bluuebunny/crossref_metadata_2025_split huggingface dataset:
IgG4‐positive plasma cells in cutaneous Rosai‐Dorfman disease: an additional immunohistochemical feature and possible relationship to IgG4‐related sclerosing disease
Authors: Kuo Tseng‐tong , Chen Tse‐Ching , Lee Li‐Yu , Lu Pei‐Hsuan 
Published: January 2009

Background: Cutaneous Rosai‐Dorfman disease (CRDD) shares the histopathological features of abundant plasma cells and stromal fibrosis with IgG4‐related sclerosing disease. The possible role of IgG4+ plasma cells in CRDD was investigated.Methods: Twelve cases of CRDD were reviewed, and their lesions were immunostained with anti‐IgG4 and anti‐IgG antibodies. The number of IgG4+ and IgG+ plasma cells and their ratios were estimated. Serum IgG4 and IgG concentrations were measured in two recent cases.Results: Many IgG4+ and IgG+ plasma cells were found in all 12 cases. IgG4+ plasma cells ranged from 21 to 204 per high‐power field (HPF) (mean 117/HPF), and IgG+ plasma cells ranged from 114 to 759/HPF (mean 349/HPF). All cases had more than 30 IgG4+ cells/HPF, except one case. The IgG4/IgG ratio ranged from 16% to 51% (mean 34%). Serum IgG4 concentration and serum IgG4/IgG ratio were increased in one recent case. Various degrees of stromal fibrosis were present in all cases.Conclusions: The presence of many IgG4+ plasma cells and stromal fibrosis suggests that CRDD may be related to IgG4‐related sclerosing disease. Many IgG4+ plasma cells is another feature of CRDD, and serum IgG4 may be elevated.
Erythema multiforme majus (Fuchs syndrome) associated with Mycoplasma pneumoniae infection in two patients
Authors: Havliza Katrin , Jakob Antje , Rompel Rainer 
Published: January 2009

SummaryIn Germany Fuchs syndrome is used to describe a variant of erythema multiforme majus which mainly involves the mucosal surfaces. As the skin may be completely unaffected, it is an under‐recognized diagnosis and often difficult to confirm. Clinical features involve erythema, erosions and ulcerations of the oral mucosa. In most cases there is severe conjunctivitis and sometimes the genital mucosa is involved. Most cases of Fuchs syndrome are triggered by infections; herpes simplex virus and Mycoplasma pneumoniae are the most common causes. We describe two women presenting with Fuchs syndrome after respiratory illness caused by Mycoplasma pneumoniae.
Perforating folliculitis, angioedema, hand‐foot syndrome – multiple cutaneous side effects in a patient treated with sorafenib
Authors: Wolber Carola , Udvardi Astrid , Tatzreiter Georg , Schneeberger Achim , Volc‐Platzer Beatrix 
Published: January 2009

SummaryA patient with clear cell renal cell carcinoma was treated with sorafenib, a multikinase inhibitor, which induced a variety of cutaneous side effects. In addition to xerosis, he developed angioedema (AE), hand‐foot syndrome (HFS) and perforating folliculitis (PF). The latter three occurred in a dose‐dependent manner. AE was observed at the recommended daily dose of 800 mg. Dose reduction to 400 mg prevented its recurrence. At this dose level, the patient exhibited HFS, which cleared upon further reduction of the dose. While receiving 200 mg, the patient developed PF. To the best of our knowledge, this is the first description of a case of PF during treatment with sorafenib.
SYNTHESIS: Cancer research meets evolutionary biology
Authors: Pepper John W. , Scott Findlay C. , Kassen Rees , Spencer Sabrina L. , Maley Carlo C. 
Published: January 2009

AbstractThere is increasing evidence that Darwin’s theory of evolution by natural selection provides insights into the etiology and treatment of cancer. On a microscopic scale, neoplastic cells meet the conditions for evolution by Darwinian selection: cell reproduction with heritable variability that affects cell survival and replication. This suggests that, like other areas of biological and biomedical research, Darwinian theory can provide a general framework for understanding many aspects of cancer, including problems of great clinical importance. With the availability of raw molecular data increasing rapidly, this theory may provide guidance in translating data into understanding and progress. Several conceptual and analytical tools from evolutionary biology can be applied to cancer biology. Two clinical problems may benefit most from the application of Darwinian theory: neoplastic progression and acquired therapeutic resistance. The Darwinian theory of cancer has especially profound implications for drug development, both in terms of explaining past difficulties, and pointing the way toward new approaches. Because cancer involves complex evolutionary processes, research should incorporate both tractable (simplified) experimental systems, and also longitudinal observational studies of the evolutionary dynamics of cancer in laboratory animals and in human patients. Cancer biology will require new tools to control the evolution of neoplastic cells.
Three-Dimensional Identification of Semi-Elliptical Crack on the Back Surface by Means of Direct-Current Electrical Potential Difference Method With Multiple-Probe Sensor (PVP2006-ICPVT-11-93359)
Authors: Tada Naoya , Funakoshi Akira 
Published: January 2009

