bluuebunny/crossref_metadata_2025 huggingface dataset:
How well can people use different color attributes?
Authors: Zhang Hongqin , Montag Ethan D.
Published: October 2006

Two psychophysical experiments were conducted to analyze the role of color attributes in simple tasks involving color matching and discrimination. In Experiment I observers made color matches using three different adjustment control methods. The results showed that the Lightness, Chroma, Hue (LCH) and the Lightness, redness/greenness, blueness/yellowness ({L, r/g, y/b}) adjustment controls elicited significantly better performance than the display RGB controls in terms of both accuracy and time, but were not significantly different from each other. Expert observers performed significantly better than naïve observers in terms of accuracy. Experiment II was a replication and extension of the experiment by Melgosa et al. [Color Res Appl 2000; 25: 356–367] in which observers judged differences and similarities for color attributes in pairs of colored patches. At a 95% confidence level, the results from judging difference were significantly better than those from judging similarity. Hue and Lightness were significantly more identifiable than Chroma, r/g, and y/b. These results indicate that people do not have ready access to the lower level color descriptors such as the common attributes used to define color spaces, and that higher level psychological processing involving cognition and language may be necessary for even apparently simple tasks involving color matching and describing color differences. © 2006 Wiley Periodicals, Inc. Col Res Appl, 31, 445–457, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.20257
Color memory in elderly adults
Authors: Pérez‐Carpinell Joaquín , Camps Vicente J. , Trottini Mario , Pérez‐Baylach Carmen M.
Published: October 2006

The methods of simultaneous and successive color matching have been compared for a set of five Munsell color samples by 50 older adult observers, 25 men and 25 women (ranging in age from 64 to 80 years). From comparison between this population and one of 50 younger adult observers, 25 men and 25 women (in the 20–27 age range), we can deduce, in general, the following: (a) In the elderly adults the mean CIELAB total color difference (ΔE*ab) in simultaneous color matching is lower than theΔE*abby memory color matching. (b) While younger adults matched well the color of all the reference tests, the elderly adults matched poorly both greens and orange. (c) Younger adults remember the original color better than do the older adults (P= 0.007), depending on gender and delay time. (d) Although with simultaneous matching, the observer's gender does not determine significant differences, by memory, men matched the color of reference test more poorly than did women (P= 0.0), independently of age, color and delay time, especially for bluish green, violet, and pink. © 2006 Wiley Periodicals, Inc. Col Res Appl, 31, 458–467, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.20258
Expanding display color gamut beyond the spectrum locus
Authors: Heckaman Rodney L. , Fairchild Mark D.
Published: October 2006

Digital video and display media are at a “sweet spot” of growth with brighter and more colorful digital projectors and displays available seemingly every day. Much more is possible in achieving brighter and more vibrant colors, colors that may even transcend our typical experience in terms of dynamic range and an expanded gamut in the perceptual sense. If the full capabilities of these technologies to produce a fuller visual experience are to be realized, new processing and encoding methodologies are required. In this article, the powers of adaptation and the CIECAM02 color appearance model are exploited to define perceptual gamut. The strategy of this methodology is, simply and in effect, to “push down” the white point of the display and demonstrate, both empirically and with a limited set of images, a striking gamut expansion in the perceptions of lightness, chroma, brightness, and colorfulness beyond the locus of pure, spectral color, and the MacAdam limits as observed with traditional display configurations. © 2006 Wiley Periodicals, Inc. Col Res Appl, 31, 475–482, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.20260
Reflection of light from semi‐infinite absorbing turbid media. Part 2: Plane albedo and reflection function
Authors: Kokhanovsky Alexander A. , Sokoletsky Leonid G.
Published: October 2006

We study the accuracy of a number of simple approximate equations for the reflection characteristics of semi‐infinite light scattering media (e.g., for the diffuse reflectance of a turbid layer under collimated illumination conditions and also for the reflection function). Spectra of diffuse reflection under monodirectional illumination by a wide beam ℜ︁ (ξ) or the plane albedo are handled in technological applications using different approximations depending on the level of light absorption in the medium. Generally speaking, the value of ℜ︁ depends not only on the cosine of incidence angle ξ and the similarity parameter $s=\sqrt{(1-{\omega}_{0})(1-{\omega}_{0}g)^{-1}}$ (ω0is the single scattering albedo, g is the asymmetry parameter), but also on the phase function of a turbid layer. The dependence on the phase function is reduced to the dependence on the asymmetry parameter for the low probability of photon absorption in the medium. We find that the influence of the angular behavior of the phase function cannot be neglected in calculations of the reflection function. Then the best choice is the solution of the nonlinear integral equation for the reflection function. We also show a number of approximate results, which can be used to model the reflection function. The results obtained can be used for the solution of both direct and inverse problems of light scattering media optics. © 2006 Wiley Periodicals, Inc. Col Res Appl, 31, 498–509, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.20263
Aiming at minimal invasiveness as a therapeutic strategy for Budd-Chiari syndrome
Authors: Plessier Aurélie , Sibert Annie , Consigny Yann , Hakime Antoine , Zappa Magaly , Denninger Marie-Hélène , Condat Bertrand , Farges Olivier , Chagneau Carine , de Ledinghen Victor , Francoz Claire , Sauvanet Alain , Vilgrain Valérie , Belghiti Jacques , Durand François , Valla Dominique
Published: October 2006

