferol; group 3, 259 control girls. Anthropometric and bone mineralisation measurements, as well as dietary, health and physical-activity data, were collected at baseline and after 12 and 24 months of the trial. Over the 2-year period the consumption of this milk, with or without added cholecalciferol, led to significant increases in the changes in height (≥0·6%), sitting height (≥0·8%), body weight (≥2·9%), and (size-adjusted) total-body bone mineral content (≥1·2%) and bone mineral density (≥3·2%). Those subjects receiving additional cholecalciferol compared with those receiving the milk without added 25-hydoxycholecalciferol had significantly greater increases in the change in (size-adjusted) total-body bone mineral content (2·4v. 1·2%) and bone mineral density (5·5v. 3·2%). The milk fortified with cholecalciferol significantly improved vitamin D status at the end of the trial compared with the milk alone or control groups. It is concluded that an increase in milk consumption, e.g. by means of school milk programmes, would improve bone growth during adolescence, particularly when Ca intake and vitamin D status are low.
Accurate detection of aneuploidies in array CGH and gene expression microarray data
Authors: Myers Chad L. , Dunham Maitreya J. , Kung S. Y. , Troyanskaya Olga G.
Published: July 2004

Motivation: Chromosomal copy number changes (aneuploidies) are common in cell populations that undergo multiple cell divisions including yeast strains, cell lines and tumor cells. Identification of aneuploidies is critical in evolutionary studies, where changes in copy number serve an adaptive purpose, as well as in cancer studies, where amplifications and deletions of chromosomal regions have been identified as a major pathogenetic mechanism. Aneuploidies can be studied on whole-genome level using array CGH (a microarray-based method that measures the DNA content), but their presence also affects gene expression. In gene expression microarray analysis, identification of copy number changes is especially important in preventing aberrant biological conclusions based on spurious gene expression correlation or masked phenotypes that arise due to aneuploidies. Previously suggested approaches for aneuploidy detection from microarray data mostly focus on array CGH, address only whole-chromosome or whole-arm copy number changes, and rely on thresholds or other heuristics, making them unsuitable for fully automated general application to gene expression datasets. There is a need for a general and robust method for identification of aneuploidies of any size from both array CGH and gene expression microarray data.

Results: We present ChARM (Chromosomal Aberration Region Miner), a robust and accurate expectation–maximization based method for identification of segmental aneuploidies (partial chromosome changes) from gene expression and array CGH microarray data. Systematic evaluation of the algorithm on synthetic and biological data shows that the method is robust to noise, aneuploidal segment size and P-value cutoff. Using our approach, we identify known chromosomal changes and predict novel potential segmental aneuploidies in commonly used yeast deletion strains and in breast cancer. ChARM can be routinely used to identify aneuploidies in array CGH datasets and to screen gene expression data for aneuploidies or array biases. Our methodology is sensitive enough to detect statistically significant and biologically relevant aneuploidies even when expression or DNA content changes are subtle as in mixed populations of cells.

Availability: Code available by request from the authors and on Web supplement at http://function.cs.princeton.edu/ChARM/
Intratumoral Arteriovenous Shunting in Malignant Gliomas
Authors: Mariani Luigi , Schroth Gerhard , Wielepp Johannes P. , Haldemann Andreas , Seiler Rolf W.
Published: July 2004

OBJECTIVE

Intratumoral arteriovenous shunting in glioblastomas has been suspected but neither proven nor quantified.

METHODS

Using a previously described technique of selective intra-arterial intratumoral injection of 99mTc-labeled microparticles (macroaggregated albumin), we measured the amount of radioactivity, by cerebral and pulmonary scintigraphy, in seven patients with malignant gliomas (six with glioblastomas and one with an anaplastic oligodendroglioma). The pulmonary shunt index was calculated as a percentage from the pulmonary/pulmonary plus cerebral radioactivity ratio.

RESULTS

The results revealed a mean pulmonary shunt index of 67% (range, 47–89%), indicating that most of the microparticles injected into the tumor via the arterial route bypassed the tumor and reached the lungs. The measured arteriovenous shunting was greater when the injection was performed in an artery exclusively perfusing the tumor.

