bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Thin-Section CT Analysis of the Enlargement and Coalescence of Low-Attenuation Clusters in Patients with Emphysema
Authors: Matsuoka Shin , Kurihara Yasuyuki , Yagihashi Kunihiro , Nakajima Yasuo
Published: September 2006

Background: The analysis of the number and size of low-attenuation clusters has been adopted as quantitative computed tomography (CT) analysis of emphysema; however, a detailed examination has not been made on the relation between the number of various cluster sizes and the extent of emphysema. Objective: The aim of this study was to evaluate the relationship between the size and number of clusters on CT scans in patients with emphysema. Methods: This retrospective study included 31 emphysema patients. The number (LAN) and mean size (LAS) of clusters below –950 HU, and relative low-attenuation area below –950 HU (RA950) were calculated using an image-processing program. The size of clusters was divided into 3 categories, and the number in each size category was obtained as follows: small (sLAN 0.4–8 mm2), medium (mLAN 8.4–40 mm2), and large (lLAN >40 mm2). The relationships between the RA950 and sLAN, mLAN, or lLAN were evaluated. Patients were divided according to the extent of RA950 (>25% = severe emphysema, <25% = mild emphysema), and the relations between RA950 and LAN, and between RA950 and sLAN, mLAN, or lLAN were evaluated. Results: The sLAN decreased as RA950 increased (r = –0.477), whereas mLAN and lLAN increased (r = 0.421, and r = 0.819). In severe emphysema, sLAN and mLAN decreased as RA950 increased (r = –0.722, and r = –0.698). In mild emphysema, mLAN and lLAN increased as RA950 increased (r = 0.732, and r = 0.972). Conclusions: The degree of the coalescence of the clusters depends on the size of clusters and the extent of emphysema. Quantitative CT analyses of clusters are helpful to elucidate the pathophysiology and progressive nature of emphysema.
Tissue Factor and Coagulation Factor VII Levels During Acute Myocardial Infarction
Authors: Campo Gianluca , Valgimigli Marco , Ferraresi Paolo , Malagutti Patrizia , Baroni Marcello , Arcozzi Chiara , Gemmati Donato , Percoco Gianfranco , Parrinello Giovanni , Ferrari Roberto , Bernardi Francesco
Published: September 2006

Objective—

We investigated in patients with ongoing myocardial infarction (MI) whether coagulation factor VII (FVII) and tissue factor (TF) levels are affected at admission by genetic components and whether they may predict subsequent cardiovascular events.

Methods and Results—

256 patients admitted for MI were evaluated for FVII and TF antigen levels before any treatment at entry, and were genotyped for FVII and TF polymorphisms. FVII gene insertions at −323, 11293 and the −402G/A change predicted FVII levels and explained 14% of variance. The −603 TF gene polymorphism failed to affect significantly TF levels (
P
=0.07). These variables were correlated with the incidence of death (36 patients) and reinfarction (9 patients) after a median follow-up of 397 days. Events were independently predicted by FVII (HR 2.1, 95% CI 1.2 to 5.7) and TF (HR 4.1, 95% CI 2 to 11) levels. Composite end point was significantly worse when both parameters were above the receiver-operating characteristics (ROC) values (HR 8.3, 95% CI 5 to 18, compared with FVII and TF below), and above the ROC value of TF (>630 pg/mL) it differed among FVII genotype groups.

Conclusions—

Admission FVII and TF antigen levels, partially predicted by polymorphisms, are independent predictors of mortality and reinfarction in patients with acute MI.
Heparin-II Domain of Fibronectin Is a Vascular Endothelial Growth Factor-Binding Domain
Authors: Wijelath Errol S. , Rahman Salman , Namekata Mayumi , Murray Jacqueline , Nishimura Tomoaki , Mostafavi-Pour Zohreh , Patel Yatin , Suda Yasuo , Humphries Martin J. , Sobel Michael
Published: September 2006

We describe extracellular interactions between fibronectin (Fn) and vascular endothelial growth factor (VEGF) that influence integrin-growth factor receptor crosstalk and cellular responses. In previous work, we found that VEGF bound specifically to fibronectin (Fn) but not vitronectin or collagens. Herein we report that VEGF binds to the heparin-II domain of Fn and that the cell-binding and VEGF-binding domains of Fn, when physically linked, are necessary and sufficient to promote VEGF-induced endothelial cell proliferation, migration, and Erk activation. Using recombinant Fn domains, the C-terminal heparin-II domain of Fn (type III repeats 13 to 14) was identified as a key VEGF-binding site. Mutation of the heparin-binding residues on FnIII
13–14
abolished VEGF binding, and peptides corresponding to the heparin-binding sequences in FnIII
13–14
inhibited VEGF binding to Fn. Fn fragments containing both the α
5
β
1
integrin-binding domain (III 9 to 10) and the VEGF-binding domain (III 13 to 14) significantly enhanced VEGF-induced EC migration and proliferation and induced strong phosphorylation of the VEGF receptor and Erk. Neither the cell-binding or VEGF-binding fragment of Fn alone had comparable VEGF-promoting effects. These results suggest that the mechanism of VEGF/Fn synergism is mediated extracellularly by the formation of a novel VEGF/Fn complex requiring both the cell-binding and VEGF-binding domains linked in a single molecular unit. These data also highlight a new function for the Fn C-terminal heparin-binding domain that may have important implications for angiogenesis and tumor growth.
Neuronal Angiotensin II Type 1 Receptor Upregulation in Heart Failure
Authors: Liu Dongmei , Gao Lie , Roy Shyamal K. , Cornish Kurtis G. , Zucker Irving H.
Published: September 2006