The 1-year spontaneous mortality rate in patients with Budd-Chiari syndrome (BCS) approaches 70%. No prospective assessment of indications and impact on survival of current therapeutic procedures has been performed. We evaluated a therapeutic strategy uniformly applied during the last 8 years in a single referral center. Fifty-one consecutive patients first received anticoagulation and were treated for associated diseases. Symptomatic patients were considered for hepatic vein recanalization; then for transjugular intrahepatic portosystemic shunt (TIPS), and finally for liver transplantation. The absence of a complete response led to the next procedure. Assessment was according to the strategy, whether procedures were technically applicable and successful. At entry, median (range) Child-Pugh score and Clichy prognostic index were 8 (5–12), and 5.4 (3.1–7.7), respectively. A complete response was achieved on medical therapy alone in 9 patients; after recanalization in 6, TIPS in 20, liver transplantation in 9, and retransplantation in 1. Of the 41 patients considered for recanalization, the procedure was not feasible in 27 and technically unsuccessful in 3. Of the 34 patients considered for TIPS, the procedure was considered not feasible in 9 and technically unsuccessful in 4. At 1 year of follow-up, a complete response to TIPS was achieved in 84%. One- and 5-year survival from starting anticoagulation were 96% (95% CI, 90–100) and 89% (95% CI, 79–100), respectively.

In conclusion

, excellent survival can be achieved in BCS patients when therapeutic procedures are introduced by order of increasing invasiveness, based on the response to previous therapy rather than on the severity of the patient's condition.
Gilbert's disease and atazanavir: From phenotype to UDP-glucuronosyltransferase haplotype
Authors: Lankisch Tim O. , Moebius Ulrike , Wehmeier Michael , Behrens Georg , Manns Michael P. , Schmidt Reinhold E. , Strassburg Christian P.
Published: October 2006

Gilbert's disease leads to intermittent non-hemolytic hyperbilirubinemia by a reduction of hepatic bilirubin glucuronidation associated with the presence of the UDP-glucuronosyltransferase (UGT) 1A1*28 polymorphism. It is considered benign because it does not result in hepatocellular damage. However, pharmacogenetic analyses have linked UGT1A1*28 to drug toxicity and cancer predisposition. The protease inhibitor atazanavir (ATV) is an inhibitor of hepatic UGT activity leading to hyperbilirubinemia in individual patients. Whether this is linked specifically to UGT1A1*28 or to more complex variants influencing glucuronidation is unclear. One hundred and six ATV-treated patients were characterized and genotyped for UGT1A1*28, the UGT1A3 (-66C) and UGT1A7 (-57G) promoter variants, and UGT1A7129K/131K. ATV treatment increased median bilirubin levels from 10 to 41 μmol/L (

P

= .001) with hyperbilirubinemia exceeding 43 μmol/L in 37%. Hyperbilirubinemia over 43 μmol/L was significantly associated not only with UGT1A1*28 but also with UGT1A3-66C, UGT1A7-57G, and UGT1A7129K/131K, although these variants do not naturally occur in linkage dysequilibrium in blood donors. Homozygous combinations of UGT1A1*28 with the other variants increased from 7.4% (normal bilirubin to 42 μmol/L) to 41% to 46.1% (43 to >85 μmol/L), and 100% (>85 μmol/L). All six patients with hyperbilirubinemia greater than 85 μmol/L were homozygous for all four variants identifying a haplotype inherited on a single allele.

In conclusion

, the genetic variant associated with Gilbert's disease is identified as part of a haplotype of four UGT1A variants spanning three genes at the

UGT1A

gene locus. This haplotype predisposes to hyperbilirubinemia in ATV treatment and may have an additional role as a pharmacogenomic risk factor for drug therapy.
Loss of IL-7 receptor alpha-chain (CD127) expression in acute HCV infection associated with viral persistence
Authors: Golden-Mason Lucy , Burton James R. , Castelblanco Nicole , Klarquist Jared , Benlloch Salvador , Wang Chia , Rosen Hugo R.
Published: October 2006

Interleukin-7 (IL-7) is required for the establishment and maintenance of memory CD4+ and CD8+ T lymphocytes, and cells lacking IL-7Rα (CD127) demonstrate impaired IL-2 secretion and have a short life-span. Chronic HCV is characterized by T cells that are functionally impaired and exhibit an immature phenotype. To investigate the potential role of IL-7/IL-7Rα in the outcome of HCV infection, we used multiparameter flow cytometry to characterize patients with acute infection (n = 24), long-term chronic infection (12) and normal subjects (13). HCV infection per se resulted in downregulation of CD127 on total CD4+ and CD8+ T lymphocytes as compared to normal controls. Total expression was lowest in those patients who subsequently developed persistence and intermediate in those patients with acute-resolving infection. This reduction affected both naïve and effector/memory T cells. CD127 correlated phenotypically with upregulation of chemokine receptors CCR7 and CXCR4, expression of the anti-apoptotic molecule B cell leukemia/lymphoma 2 (Bcl-2), and enhanced IL-2 production. In six HLA A2-positive patients, we longitudinally tracked tetramer responses to HCV and CMV epitopes; at baseline, reflecting the expression of CD127 on whole T cell populations, viral-specific CTLs in patients who became chronic demonstrated lower CD127.

In conclusion

, CD127 is a useful marker of functional CD4+ and CD8+ T cells and its expression correlates with virologic outcome of acute HCV. These data provide a mechanistic basis for the observation that CTLs generated in early infection rapidly decline as chronicity is established; CD127 expression should be considered in the design of novel immunotherapeutic approaches.