CONCLUSION

Important intratumoral arteriovenous shunting exists in glioblastomas. The potential consequences of this finding for intra-arterial treatment strategies are discussed.
Primary Intradural Classic Chondrosarcoma: Case Report and Literature Review
Authors: Bosma Jark Jan Daniël , Kirollos Ramez Wadie , Broome John , Eldridge Paul Richard
Published: July 2004

OBJECTIVE AND IMPORTANCE

The exact origin of rare intradural chondrosarcomas remains obscure. We present a case report of an intradural classic chondrosarcoma (a very rare subtype of chondrosarcoma in this location), with a review of the literature, in an attempt to clarify the histogenesis of these tumors.

CLINICAL PRESENTATION

A 48-year-old man presented with a 12-month history of progressive right hemiparesis. Computed tomography and magnetic resonance imaging demonstrated a left parietal space-occupying lesion.

INTERVENTION

The patient underwent an image-guided, left parietal parasagittal craniotomy. An extrinsic tumor, which seemed to arise from the dura, was macroscopically removed. There was no bone involvement. The histological examination revealed a Grade II classic chondrosarcoma with tumor infiltration into the dura. Adjuvant radiotherapy was administered.

CONCLUSION

Intradural chondrosarcomas are rare tumors, the majority of which are mesenchymal. Classic chondrosarcomas in this location are much rarer. Their histogenesis is uncertain. In this case, the origin seems to be from the dura. Because of the malignant potential of these tumors, radical extirpation whenever possible, followed by radiotherapy, is indicated.
Concepts and Methods in Chronic Thalamic Stimulation for Treatment of Tremor: Technique and Application
Authors: Krauss Joachim K. , Simpson Richard K. , Ondo William G. , Pohle Thomas , Burgunder Jean-Marc , Jankovic Joseph
Published: July 2004

OBJECTIVE

To rationalize the technique and reduce the costs associated with chronic deep brain stimulation of the thalamus for treatment of refractory tremor.

METHODS

The efficacy and safety of a modification in surgical techniques was prospectively assessed in 94 patients with tremor. Bilateral electrodes were implanted in 29 patients, and 65 patients received unilateral implants. Forty-five patients had Parkinson's disease tremor, 42 patients had essential tremor, and 7 patients had kinetic tremors of different causes. In all instances, intraoperative stimulations to analyze the thresholds of intrinsic and extrinsic responses were performed directly with the implanted leads. The electrodes were repositioned until satisfactory results were achieved. The pulse generators were implanted directly after the first step in the same operative session. Patients were not subjected to interoperative test stimulation trials.

RESULTS

Postoperative improvement of tremor at a mean follow-up of 11.9 months was rated as excellent in 47 patients (50%), marked in 37 patients (39%), moderate in 8 patients (9%), and minor in 2 patients (2%). There was no persistent morbidity related to surgery. In patients with Parkinson's disease, the symptomatic improvement of tremor was rated as excellent in 51% of patients, marked in 36%, moderate in 11%, and minor in 2%. In patients with essential tremor, symptomatic outcome was classified as excellent in 57% of patients, marked in 36%, moderate in 5%, and minor in 2%. Six of the seven patients with kinetic tremor achieved marked symptomatic improvement, and one patient experienced moderate improvement. Forty patients experienced stimulation-related side effects. Side effects were mild in general, and they were reversible with a change in electrical parameters. They occurred more frequently in patients who had bilateral stimulation.

CONCLUSION

Excellent to marked improvement of tremor is achieved in the majority of patients with physiological target determination via implanted leads in thalamic deep brain stimulation. Interoperative test stimulation trials are unnecessary. Modifications in technique may help to reduce the costs of the related hospital stay.
Slit-ventricle Syndrome Secondary to Shunt-induced Suture Ossification
Authors: Albright A. Leland , Tyler-Kabara Elizabeth
Published: July 2004

OBJECTIVE

To report five children with slit-ventricle syndrome who were found to have increased intracranial pressure despite functioning cerebrospinal fluid shunts.

METHODS

Computed tomographic scans demonstrated erosion of the inner table of the cranium and sclerosis of the cranial sutures, particularly the coronal suture. Magnetic resonance imaging scans demonstrated no cerebrospinal fluid over the convexities. The patients were treated with cranial expansion operations that included removal of the sclerotic sutures, which were examined histologically.

RESULTS

Postoperatively, symptoms resolved for all children. Sutures were abnormal and contained foci of cartilage and bone within abnormally arranged fibrous tissue.

