bluuebunny/crossref_metadata_2025 huggingface dataset:
Microsolvation effects on the π*←π electronic transitions in simple aromatic chromophores: The role of the Slater-type Gaussian orbitals in the complete active space self-consistent field approach
Authors: Satta Mauro , Sanna Nico , Giardini Anna , Speranza Maurizio
Published: September 2006

One of the most studied feature of aromatic molecular clusters in the gas phase is the shift of the π*←π electronic transitions between the bare aromatic chromophore and its clusters. In the present ab initio complete active space self-consistent field study the coupling of the basis set superposition error and counterpoise procedure and a combination of Pople- and Slater-type Gaussian basis sets has been proven to reproduce quantitatively the gas-phase experimental shifts. The quantal results are here analyzed with respect to the electrostatic and polarization forces and electron density differences, and connected with the sign of the shifts of the electronic transitions.
Evaluation of disulfide reduction during receptor-mediated endocytosis by using FRET imaging
Authors: Yang Jun , Chen Hongtao , Vlahov Iontcho R. , Cheng Ji-Xin , Low Philip S.
Published: September 2006

Despite functional evidence for disulfide bond-reducing activity in endosomal compartments, the mechanistic details pertaining to such process (e.g., kinetics and sites of disulfide reduction) remain largely controversial. To address these questions directly, we have synthesized a previously uncharacterized fluorescent folate conjugate, folate-(BODIPY FL)-SS-rhodamine (folate-FRET), that changes fluorescence from red to green upon disulfide bond reduction. Using this construct, we have observed that disulfide reduction: (
i
) occurs with a half-time of 6 h after folate-FRET endocytosis, (
ii
) begins in endosomes and does not depend significantly on redox machinery located on the cell surface or within the lysosome or the Golgi apparatus, (
iii
) occurs independently of endocytic vesicle trafficking along microtubules, and (
iv
) yields products that are subsequently sorted into distinct endosomes and trafficked in different directions. Finally, colocalization of folate and transferrin receptors suggest that conclusions derived from this study may apply to other endocytic pathways.
Nonimmune immunoglobulin binding and multiple adhesion characterize
Plasmodium falciparum
-infected erythrocytes of placental origin
Authors: Rasti Niloofar , Namusoke Fatuma , Chêne Arnaud , Chen Qijun , Staalsoe Trine , Klinkert Mo-Quen , Mirembe Florence , Kironde Fred , Wahlgren Mats
Published: September 2006

The harmful effects of pregnancy-associated malaria (PAM) are engendered by the heavy sequestration of
Plasmodium falciparum
-parasitized RBCs in the placenta. It is well documented that this process is mediated by interactions of parasite-encoded variant surface antigens and placental receptors. A
P. falciparum
erythrocyte membrane protein 1 variant, VAR2CSA, and the placental receptor chondroitin sulfate A (CSA) are currently the focus of PAM research. A role for immunoglobulins (IgG and IgM) from normal human serum and hyaluronic acid as additional receptors in placental sequestration have also been suggested. We show here (
i
) that CSA and nonimmune IgG/IgM binding are linked phenotypes of
in vitro
-adapted parasites, (
ii
) that a VAR2CSA variant shown to bind CSA also harbors IgG- and IgM-binding domains (DBL2-X, DBL5-ε, and DBL6-ε), and (
iii
) that IgG and IgM binding and adhesion to multiple receptors (IgG/IgM/HA/CSA) rather than the exclusive binding to CSA is a characteristic of fresh Ugandan placental isolates. These findings are of importance for the understanding of the pathogenesis of placental malaria and have implications for the ongoing efforts to develop a global PAM vaccine.
Inhibition of a spliceosome turnover pathway suppresses splicing defects
Authors: Pandit Shatakshi , Lynn Bert , Rymond Brian C.
Published: September 2006

Defects in assembly are suggested to signal the dissociation of faulty splicing complexes. A yeast genetic screen was performed to identify components of the putative discard pathway. Weak mutant alleles of
SPP382
(also called
NTR1
) were found to suppress defects in two proteins required for spliceosome activation, Prp38p and Prp8p. Spp382p is shown necessary for cellular splicing, with premRNA and, for some alleles, excised intron, accumulating after inactivation. Like
spp382-1
, a mutant allele of
AAR2
was identified in this suppressor screen. Like Spp382p, Aar2p has a reported role in spliceosome recycling and is found with Spp382p in a complex recovered with a mutant version of the spliceosomal core protein Prp8p. Possible insight into to the
spp382
suppressor phenotype is provided by the observation that defective splicing complexes lacking the 5′ exon cleavage intermediate are recovered by a tandem affinity purification-tagged Spp382 derivative. Stringent proteomic and two-hybrid analyses show that Spp382p also interacts with Cwc23p, a DNA J-like protein present in the spliceosome and copurified with the Prp43p DExD/H-box ATPase. Spp382p binds Prp43p and Prp43p requires Spp382p for intron release from the spliceosome. Consistent with a related function in the removal of defective complexes, three
prp43
mutants are also shown to suppress splicing defects, with efficiencies inversely proportionate to the measured ATPase activities. These and related genetic data support the existence of a Spp382p-dependent turnover pathway acting on defective spliceosomes.
Molecular characterization of embryonic gonads by gene expression profiling in
Drosophila melanogaster
Authors: Shigenobu Shuji , Kitadate Yu , Noda Chiyo , Kobayashi Satoru
Published: September 2006