Chronic heart failure (CHF) is a leading cause of mortality in developed countries. Angiotensin II (Ang II) plays an important role in the development and progression of CHF. Many of the important functions of Ang II are mediated by the Ang II type 1 receptor (AT
1
R), including the increase in sympathetic nerve activity in CHF. However, the central regulation of the AT
1
R in the setting of CHF is not well understood. This study investigated the AT
1
R in the rostral ventrolateral medulla (RVLM) of rabbits with CHF, its downstream pathway, and its gene regulation by the transcription factor activator protein 1 (AP-1). Studies were performed in 5 groups of rabbits: sham (n=5), pacing-induced (3 to 4 weeks) CHF (n=5), CHF with intracerebroventricular (ICV) losartan treatment (n=5), normal with ICV Ang II treatment (n=5), and normal with ICV Ang II plus losartan treatment (n=5). AT
1
R mRNA and protein expressions, plasma Ang II, and AP-1–DNA binding activity were significantly higher in RVLM of CHF compared with Sham rabbits (240.4±30.2%,
P
<0.01; 206.6±25.8%,
P
<0.01; 280±36.5%,
P
<0.05; 207±16.4%,
P
<0.01, respectively). Analysis of the stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) pathway showed that phosphorylated c-Jun proteins, phosphorylated JNK proteins, and JNK activity increased significantly in RVLM of CHF compared with sham (262.9±48.1%, 213.8±27.7%, 148.2±10.1% of control, respectively). Importantly, ICV losartan in CHF rabbits attenuated these increases. ICV Ang II in normal rabbits simulated the molecular changes seen in CHF. This effect was blocked by concomitant ICV losartan. In addition, Ang II–induced AT
1
R expression was blocked by losartan and a JNK inhibitor, but not by extracellular signal-regulated kinase or p38 MAP kinase inhibitors in a neuronal cell culture. These data suggest that central Ang II activates the AT
1
R, SAPK/JNK pathway. AP-1 may further regulate gene expression in RVLM in the CHF state.
Increases in Mitochondrial Reactive Oxygen Species Trigger Hypoxia-Induced Calcium Responses in Pulmonary Artery Smooth Muscle Cells
Authors: Waypa Gregory B. , Guzy Robert , Mungai Paul T. , Mack Mathew M. , Marks Jeremy D. , Roe Michael W. , Schumacker Paul T.
Published: September 2006

Mitochondria have been implicated as a potential site of O
2
sensing underlying hypoxic pulmonary vasoconstriction (HPV), but 2 disparate models have been proposed to explain their reaction to hypoxia. One model proposes that hypoxia-induced increases in mitochondrial reactive oxygen species (ROS) generation activate HPV through an oxidant-signaling pathway, whereas the other proposes that HPV is a result of decreased oxidant signaling. In an attempt to resolve this debate, we use a novel, ratiometric, redox-sensitive fluorescence resonance energy transfer (HSP-FRET) probe, in concert with measurements of reduced/oxidized glutathione (GSH/GSSG), to assess cytosolic redox responses in cultured pulmonary artery smooth muscle cells (PASMCs). Superfusion of PASMCs with hypoxic media increases the HSP-FRET ratio and decreases GSH/GSSG, indicating an increase in oxidant stress. The antioxidants pyrrolidinedithiocarbamate and
N
-acetyl-
l
-cysteine attenuated this response, as well as the hypoxia-induced increases in cytosolic calcium ([Ca
2+
]
i
), assessed by the Ca
2+
-sensitive FRET sensor YC2.3. Adenoviral overexpression of glutathione peroxidase or cytosolic or mitochondrial catalase attenuated the hypoxia-induced increase in ROS signaling and [Ca
2+
]
i
. Adenoviral overexpression of cytosolic Cu, Zn-superoxide dismutase (SOD-I) had no effect on the hypoxia-induced increase in ROS signaling and [Ca
2+
]
i
, whereas mitochondrial matrix–targeted Mn-SOD (SOD-II) augmented [Ca
2+
]
i
. The mitochondrial inhibitor myxothiazol attenuated the hypoxia-induced changes in the ROS signaling and [Ca
2+
]
i
, whereas cyanide augmented the increase in [Ca
2+
]
i
. Finally, simultaneous measurement of ROS and Ca
2+
signaling in the same cell revealed that the initial increase in these 2 signals could not be distinguished temporally. These results demonstrate that hypoxia triggers increases in PASMC [Ca
2+
]
i
by augmenting ROS signaling from the mitochondria.
Combined Measurement of Carotid Stiffness and Intima-Media Thickness Improves Prediction of Complex Aortic Plaques in Patients With Ischemic Stroke
Authors: Harloff Andreas , Strecker Christoph , Reinhard Matthias , Kollum Marc , Handke Michael , Olschewski Manfred , Weiller Cornelius , Hetzel Andreas
Published: September 2006

Background and Purpose—

We hypothesized that for the prediction or exclusion of aortic thrombi or plaques ≥4 mm, the combination of intima-media thickness (IMT) and distensibility (DC) of the common carotid arteries would be superior to the measurement of IMT alone.

Methods—

We prospectively included 208 stroke patients (mean age, 60 years) undergoing transesophageal echocardiography for screening of aortic plaques. IMT and DC were determined by ultrasound, and DC was quantified by measuring blood pressure and the common carotid arteries diameter change on M-mode ultrasound during the cardiac cycle.

Results—

Negative predictive values of IMT <0.9 mm and DC ≥24×10
−3
/kPa for the exclusion of aortic atheroma ≥4 mm were similar (92.0% and 91.7%, respectively). However, negative predictive values increased to 98.2% and to 100.0% for the exclusion of aortic thrombi when both parameters were combined. Positive predictive values of IMT ≥0.9 mm and DC <24 were lower (46.3%, 41.1%; respectively), but they also increased in combination (54.3%).