CONCLUSION

We postulate that chronic overdrainage of cerebrospinal fluid via shunts dampens the normal cerebral pressure waves; growth of the calvarium is thus understimulated, and this leads to ossification of the sutures, which become unable to expand to allow normal brain growth. Shunt-induced craniostenosis should be considered for children with symptoms of slit-ventricle syndrome for whom shunts are functional but intracranial pressure is increased. Cranial expansion operations may be more appropriate treatments than subtemporal decompressions for such children, given the diffuseness of the suture pathological features.
Stereotactic Navigation for Placement of Pedicle Screws in the Thoracic Spine
Authors: Youkilis Andrew S. , Quint Douglas J. , McGillicuddy John E. , Papadopoulos Stephen M.
Published: July 2004

OBJECTIVE

Pedicle screw fixation in the lumbar spine has become the standard of care for various causes of spinal instability. However, because of the smaller size and more complex morphology of the thoracic pedicle, screw placement in the thoracic spine can be extremely challenging. In several published series, cortical violations have been reported in up to 50% of screws placed with standard fluoroscopic techniques. The goal of this study is to evaluate the accuracy of thoracic pedicle screw placement by use of image-guided techniques.

METHODS

During the past 4 years, 266 image-guided thoracic pedicle screws were placed in 65 patients at the University of Michigan Medical Center. Postoperative thin-cut computed tomographic scans were obtained in 52 of these patients who were available to enroll in the study. An impartial neuroradiologist evaluated 224 screws by use of a standardized grading scheme. All levels of the thoracic spine were included in the study.

RESULTS

Chart review revealed no incidence of neurological, cardiovascular, or pulmonary injury. Of the 224 screws reviewed, there were 19 cortical violations (8.5%). Eleven (4.9%) were Grade II (≤2 mm), and eight (3.6%) were Grade III (>2 mm) violations. Only five screws (2.2%), however, were thought to exhibit unintentional, structurally significant violations. Statistical analysis revealed a significantly higher rate of cortical perforation in the midthoracic spine (T4–T8, 16.7%; T1–T4, 8.8%; and T9–T12, 5.6%).

CONCLUSION

The low rate of cortical perforations (8.5%) and structurally significant violations (2.2%) in this retrospective series compares favorably with previously published results that used anatomic landmarks and intraoperative fluoroscopy. This study provides further evidence that stereotactic placement of pedicle screws can be performed safely and effectively at all levels of the thoracic spine.
Spinal Cord Stimulation for Nonspecific Limb Pain versus Neuropathic Pain and Spontaneous versus Evoked Pain
Authors: Kim Seong H. , Tasker Ronald R. , Oh Michael Y.
Published: July 2004

OBJECTIVE

To compare the outcome of spinal cord stimulation (SCS) in patients with nonspecific limb pain versus patients with neuropathic pain syndromes and in patients with spontaneous versus evoked pain.

METHODS

A retrospective review of 122 patients accepted for treatment with SCS between January 1990 and December 1998 was conducted. All patients first underwent a trial of SCS with a monopolar epidural electrode. Seventy-four patients had a successful trial and underwent permanent implantation of the monopolar electrode used for the trial (19 patients), or a quadripolar electrode (53 patients), or a Resume quadripolar electrode via laminotomy (2 patients).

RESULTS

Of the 74 patients, 60.7% underwent implantation of a permanent device and were followed for an average of 3.9 years (range, 0.3–9 yr). Early failure (within 1 yr) occurred in 20.3% of patients, and late failure (after 1 yr) occurred in 33.8% of patients. Overall, 45.9% of patients were still receiving SCS at latest follow-up. Successful SCS (>50% reduction in pain for 1 yr) occurred in 83.3% of patients with nonspecific leg pain, 89.5% of patients with limb pain associated with root injury, and 73.9% of patients with nerve neuropathic pain. SCS was less effective for the control of allodynia or hyperpathia than for spontaneous pain associated with neuropathic pain syndromes. Third-party involvement did not influence outcome. There was a lesser incidence of surgical revisions when quadripolar leads were used than with monopolar electrodes.