In many animal species, germ-line progenitors associate with gonadal somatic cells to form the embryonic gonads (EGs) that later develop into functional organ producing gametes. To explore the genetic regulation of the germ-line development, we initiated a comprehensive identification and functional analysis of the genes expressed within the EGs. First, we generated a cDNA library from gonads purified from
Drosophila
embryos by FACS. Using this library, we catalogued the genes expressed in the gonad by EST analysis. A total of 17,218 high-quality ESTs representing 3,051 genes were obtained, corresponding to 20% of the predicted genes in the genome. The EG transcriptome is unexpectedly distinct from that of adult gonads and includes an extremely high proportion of retrotransposon-derived transcripts. We verified 101 genes preferentially expressed in the EGs by whole-mount
in situ
hybridization. Within this subset, 39 and 58 genes were expressed predominantly in germ-line and somatic cells, respectively, whereas four genes were expressed in the both cell lineages. The gonad-enriched genes encompassed a variety of predicted functions. However, genes implicated in SUMOylation and protein translation, including germ-line-specific ribosomal proteins, are preferentially expressed in the germ line, whereas the expression of various retrotransposons and RNAi-related genes are more prominent in the gonadal soma. These transcriptome data are a resource for understanding the mechanism of various cellular events during germ-line development.
Hmgb3 regulates the balance between hematopoietic stem cell self-renewal and differentiation
Authors: Nemeth Michael J. , Kirby Martha R. , Bodine David M.
Published: September 2006

Hmgb3 is an X-linked member of a family of sequence-independent chromatin-binding proteins that is preferentially expressed in hematopoietic stem cells (HSC).Hmgb3-deficient mice (Hmgb3−/Y) contain normal numbers of HSCs, capable of self-renewal and hematopoietic repopulation, but fewer common lymphoid (CLP) and common myeloid progenitors (CMP). In this study, we tested the hypothesis thatHmgb3−/YHSCs are biased toward self-renewal at the expense of progenitor production. Wild-type andHmgb3−/YCLPs and CMPs proliferate and differentiate equallyin vitro, indicating that CLP and CMP function normally inHmgb3−/Ymice.Hmgb3−/YHSCs exhibit constitutive activation of the canonical Wnt signaling pathway, which regulates stem cell self-renewal. Increased Wnt signaling inHmgb3−/YHSCs corresponds to increased expression ofDvl1, a positive regulator of the canonical Wnt pathway. To induce hematopoietic stress and a subsequent response from HSCs, we treatedHmgb3−/Ymice with 5-fluorouracil.Hmgb3−/Ymice exhibit a faster recovery of functional HSCs after administration of 5-fluorouracil compared with wild-type mice, which may be due to the increased Wnt signaling. Furthermore, the recovery of HSC number inHmgb3−/Ymice occurs more rapidly than CLP and CMP recovery. From these data, we propose a model in whichHmgb3is required for the proper balance between HSC self-renewal and differentiation.
Stable four-π-electron, four-membered heterocyclic cations and carbenes
Authors: Ishida Yutaka , Donnadieu Bruno , Bertrand Guy
Published: September 2006

Replacement of halide from
N
-(haloboryl)formamidines for the weakly coordinating anion [B(C
6
F
5
)
4
]
−
, using [Et
3
Si(toluene)]
+
[B(C
6
F
5
)
4
]
−
, induces a ring closure leading to the cationic four-π-electron four-membered heterocycles [HC(
N
-2,6-diisopropylphenyl)
2
BR]
+
[R = N(
i
-Pr)
2
, Ph]. Subsequent deprotonation of the B-amino derivative affords the corresponding
N
-heterocyclic carbene, which has been isolated as yellow crystals. According to single-crystal x-ray diffraction studies, both the carbene and its conjugate acid precursor have a planar structure, with no pyramidalization of the ring atoms. The structural parameters indicate that the four π electrons are mostly distributed over the N-C-N fragment with little involvement of the boron center, and therefore both types of heterocycles escape from antiaromaticity. However, considering the ring strain and the presence of the Lewis acid center, the thermal stability of the carbene (mp 98°C without decomposition) is rather surprising. These results clearly suggest that the backbone of
N
-heterocyclic carbenes can be modified at will, without preventing their isolation.
Amber from western Amazonia reveals Neotropical diversity during the middle Miocene
Authors: Antoine Pierre-Olivier , De Franceschi Dario , Flynn John J. , Nel André , Baby Patrice , Benammi Mouloud , Calderón Ysabel , Espurt Nicolas , Goswami Anjali , Salas-Gismondi Rodolfo
Published: September 2006

Tertiary insects and arachnids have been virtually unknown from the vast western Amazonian basin. We report here the discovery of amber from this region containing a diverse fossil arthropod fauna (13 hexapod families and 3 arachnid species) and abundant microfossil inclusions (pollen, spores, algae, and cyanophyceae). This unique fossil assemblage, recovered from middle Miocene deposits of northeastern Peru, greatly increases the known diversity of Cenozoic tropical–equatorial arthropods and microorganisms and provides insights into the biogeography and evolutionary history of modern Neotropical biota. It also strengthens evidence for the presence of more modern, high-diversity tropical rainforest ecosystems during the middle Miocene in western Amazonia.
Enhancement of antinociception by coadministration of nonsteroidal anti-inflammatory drugs and soluble epoxide hydrolase inhibitors
Authors: Schmelzer Kara R. , Inceoglu Bora , Kubala Lukas , Kim In-Hae , Jinks Steven L. , Eiserich Jason P. , Hammock Bruce D.
Published: September 2006