Conclusions—

Our findings suggest that IMT and DC represent different vessel wall properties and that measuring both parameters provides optimized characterization of carotid atherosclerosis. Combining IMT and DC increases the predictive power of carotid ultrasound, making transesophageal echocardiography dispensable for assessment of the aorta for those with normal carotid arteries and indispensable for those patients with carotid atherosclerosis.
Impact of Basilar Artery Vasospasm on Outcome in Patients With Severe Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage
Authors: Sviri Gill E. , Newell David W. , Lewis David H. , Douville Colleen , Ghodke Basavaraj , Chowdhary Minku , Lam Arthur M. , Haynor David , Zaaroor Menashe , Britz Gavin W.
Published: September 2006

Background and Purpose—

The purpose of the present study was to evaluate the impact of basilar artery (BA) vasospasm on outcome in patients with severe vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).

Methods—

Sixty-five patients with clinically suspect severe cerebral vasospasm after aSAH underwent cerebral angiography before endovascular treatment. Vasospasm severity was assessed for each patient by transcranial Doppler measurements, angiography, and
99m
Tc-ethylcysteinate dimer single-photon emission computed tomography (ECD-SPECT) imaging. Percentage of BA narrowing was calculated in reference to the baseline angiogram.

Results—

BA narrowing ≥25% was found in 23 of 65 patients, and delayed brain stem (BS) hypoperfusion, as estimated by ECD-SPECT, was found in 16. Fourteen of 23 patients with BA narrowing ≥25% experienced BS hypoperfusion, whereas only 2 of 42 patients with ≥25% BA narrowing experienced BS ischemia (
P
<0.001). Stepwise logistic regression after adjusting for age with Hunt and Hess grade, Fisher grade, hydrocephalus, and aneurysmal location as covariables revealed BA narrowing ≥25% and delayed BS hypoperfusion to be significantly and independently associated with unfavorable 3-month outcome (
P
=0.0001; odds ratio, 10.1; 95% CI, 2.5 to 40.8; and
P
=0.007; odds ratio, 13.8, 95% CI, 2.18 to 91.9, respectively).

Conclusions—

These findings suggest for the first time that BA vasospasm after aSAH is an independent and significant prognostic factor associated with poor outcome in patients with severe cerebral vasospasm requiring endovascular therapy. Further study should be done to evaluate the role of interventional therapy on outcome in patients with posterior circulation vasospasm.
Hyperoxic Exposure Leads to Nitrative Stress and Ensuing Microvascular Degeneration and Diminished Brain Mass and Function in the Immature Subject
Authors: Sirinyan Mirna , Sennlaub Florian , Dorfman Allison , Sapieha Przemyslaw , Gobeil Fernand , Hardy Pierre , Lachapelle Pierre , Chemtob Sylvain
Published: September 2006

Background and Purpose—

Neonates that survive very preterm birth have a high prevalence of cognitive impairment in later life. A common factor detected in premature infants is their postnatal exposure to high oxygen tension relative to that in utero. Hyperoxia is known to elicit injury to premature lung and retina. Because data on the exposure of the brain to hyperoxia are limited, we studied the effects of high oxygen on this tissue.

Methods—

Rat pups were exposed from birth until day 6 to 21% or 80% O
2
. Cerebral vascular density was quantified by lectin immunohistochemistry. Immunoblots for several proteins were performed on brain extracts. We assessed cerebral functional deficits by visual evoked potentials.

Results—

Exposure of pups to hyperoxia leads to cerebral microvascular degeneration, diminished brain mass, and cerebral functional deficits. These effects are preceded by an upregulation of endothelial nitric oxide synthase (eNOS) in cerebral capillaries and a downregulation of Cu/Zn superoxide dismutase (SOD). The imbalance in nitric oxide (NO) production and antioxidant defenses favors the formation of nitrating agents in the microvessels revealed by increased nitrotyrosine (3-nt) immunoreactivity and decreased expression of NF-κB and the dependent vascular endothelial growth factor receptor 2. NOS inhibitors and eNOS deletion as well as an SOD mimetic (CuDIPS) restore vascular endothelial growth factor receptor-2 levels and nearly abolish the vasoobliteration. NOS inhibitors and SOD mimetic also prevent O
2
-induced diminished brain mass and functional deficit.

Conclusions—

Data identify NO and nitrating agents as major mediators of cerebral microvascular damage, ensuing impaired brain development and function in immature subjects exposed to hyperoxia.
Cortical Neuronal Apoptosis in CADASIL
Authors: Viswanathan Anand , Gray Francoise , Bousser Marie-Germaine , Baudrimont Marielle , Chabriat Hugues
Published: September 2006

Background and Purpose—

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations of the
NOTCH3
gene and is a model of pure vascular dementia. Cortical atrophy has been reported to be associated with cognitive decline in the disease, although the underlying mechanism is unknown. We postulated that apoptosis may be involved in this process.

Methods—

We report the clinical history, magnetic resonance imaging findings, and pathologic examinations of 4 patients (2 of whom were demented) who died from complications of the disease. Apoptosis was evaluated in brain tissue using antibodies against activated caspase3 and in situ end labeling assays for DNA fragmentation.

Results—

Widespread neuronal apoptosis in the cerebral cortex (predominantly in layers 3 and 5) was observed in all patients. This was not seen in 3 non-CADASIL controls. Semiquantitative analysis suggested that apoptosis was more extensive in the presence of larger load of subcortical ischemic lesions and smaller brain volumes.