Supplementary material for this article can be found on the HEPATOLOGY website
(http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
Gabapentin in patients with the pruritus of cholestasis: A double-blind, randomized, placebo-controlled trial
Authors: Bergasa Nora V. , McGee Monnie , Ginsburg Iona H. , Engler Danielle
Published: October 2006

Pruritus is defined as the second order of nociception, the first being pain; thus, there is a rationale to study gabapentin, a drug that increases the threshold to experience nociception. The aim of this double-blind, randomized, placebo-controlled trial was to study the effect of gabapentin on the perception of pruritus and its behavioral manifestation, scratching, in cholestasis. The participants were 16 women with chronic liver disease and chronic pruritus. Hourly scratching activity (HSA) was continuously recorded for up to 48 hours at baseline and on treatment for at least 4 weeks in an inpatient setting. The perception of pruritus was assessed by interviews and by a visual analog score (VAS) of pruritus recorded every hour while patients were awake. Patients were randomized to the study drug (gabapentin or placebo) at a starting dose of 300 mg orally per day in divided doses to a maximum of 2,400 mg or until relief from pruritus. Gabapentin was associated with an increase in mean HSA, in contrast to the placebo, which was associated with a decrease. The mean VAS decreased significantly among those taking the placebo and in some patients on gabapentin.

In conclusion

, gabapentin did not provide a significant therapeutic advantage over the placebo; in fact, it was associated with an increase in the perception of pruritus and in HSA in some patients.
Inactivation of oxidized and S -nitrosylated mitochondrial proteins in alcoholic fatty liver of rats
Authors: Moon Kwan-Hoon , Hood Brian L. , Kim Bong-Jo , Hardwick James P. , Conrads Thomas P. , Veenstra Timothy D. , Song Byoung J.
Published: October 2006

Increased oxidative/nitrosative stress is a major contributing factor to alcohol-mediated mitochondrial dysfunction. However, which mitochondrial proteins are oxidatively modified under alcohol-induced oxidative/nitrosative stress is poorly understood. The aim of this study was to systematically investigate oxidized and/or

S

-nitrosylated mitochondrial proteins and to use a biotin-
N

-maleimide probe to evaluate their inactivation in alcoholic fatty livers of rats. Binge or chronic alcohol exposure significantly elevated nitric oxide, inducible nitric oxide synthase, and ethanol-inducible CYP2E1. The biotin-
N

-maleimide-labeled oxidized and/or

S

-nitrosylated mitochondrial proteins from pair-fed controls or alcohol-fed rat livers were subsequently purified with streptavidin-agarose. The overall patterns of oxidized and/or

S

-nitrosylated proteins resolved by 2-dimensional polyacrylamide gel electrophoresis were very similar in the chronic and binge alcohol treatment groups. Seventy-nine proteins that displayed differential spot intensities from those of control rats were identified by mass spectrometry. These include mitochondrial aldehyde dehydrogenase 2 (ALDH2), ATP synthase, acyl-CoA dehydrogenase, 3-ketoacyl-CoA thiolase, and many proteins involved in chaperone activity, mitochondrial electron transfer, and ion transport. The activity of 3-ketoacyl-CoA thiolase involved in mitochondrial β-oxidation of fatty acids was significantly inhibited in alcohol-exposed rat livers, consistent with hepatic fat accumulation, as determined by biochemical and histological analyses. Measurement of activity and immunoblot results showed that ALDH2 and ATP synthase were also inhibited through oxidative modification of their cysteine or tyrosine residues in alcoholic fatty livers of rats.

In conclusion

, our results help to explain the underlying mechanism for mitochondrial dysfunction and increased susceptibility to alcohol-mediated liver damage.

Supplementary material for this article can be found on the HEPATOLOGY website
(http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
HCV kinetics, quasispecies, and clearance in treated HCV-infected and HCV/HIV-1-coinfected patients with hemophilia
Authors: Shire Norah J. , Horn Paul S. , Rouster Susan D. , Stanford Sandra , Eyster Elaine M. , Sherman Kenneth E.
Published: October 2006

Hepatitis C virus (HCV) treatment response rates remain low in HCV/HIV-1-coinfected individuals compared with those with HCV alone. Persons with inherited coagulation disorders have high rates of HCV and HIV-1 infection, but HCV treatment trials in this patient population are scarce. We hypothesized that differences by infection status in HCV viral kinetics would be associated with differences in HCV quasispecies complexity over time and with treatment response disparities. Coinfected and monoinfected patients were enrolled in a treatment trial for pegylated-interferon alpha-2a (peg-IFN) + ribavirin. Patients were treated for 48 weeks and followed for an additional 24. Quantitative HCV RNA was tested at multiple times during and after treatment. Viral kinetic parameters associated with response were estimated with a mathematical model. Quasispecies emergence was determined via heteroduplex complexity assay. Twenty-two patients were HCV RNA-positive at baseline, with no significant demographic or virological differences by infection status. Five of eleven (45%) of monoinfected and 3 of 11 (27%) of coinfected patients achieved sustained viral response (SVR). Peg-IFN efficacy (ε) of 90% or greater was associated with probability of end-of-treatment response (ETR) (

P

= .001) and SVR (

P

= .06). Patients with SVR had lower baseline quasispecies complexity than those without SVR (

P

= .07). Those with ε of 90% or greater also had lower baseline complexity (

P

= .07). Coinfection status mediated changes in complexity over time (

P

= .04).