Combination therapies have long been used to treat inflammation while reducing side effects. The present study was designed to evaluate the therapeutic potential of combination treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and previously undescribed soluble epoxide hydrolase inhibitors (sEHIs) in lipopolysaccharide (LPS)-challenged mice. NSAIDs inhibit cyclooxygenase (COX) enzymes and thereby decrease production of metabolites that lead to pain and inflammation. The sEHIs, such as 12-(3-adamantan-1-yl-ureido)-dodecanoic acid butyl ester (AUDA-BE), stabilize anti-inflammatory epoxy-eicosatrienoic acids, which indirectly reduce the expression of COX-2 protein. Here we demonstrate that the combination therapy of NSAIDs and sEHIs produces significantly beneficial effects that are additive for alleviating pain and enhanced effects in reducing COX-2 protein expression and shifting oxylipin metabolomic profiles. When administered alone, AUDA-BE decreased protein expression of COX-2 to 73 ± 6% of control mice treated with LPS only without altering COX-1 expression and decreased PGE
2
levels to 52 ± 8% compared with LPS-treated mice not receiving any therapeutic intervention. When AUDA-BE was used in combination with low doses of indomethacin, celecoxib, or rofecoxib, PGE
2
concentrations dropped to 51 ± 7, 84 ± 9, and 91 ± 8%, respectively, versus LPS control, without disrupting prostacyclin and thromboxane levels. These data suggest that these drug combinations (NSAIDs and sEHIs) produce a valuable beneficial analgesic and anti-inflammatory effect while prospectively decreasing side effects such as cardiovascular toxicity.
The iminosugar isofagomine increases the activity of N370S mutant acid β-glucosidase in Gaucher fibroblasts by several mechanisms
Authors: Steet Richard A. , Chung Stephen , Wustman Brandon , Powe Allan , Do Hung , Kornfeld Stuart A.
Published: September 2006

Gaucher disease is a lysosomal storage disorder caused by deficiency in lysosomal acid β-glucosidase (GlcCerase), the enzyme responsible for the catabolism of glucosylceramide. One of the most prevalent disease-causing mutations, N370S, results in an enzyme with lower catalytic activity and impaired exit from the endoplasmic reticulum. Here, we report that the iminosugar isofagomine (IFG), an active-site inhibitor, increases GlcCerase activity 3.0 ± 0.6-fold in N370S fibroblasts by several mechanisms. A major effect of IFG is to facilitate the folding and transport of newly synthesized GlcCerase in the endoplasmic reticulum, thereby increasing the lysosomal pool of the enzyme. In addition, N370S GlcCerase synthesized in the presence of IFG exhibits a shift in pH optimum from 6.4 to 5.2 and altered sensitivity to SDS. Although IFG fully inhibits GlcCerase in the lysosome in an
in situ
assay, washout of the drug leads to partial recovery of GlcCerase activity within 4 h and full recovery by 24 h. These findings provide support for the possible use of active-site inhibitors in the treatment of some forms of Gaucher disease.
Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6
Authors: Poët Mallorie , Kornak Uwe , Schweizer Michaela , Zdebik Anselm A. , Scheel Olaf , Hoelter Sabine , Wurst Wolfgang , Schmitt Anja , Fuhrmann Jens C. , Planells-Cases Rosa , Mole Sara E. , Hübner Christian A. , Jentsch Thomas J.
Published: September 2006

Mammalian CLC proteins function as Cl
−
channels or as electrogenic Cl
−
/H
+
exchangers and are present in the plasma membrane and intracellular vesicles. We now show that the ClC-6 protein is almost exclusively expressed in neurons of the central and peripheral nervous systems, with a particularly high expression in dorsal root ganglia. ClC-6 colocalized with markers for late endosomes in neuronal cell bodies. The disruption of ClC-6 in mice reduced their pain sensitivity and caused moderate behavioral abnormalities. Neuronal tissues showed autofluorescence at initial axon segments. At these sites, electron microscopy revealed electron-dense storage material that caused a pathological enlargement of proximal axons. These deposits were positive for several lysosomal proteins and other marker proteins typical for neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. However, the lysosomal pH of

Clcn6
−/−

neurons appeared normal.
CLCN6
is a candidate gene for mild forms of human NCL. Analysis of 75 NCL patients identified ClC-6 amino acid exchanges in two patients but failed to prove a causative role of
CLCN6
in that disease.
Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells
Authors: Liuzzi Juan P. , Aydemir Fikret , Nam Hyeyoung , Knutson Mitchell D. , Cousins Robert J.
Published: September 2006

Zip14 is a member of the SLC39A zinc transporter family, which is involved in zinc uptake by cells. Up-regulation of Zip14 by IL-6 appears to contribute to the hepatic zinc accumulation and hypozincemia of inflammation. At least three members of the SLC39A family transport other trace elements, such as iron and manganese, in addition to zinc. We analyzed the capability of Zip14 to mediate non-transferrin-bound iron (NTBI) uptake by overexpressing mouse Zip14 in HEK 293H cells and Sf9 insect cells. Zip14 was found to localize to the plasma membrane, and its overexpression increased the uptake of both
65
Zn and
59
Fe. Addition of bathophenanthroline sulfonate, a cell-impermeant ferrous iron chelator, inhibited Zip14-mediated iron uptake from ferric citrate, suggesting that iron is taken up by HEK cells as Fe
2+
. Iron uptake by HEK and Sf9 cells expressing Zip14 was inhibited by zinc. Suppression of endogenous Zip14 expression by using Zip14 siRNA reduced the uptake of both iron and zinc by AML12 mouse hepatocytes. Zip14 siRNA treatment also decreased metallothionein mRNA levels, suggesting that compensatory mechanisms were not sufficient to restore intracellular zinc. Collectively, these results indicate that Zip14 can mediate the uptake of zinc and NTBI into cells and that it may play a role in zinc and iron metabolism in hepatocytes, where this transporter is abundantly expressed. Because NTBI is commonly found in plasma of patients with hemochromatosis and transfusional iron overload, Zip14-mediated NTBI uptake may contribute to the hepatic iron loading that characterizes these diseases.
Social Polarisation: Comparing Singapore, Hong Kong and Taipei
Authors: Tai Po-Fen
Published: September 2006