Conclusions—

Neuronal apoptosis may be involved in cortical atrophy in CADASIL and appears related to the burden of subcortical ischemic lesions. These findings may have important implications in other small vessel diseases and may provide a potential target for future therapeutic interventions.
Similarities and Contrasts in Artistic and Scientific Creation-Discovery
Authors: Mandelbrojt Jacques
Published: September 2006

The author summarizes 13 of his publications in Leonardo on the comparison of artistic and scientific creation-discovery. This article details how fundamental aspects of artistic creation are clarified by mechanisms initially introduced to describe scientific discovery. These aspects are linked to the equilibrium between an artist's pictorial idea and the material or technique used. The author also sheds light on art by contrasting it to science. He further addresses the muscular image or kinesthetic aspect of art, which is also shown to be essential in much scientific thinking. He then links aspects of his own paintings to his practice of science.
Little Earth: A Solar-Planetary Investigation
Authors: Joelson Jo , Cowley Stanley W.H.
Published: September 2006

The authors present Little Earth, the result of collaboration between artist Jo Joelson and the Radio and Space Plasma Physics Group at the University of Leicester. The project draws on the historical research of Kristian Birkeland and C.T.R. Wilson to examine how developments in technology have affected the relationships between artists and scientists in observing and representing the natural world. The principal output of the project was a multi-channel video work representing a fictional dialogue between Birkeland and Wilson, projected onto the faces of a sculptural form inspired by contemporary spacecraft design.
Impact of Explicit Atmosphere–Ocean Coupling on MJO-Like Coherent Structures in Idealized Aquaplanet Simulations
Authors: Grabowski Wojciech W.
Published: September 2006

This paper discusses the impact of the atmosphere–ocean coupling on the large-scale organization of tropical convection simulated by an idealized global model applying the Cloud-Resolving Convection Parameterization (CRCP; superparameterization). Because the organization resembles the Madden–Julian Oscillation (MJO), the results contribute to the debate concerning the role of atmosphere–ocean coupling in tropical intraseasonal oscillations.

The modeling setup is an aquaplanet with globally uniform mean sea surface temperature (SST) of 30°C (tropics everywhere) in radiative–convective quasi equilibrium. The simulations apply an interactive radiation transfer model and a slab ocean model with a fixed oceanic mixed layer depth. Results from several 80- and 100-day-long simulations are discussed, where the only difference between the simulations is the prescribed oceanic mixed layer depth, which varied from 5 to 45 m. A simulation with a very deep oceanic mixed layer is also performed to represent constant-SST conditions. The simulations demonstrate that the interactive SST impedes the development of large-scale organization and has insignificant impact on the dynamics of mature MJO-like systems. The impediment is the result of a negative feedback between the large-scale organization of convection and SST, the convection–SST feedback. In this feedback, SST increases in regions of already suppressed convection and decreases in regions with enhanced convection, thus hindering the large-scale organization. Once developed, however, the MJO-like systems are equally strong in interactive and constant-SST simulations, and compare favorably with the observed MJO.

The above impacts of the atmosphere–ocean coupling contradict the majority of previous studies using traditional general circulation models, where, typically, an enhancement of the intraseasonal signal occurs compared to prescribed-SST simulations. An explanation of this discrepancy is suggested.
Simultaneous Determination of Aerosol and Thin Cirrus Optical Depths over Oceans from MODIS Data: Some Case Studies
Authors: Roskovensky J. K. , Liou K. N.
Published: September 2006

The importance of separating thin cirrus and aerosols from satellite remote sensing to produce broader and more accurate fields for the determination of respective radiative forcings is highlighted. This has been accomplished through the development of a new methodology for retrieving both thin cirrus and aerosol optical depths simultaneously over oceans from the Moderate Resolution Imaging Spectroradiometer (MODIS) data. This method employs a procedure to quantify and remove the thin cirrus contribution to the observed reflectance through a correlation of visible and 1.38-μm reflectances so that the aerosol signal can be extracted. Aerosol optical depths are then retrieved through comparisons with the simulated reflectances created a priori. Using the aerosol optical depth along with the specific viewing geometry and surface reflectance as pointers to locations in a lookup table of modeled reflectances, cirrus optical depth and an effective ice crystal size can be retrieved. An iterative scheme has been created that uses the retrieved effective cirrus ice crystal size to account for the effect that the particle size distribution has on the correlation of visible and 1.38-μm reflectance. Retrievals of both aerosol and thin cirrus optical depths over the Atmospheric Radiation Measurement (ARM) Tropical Western Pacific (TWP) site of Nauru performed on a limited number of cases have proven to be consistent with values determined from ground measurements. Also, comparisons with the MODIS aerosol retrievals over a broad area of ocean have highlighted the potential usefulness of this procedure in increasing the amount of potential aerosol information recovered and removing the ever-present thin cirrus contamination.
Multiscale Temporal Variability of Warm-Season Precipitation over North America: Statistical Analysis of Radar Measurements
Authors: Hsu Hsiao-ming , Moncrieff Mitchell W. , Tung Wen-wen , Liu Changhai
Published: September 2006

Directionally averaged time series of precipitation rates for eight warm seasons (1996–2003) over the continental United States derived from Next Generation Weather Radar (NEXRAD) measurements are analyzed using spectral decomposition methods. For the latitudinally averaged data, in addition to previously identified diurnal and semidiurnal cycles, the temporal spectra show cross-scale self-similarity and periodicity. This property is revealed by a power-law scaling with an exponent of −4/3 for the frequency band higher than semidiurnal and −3/4 for the 1–3-day band. For the longitudinally averaged series the scaling exponent for the frequency band higher than semidiurnal changes from −4/3 to −5/3 revealing anisotropic properties.