In conclusion

, low pretreatment quasispecies complexity may predict peg-IFN response; early peg-IFN response is critical for sustained HCV clearance and is altered in coinfection. Further studies are warranted.
Hepatitis C virus reinfection in injection drug users
Authors: Grebely Jason , Conway Brian , Raffa Jesse D. , Lai Calvin , Krajden Mel , Tyndall Mark W.
Published: October 2006

Spontaneous clearance of hepatitis C (HCV) may provide protection against reinfection. In a large community-based cohort study of 3,553 inner-city residents (mainly injection drug users), we identified HCV-infected individuals in whom virological clearance had occurred and compared the rate of reinfection in this group with that observed in previously uninfected members of the same cohort. We identified 926 HCV-uninfected and 658 HCV-infected viremic subjects at baseline, with 152 of 658 (23.1%) spontaneously clearing viremia over a median follow-up of 5.2 years (IQR, 2.8-7.4). At baseline, individuals with HCV clearance were more likely to be HIV coinfected (

P

< .001) and to be engaged in frequent illicit drug use (

P

= .004) and injection drug use (

P

< .001). The occurrence of HCV infection was lower in individuals with previous infection (14/152, 9.2%) compared with that in those without previous infection (172/926, 18.6%), with incidence rates of 1.8 (95% CI, 0.9-3.0 cases/100 person-years) and 8.1 (95% CI, 6.9-9.4 cases/100 person-years) cases/100 person-years, respectively, after accounting for follow-up. In a logistic regression analysis, with previous HCV infection assessed as a covariate with other potential confounding variables (age, sex, ethnicity, HIV infection, housing status, and illicit and injection drug use), individuals with previous HCV infection and viral clearance were 4 times less likely to develop infection than those infected for the first time (adjusted odds ratio, 0.23; 95% CI, 0.10-0.51,

P

< .001).

In conclusion

, individuals with clearance of HCV infection may have a lower risk of acquiring HCV than individuals who have never been infected, despite ongoing exposure to HCV.
T lymphocytes interact with hepatocytes through fenestrations in murine liver sinusoidal endothelial cells
Authors: Warren Alessandra , Le Couteur David G. , Fraser Robin , Bowen David G. , McCaughan Geoffrey W. , Bertolino Patrick
Published: October 2006

The liver has an established ability to induce tolerance. Recent evidence indicates that this unique property might be related to its distinctive architecture allowing T cells to be activated

in situ

independently of lymphoid tissues. Unlike lymph node–activated T cells, liver-activated T cells are short-lived, a mechanism that might contribute to the “liver tolerance effect.” Although the potential role of hepatocytes as tolerogenic antigen-presenting cells has been demonstrated, the question as to whether these cells are able to interact with CD8+ T cells in physiological settings remains controversial. Contradicting the immunological dogma stating that naïve T lymphocytes are prevented from interacting with parenchymal cells within non-lymphoid organs by an impenetrable endothelial barrier, we show here that the unique morphology of the liver sinusoidal endothelial cell (LSEC) permits interactions between lymphocytes and hepatocytes. Using electron microscopy, we demonstrate that liver resident lymphocytes as well as circulating naïve CD8+ T cells make direct contact with hepatocytes through cytoplasmic extensions penetrating the endothelial fenestrations that perforate the LSECs. Furthermore, the expression of molecules required for primary T cell activation, MHC class I and ICAM-1, is polarized on hepatocytes to the perisinusoidal cell membrane, thus maximizing the opportunity for interactions with circulating lymphocytes.

In conclusion

, this study has identified, at the ultrastructural level, a unique type of interaction between naïve T lymphocytes and liver parenchymal cells

in vivo

. These results hold implications for the pathogenesis of viral hepatitis in which hepatocytes may represent the main antigen-presenting cell, and for the development of immune tolerance as lymphocytes pass through the liver.
In vivo immune modulatory activity of hepatic stellate cells in mice
Authors: Chen Cheng-Hsu , Kuo Liang-Mou , Chang Yigang , Wu Wenhan , Goldbach Christina , Ross Mark A. , Stolz Donna B. , Chen Liepin , Fung John J. , Lu Lin , Qian Shiguang
Published: October 2006

Accumulating data suggest that hepatic tolerance, initially demonstrated by spontaneous acceptance of liver allografts in many species, results from an immune regulatory activity occurring in the liver. However, the responsible cellular and molecular components have not been completely understood. We have recently described profound T cell inhibitory activity of hepatic stellate cells (HSCs)

in vitro

. In this study, we demonstrate

in vivo

evidence of immune modulatory activity of HSCs in mice using an islet transplantation model. Co-transplanted HSCs effectively protected islet allografts from rejection, forming a multi-layered capsule, which reduced allograft immunocyte infiltrates by enhancement of apoptotic death. The immune modulation by HSCs appeared to be a local effect, and regulated by inducible expression of B7-H1, an inhibitory molecule of B7 family. This may reflect an intrinsic mechanism of immune inhibition mediated by liver-derived tissue cells.