CONCLUSION

SCS is as effective for treating nonspecific limb pain as it is for treating neuropathic pain, including limb pain associated with root damage.
Clinical and Neurophysiological Observations after Superior Petrosal Vein Obstruction during Surgery of the Cerebellopontine Angle: Case Report
Authors: Strauss Christian , Neu Mandana , Bischoff Barbara , Romstöck Johann
Published: July 2004

IMPORTANCE

Preservation of venous drainage during surgery of the cerebellopontine angle has received little attention.

CLINICAL PRESENTATION

We describe changes in brainstem auditory evoked potentials after temporary obstruction of the superior petrosal vein during surgical resection of a small meningioma at the petrous apex via a standard suboccipital-lateral approach. Temporary clipping of the petrosal vein resulted in deterioration of the brainstem auditory evoked potentials. The tumor was removed with preservation of the superior petrosal vein.

CONCLUSION

A transient postoperative cochlear nerve deficit emphasizes the importance of venous drainage and its preservation during surgery for small lesions of the cerebellopontine angle that do not distort normal anatomic structures.
New Technique for Application of Fibrin Sealant: Rubbing Method Devised to Prevent Cerebrospinal Fluid Leakage from Dura Mater Sites Repaired with Expanded Polytetrafluoroethylene Surgical Membranes
Authors: Nakajima Satoshi , Fukuda Tadaharu , Hasue Masamichi , Sengoku Yuichi , Haraoka Jo , Uchida Takanori
Published: July 2004

OBJECTIVE

The effectiveness of a strong, pressure-tight method for fibrin sealant application was experimentally and clinically evaluated, using expanded polytetrafluoroethylene (ePTFE) surgical membranes.

METHODS

Two application methods were examined in two groups. For Group 1, 1 ml each of Solutions A and B was simply sprayed over the surface (spray method). For Group 2, a small amount of Solution A was rubbed into the sutured site and then Solutions A and B were sprayed over the surface (rubbing method). In the experimental study, a moment pressure elevation test and a continuous stepwise pressure elevation test were performed for both groups. The clinical study was conducted using 350 patients undergoing craniotomies. The ePTFE surgical membrane was used for 180 patients but not the other 170 patients.

RESULTS

In the experimental study, the bursting pressures were 51.4 ± 13.0 cm H2O for Group 1 and 129 ± 35.0 cm H2O for Group 2 in the moment pressure elevation test and 27.0 ± 6.7 cm H2O and 100 ± 31.9 cm H2O, respectively, in the continuous stepwise pressure elevation test. The sealing effect was significantly greater for Group 2 than for Group 1 in both tests (P < 0.001). In the clinical study using ePTFE surgical membranes, the rubbing method significantly reduced the incidence of postoperative cerebrospinal fluid leakage (1.4%), compared with the spray method (18.3%), when external decompression was not concomitantly used (P < 0.01).

CONCLUSION

The sealing effect of fibrin sealant on cerebrospinal fluid leakage was significantly greater with the rubbing method than with the spray method. The strong sealing effect obtained with the rubbing method is thought to result from firm linkage between the ePTFE surgical membrane and the fibrin sealant and also from fibrin being formed even in needle holes and spaces in the sutured site.
Nonaccidental Pediatric Head Injury: Diffusion-weighted Imaging Findings
Authors: Suh Daniel Y. , Davis Patricia C. , Hopkins Katherine L. , Fajman Nancy N. , Mapstone Timothy B.
Published: July 2004

OBJECTIVE

Diffusion-weighted imaging (DWI) reveals nonhemorrhagic posttraumatic infarction hours to days before conventional computed tomographic scanning or magnetic resonance imaging (MRI). We evaluated the diagnostic utility of DWI in children with nonaccidental head trauma.

METHODS

The medical records and imaging examinations obtained between January 1998 and May 2000 for all children less than 2 years of age with presumed or suspected nonaccidental head injury were reviewed retrospectively. Twenty children who had undergone DWI within 5 days of presentation were included in the study. Computed tomographic scans, conventional MRI sequences, and DWI combined with apparent diffusion coefficient (ADC) maps were evaluated.