The dominant periods and propagation speeds display temporal variability on about 1/2, 1, 4, 11, and 25 days. Composite patterns describing periods of <5 days display the eastward propagation characteristic of classical mesoscale convective organization. The lower-frequency (>5 days) patterns propagate westward suggesting the influence of large-scale waves, and both dominant periods and propagation speeds show marked interannual variability. The implied dependence between propagation and mean-flow for <5 days is consistent with the macrophysics of warm-season convective organization, and extends known dynamical mechanisms to a statistical framework.
Efficient Monte Carlo Methods for Radiative Transfer Modeling
Authors: Iwabuchi Hironobu
Published: September 2006

Demands for Monte Carlo radiative transfer modeling have grown with the increase in computational power in recent decades. This method provides realistic simulations of radiation processes for various types of application, including radiation budgets in cloudy conditions and remote measurements of clouds, aerosols, and gases. Despite many advantages, such as explicit treatment of three-dimensional radiative transfer, issues of numerical efficiency can make the method intractable, especially in radiance calculations. The commonly used local estimation method requires computationally intensive ray tracing at each collision. Furthermore, the realistic phase function of Mie scattering by cloud and aerosol particles has very sharp peaks in the forward direction. Radiance computations by Monte Carlo methods are inefficient for such spiky phase functions because of significant noise. Moreover, in optically thin regions, sampling of radiance contributions is so rare that long computing times are required to reduce noise. To solve these issues, several variance reduction methods have been proposed. This paper discusses a modified local estimation method, a truncation approximation for a highly anisotropic phase function, a collision-forcing method for optically thin media, a numerical diffusion technique, and several related topics. Numerical experiments demonstrated significant improvements in efficiency for solar radiance calculations in a limited number of cloudy cases.
Precipitation over Concave Terrain
Authors: Jiang Qingfang
Published: September 2006

Many topographic barriers are comprised of a series of concave or convex ridges that modulate the intensity and distribution of precipitation over mountainous areas. In this model-based idealized study, stratiform precipitation associated with stratified moist airflow past idealized concave ridges is investigated with a focus on windward blocking, flow confluence, and the associated precipitation enhancement.

It is found that flow confluence and precipitation enhancement by a concave ridge are controlled by the nondimensional ridge height M (M = Nmhm/U, where Nm is the moist buoyancy frequency, hm is the maximum ridge height, and U is the wind speed), based on which three dynamical regimes can be defined. In the linear regime (M < 0.4), a flow confluence zone is present over the upwind slope of the ridge vertex, where precipitation is significantly enhanced. The precipitation enhancement is due to the additional updraft driven by the horizontal flow convergence with a considerable contribution from lateral confluence. In the blocking regime (0.4 < M < Mc), the area and intensity of the flow confluence zone decrease with increasing mountain height due to low-level blocking. The critical nondimensional ridge height (Mc) for windward flow stagnation decreases with increasing concave angle. In the two regimes, flow confluence and precipitation enhancement are more pronounced for concave ridges with a longer cross-stream dimension or a larger concave angle. In the flow reversal regime (M > Mc), no steady state can be achieved and the precipitation enhancement at the vertex is absent.

In addition, the flow confluence and precipitation enhancement upstream of a concave ridge are sensitive to the presence of a relative gap or peak at the vertex, the earth’s rotation, and the incident wind. The relevant dynamics has been examined.
Apoptotic cells induce Mer tyrosine kinase–dependent blockade of NF-κB activation in dendritic cells
Authors: Sen Pradip , Wallet Mark A. , Yi Zuoan , Huang Yingsu , Henderson Michael , Mathews Clayton E. , Earp H. Shelton , Matsushima Glenn , Baldwin Albert S. , Tisch Roland M.
Published: September 2006

Dendritic cells (DCs) play a key role in immune homeostasis and maintenance of self-tolerance. Tolerogenic DCs can be established by an encounter with apoptotic cells (ACs) and subsequent inhibition of maturation and effector functions. The receptor(s) and signaling pathway(s) involved in AC-induced inhibition of DCs have yet to be defined. We demonstrate that pretreatment with apoptotic but not necrotic cells inhibits activation of IκB kinase (IKK) and downstream NF-κB. Notably, receptor tyrosine kinase Mer (MerTK) binding of ACs is required for mediating this effect. Monocyte-derived DCs lacking MerTK expression (MerTKKD) or treated with blocking MerTK-specific antibodies (Abs) are resistant to AC-induced inhibition and continue to activate NF-κB and secrete proinflammatory cytokines. Blocking MerTK activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway prevents AC-induced inhibition. These results demonstrate an essential role for MerTK-mediated regulation of the PI3K/AKT and NF-κB pathways in AC-induced inhibition of monocyte-derived DCs.
Attenuation of phagocytosis of xenogeneic cells by manipulating CD47
Authors: Wang Hui , VerHalen Jon , Madariaga Maria Lucia , Xiang Shuanglin , Wang Shumei , Lan Ping , Oldenborg Per-Arne , Sykes Megan , Yang Yong-Guang
Published: September 2006