In conclusion

, these results may lead to better understanding of liver immunobiology and development of new strategies for treatment of liver diseases.
IL-2 receptor α−/− mice and the development of primary biliary cirrhosis
Authors: Wakabayashi Kanji , Lian Zhe-Xiong , Moritoki Yuki , Lan Ruth Y. , Tsuneyama Koichi , Chuang Ya-Hui , Yang Guo-Xiang , Ridgway William , Ueno Yoshiyuki , Ansari Aftab A. , Coppel Ross L. , Mackay Ian R. , Gershwin Eric M.
Published: October 2006

Recently, we identified a child born with a genetic deficiency of IL-2 receptor α (IL-2Rα, CD25) expression who had several clinical manifestations of primary biliary cirrhosis (PBC). In addition, there has been suggestive evidence in both patients with PBC and their first-degree relatives that a deficiency of regulatory T cells (Tregs) is an integral component for susceptibility to PBC. Based on these observations, we generated IL-2Rα/CD25 deficient (IL-2Rα−/−) mice and wild-type littermate controls and followed them longitudinally for the natural history of liver immunopathology and appearance of antimitochondrial antibodies (AMAs). The analyses included immunohistochemical staining of liver and portal tract infiltrates as well as FACS profiles of lymphoid subpopulations in liver and spleen. In addition, serum cytokine profiles were quantitated. Importantly, IL-2Rα−/−, but not littermate controls, develop portal inflammation and biliary ductular damage similar to human patients with PBC. CD4+ and CD8+ T cells predominate among portal cell infiltrates and sera reflect a Th1 cytokine bias with increased levels of IFN-γ, TNF-α, IL-2 and IL-12p40. Of importance is the finding that the IL-2Rα−/− mice not only develop significantly increased serum levels of IgG and IgA, but they also develop AMAs with specificity for PDC-E2, which maps to the inner lipoyl domain of the autoantigen, all characteristics which are hallmarks of human PBC.

In conclusion

, the IL-2Rα−/− mice should facilitate studies of the early events in PBC and especially the tantalizing connection between Treg deficiency and autoimmunity specifically directed to mitochondrially located PDC-E2 and subsequent biliary ductular cell damage.
Sclerosing cholangitis: A focus on secondary causes
Authors: Abdalian Rupert , Heathcote Jenny E.
Published: October 2006

Secondary sclerosing cholangitis (SSC) is a disease that is morphologically similar to primary sclerosing cholangitis (PSC) but that originates from a known pathological process. Its clinical and cholangiographic features may mimic PSC, yet its natural history may be more favorable if recognition is prompt and appropriate therapy is introduced. Thus, the diagnosis of PSC requires the exclusion of secondary causes of sclerosing cholangitis and recognition of associated conditions that may potentially imitate its classic cholangiographic features. Well-described causes of SSC include intraductal stone disease, surgical or blunt abdominal trauma, intra-arterial chemotherapy, and recurrent pancreatitis. However, a wide variety of other associations have been reported recently, including autoimmune pancreatitis, portal biliopathy, eosinophillic and/or mast cell cholangitis, hepatic inflammatory pseudotumor, recurrent pyogenic cholangitis, primary immune deficiency, and AIDS-related cholangiopathy. This article offers a comprehensive review of SSC.
Lung cancer risk prediction: A tool for early detection
Authors: Cassidy Adrian , Duffy Stephen W. , Myles Jonathan P. , Liloglou Triantafillos , Field John K.
Published: October 2006

Although 45% of men and 39% of women will be diagnosed with cancer in their lifetime, it is difficult to predict which individuals will be affected. For some cancers, substantial progress in individual risk estimation has already been made. However, relatively few models have been developed to predict lung cancer risk beyond effects of age and smoking. This paper reviews published models for lung cancer risk prediction, discusses their potential contribution to clinical and research settings and suggests improvements to the risk modeling strategy for lung cancer. The sensitivity and specificity of existing cancer risk models is less than optimal. Improvement in individual risk prediction is important for selection of individuals for prevention or early detection interventions. In addition to smoking, factors related to occupational exposure, personal medical history and family history of cancer can add to the predictive power. A good risk prediction model is one that can identify a small fraction of the population in which a large proportion of the disease cases will occur. In the future, genetic and other biological markers are likely to be useful, although they will require rigorous evaluation. Validation is essential to establish the predictive effect and for ongoing monitoring of the model's continued relevance. © 2006 Wiley‐Liss, Inc.
Water soluble complexes of chitosan‐g‐MPEG and hyaluronic acid
Authors: Wu Jun , Wang Xuefen , Keum Jong Kahk , Zhou Hongwen , Gelfer Mikhail , Avila‐Orta Carlos‐Alberto , Pan Hui , Chen Weiliam , Chiao Shu‐Min , Hsiao Benjamin S. , Chu Benjamin
Published: October 2006

Novel water soluble, biocompatible, and highly viscoelastic polyelectrolyte complexes were prepared by mixing of positively charged chitosan grafted with poly (ethylene glycol) monomethyl ether (CS‐g‐MPEG) and negatively charged hyaluronic acid (HA). CS‐g‐MPEGs having different degrees of substitution were synthesized by reacting chitosan with MPEG‐aldehyde. The molecular structure, thermal and rheological properties, as well as biocompatibility of CS‐g‐MPEG/HA complexes were characterized. Rheological results showed that a small amount of HA could greatly enhance the viscosity of CS‐g‐MPEG solution. The highest viscosity was obtained when the charge ratio of CS‐g‐MPEG/HA was close to 1.0. Small‐angle X‐ray scattering measurements provided some insights into the lamellar structure of the CS‐g‐MPEG/HA complex. The CS‐g‐MPEG/HA complex system offers promising potentials in pharmaceutical, cosmetic, and biotechnology applications (e.g., cell scaffold, artificial synovial fluid, and drug/gene delivery medium). © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
The kth Laplacian eigenvalue of a tree
Authors: Guo Ji‐Ming
Published: October 2006