Social polarisation theory assumes that the world's major cities tend to divide into dual social strata. However, in the context of developmental states integrated into the Greater South China economic zone, an empirical study of three Asian cities challenges the social polarisation hypothesis and suggests alternative forms of social transformation. Data on changes in employment, occupation and household income in Singapore, Hong Kong and Taipei show that urban regimes and social policies instigated by developmental states play a decisive role in the formation of social inequality and marginal urban populations.
Power Relations in Urban Decision-making: Neo-liberalism, 'Techno-politicians' and Authoritarian Redevelopment in Santiago, Chile
Authors: Zunino Hugo Marcelo
Published: September 2006

Taking as a subject of study an on-going urban development project in Santiago, Chile, the paper interprets how public and private actors came together in an urban decision-making episode which represented a particular power configuration. To consider both the structural forms of constraint and the differential capacity of actors to exert power, an analytical framework is constructed, derived from Giddens' structuration theory and from Foucault's approach to power. The analysis of the specific relationships established between the project's participants shows how individuals from the central state apparatus and private investors were controlling local redevelopment, relegating the local government (the municipality) and the people living near the project to non-influential positions. The concluding section considers the potentials and limitations of the analytical framework deployed and the degree to which its outcome could be generalised to the Chilean situation.
Lumbar spinal dural arteriovenous fistula presenting with brainstem symptomatology: a case report
Authors: Wu S.-L. , Tsui H.-W. , Chuang Y.-C. , Kuo H.-C. , Chen C.-J.
Published: September 2006

This report is about a rare case of a lumbar spinal dural arteriovenous fistula (DAVF) with distant brainstem symptoms of vertigo and ataxia. Brain magnetic resonance imaging (MRI) demonstrated a high signal abnormality in the lower pons, medulla, and cervico-medullary junction, presumably related to venous hypertension. Spinal MRI revealed markedly dilated veins along the dorsal aspect of the cord, while spinal angiography confirmed the presence of a lumbar spinal DAVF. Because lumbar DAVF may cause remote brainstem symptoms, spinal DAVF should be considered in the differential diagnosis of high signal MRI abnormalities localized in the brainstem. Properly extending the scanning range is essential in the diagnosis.
Role of diffusion-weighted magnetic resonance imaging in diffuse axonal injury
Authors: Ezaki Y. , Tsutsumi K. , Morikawa M. , Nagata I.
Published: September 2006

Purpose: To determine whether the signal changes on magnetic resonance imaging (MRI), including fluid attenuated inversion recovery (FLAIR), T2*-weighted gradient echo (GE) imaging, and diffusion-weighted imaging (DWI) in diffuse axonal injury (DAI) patients correlate with the clinical outcome.

Material and Methods: We diagnosed patients with DAI based on the following criteria: 1) a loss of consciousness from the time of injury that persisted beyond 6 h; 2) no apparent hemorrhagic contusion on computed tomography (CT); 3) the presence of white matter injury on MRI. Twenty-one DAI patients were analyzed (19 M, 2 F, mean age 34 years) with MRI (FLAIR, T2*-weighted GE imaging, and DWI).

Results: 325 abnormalities were detected by MRI within a week after injury. The T2*-weighted GE imaging was significantly more sensitive than FLAIR and DWI in diagnosing DAI. DWI detected only 32% of all lesions, but could depict additional shearing injuries not visible on either T2*-weighted GE imaging or FLAIR. The mean number of lesions in brainstem detected by DWI in the favorable group (good recovery/moderately disabled) was significantly smaller than in the unfavorable group (severely disabled/vegetative survival/death). This trend was not observed on the T2*-weighted GE imaging and FLAIR findings.

Conclusion: DWI cannot detect all DAI-related lesions, but is a potentially useful imaging modality for both diagnosing and assessing patients with DAI.
A simple technique for shoulder arthrography
Authors: Berná-Serna J. D. , Redondo M. V. , Martínez F. , Reus M. , Alonso J. , Parrilla A. , Campos P. A.
Published: September 2006

Purpose: To present a systematic approach to teaching a technique for arthrography of the shoulder. Using an adhesive marker-plate with radiopaque coordinates, precise sites for puncture can be identified and the need for fluoroscopic guidance obviated.

Material and Methods: Forty-six glenohumeral arthrograms were performed in 45 patients; in 1 case involving examination of both shoulders. The stages of the technique are described in detail, as are the fundamental aspects of achieving an effective glenohumeral injection. Pain intensity was measured in all patients using a verbal description scale.

Results: Shoulder arthrography was successful in all cases. Average time taken for the procedure was 7 min, with no difference in the respective times required by an experienced radiologist and a resident. The procedure was well tolerated by most patients, with slight discomfort being observed in a very few cases.

Conclusion: The arthrographic technique used in this study is simple, safe, rapid, and reproducible, and has the advantage of precise localization of the site for puncture without need for fluoroscopic guidance. The procedure described in this study can be of help in teaching residents and can reduce the learning curve for radiologists with no experience in arthrographic methods. It also reduces the time of exposure to fluoroscopy.
Impact of the number of readers on mammography interpretation
Authors: Hukkinen K. , Kivisaari L. , Vehmas T.
Published: September 2006

Purpose: To evaluate the impact of the number of readers on sensitivity and specificity, and compare it with conference consensus reading.