Signal regulatory protein α (SIRPα) is a critical immune inhibitory receptor on macrophages, and its interaction with CD47, a ligand for SIRPα, prevents autologous phagocytosis. We hypothesized that interspecies incompatibility of CD47 may contribute to the rejection of xenogeneic cells by macrophages. Here, we show that pig CD47 does not interact with mouse SIPRα. Similar to CD47−/− mouse cells, porcine red blood cells (RBCs) failed to induce SIRPα tyrosine phosphorylation in mouse macrophages. Blocking SIRPα with antimouse SIRPα mAb (P84) significantly enhanced the phagocytosis of CD47+/+ mouse cells, but did not affect the engulfment of porcine or CD47−/− mouse cells by mouse macrophages. CD47-deficient mice, whose macrophages do not phagocytose CD47−/− mouse cells, showed markedly delayed clearance of porcine RBCs compared with wild-type mouse recipients. Furthermore, mouse CD47 expression on porcine cells markedly reduced their phagocytosis by mouse macrophages both in vitro and in vivo. These results indicate that interspecies incompatibility of CD47 contributes significantly to phagocytosis of xenogeneic cells by macrophages and suggest that genetic manipulation of donor CD47 to improve its interaction with the recipient SIRPα may provide a novel approach to prevent phagocyte-mediated xenograft rejection.
Expression of a bcr-1 isoform of RARα-PML does not affect the penetrance of acute promyelocytic leukemia or the acquisition of an interstitial deletion on mouse chromosome 2
Authors: Walter Matthew J. , Ries Rhonda E. , Armstrong Jon R. , Park John S. , Mardis Elaine R. , Ley Timothy J.
Published: September 2006

Expression of a bcr-3 isoform of retinoic acid receptor α–promyelocytic leukemia (RARα-PML) in mice expressing a bcr-1 isoform of PML-RARα is associated with increased penetrance of murine acute promyelocytic leukemia (APL) and the frequent acquisition of an interstitial deletion of one copy of mouse chromosome 2 (del(2)). To determine whether the isoform of RARα-PML is important for these effects, we created mice that expressed a bcr-1 isoform of RARα-PML. Coexpression with the bcr-1 isoform of PML-RARα did not increase the penetrance of APL (7 of 45 animals developed APL with PML-RARα alone vs 12 of 44 with both transgenes; P = .19). Furthermore, the frequency of del(2) in APL cells from doubly transgenic mice was not different from that of mice expressing PML-RARα alone (3 of 6 vs 6 of 12, respectively—P = 1.38—compared with 11 of 11 for mice coexpressing PML-RARα and bcr-3 RARα-PML). The bcr-1 and bcr-3 isoforms of RARα-PML, therefore, have different biological activities that may be relevant for the pathogenesis of murine APL.
Disparities in preventive procedures: comparisons of self-report and Medicare claims data
Authors: Fiscella Kevin , Holt Kathleen , Meldrum Sean , Franks Peter
Published: September 2006

Background

Racial/ethnic disparities are assessed using either self-report or claims data. We compared these two data sources and examined contributors to discrepancies in estimates of disparities.

Methods

We analyzed self-report and matching claims data from Medicare Beneficiaries 65 and older who participated in the Medicare Current Beneficiary Survey, 1999–2002. Six preventive procedures were included: PSA testing, influenza vaccination, Pap smear testing, cholesterol testing, mammography, and colorectal cancer testing. We examined predictors of self-reports in the absence of claims and claims in the absence of self-reports.

Results

With the exception of PSA testing, racial/ethnic disparities in preventive procedures are generally larger when using Medicare claims than when using patients' self-report. Analyses adjusting for age, gender, income, educational level, health status, proxy response and supplemental insurance showed that minorities were more likely to self-report preventive procedures in the absence of claims. Adjusted odds ratios ranged from 1.07 (95% CI: 0.88 – 1.30) for PSA testing to 1.83 (95% CI: 1.46 – 2.30) for Pap smear testing. Rates of claims in the absence of self-report were low. Minorities were more likely to have PSA test claims in the absence of self-reports (1.55 95% CI: 1.17 – 2.06), but were less likely to have influenza vaccination claims in the absence of self-reports (0.69 95% CI: 0.51 – 0.93).

Conclusion

These findings are consistent with either racial/ethnic reporting biases in receipt of preventive procedures or less efficient Medicare billing among providers with large minority practices.
Discovery of significant variants containing large deletions in the 5'UTR of human hepatitis C virus (HCV)
Authors: Revie Dennis , Alberti Michael O , Braich Ravi S , Bayles David , Prichard John G , Salahuddin S Zaki
Published: September 2006

We recently reported the isolation and in vitro replication of hepatitis C virus. These isolates were termed CIMM-HCV and analyzed to establish genotypes and subtypes, which are reported elsewhere. During this analysis, an HCV isolated from a patient was discovered that had large deletions in the 5'UTR. 57% of the HCV RNA found in this patient's sera had 113 or 116 bp deletions. Sequence data showed that domains IIIa to IIIc were missing. Previous studies have suggested that these domains may be important for translation. In vitro replicated HCV from this patient did not contain these deletions, however, it contained a 148 bp deletion in the 5'UTR. Whereas the patient HCV lacked domains IIIa through IIIc, the isolate lacked domains IIIa through IIId. HCV from this patient continues to produce large deletions in vitro, suggesting that the deletion may not be important for the assembly or replication of the virus. This is the first report describing these large deletions.
A Purine Analog Kinase Inhibitor, Calcium/Calmodulin-Dependent Protein Kinase II Inhibitor 59, Reveals a Role for Calcium/Calmodulin-Dependent Protein Kinase II in Insulin-Stimulated Glucose Transport
Authors: Konstantopoulos Nicky , Marcuccio Seb , Kyi Stella , Stoichevska Violet , Castelli Laura A. , Ward Colin W. , Macaulay S. Lance
Published: September 2006