AbstractCracks are popular defects initiated in structural components and their accurate evaluation is very important to assure the reliability of various plants. The direct-current electrical potential difference method is known as one of the most effective methods for the evaluation of the cracks. In this paper, a method of three-dimensional identification of a semi-elliptical crack existing on the back surface of a conductive plate by the direct-current electrical potential difference method with a multiple-probe sensor is proposed. The geometrical condition of the crack was specified by six parameters, the surface and inward angles of the crack plane, θsur and θin, the length and depth of the crack, c and a, and the two-dimensional location of the crack center, (yc,zc), on the back surface. The identification was carried out based on the distribution of electrical potential difference on the surface of the plate measured with a sensor composed of grid-arranged multiple probes called the “multiple-probe sensor.” As an approximate cracked body and a quick analysis method were used, a number of repeated electrical potential field analyses necessary for the identification of the crack became possible within a practical time. The validity of the method was numerically confirmed by carrying out the identification based on the result of the finite element analysis. The proposed method could be extended to the online monitoring of a semi-elliptical crack initiated on the inner surface of tubular components by means of the multiple-probe sensor placed on the outer surface.
Optimal Design of Measurement Point Layout for Workpiece Localization
Authors: Zhu LiMin , Luo HongGen , Ding Han 
Published: January 2009

AbstractThis paper presents a methodology for the optimal design of the measurement point layout for 3D workpiece localization in the presence of part surface errors and measurement errors. A number of frame-invariant norms of the infinitesimal rigid body displacement, two of which give Riemann metrics on the Euclidean group, are defined to quantify the localization accuracy required by manufacturing processes. Then, two types of indices, both frame invariant and scale invariant, are derived to characterize the sensitivities of the accuracy measures to the sampling errors at the measurement points. With a dense set of discrete points on the workpiece datum surfaces predefined as candidates for measurement, planning of probing points to accurately recover part location is modeled as a combinatorial problem focusing on minimizing the accuracy sensitivity index. It is shown that if the number of measurement points is large enough, there is no need to optimize their positions, and that if the systematic error component of the sampled geometric errors is not negligible as compared with the random error component, addition of measurement points offers no guarantee of a smaller upper bound of the localization error. A heuristic floating forward search algorithm is employed to efficiently find a near-optimal solution. Two relevant problems of sensor placement optimization for geometric imperfection diagnosis and fixture fault diagnosis are also briefly revisited in the same framework. Examples are given to illustrate the effectiveness of the proposed design criteria and algorithm.
In Vitro Activity and Preclinical Profile of TMC435350, a Potent Hepatitis C Virus Protease Inhibitor
Authors: Lin Tse-I , Lenz Oliver , Fanning Gregory , Verbinnen Thierry , Delouvroy Frédéric , Scholliers Annick , Vermeiren Katrien , Rosenquist Åsa , Edlund Michael , Samuelsson Bertil , Vrang Lotta , de Kock Herman , Wigerinck Piet , Raboisson Pierre , Simmen Kenneth 
Published: January 2009

ABSTRACTThe hepatitis C virus (HCV) NS3/4A serine protease has been explored as a target for the inhibition of viral replication in preclinical models and in HCV-infected patients. TMC435350 is a highly specific and potent inhibitor of NS3/4A protease selected from a series of novel macrocyclic inhibitors. In biochemical assays using NS3/4A proteases of genotypes 1a and 1b, inhibition constants of 0.5 and 0.4 nM, respectively, were determined. TMC435350 inhibited HCV replication in a cellular assay (subgenomic 1b replicon) with a half-maximal effective concentration (EC50) of 8 nM and a selectivity index of 5,875. The compound was synergistic with alpha interferon and an NS5B inhibitor in the replicon model and additive with ribavirin. In rats, TMC435350 was extensively distributed to the liver and intestinal tract (tissue/plasma area under the concentration-time curve ratios of >35), and the absolute bioavailability was 44% after a single oral administration. Compound concentrations detected in both plasma and liver at 8 h postdosing were above the EC99value measured in the replicon. In conclusion, given the selective and potent in vitro anti-HCV activity, the potential for combination with other anti-HCV agents, and the favorable pharmacokinetic profile, TMC435350 has been selected for clinical development.
Using a Field Quantitative Real-Time PCR Test To Rapidly Identify Highly Viremic Rift Valley Fever Cases
Authors: Njenga M. Kariuki , Paweska Janusz , Wanjala Rose , Rao Carol Y. , Weiner Matthew , Omballa Victor , Luman Elizabeth T. , Mutonga David , Sharif Shanaaz , Panning Marcus , Drosten Christian , Feikin Daniel R. , Breiman Robert F. 
Published: January 2009