RESULTS

Eleven girls and nine boys (median age, 5 mo) were studied. Eighteen children had presumed nonaccidental head trauma, and two children had suspected nonaccidental head trauma. Of the 18 children with presumed nonaccidental trauma, 16 (89%) demonstrated abnormalities on DWI/ADC, as compared with neither of the two children with suspected nonaccidental trauma. In 13 (81%) of 16 positive cases, DWI revealed more extensive brain injury than was demonstrated on conventional MRI sequences or showed injuries not observed on conventional MRI. DWI combined with ADC maps allowed better delineation of the extent of white matter injury. DWI/ADC abnormalities in the nonaccidental head-injured children were likely to involve posterior aspects of the cerebral hemispheres, with relative sparing of the frontal and temporal poles. Severity on DWI correlated significantly with poor outcome (P < 0.005).

CONCLUSION

DWI has broad applications in the early detection of infarction in children with nonaccidental head injury and enhances the sensitivity of conventional MRI. In the patients in this study, early DWI provided an indicator of severity that was more complete than any other imaging modality. The use of DWI may help to identify children at high risk for poor outcome and to guide management decisions.
αvβ3 and αvβ5 Integrin Expression in Glioma Periphery
Authors: Bello Lorenzo , Francolini Maura , Marthyn Paola , Zhang Jianping , Carroll Rona S. , Nikas Demetrios C. , Strasser Jon F. , Villani Roberto , Cheresh David A. , Black Peter McL.
Published: July 2004

OBJECTIVE

This study analyzed the expression of integrins αvβ3 and αvβ5 in glioma tissue and focused on the periphery of high-grade gliomas.

METHODS

The analysis was performed with Western blot, immunohistochemistry, and immunofluorescence, by use of two monoclonal antibodies able to recognize the functional integrin heterodimer. The expression of integrin-related ligands and growth factors also was studied. Sections from the tumor periphery were classified as either tumor periphery (light tumor infiltrate or scant visible cells) or peritumor (heavy tumor infiltration).

RESULTS

Our data on glioma tissues demonstrated that both integrins were expressed in glioma cells and vasculature and their expression correlated with the histological grade. αvβ3 expression was prominent in astrocytic tumors. Both integrins were markers of tumor vasculature, particularly of endothelial proliferation. A high-grade glioma periphery demonstrated a prominent expression of integrin αvβ3. Cells demonstrating αvβ3 positivity were identified as tumor astrocytes and endothelial cells by double imaging. The same cells were surrounded by some αvβ3 ligands and co-localized fibroblast growth factor 2. Matrix metalloproteinase 2 also was found to be co-localized with αvβ3 in the same cells. αvβ3 expression was more relevant in tumor astrocytes. αvβ3 integrin and vascular endothelial growth factor expression increased from the periphery to the tumor center.

CONCLUSION

Our data support the role of integrins αvβ3 and αvβ5 in glioma-associated angiogenesis. In addition, they suggest a role for integrin αvβ3 in neoangiogenesis and cell migration in high-grade glioma periphery.
Radiosurgery-induced Microvascular Alterations Precede Necrosis of the Brain Neuropil
Authors: Kamiryo Toshifumi , Lopes M. Beatriz S. , Kassell Neal F. , Steiner Ladislau , Lee Kevin S.
Published: July 2004

OBJECTIVE

Radiosurgery is used as a therapeutic modality for a wide range of cerebral disorders. It is important to understand the underlying causes of deleterious side effects that may accompany gamma-irradiation of brain tissue. In this study, structural alterations in rat cerebral vessels subjected to gamma knife irradiation in vivo were examined, for elucidation of their potential role in necrosis formation.

METHODS

A maximal center dose of 75 Gy was delivered to the rat parietal cortex with a 4-mm collimator, and changes occurring before necrosis formation were assessed 3.5 months after irradiation. Transmission electron microscopy, using horseradish peroxidase as a tracer, and scanning electron microscopy with vascular casting were performed.

RESULTS

The capillary network in the irradiated area exhibited thickening and vacuolation of the basement membrane. The capillary density in the irradiated area was lower and the average capillary diameter was larger, compared with the nonirradiated side. These results indicate that substantial changes in the neuropil do not occur 2 weeks before the time of definite necrosis formation, whereas changes in the basement membrane are prominent.