Olomoucine is known as a cyclin-dependent kinase inhibitor. We found that olomoucine blocked insulin’s ability to stimulate glucose transport. It did so without affecting the activity of known insulin signaling proteins. To identify the olomoucine-sensitive kinase(s), we prepared analogs that could be immobilized to an affinity resin to isolate binding proteins. One of the generated analogs inhibited insulin-stimulated glucose uptake with increased sensitivity compared with olomoucine. The IC50 for inhibition of insulin-stimulated glucose uptake occurred at analog concentrations as low as 0.1 μm. To identify proteins binding to the analog, [35S]-labeled cell lysates prepared from 3T3-L1 adipocytes were incubated with analog chemically cross-linked to a resin support and binding proteins analyzed by SDS-PAGE. The major binding species was a doublet at 50–60 kDa, which was identified as calcium/calmodulin-dependent protein kinase II (CaMKII) by N-terminal peptide analysis and confirmed by matrix-assisted laser desorption ionization-mass spectrometry as the δ- and β-like isoforms. To investigate CaMKII involvement in insulin-stimulated glucose uptake, 3T3-L1 adipocytes were infected with retrovirus encoding green fluorescent protein (GFP)-hemagluttinin tag (HA)-tagged CaMKII wild-type or the ATP binding mutant, K42M. GFP-HA-CaMKII K42M cells had less kinase activity than cells expressing wild-type GFP-HA-CaMKII. Insulin-stimulated glucose transport was significantly decreased (∼80%) in GFP-HA-CaMKII K42M cells, compared with nontransfected cells, and cells expressing either GFP-HA-CaMKII or GFP-HA. There was not a concomitant decrease in insulin-stimulated GLUT4 translocation in GFP-HA-CaMKII K42M cells when compared with GFP-HA alone. However, insulin-stimulated GLUT4 translocation in GFP-HA-CaMKII cells was significantly higher, compared with either GFP-HA or GFP-HA-CaMKII K42M cells. Our results implicate the involvement of CaMKII in glucose transport in a permissive role.
NFκB1/p50 Is Not Required for Tumor Necrosis Factor-Stimulated Growth of Primary Mammary Epithelial Cells: Implications for NFκB2/p52 and RelB
Authors: Zhang Jiping , Warren Mary Ann , Shoemaker Suzanne F. , Ip Margot M.
Published: September 2006

Nuclear factor κB (NFκB) plays an important role in mammary gland development and breast cancer. We previously demonstrated that TNF stimulates growth of mammary epithelial cells (MEC) in a physiologically relevant three-dimensional primary culture system, accompanied by enhanced DNA-binding of the NFκB p50 homodimer. To further understand the mechanism of TNF-stimulated growth of primary MEC, the requirement for NFκB1/p50, and the role of cyclin D1 in TNF-stimulated growth were examined. TNF induced the formation of DNA-binding complexes of p50 and p52 with their coactivator bcl3 in MEC nuclear extracts. Concomitantly, TNF increased the binding of NFκB proteins to the κB site on the cyclin D1 promoter, and increased expression of cyclin D1 mRNA and protein. Using MEC from p50 null mice, we found that p50 was not required for TNF-induced growth nor for up-regulation of cyclin D1. However, TNF induced a p52/RelB NFκB DNA-binding complex in p50 null MEC nuclear extracts. In addition, we found that in wild-type MEC, TNF stimulated the occupancy of p52 and RelB on the cyclin D1 promoter κB site, whereas p50 was present constitutively. These data suggest that in wild-type MEC, TNF stimulates the interaction of bcl3 with p50 and p52, and the binding of p52, as well as RelB, to cyclin D1 promoter κB sites, and as a consequence, stimulates the growth of MEC. In the absence of p50, p52 and RelB can compensate for p50 in TNF-stimulated growth and cyclin D1 induction in MEC.
Potential Antiinflammatory Role of Insulin via the Preferential Polarization of Effector T Cells toward a T Helper 2 Phenotype
Authors: Viardot Alexander , Grey Shane T. , Mackay Fabienne , Chisholm Donald
Published: September 2006

Hyperglycemia in critical illness is a common complication and a strong independent risk factor for morbidity and death. Intensive insulin therapy decreases this risk by up to 50%. It is unclear to what extent this benefit is due to reversal of glucotoxicity or to a direct effect of insulin, because antiinflammatory effects of insulin have already been described, but the underlying mechanisms are still poorly understood. The insulin receptor is expressed on resting neutrophils, monocytes, and B cells, but is not detectable on T cells. However, significant up-regulation of insulin receptor expression is observed on activated T cells, which suggests an important role during T cell activation. Exogenous insulin in vitro induced a shift in T cell differentiation toward a T helper type 2 (Th2)-type response, decreasing the T helper type 1 to Th2 ratio by 36%. This result correlated with a corresponding change in cytokine secretion, with the interferon-γ to IL-4 ratio being decreased by 33%. These changes were associated with increased Th2-promoting ERK phosphorylation in the presence of insulin. Thus, we demonstrate for the first time that insulin treatment influences T cell differentiation promoting a shift toward a Th2-type response. This effect of insulin in changing T cell polarization may contribute to its antiinflammatory role not only in sepsis, but also in chronic inflammation associated with obesity and type 2 diabetes.
Synthesis and Applications of 1,1-Diborylated Cyclopropanes: Facile Route to 1,2-Diboryl-3-methylenecyclopentenes
Authors: Shimizu Masaki , Schelper Michael , Nagao Ikuhiro , Shimono Katsuhiro , Kurahashi Takuya , Hiyama Tamejiro
Published: October 2006

Cyclopropylidene lithium carbenoids reacted with bis(pinacolato)diboron in THF/Et2O at −110 °C to give various 1,1-diborylated cyclopropanes in good yields. Treatment of the diborylated cyclopropanes with 3-chloro-1-lithio-3-methyl-1-butyne produced the corresponding diborylated allenylcyclopropanes, which underwent ring-expansion in the presence of a Rh catalyst to give 1,2-diborylated methylenecyclopentenes conveniently.
The relationship of the anatomy and physiology to the pathology of the nose, throat and ear
Authors: Henry  , Wieder S.
Published: September 2006

(Original Communications are received with the understandine that they are contributed exclusively to The Laryngoscope.)
The fate of pedicle osteocutaneous grafts in mandibulo‐facial restoration
Authors: Canalis Rinaldo F. , Saffouri Muhammed , Mirka Joseph , Ward Paul H.
Published: September 2006

To overcome some of the problems encountered in the repair of extensive composite defects of the head and neck, several means of transfering bone and soft tissue — while preserving the blood supply by means of a pedicle — have been clinically attempted.