ABSTRACT

Approximately 8% of Rift Valley fever (RVF) cases develop severe disease, leading to hemorrhage, hepatitis, and/or encephalitis and resulting in up to 50% of deaths. A major obstacle in the management of RVF and other viral hemorrhagic fever cases in outbreaks that occur in rural settings is the inability to rapidly identify such cases, with poor prognosis early enough to allow for more-aggressive therapies. During an RVF outbreak in Kenya in 2006 to 2007, we evaluated whether quantitative real-time reverse transcription-PCR (qRT-PCR) could be used in the field to rapidly identify viremic RVF cases with risk of death. In 52 of 430 RVF cases analyzed by qRT-PCR and virus culture, 18 died (case fatality rate [CFR] = 34.6%). Levels of viremia in fatal cases were significantly higher than those in nonfatal cases (mean of 10
5.2
versus 10
2.9
per ml;
P
< 0.005). A negative correlation between the levels of infectious virus particles and the qRT-PCR crossover threshold (
C

T

) values allowed the use of qRT-PCR to assess prognosis. The CFR was 50.0% among cases with
C

T

values of <27.0 (corresponding to 2.1 × 10
4
viral RNA particles/ml of serum) and 4.5% among cases with
C

T

values of ≥27.0. This cutoff yielded 93.8% sensitivity and a 95.5% negative predictive value; the specificity and positive predictive value were 58% and 50%, respectively. This study shows a correlation between high viremia and fatality and indicates that qRT-PCR testing can identify nearly all fatal RVF cases.
Human-to-Human Transmission of Tuberculosis Caused by
Mycobacterium bovis
in Immunocompetent Patients
Authors: Sunder S. , Lanotte P. , Godreuil S. , Martin C. , Boschiroli M. L. , Besnier J. M. 
Published: January 2009

ABSTRACT

Human-to-human transmission
of Mycobacterium bovis in
two immunocompetent patients from the same family was confirmed by spoligotyping (pattern F35, which was only observed in cattle from the same area in France). A single allelic difference between animal and human isolates was observed with mycobacterial interspersed repetitive units containing variable-number tandem repeats, suggesting a jump across the species barrier.
Visualising vitreous through modified trans-scleral illumination by maximising the Tyndall effect
Authors: Veckeneer M , Wong D 
Published: January 2009

Background:A new technique for visualisation of the vitreous base is described. It uses a standard lightpipe for scleral indentation and transillumination. Visualisation of the vitreous using low light levels can be achieved by enhancing the Tyndall effect.Discussion:Perfluorocarbon liquid (PFCL) is used to confine the aqueous environment to the anterior vitreous cavity and triamcinolone is added to increase light scatter. The technique clearly differentiates vitreous from PFCL and infusion fluid, and facilitates trimming of the vitreous base, draining of subretinal fluid and air/fluid exchange.
Central aponeurosis tears of the rectus femoris: practical sonographic prognosis
Authors: Balius R , Maestro A , Pedret C , Estruch A , Mota J , Rodríguez L , García P , Mauri E 
Published: January 2009

Objective:This study is a statistical analysis to establish whether a correlation exists between the level and degree of rectus femoris (RF) central tendon injury and the amount of time that an athlete is unable to participate subsequently, referred to as “sports participation absence” (SPA).Design:Causal–comparative study.Patients:35 players from two high-level Spanish soccer teams with an injury to the central tendon of the RF based on clinical and ultrasound criteria.Main Outcome Measure:Ultrasound examination was performed with an 8–2 MHz linear multifrequency transducer. All studies included both longitudinal and transverse RF sections.Results:At the proximal level the SPA time is 45.1 days when the injury length is 4.0 cm. This value increases by 5.3 days with each 1 cm increase in the length of injury. In the case of distal level injury, SPA time is 32.9 days when the injury length is 3.9 cm. This value increases by 3.4 days with each 1 cm increase. In the total representative sample, SPA time when the injury length is 4.2 cm corresponds to 39.1 days. This value increases by 4.2 days per length unit.Conclusions:RF central tendon injury at the proximal level is associated with a greater SPA time than at the distal level. Patients with a grade II injury have an SPA time longer than those with a grade I injury whether the injury is located proximal or distal.
A prospective cohort study of hamstring injuries in competitive sprinters: preseason muscle imbalance as a possible risk factor
Authors: Yeung S S , Suen A M Y , Yeung E W 
Published: January 2009