Material and Methods: Eight readers read mammography films of 200 women (including 35 false-negative and 16 screen-detected cancers). The sensitivities and specificities of the two methods were calculated: either at least a single cancer-positive opinion within the group (summarized independent reading) or the cancer-positive opinion of the reader majority (conference consensus reading) was considered decisive.

Results: The mean sensitivity for summarized independent readings of different groups was 64.7% as compared to the 43.1% mean sensitivity of conference consensus readings. The mean specificities were 92.4% and 97.7%, respectively. The greatest sensitivity of 74.5% was achieved when the readings of the four best-performing readers were combined.

Conclusion: The sensitivity of reading is maximal when any positive opinion within a pair or a group of readers is taken into consideration. Discordant double reading may best be judged as screening positive, and the value of a third opinion should be questioned.
The iodinated radiographic contrast medium iohexol mimics the vasodilator effect seen with small increases in extracellular K+ in the isolated rabbit central ear artery
Authors: Frønes S. , Støen R. , Gregersen M. , Refsum H. , Krane J. , Karlsson J. O. G.
Published: September 2006

Purpose: To investigate whether iodinated radiographic contrast media (IRCM) mimic the hyperpolarizing and vasodilator effects of K+ by comparing the vasodilator effect of a transient rise in extracellular K+ with that of the IRCM iohexol.

Material and Methods: Immersed rabbit central ear arterial rings with and without endothelium and pre-contracted with phenylephrine (PE) were used to investigate the dependency of the endothelium in K+-induced vasodilatation. Perfused rabbit central ear arteries, pre-contracted with PE, were used to study the effects of bolus administrations of the IRCM iohexol or KCl on arterial tone under conditions that mimic those employed during clinical arteriography.

Results: A small rise in K+ caused an endothelium-independent and ouabain-sensitive relaxation of PE-constricted rabbit central ear artery rings. The relaxation was not changed in the presence of barium. The IRCM iohexol and KCl, injected as boluses into perfused PE-constricted rabbit ear arteries, caused transient decreases in perfusion pressure. Iohexol- and K+-induced pressure decreases were significantly reduced in the presence of 10 µM ouabain alone or in combination with 30 µM barium. Neither iohexol- nor K+-induced pressure decrease was significantly changed in the presence of barium alone compared to controls.

Conclusion: The vasodilator effect of IRCM mimics the vasodilator effect seen upon small increase in extracellular K+. Under the experimental conditions employed in the present study, a considerable part of the IRCM-induced vasodilatation appears to be due to activation of Na+/K+-ATPase in the smooth muscle cells.
Renal capsular leiomyoma: report of a case with unusual CT appearance
Authors: Mak C.-W. , Chou C.-K. , Tzeng W.-S.
Published: September 2006

Clinically symptomatic renal capsular leiomyomas are rare. Previous research has shown that these tumors are usually well-defined cystic lesions, solid lesions, or a mixture of the two. We report an unusual case of renal capsular leiomyoma which was well defined by ultrasonography, but lacked a well-defined edge in CT. The reason for the absence of a well-defined tumor edge is probably due to degeneration in certain parts of the tumor resulting in a different degree of enhancement. Thus, the possibility of renal capsular leiomyoma should be included in the differential diagnosis whenever a renal mass is found, especially when either CT or ultrasonography shows that the tumor has a smooth, well-defined contour.
Lessons after 3 years of running GENIUS-TF in Gran Sasso
Authors: Krivosheina I V , Klapdor-Kleingrothaus H V
Published: September 2006

After operation of GENIUS-TF over 3 years with finally six naked Ge detectors (15 kg) in liquid nitrogen in Gran Sasso, we realize serious problems for realization of a full-size GENIUS-like experiment: (i) background from222Rn diffusing into the setup, on a level far beyond the expectation. (ii) Limited long-term stability of naked detectors in liquid nitrogen. None of the six detectors is running after 3 years with the nominal high voltage. Three of the six detectors do not work at all any more. The HDMS (Heidelberg Dark Matter Search) setup at LNGS, operates the first enriched73Ge detector worldwide, and looks for spin-dependent WIMP-nucleon coupling at the Gran Sasso Underground Laboratory. The results (85.48 kg d) improve the best present existing limits on the WIMP–neutron spin-dependent cross-section (obtained from129Xe) for low WIMP masses (Klapdor-Kleingrothauset al2005Phys. Lett.B609226–31).
Visually Enhanced Vestibulo‐Ocular Reflex: A Diagnostic Tool for Migraine Vestibulopathy
Authors: Arriaga Moisés A. , Chen Douglas A. , Hillman Todd A. , Kunschner Lara , Arriaga Rebecca Y.
Published: September 2006

Objectives: 1) To compare the incidence of elevated visually enhanced vestibular‐ocular reflex (VVOR) rotational gain during rotational chair testing in a normal control group versus a group of patients diagnosed with migraine vestibulopathy; 2) to discuss the possible application of VVOR gain during rotational chair testing for diagnosing migraine vestibulopathy.

Study Design: Prospective normal control group and retrospective cohort comparison.

Methods: 1) Prospective rotational chair studies including VVOR in 20 normal control patients; 2) retrospective review of vestibular studies including VVOR in 100 consecutive patients with migraine vestibulopathy.

Results: Twenty of the normal controls and 69 of the migraine vestibulopathy patients met all inclusion criteria. One of 20 (5%) normal control patients had elevated VVOR gain, whereas 49 of 69 (71%) of migraine vestibulopathy patients had elevated VVOR gain.