The superiority of pedicle osteocutaneous grafts compared to free grafts is demonstrated in a series of experiments in monkeys and dogs. Conventional and tetracycline labelled histological specimens, from animals sacrificed at intervals from two weeks to six months after grafting, illustrate the dynamic changes in the grafts. Pedicle supported grafts appeared superior to free grafts and participated actively in bone reconstruction.
Mandibular trauma: Secondary problems in reconstruction
Authors: Bone Robert C. , Davidson Terence M. , Nahum Alan M. , Dahlberg Roger
Published: September 2006

Cosmetic and functional restoration of the fractured mandible in the great majority of cases is the sine qua non of therapeutic success. Not only must an acceptable low complication rate be obtained, but when present, their complex nature must be understood from the onset. Successful treatment of complications is a multifaceted problem requiring planned, interdisciplinary, often times staged reconstruction. The radiologist and dental prosthodontist make valuable contributions towards the surgeon's ultimate rehabilitation of the patient.

A three year experience of 111 mandibular fractures treated on the UCSD Otolaryngology Service is characterized. Sixteen complications nine of which were seen after initial treatment elsewhere provide the focus of this report. Special emphasis is given to the pre‐treatment planning and surgical techniques necessary to correct malunion and nonunion. Particular advantages achieved by the use of osteogenic autogenous marrow, cellulose acetate filters and Vitalliumf (chrome cobalt) trays are detailed.
A new concept in the treatment of frey's syndrome: The use of interpositional dermal grafts. an experimental study in the dog
Authors: Cassady Charles L.
Published: September 2006

Frey's syndrome or gustatory sweating is a common complication of parotid gland injury or surgery. Forty to 60 percent of the patients undergoing parotidectomy will develop manifestations of this syndrome but only 10‐15 percent of these require treatment. To date tympanic neurec‐tomy is the most efficacious method of treating the problem but relief is not obtained in all cases. Based on an experimental study in the dog, a new approach to the prevention of Frey's syndrome is presented. Since Frey's syndrome is clue to the aberrent regeneration of parasympathetic nerve fibers of the parotid gland into the severed sympathetic nerve endings in skin overlying the gland, it is proposed that the insertion of a dermal graft barrier between the resected parotid gland and the skin will prevent Frey's syndrome. Histological sections of dermal grafts, buried for three to six months tend to confirm that this idea has some merit.
Surgical anatomy of the temporal bone posterior to the internal auditory canal: An operative approach
Authors: Geurkink Nathan A.
Published: September 2006

A microsurgical technique for approaching the posterior one half of the internal auditory canal, by utilizing the structures within this area as specific surgical landmarks, is described. Results of 19 tumor excisions using this technique are presented.
Lipomas presenting as parotid tumors
Authors: Janecka Ivo P. , Conley John , Perzin Karl H. , Pitman Gerald
Published: September 2006

Eleven cases of lipoma in the parotid region have been reviewed. Nine tumors were found to be compressing the lateral surface of the parotid gland (periparotidlipoma). One lesion was totally surrounded by salivary tissue, and another involved both the superficial and the deep lobes of a parotid gland (intraparotid lipoma). The tail of the gland was involved most frequently (six patients). The tumors were predominantly right sided (eight cases). All patients were treated by surgical excision. Only one tumor has recurred and this has apparently been successfully treated by a reexcision.
Mastoidectomy update
Authors: Paparella Michael M. , Kim Chong Sun
Published: September 2006

The long‐term results of 375 primary mastoidectomy operations for chronic otitis media and chronic mastoiditis are described and discussed. Two‐thirds of these cases were open cavity mastoidectomies and 1/3 closed cavity mastoidectomies. Primary pathology was cholesteatoma in 1/3 and granulation tissue in 2/3 of the cases. The method of reducing the size of the mastoid cavity by sculpturing mastoid cortical bone is most important in avoiding large postoperative cavity problems.

Principles and methods are described. Healing (dry ear) is a more important management objective than hearing and, indeed, enhances the prospects of obtaining a long‐term hearing result. Three important phases of controlling mastoid disease (preoperative, operative, and postoperative) are equally stressed. Intact wall tympanomastoidectomy is not recommended in sclerotic mastoids (the majority of our cases) as being unsafe and unnecessary. Revisions, mostly minor, were done in 31% of the cases for a total of 521 procedures. We recommend a one‐stage tympanomastoidectomy. Multiple planned procedures are, in the main, unnecessary and should be avoided to reduce unnecessary hospitalization and expense.
Sarcoidosis of the head and neck
Authors: Miglets Andrew W. , Viall John H. , Kataria Yash P.
Published: September 2006

Sarcoidosis is a multisystem granulomatous disease of unknown etiology, occasionally presenting with signs or symptoms that occur within the head and neck.

The diagnosis may be made by a combination of histological evaluation of involved tissue, the presence of a relative cutaneous anergy, a positive Kveim test, and certain abnormal laboratory or radiographic findings.

Although pulmonary sarcoidosis is by far the most common manifestation of the disease, an occasional patient will present with involvement of the nose, tonsils, larynx, or parotid gland. The otolaryngologist should include this entity in his differential diagnosis of lesions which occur in these areas.