CONCLUSION

The necrotic response to intermediate doses of focused-beam irradiation appears after a considerable latency period and then progresses rapidly. This contrasts with previously reported responses to fractionated whole-brain irradiation, in which damage occurs slowly and gradually. Alterations in the microvascular basement membrane precede overt cellular changes in neuronal and vascular cells and provide an early index of cerebrovascular dysfunction in regions destined to undergo necrosis.
Conus Perimedullary Arteriovenous Fistula with Intracranial Drainage: Case Report
Authors: Vates G. Edward , Quiñones-Hinojosa Alfredo , Halbach Van V. , Lawton Michael T.
Published: July 2004

OBJECTIVE AND IMPORTANCE

Perimedullary arteriovenous fistulae (AVFs) do not commonly present with subarachnoid hemorrhage or intracranial venous drainage causing neurological symptoms. We present a case with both of these features. The patient was inadvertently treated for an unruptured intracranial aneurysm before his true problem was recognized.

CLINICAL PRESENTATION

A 65-year-old man presented with sudden-onset lower-extremity weakness, diplopia, nausea, and dysarthria on the day of admission. A lumbar puncture documented subarachnoid hemorrhage, and imaging studies revealed a left middle cerebral artery aneurysm. It was noted during surgery that this aneurysm was unruptured, and the patient did not exhibit improvement after surgery.

INTERVENTION

Spinal angiography demonstrated a spinal perimedullary AVF feeding from the left T12 radicular artery; venous drainage extended rostrally into the posterior fossa venous system. The AVF was surgically occluded via a posterior laminectomy at the level of the AVF. After surgery, the patient's symptoms began to abate.

CONCLUSION

Conus perimedullary AVFs can have venous drainage that extends as far as intracranial veins, which can lead to confusing clinical findings because the symptoms may suggest an intracranial process, although the lesion is in the spine. Surgeons must be aware of this confusing presentation.
Effects of Surgical Revascularization on Peripheral Artery Aneurysms in Moyamoya Disease: Report of Three Cases
Authors: Kuroda Satoshi , Houkin Kiyohiro , Kamiyama Hiroyasu , Abe Hiroshi
Published: July 2004

OBJECTIVE AND IMPORTANCE

The beneficial effects of surgical revascularization on rebleeding in moyamoya disease remain unclear. This report is intended to clarify the effects of surgical revascularization on peripheral artery aneurysms, which represent one of the causes of intracranial bleeding in moyamoya disease.

CLINICAL PRESENTATION

Findings for three female patients who experienced intracranial bleeding are presented. Cerebral angiography revealed that intracranial bleeding resulted from the rupture of peripheral artery aneurysms arising from dilated collateral vessels such as the lenticulostriate artery.

INTERVENTION

The patients successfully underwent superficial temporal artery-middle cerebral artery anastomosis combined with encephaloduromyoarteriosynangiosis. Angiography demonstrated obliteration of the peripheral artery aneurysms, together with the disappearance or decrease in caliber of the parent collateral arteries, after surgery. None of the patients experienced rebleeding during the follow-up period (up to 52 mo).

CONCLUSION

The results strongly suggest that surgical revascularization potentially improves cerebral circulation and decreases hemodynamic stress on collateral vessels, obliterating peripheral artery aneurysms.
Serial [18F]Fluorodeoxyglucose Positron Emission Tomography after Human Neuronal Implantation for Stroke
Authors: Meltzer Carolyn Cidis , Kondziolka Douglas , Villemagne Victor L. , Wechsler Lawrence , Goldstein Steven , Thulborn Keith R. , Gebel James , Elder Elaine M. , DeCesare Sharon , Jacobs Alan
Published: July 2004

OBJECTIVE

There is no known effective treatment for chronic stroke. In this report, we used positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) to map the metabolic brain response to neuronal cell implantation in the first human neuroimplantation trial for stroke.

METHODS

Twelve patients (nine men, three women; mean age ± standard deviation, 60.8 ± 8.3 yr) with chronic basal ganglia infarction and persistent motor deficit underwent FDG PET within 1 week before and 6 and 12 months after stereotactic implantation of human neuronal cells. Serial neurological evaluations during a 52-week postoperative period included the National Institutes of Health stroke scale and the European stroke scale.

RESULTS

Alterations in glucose metabolic activity in the stroke and surrounding tissue at 6 and 12 months after implantation correlated positively with motor performance measures.

CONCLUSION

FDG PET performed as part of an initial open-label human trial of implanted LBS-Neurons (Layton BioScience, Sunnyvale, CA) for chronic stroke demonstrates a relationship between relative regional metabolic changes and clinical performance measures. These preliminary findings suggest improved local cellular function or engraftment of implanted cells in some patients.