Conclusions: VVOR gain normal criteria were appropriate in 95% of our normal control test group. VVOR gain was more frequently elevated in migraine vestibulopathy patients than in the normal controls, and the difference was significant (P < .001). VVOR gain elevation was the most common vestibular test abnormality in this cohort of patients with migraine vestibulopathy. Because VVOR measures visual‐vestibular interaction and its central connections, this parameter may be a useful diagnostic tool for migraine vestibulopathy in patients manifesting disequilibrium and motion sensitivity.
Glucocorticoids Inhibit Diastrophic Dysplasia Sulfate Transporter Activity in Otosclerosis by Interleukin‐6
Authors: Imauchi Yutaka , Lombès Marc , Lainé Pascale , Sterkers Olivier , Ferrary Evelyne , Grayeli Alexis Bozorg
Published: September 2006

Hypothesis/Objective: Otosclerosis is a bone remodeling disorder localized to the otic capsule and associated with inflammation. In vitro, increased activity of the diastrophic dysplasia sulf/te transporter (DTDST), which is implicated in bone metabolism, has been reported. Because glucocorticoids modulate the bone turnover and inhibit inflammatory processes, we investigated the effect of dexamethasone (Dex) on interleukin‐6 and DTDST in otosclerosis.

Study Design: The authors conducted a prospective, case–control study.

Materials and Methods: Primary cell cultures were obtained from stapes and external auditory canals in otosclerosis (n = 21) and control patients (n = 18). Assays with [3H]Dex evaluated specific binding sites in otosclerotic and control stapes. The effects of Dex (10−9 to 10−6 M) and RU486 (10−7 M), a glucocorticoid antagonist, were studied on DTDST activity by sulfate uptake. IL‐6 secretion was measured in culture media before and after Dex (10−7 M, 24 hours). The effect of IL‐6 (10−7 M, 24 hours) was assessed on DTDST activity in control stapes.

Results: The number of specific Dex‐binding sites was similar in all stapedial cultures. Dex inhibited DTDST activity (19.4 ± 1.02 vs. 29.4 ± 3.94 pmol/μg prot/5 minutes) only in otosclerotic stapes. This effect was dose‐dependent, antagonized by RU 486 and only observed 24 hours after Dex exposure. Interleukin (IL)‐6 stimulated DTDST activity in normal stapes, whereas Dex inhibited IL‐6 production only in otosclerotic stapes.

Conclusion: Dex inhibits the DTDST activity, at least in part, through a reduction of IL‐6 secretion only in otosclerotic cells. This effect is mediated through the glucocorticoid receptors and may lead to the reduction of bone turnover.
Organotypic (Raft) Culture of Biopsy‐Derived Upper Respiratory Epithelium
Authors: Schweinfurth John Mark , Meyers Craig
Published: September 2006

Objective: The objective of this study was to derive a reliable technique for culturing biopsy‐derived upper respiratory epithelium in a system that supports epithelial differentiation and simulates the normal epithelial life cycle.

Study Design: The authors conducted a prospective study of modification and development of an in vitro tissue culture method.

Methods: Thirty biopsy specimens from 16 individuals with recurrent respiratory papillomatosis and chronic tonsillitis, pretreated to prevent bacterial and fungal overgrowth, were digested with trypsin to create a supernatant of individual cells. The cells were plated and incubated. At 14 to 16 days, the resulting colonies were placed on a wire cloth raft and fed through diffusion from the underlying culture medium in an air–liquid interface.

Results: Eight specimens were successfully cultured for an average of over 32 days. The longest duration of sustained growth was 60 days. Low‐risk human papillomavirus specimen‐based cultures reproduced infection in cultured squamous epithelium with corresponding histopathologic features indicating a high level of stratification and differentiation.

Conclusions: Unlike commercially available cell lines, biopsy‐derived material is predisposed to contamination, and successful in vitro culture and experimentation creates many unique challenges. An organotypic culture system, capable of reproducing the differentiation‐dependent replication cycle of human papillomavirus, may be used for culturing biopsy‐derived specimens for a variety of studies.
Retropharyngeal Pseudomeningocele Presenting as Dysphagia After Atlantooccipital Dislocation
Authors: Cognetti David M. , Enochs W Scott , Willcox Thomas O.
Published: September 2006

Educational Objective: At the conclusion of this paper, the readers should be able to recognize a retropharyngeal pseudomeningocele as a potential complication of atlanto occipital dislocation.

Objectives: To demonstrate how a retropharyngeal pseudomeningocele may present as dysphagia in a patient who is recovering from atlanto occipital dislocation as well as to discuss the treatment options in this situation.

Study Design: Case report and literature review.

Methods: Analysis of a case through medical record and literature review.

Results: A retropharyngeal pseudomeningocele is a very rare complication of atlanto occipital dislocation. It may develop weeks after the initial injury and can present with respiratory or swallowing difficulties. Decompression via a ventriculoperitoneal or lumboperitoneal shunt facilitates resolution of the cerebral spinal fluid collection.

Conclusions: A retropharyngeal pseudomeningocele should be considered in all patients status post‐atlanto occipital dislocation who are experiencing respiratory distress or dysphagia.
Vocal Fold Healing after Laser Cordectomy with Adjuvant Cryotherapy
Authors: Knott P Daniel , Byrd Michael C. , Hicks David G. , Strome Marshall
Published: September 2006

Objectives: To understand the effect of adjuvant cryotherapy on glottic wound healing after endoscopic CO2 laser cordectomy.