Let λk(G) be the kth Laplacian eigenvalue of a graph G. It is shown that a tree T with n vertices has $\lambda_{k}(T)\le \lceil { {n}\over{k}}\rceil$ and that equality holds if and only if k < n, k|n and T is spanned by k vertex disjoint copies of ${K}_{{1}, { {n}\over {k}}-1}$, the star on ${{n}\over{k}}$ vertices. © 2006 Wiley Periodicals, Inc. J Graph Theory
Multicolored trees in complete graphs
Authors: Akbari S. , Alipour A.
Published: October 2006

A multicolored tree is a tree whose edges have different colors. Brualdi and Hollingsworth 5 proved in any proper edge coloring of the complete graph K2n(n > 2) with 2n − 1 colors, there are two edge‐disjoint multicolored spanning trees. In this paper we generalize this result showing that if (a1,…, ak) is a color distribution for the complete graph Kn, n ≥ 5, such that $2 \leq a_{1} \leq a_{2} \leq \cdots \leq a_{k} \leq (n+ 1)/ 2$, then there exist two edge‐disjoint multicolored spanning trees. Moreover, we prove that for any edge coloring of the complete graph Kn with the above distribution if T is a non‐star multicolored spanning tree of Kn, then there exists a multicolored spanning tree T' of Kn such that T and T' are edge‐disjoint. Also it is shown that if Kn, n ≥ 6, is edge colored with k colors and $k \geq {{{n}-{2}} \choose {2}}+{3}$, then there exist two edge‐disjoint multicolored spanning trees. © 2006 Wiley Periodicals, Inc. J Graph Theory 54: 221–232, 2007
Impaired Erythropoietin Production in Liver Transplant Recipients: the Role of Calcineurin Inhibitors
Authors: Bardet Valérie , Junior Alcindo Pissaia , Coste Joël , Lecoq-Lafon Carinne , Chouzenoux Sandrine , Bernard Denis , Soubrane Olivier , Lacombe Catherine , Calmus Yvon , Conti Filoména
Published: October 2006

Anemia is common following liver transplantation. Because cyclosporine inhibits erythropoietin (Epo) production in experimental models, we investigated whether Epo production was impaired in liver transplant recipients receiving a cyclosporine- or tacrolimus-based immunosuppressive regimen. First, serum Epo levels were measured before and 1 year after transplantation in 35 liver transplant recipients. Second, serum Epo levels were compared in a large series of liver transplant recipients with stable graft and renal functions: 27 receiving a cyclosporine-based and 31 receiving a tacrolimus-based immunosuppressive regimen. A reference group was made up of 22 blood donors and 21 nontransplanted subjects with iron-deficiency anemia. Serum Epo levels were significantly lower after than before liver transplantation, especially in cyclosporine-treated patients. Serum Epo concentrations correlated with hematocrit values in both transplant recipients and control subjects. Using multiple linear regression models, the polynomial relationship between hematocrit and serum Epo values was similar to the control group in patients under tacrolimus, whereas Epo production was significantly reduced in patients under cyclosporine-based immunosuppression. Hematocrit values and the type of calcineurin inhibitor were the only parameters independently related to Epo levels. In conclusion, cyclosporine, but not tacrolimus, inhibits Epo production at the doses used in clinical practice.
Liver Transpl 12:1649–1654, 2006.

© 2006 AASLD.
Bullous Pemphigoid After Liver Transplantation for Liver Failure
Authors: Kerkar Nanda , Cohen Steven , Dugan Christina , Morotti Raffaella A. , Phelps Robert G. , Herold Betsy , Shneider Benjamin , Emre Sukru
Published: October 2006

Coomb's positive autoimmune hemolytic anemia with giant cell hepatitis (GCH) is a rare cause of liver failure and is usually associated with poor prognosis. A child with liver kidney microsomal (LKM) antibody positivity underwent successful liver transplantation for liver failure secondary to GCH with Coomb's positive hemolytic anemia. Autoimmune neutropenia developed ten months after transplant. Four months later, pemphigoid skin lesions developed. The diagnosis of bullous pemphigoid (BP) was made on the basis of skin biopsy, direct and indirect immunofluorescence test results. Treatment was with immunosuppressants – prednisone and azathioprine/rapamycin, with addition of dapsone when lesions persisted. This child is unique in that his liver function and hemolytic anemia appeared to normalize after liver transplant, but neutropenia and BP both thought to be autoimmune in etiology, developed more than a year post-transplant.
Liver Transpl 12: 1705–1710, 2006.