Background:Hamstring injuries are common in sprinters. Identifying preseason risk factors is essential to target injury-prone athletes and develop injury preventive measures.Objective:To investigate the incidence of hamstring muscle injury in sprinters over an athletic season and to explore the preseason predictor of this injury.Design:Prospective cohort study.Participants:44 sprinters from the Hong Kong Sports Institute, the Hong Kong Amateur Athletic Association and intercollegiate athletic teams were recruited.Methods:Preseason assessment of hamstring flexibility, concentric and eccentric isokinetic peak torque and peak torque angle were obtained at the beginning of an athletic season. The athletes were followed over 12 months and were asked to report all injuries resulting from training and competition.Results:Eight athletes sustained hamstring injuries over the season. The injury rate was 0.87 per 1000 h of exposure. The incidence of injuries was higher at the beginning of the season, with 58.3% injuries occurring in the first 100 h of exposure. Cox regression analysis revealed that athletes with a decrease in the hamstring : quadriceps peak torque ratio of less than 0.60 at an angular velocity of 180°/s have a 17-fold increased risk of hamstring injury.Conclusion:Performing preseason hamstring : quadriceps peak torque ratio assessments may be useful to identify sprinters susceptible to hamstring injury.
Targeting Heat Shock Protein 90 Overrides the Resistance of Lung Cancer Cells by Blocking Radiation-Induced Stabilization of Hypoxia-Inducible Factor-1α
Authors: Kim Woo-Young , Oh Seung Hyun , Woo Jong-Kyu , Hong Waun Ki , Lee Ho-Young 
Published: January 2009

Abstract
Hypoxia-inducible factor-1 (HIF-1) has been suggested to play a major role in tumor radioresistance. However, the mechanisms through which irradiation regulates HIF-1α expression remain unclear. The purpose of this study was to investigate the mechanisms that mediate HIF-1 activation and thus radioresistance. Here, we show that irradiation induces survival and angiogenic activity in a subset of radioresistant lung cancer cell lines by elevating HIF-1α protein expression. Radiation induced HIF-1α protein expression mainly through two distinct pathways, including an increase in de novo protein synthesis via activation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and stabilization of HIF-1α protein via augmenting the interaction between heat shock protein 90 (Hsp90) and HIF-1α protein. Whereas the PI3K/Akt/mTOR pathway was activated by irradiation in all the lung cancer cells examined, the Hsp90-HIF-1α interaction was enhanced in the resistant cells only. Inhibition of Hsp90 function by 17-allylamino-17-demethoxygeldanamycin or deguelin, a novel natural inhibitor of Hsp90, suppressed increases in HIF-1α/Hsp90 interaction and HIF-1α expression in radioresistant cells. Furthermore, combined treatment of radiation with deguelin significantly decreased the survival and angiogenic potential of radioresistant lung cancer cells in vitro. We finally determined in vivo that systemic administration of deguelin resulted in profound inhibition of tumor growth and angiogenesis when combined with radiation. These results provide a strong rationale to target Hsp90 as a means to block radiation-induced HIF-1α and thus to circumvent radioresistance in lung cancer cells. [Cancer Res 2009;69(4):1624–32]
Expression and Functions of Transmembrane Mucin MUC13 in Ovarian Cancer
Authors: Chauhan Subhash C. , Vannatta Kelley , Ebeling Mara C. , Vinayek Namita , Watanabe Akira , Pandey Krishan K. , Bell Maria C. , Koch Michael D. , Aburatani Hiroyuki , Lio Yuhlong , Jaggi Meena 
Published: January 2009