Study Design: Canine acute injury model with videolaryngostroboscopic and histopathologic outcomes analysis.

Methods: Twelve adult male dogs underwent bilateral endoscopic CO2 laser transmuscular cordectomy followed by randomized unilateral endoscopic glottic cryotherapy. The animals were randomly divided into four groups and underwent videolaryngostroboscopy followed by sacrifice at 0, 2, 6, and 12 weeks postoperatively. Three untreated male dogs served as controls. Histopathologic sections were prepared with Alcian blue, Giemsa, hematoxylin‐eosin, movat's, Masson's trichrome, and picrosirius stains.

Results: Videostroboscopy demonstrated an earlier restoration of glottic volume and a return of mucosal waves among vocal folds treated with combined therapy by 6 weeks posttreatment. The mean depth of inflammatory reaction in the vocal cords treated with combined therapy was 1.07 mm versus 1.15 mm in vocal cords treated with CO2 laser therapy alone. At 2 and 6 weeks postoperatively, combined treatment was associated with a decreased volume of collagen. At 12 weeks postoperatively, combined treatment was associated with greater collagen organization, normalized collagen histoarchitecture, and decreased keratinization.

Conclusions: Adjuvant cryotherapy appears to alter glottis‐specific wound healing, leading to decreased and more organized collagen formation and decreased keratinization with a resultant improvement in glottic function, when compared with CO2 laser surgery alone, in an acute canine injury model. Studies in humans are ongoing to further evaluate the clinical potential of cryotherapy on glottic wound healing.
Lateral Tympanoplasty for Total or Near‐Total Perforation: Prognostic Factors
Authors: Angeli Simon I. , Kulak Jessica L. , Guzmán Jose
Published: September 2006

Objective: To identify prognostic factors affecting outcome in lateral tympanoplasty for total or near‐total tympanic membrane perforation.

Study Design: Retrospective case series.

Methods: Patients were those presenting with total or near‐total tympanic membrane perforation undergoing lateral tympanoplasty from 1999 to 2004. We systematically collected demographic, clinical, audiologic, and outcome information. Student t test was used to determine group differences. Logistic regression analysis was used to examine the relationship between success of grafting (dependent variable) and the independent variables. Multiple regression analysis was used to examine the relationship between postoperative air‐bone gap (ABG) and independent variables.

Results: There were seventy‐seven cases (58 primary and 19 revision cases) with average follow‐up of 17 months. Successful tympanic membrane grafting occurred in 91% of cases. None of the independent variables studied was predictive of the success of graft incorporation (P > .05). The mean preoperative ABG was 29.8 ± 10 dB and improved to a postoperative ABG of 16.5 ± 11 dB (P < .001). Smaller preoperative ABG and normal malleus handle were associated with smaller postoperative ABG. In revision cases, mastoidectomy was associated with better functional results.

Conclusions: Successful grafting of near‐total and total tympanic membrane perforations occurred in 91% of the cases and was independent of demographic, disease, and technical variables. Disease variables (preoperative ABG and status of malleus handle) had a greater prognostic value on postoperative ABG than other variables. In revision tympanoplasty, mastoidectomy is associated with a better functional outcome.
Effect of Inhibitor of Tumor Necrosis Factor‐α and Oxatomide on Immune Mediated Otitis Media
Authors: Park Yong‐Soo , Auo Hyeon‐Jin , Jeon Eun‐ju , Chang Ki‐Hong , Lee Seung Kyun , Lee Dong‐Hee
Published: September 2006

Objective: Inflammatory mediators (IMs) play a major role in the production of middle ear effusion (MEE). Tumor necrosis factor (TNF)‐α and leukotrienes (LTs) appear to be important in the pathogenesis of otitis media with effusion (OME). The purpose of this study is to determine the effect of TNF‐α and LT antagonist on the outcome of experimental immune‐mediated OME.

Study Design: Prospective.

Methods: Otitis media was induced in rats by injecting keyhole limpet hemocyanin (KLH) transtympanically 7 days after systemic immunization. Experimental groups were treated with soluble TNF receptor type I (sTNF RI) or oxatomide simultaneously. Seventy‐two hours after transtympanic injection, MEE was aspirated, and temporal bone was taken. Vascular permeability (VP) of the middle ear mucosa was measured using the Evans blue dye technique. Hematoxylin‐eosin stain and immunohistochemical stain for leukocyte common antigen was performed.

Results: In KLH, sTNF RI, and oxatomide groups, MEE was developed in 83%, 0%, and 66% of the ears, respectively. The sTNF RI group showed significant decrease in effusion production, inflammation, mucosal thickening, and VP compared with the KLH group. These parameters were less significant in the oxatomide group than in the sTNF RI group.

Conclusion: Transtympanic administration of sTNF RI and oxatomide appears to suppress the development of immune‐mediated MEE.
Posterior Cranial Fossa Tumors in Young Adults
Authors: Chen Chien‐Cheng , Cheng Po‐Wen , Tseng Ham‐Min , Young Yi‐Ho
Published: September 2006

Objective/Hypothesis: This retrospective study presents our experience on the posterior cranial fossa tumors in young adults during the past 15 years.

Methods. From 1991 to 2005, 16 (0.8%) of 2,091 young adults (range, 16‐29 years) with dizziness/vertigo, hearing loss, or tinnitus were diagnosed with posterior fossa tumor. Each patient underwent a battery of audiovestibular tests and image study.