© 2006 AASLD.
2D‐GRAPPA‐operator for faster 3D parallel MRI
Authors: Blaimer Martin , Breuer Felix A. , Mueller Matthias , Seiberlich Nicole , Ebel Dmitry , Heidemann Robin M. , Griswold Mark A. , Jakob Peter M.
Published: October 2006

When using parallel MRI (pMRI) methods in combination with three‐dimensional (3D) imaging, it is beneficial to subsample the k‐space along both phase‐encoding directions because one can then take advantage of coil sensitivity variations along two spatial dimensions. This results in an improved reconstruction quality and therefore allows greater scan time reductions as compared to subsampling along one dimension. In this work we present a new approach based on the generalized autocalibrating partially parallel acquisitions (GRAPPA) technique that allows Fourier‐domain reconstructions of data sets that are subsampled along two dimensions. The method works by splitting the 2D reconstruction process into two separate 1D reconstructions. This approach is compared with an extension of the conventional GRAPPA method that directly regenerates missing data points of a 2D subsampled k‐space by performing a linear combination of acquired data points. In this paper we describe the theoretical background and present computer simulations and in vivo experiments. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Cardiorespiratory‐resolved magnetic resonance imaging: Measuring respiratory modulation of cardiac function
Authors: Thompson Richard B. , McVeigh Elliot R.
Published: October 2006

A technique for cardiac‐ and respiratory‐resolved MRI is described. A retrospectively gated‐segmented acquisition scheme similar to that used in conventional cine cardiac imaging was used to collect image data that spanned both the cardiac and respiratory cycles. Raw k‐space data were regridded in a cardiorespiratory phase space to allow image reconstruction at target cardiac and respiratory phases. The approach can be applied with various k‐space trajectories and pulse sequences, and was implemented in this study with both a Cartesian steady‐state free precession (SSFP) sequence and a radial phase‐contrast (PC) pulse sequence. Free‐breathing short‐axis SSFP images of the heart were reconstructed at multiple respiratory and cardiac phases to illustrate separation of cardiac and respiratory motion without artifacts. A respiratory‐resolved radial PC experiment was used to quantify the volumetric flow rates in the inferior vena cava (IVC), pulmonary artery (PA), and aorta (Ao) in five free‐breathing normal volunteers and a positive‐pressure ventilated dog. Total flow (ml/min) in each vessel was quantified as a function of respiratory phase (peak/minimum output = 1.85 ± 0.29 (IVC), 1.36 ± 0.15 (PA), 1.24 ± 0.09 (Ao)). Peak flow occurred during inspiration for the IVC and PA, and during expiration for the Ao, and there was a complete pattern reversal for the positive‐pressure ventilated dog. Magn Reson Med, 2006. Published 2006 Wiley‐Liss, Inc.
Hyperpolarized 3He diffusion MRI and histology in pulmonary emphysema
Authors: Woods Jason C. , Choong Cliff K. , Yablonskiy Dmitriy A. , Bentley John , Wong Jonathan , Pierce John A. , Cooper Joel D. , Macklem Peter T. , Conradi Mark S. , Hogg James C.
Published: October 2006

Diffusion MRI of hyperpolarized 3He shows that the apparent diffusion coefficient (ADC) of 3He gas is highly restricted in the normal lung and becomes nearly unrestricted in severe emphysema. The nature of this restricted diffusion provides information about lung structure; however, no direct comparison with histology in human lungs has been reported. The purpose of this study is to provide information about 3He gas diffusivity in explanted human lungs, and describe the relationship between 3He diffusivity and the surface area to lung volume ratio (SA/V) and mean linear intercept (Lm) measurements—the gold standard for diagnosis of emphysema. Explanted lungs from patients who were undergoing lung transplantation for advanced COPD, and donor lungs that were not used for transplantation were imaged via 3He diffusion MRI. Histological measurements were made on the same specimens after they were frozen in the position of study. There is an inverse correlation between diffusivity and SA/V (and a positive correlation between diffusivity and Lm). An important result is that restricted 3He diffusivity separated normal from emphysematous lung tissue more clearly than the morphometric analyses. This effect may be due to the smaller histologic sampling size compared to the MRI voxel sizes. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Electrophysiological differences in seropositive and seronegative Lambert–Eaton myasthenic syndrome
Authors: Oh Shin J. , Hatanaka Yuki , Claussen Gwen C. , Sher Emanuele
Published: October 2006

In order to determine whether there is any difference between voltage‐gated calcium‐channel antibody (VGCC‐Ab)–positive and –negative groups in Lambert–Eaton myasthenic syndrome (LEMS), we compared the clinical and electrophysiological features between 13 patients with VGCC‐Ab and 6 VGCC‐Ab–negative patients. No obvious difference was observed in the various clinical features or findings on single‐fiber electromyography between seropositive and seronegative cases. In seropositive cases, the compound muscle action potential (CMAP) amplitude was lower but the increment on post‐exercise facilitation (PEF) and high‐rate stimulation (HRS) was significantly higher than in the seronegative group, indicating that the repetitive nerve stimulation (RNS) test in the seropositive group is more typical of LEMS and more severe. A 100% increment as the diagnostic criterion in the routine RNS test was satisfied in all seropositive cases but in only three seronegative cases, whereas a 60% increment as the diagnostic criterion was found in all seronegative cases. The classic triad (low CMAP amplitude, decrement at low rate of stimulation, and increment at PEF or HRS) of RNS is rare, adding to the difficulty in diagnosing LEMS in the seronegative group, and making a 60% increment criterion more critical for the diagnosis of this disorder. Muscle Nerve, 2006
Electrophysiological study of ephaptic axono‐axonal responses in hemifacial spasm
Authors: Montero J. , Junyent J. , Calopa M. , Povedano M. , Valls‐Sole J.
Published: October 2006