Abstract
MUC13, a transmembrane mucin, is normally expressed in gastrointestinal and airway epithelium. Its aberrant expression has been correlated with gastric colon and cancer. However, the expression and functions of MUC13 in ovarian cancer are unknown. In the present study, the expression profile and functions of MUC13 were analyzed to elucidate its potential role in ovarian cancer diagnosis and pathogenesis. A recently generated monoclonal antibody (clone PPZ0020) was used to determine the expression profile of MUC13 by immunohistochemistry using ovarian cancer tissue microarrays and 56 additional epithelial ovarian cancer (EOC) samples. The expression of MUC13 was significantly (P &lt; 0.005) higher in cancer samples compared with the normal ovary/benign tissues. Among all ovarian cancer types, MUC13 expression was specifically present in EOC. For the functional analyses, a full-length MUC13 gene cloned in pcDNA3.1 was expressed in a MUC13 null ovarian cancer cell line, SKOV-3. Here, we show that the exogenous MUC13 expression induced morphologic changes, including scattering of cells. These changes were abrogated through c-Jun NH2 kinase (JNK) chemical inhibitor (SP600125) or JNK2 siRNA. Additionally, a marked reduction in cell-cell adhesion and significant (P &lt; 0.05) increases in cell motility, proliferation, and tumorigenesis in a xenograft mouse model system were observed upon exogenous MUC13 expression. These cellular characteristics were correlated with up-regulation of HER2, p21-activated kinase 1, and p38 protein expression. Our findings show the aberrant expression of MUC13 in ovarian cancer and that its expression alters the cellular characteristics of SKOV-3 cells. This implies a significant role of MUC13 in ovarian cancer. [Cancer Res 2009;69(3):765–74]
The Hypoxia-Activated ProDrug AQ4N Penetrates Deeply in Tumor Tissues and Complements the Limited Distribution of Mitoxantrone
Authors: Trédan Olivier , Garbens Alaina B. , Lalani Alshad S. , Tannock Ian F. 
Published: January 2009

Abstract
Hypoxic tumor cells are likely to be resistant to conventional chemotherapy, in large part because many anticancer drugs are unable to penetrate into poorly oxygenated tumor tissue. Here, we used quantitative immunofluorescence to study the distribution of mitoxantrone and AQ4N in tumor tissue. AQ4N is a prodrug activated under hypoxic conditions to AQ4, which is structurally similar to mitoxantrone and inhibits topoisomerase II. We characterized the penetration of mitoxantrone and AQ4N/AQ4 through multilayered cell cultures (MCC) and in relation to blood vessels and hypoxic regions in human tumor xenografts. We also studied tumor growth delay after treatment with each agent alone and with the combination. In both MCC and xenografts, mitoxantrone is taken up by proximal cells and penetrates slowly to distant regions. In contrast, AQ4N rapidly penetrates MCC and tumor tissue in vivo, and AQ4N (or its reduced form AQ4) is detected at high concentration within hypoxic regions. The targeting of mitoxantrone to oxygenated regions and AQ4N/AQ4 to hypoxic tumor regions results in effective drug exposure over the entire tumor after combined treatment and increases tumor growth delay compared with either drug alone. The combination of a clinically used anticancer drug with limited tissue penetration and a structurally related drug activated in regions of tumor hypoxia is an effective strategy to overcome chemoresistance due to the tumor microenvironment. This study supports clinical evaluation of AQ4N in combination with conventional anticancer agents, such as mitoxantrone. [Cancer Res 2009;69(3):940–7]
A Multiscale Mathematical Model for Oncolytic Virotherapy
Authors: Paiva Leticia R. , Binny Christopher , Ferreira Silvio C. , Martins Marcelo L. 
Published: January 2009

Abstract
One of the most promising strategies to treat cancer is attacking it with viruses. Oncolytic viruses can kill tumor cells specifically or induce anticancer immune response. A multiscale model for virotherapy of cancer is investigated through simulations. It was found that, for intratumoral virus administration, a solid tumor can be completely eradicated or keep growing after a transient remission. Furthermore, the model reveals undamped oscillatory dynamics of tumor cells and virus populations, which demands new in vivo and in vitro quantitative experiments aiming to detect this oscillatory response. The conditions for which each one of the different tumor responses dominates, as well as the occurrence probabilities for the other nondominant therapeutic outcomes, were determined. From a clinical point of view, our findings indicate that a successful, single agent virotherapy requires a strong inhibition of the host immune response and the use of potent virus species with a high intratumoral mobility. Moreover, due to the discrete and stochastic nature of cells and their responses, an optimal range for viral cytotoxicity is predicted because the virotherapy fails if the oncolytic virus demands either a too short or a very large time to kill the tumor cell. This result suggests that the search for viruses able to destroy tumor cells very fast does not necessarily lead to a more effective control of tumor growth. [Cancer Res 2009;69(3):1205–11]