Results: Audiometry revealed sensorineural hearing loss in 12 patients (75%). Spontaneous nystagmus was disclosed in eight patients (50%), consisting of bilateral gaze nystagmus in five, unilateral gaze nystagmus in two, and downbeat nystagmus in one. Electronystagmographic examination displayed abnormal eye tracking test in 75% and abnormal optokinetic nystagmus test in 81% of cases. Magnetic resonance imaging scan demonstrated space‐occupying lesions at the cerebellopontine angle in 11, cerebellum in two, brainstem in two, and jugular fossa in one. Diagnoses consisted of vestibular schwannoma and neurofibromatosis II in eight patients (50%), glial neoplasm (including astrocytoma, ependymoma, glioma) in four patients (25%), epidermoid cyst in three patients, and glomus jugulare tumor in one patient. At study close, excluding one lost patient, three patients died as a result of recurrent or residual tumor at the primary site. Restated, 12 of 15 (80%) patients were alive.

Conclusions: Unlike predominant medulloblastoma in children, the most frequent posterior fossa tumor in young adults is vestibular schwannoma and neurofibroma. However, the second most frequent one in young adults is glial neoplasm as opposed to meningioma in adults.
Late‐Onset Medullary Carcinoma of the Thyroid: Need for Genetic Testing and Prophylactic Thyroidectomy in Adult Family Members
Authors: Shaha Ashok R. , Cohen Tzeela , Ghossein Ronald , Tuttle R Michael
Published: September 2006

Objective: Sporadic late‐onset medullary carcinoma of the thyroid is quite rare. Usually, the patient presents with a thyroid mass or neck node metastasis along with high levels of calcitonin and preoperative fine needle aspiration biopsy suggestive of medullary carcinoma of the thyroid. The role of genetic testing in such individuals, along with testing of other family members, remains somewhat unclear at this stage, especially in patients presenting with familial medullary thyroid carcinoma. Genetic testing with RET proto‐oncogene mutational studies is very popular in familial medullary thyroid carcinoma, especially in children, with routine prophylactic thyroidectomy. However, its indications in adults remain unclear at this time.

Case Study: Recently, a 69‐year‐old woman presented with a thyroid mass and underwent total thyroidectomy and central compartment dissection. She was found to have medullary carcinoma of the thyroid. The patient had four children, three of whom were found to have a RET mutation similar to their mother's, V804M. In view of the RET mutation, the three children were offered prophylactic thyroidectomy at ages 42, 45, and 47. The patient's son was noted to have extensive C‐cell hyperplasia in both lobes of the thyroid. The other two individuals had benign pathology with no evidence of C‐cell hyperplasia.

Conclusions: There is no definite consensus of opinion about the need for prophylactic total thyroidectomy in adults with RET mutation. The rarely reported 804 mutation is, however, a predictor of medullary carcinoma of the thyroid. One individual in this group had extensive C‐cell hyperplasia, suggesting that he would have developed medullary carcinoma of the thyroid in the future. Prophylactic thyroidectomy should be recommended in patients with RET mutation and a family history of medullary carcinoma of the thyroid; however, its role in adult family members needs to be evaluated with larger registry of prophylactic thyroidectomy. Whether these adults with rare 804‐mutation could be observed and followed with serial calcitonin, ultrasound, or calcitonin stimulation tests remains to be studied.
Cervical Metastasis From Squamous Cell Carcinoma of the Maxillary Alveolus and Hard Palate
Authors: Simental Alfred A. , Johnson Jonas T. , Myers Eugene N.
Published: September 2006

Objectives: Squamous cell carcinoma has a predilection for regional lymphatic metastasis. The occurrence of occult cervical metastases from squamous cell carcinoma of the hard palate and maxillary alveolar ridge has not been studied systematically. We have observed many patients who have returned after resection of a primary cancer in these sites with a delayed cervical metastasis. Some of these patients have died of regional or distant metastasis despite control of their primary cancer.

Methods: We have studied 26 patients with squamous cell carcinoma of the maxillary alveolar ridge and hard palate to define incidence of cervical metastasis.

Results: Overall incidence of cervical metastasis was: clinical 2 of 26 (7.6%) and occult 7 of 26 (27%) for a total of 9 of 26 (34.6%). The 5‐year disease‐specific survival was 13 of 22 (59%). Surgery for regional failure was successful in 66% (6 of 9). Radiation was administered after surgery in eight of nine patients.

Conclusion: Cervical metastasis from cancer of the palate and alveolar ridge is significant. Regional surgery for recurrent disease usually requires radical or modified radical neck dissection. Selective elective neck dissection should be offered to patients with cancer of the hard palate and alveolar ridge. It affords the patient and the treatment team valuable histologic information, which may help to guide therapy and reduce the potential need for future hospitalization, chemoradiation, and more radical surgery.
Preservation of the Marginal Mandibular Branch of the Facial Nerve Using a Plexus Block Nerve Stimulator
Authors: Sadoughi Babak , Hans Stéphane , de Monès Erwan , Brasnu Daniel F.
Published: September 2006

Preserving the marginal mandibular branch of the facial nerve is essential in submandibular neck dissection to avert disfiguring complications. Despite the high incidence of postoperative palsy, old‐fashioned techniques of nerve identification remain widespread. The use of disposable plexus block nerve stimulators as a safe and accurate method to localize the nerve intraoperatively is suggested herein. Such devices are significantly more affordable and user‐friendly than larger facial nerve monitoring devices, which are rather favored for those procedures more extensively jeopardizing the branches of the facial nerve. In this report, disposable stimulators led to successful identification of the nerve in 100% of 25 patients between 2003 and 2005, with no postoperative paralysis. In addition, stimulation devices are constantly gaining in reliability and safety, and the number of surgical fields supporting their use is expanding. Therefore, their routine use for surgery on the submandibular area is recommended by the authors.