One of the classic features of hemifacial spasm (HFS) is spread of the blink reflex responses to muscles other than the orbicularis oculi. The pathophysiological mechanisms underlying the generation of such abnormal responses include lateral spread of activity between neighboring fibers of the facial nerve and hyperexcitability of facial motoneurons. In this report we present evidence for another mechanism that can contribute to the generation of responses in lower facial muscles resembling the R1 response of the blink reflex. In 13 HFS patients, we studied the responses induced in orbicularis oris by electrical stimuli applied at various sites between the supraorbital and zygomatic areas. We identified responses with two different components: an early and very stable component, with an onset latency ranging from 10.5 to 14.8 ms, and a more irregular longer‐latency component. Displacement of the stimulation site away from the supraorbital nerve and towards the extracranial origin of the facial nerve caused a progressive shortening of response latency. These features indicate that, in our patients, the shortest latency component of the orbicularis oris response was likely generated by antidromic conduction in facial nerve motor axons followed by axono‐axonal activation of the fibers innervating the lower facial muscles. Our results suggest that motor axono‐axonal responses are generated by stimulation of facial nerve terminals in HFS. Muscle Nerve, 2006
A comparison of factors associated with collagen metabolism in different skeletal muscles from dystrophic (mdx) mice: Impact of pirfenidone
Authors: Gosselin Luc E. , Williams Jacqueline E. , Personius Kirkwood , Farkas Gaspar A.
Published: October 2006

Skeletal muscles in mdx mice exhibit differential degrees of pathological changes and fibrosis. The purpose of this study was to examine differences in various indices of collagen metabolism in skeletal muscles with widely different functions and activity profiles in mdx mice, and to determine whether pirfenidone would attenuate the development of fibrosis. Mice in the pirfenidone group were orally fed pirfenidone (500 mg/kg) daily for 4 weeks. Marked differences were noted in hydroxyproline concentration between muscles, which could not be explained solely by the level of type I collagen and transforming growth factor‐β1 (TGF‐β1) mRNA. In normal mice, matrix metalloproteinase (MMP)‐2 mRNA was significantly higher in the gastrocnemius than in the diaphragm or genioglossus muscles, suggesting that collagen degradation plays an important role in regulating collagen accretion in skeletal muscle. In mdx mice, the levels of both MMP‐2 and MMP‐9 mRNA were significantly elevated relative to control, although the response was muscle specific. Pirfenidone treatment resulted in a significant reduction in the level of hydroxyproline concentration across all muscles, although the effect was small. Results from this study reveal intrinsic dissimilarities in collagen metabolism between functionally different skeletal muscles. Moreover, the pharmacological use of pirfenidone may be beneficial in preventing fibrosis in muscular dystrophy. Muscle Nerve, 2006
High‐resolution analysis of neuronal growth cone morphology by comparative atomic force and optical microscopy
Authors: Grzywa Emilie L. , Lee Aih Cheun , Lee Gil U. , Suter Daniel M.
Published: October 2006

Neuronal growth cones are motile sensory structures at the tip of axons, transducing guidance information into directional movements towards target cells. The morphology and dynamics of neuronal growth cones have been well characterized with optical techniques; however, very little quantitative information is available on the three‐dimensional structure and mechanical properties of distinct subregions. In the present study, we imaged the large Aplysia growth cones after chemical fixation with the atomic force microscope (AFM) and directly compared our data with images acquired by light microscopy methods. Constant force imaging in contact mode in combination with force‐distant measurements revealed an average height of 200 nm for the peripheral (P) domain, 800 nm for the transition (T) zone, and 1200 nm for the central (C) domain, respectively. The AFM images show that the filopodial F‐actin bundles are stiffer than surrounding F‐actin networks. Enlarged filopodia tips are 60 nm higher than the corresponding shafts. Measurements of the mechanical properties of the specific growth cone regions with the AFM revealed that the T zone is stiffer than the P and the C domain. Direct comparison of AFM and optical data acquired by differential interference contrast and fluorescence microscopy revealed a good correlation between these imaging methods. However, the AFM provides height and volume information at higher resolution than fluorescence methods frequently used to estimate the volume of cellular compartments. These findings suggest that AFM measurements on live growth cones will provide a quantitative understanding of how proteins can move between different growth cone regions. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006
Consistent dynamics suggests tight regulation of biophysical parameters in a small network of bursting neurons
Authors: Szücs Attila , Selverston Allen I.
Published: October 2006

The neuronal firing patterns in the pyloric network of crustaceans are remarkably consistent among animals. Although this characteristic of the pyloric network is well‐known, the biophysical mechanisms underlying the regulation of the systems output are receiving renewed attention. Computer simulations of the pyloric network recently demonstrated that consistent motor output can be achieved from neurons with disparate biophysical parameters among animals. Here we address this hypothesis by pharmacologically manipulating the pyloric network and analyzing the emerging voltage oscillations and firing patterns. Our results show that the pyloric network of the lobster stomatogastric ganglion maintains consistent and regular firing patterns even when entire populations of specific voltage‐gated channels and synaptic receptors are blocked. The variations of temporal parameters used to characterize the burst patterns of the neurons as well as their intraburst spike dynamics do not display statistically significant increase after blocking the transient K‐currents (with 4‐aminopyridine), the glutamatergic inhibitory synapses (with picrotoxin), or the cholinergic synapses (with atropine) in pyloric networks from different animals. These data suggest that in this very compact circuit, the biophysical parameters are cell‐specific and tightly regulated. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006