bluuebunny/crossref_metadata_2025 huggingface dataset:
INVESTIGATIONS OF THE VISCOELASTICITY OF ESOPHAGEAL TISSUE USING INCREMENTAL STRESS-RELAXATION TEST AND CYCLIC EXTENSION TEST
Authors: YANG W. , FUNG T. C. , CHIAN K. S. , CHONG C. K.
Published: October 2006

The time-dependent mechanical properties of porcine esophagus were investigated experimentally and theoretically. It was hypothesized that the viscoelasticity was quasi-linear. The incremental stress-relaxation test was conducted to identify the material constants included in the quasi-linear viscoelastic (QLV) model. To verify the predictive ability of the model, the incremental cyclic test was performed. Hysteresis was calculated and compared with that predicted by the model. Results showed that stresses relaxed by 20–30% within the first 10 s and stabilized at 50% at 300 s. The QLV model was shown to be able to describe the viscoelasticity of esophagus across various stretch levels. The model could also predict the hysteresis during cyclic test well. It suggested that the QLV could be used as the material characterization of esophageal tissue.
ON THE VALUES OF CONTINUED FRACTIONS: q-SERIES II
Authors: MATALA-AHO TAPANI , MERILÄ VILLE
Published: October 2006

Let polynomials S(t), T(t) be given, then the convergence of the q-continued fraction [Formula: see text] will be studied using the Poincaré–Perron Theorem and Frobenius series solutions of the corresponding q-difference equation S(t)H(q2t) = -T(t)H(qt) + H(t). Our applications include a generalization of a q-continued fraction identity of Ramanujan and certain q-fractions, which arise in the theory of q-orthogonal polynomials.
TNF-α potentiates protein-tyrosine nitration through activation of NADPH oxidase and eNOS localized in membrane rafts and caveolae of bovine aortic endothelial cells
Authors: Yang Baohua , Rizzo Victor
Published: October 2006

A major source of reactive oxygen species (ROS) in endothelial cells is the NADPH oxidase enzyme complex. The selective distributions of any enzyme within cells have important implications in regulating enzyme effectiveness through facilitation of access to local substrates and/or product targets. Because membrane rafts provide a spatially preferable environment for a variety of enzyme systems, we sought to determine whether NADPH oxidase is present and functional in this plasma membrane compartment in endothelial cells. We found that, in resting endothelial cells, NADPH oxidase subunits were preassembled and the enzyme functional in membrane rafts, specifically in caveolae. Stimulation with TNF-α induced additional recruitment of the p47phoxregulatory subunit to raft-localized NADPH oxidase and enhanced ROS production within raft domains. TNF-α also induced nitric oxide production through activation of endothelial nitric oxide synthase (eNOS) present in the same membrane compartment. The dual activation of superoxide and nitric oxide-generating systems provided a spatially favorable environment for nitration of tyrosine-containing proteins localized to rafts. Perturbation of membrane raft structural integrity with cholesterol-sequestering compounds caused the delocalization of NADPH oxidase subunits and eNOS from the rafts and inhibited TNF-α-induced ROS production and protein tyrosine nitration. Together, these data provide evidence that membrane rafts and caveolae play a role in the spatial regulation of NADPH oxidase and subsequent ROS/reactive nitrogen species in endothelial cells.
Characterization and localization of Ac-SDKP receptor binding sites using125I-labeled Hpp-Aca-SDKP in rat cardiac fibroblasts
Authors: Zhuo Jia L. , Carretero Oscar A. , Peng Hongmei , Li Xiao C. , Regoli Domenico , Neugebauer Witold , Rhaleb Nour-Eddine
Published: October 2006

We have shown that the tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) inhibited endothelin-1 (ET-1)-induced cell proliferation and collagen synthesis in cultured rat cardiac fibroblasts (CFs) and reduced left ventricle collagen deposition in rats with aldosterone (salt)- and ANG II-induced hypertension. However, it is not known whether these effects are mediated by receptor binding sites specific for Ac-SDKP. We hypothesized that Ac-SDKP exerts antifibrotic effects by binding to specific receptor sites in cultured rat CFs, which mediate the inhibitory effects of Ac-SDKP on ET-1-stimulated collagen synthesis. Ac-SDKP binding sites in rat CFs and hearts were characterized by a specific radioligand,125I-labeled 3-( p-hydroxyphenyl)-propionic acid (or desaminotyrosine) (Hpp)-Aca-SDKP, a biologically active analog of Ac-SDKP.125I-labeled Hpp-Aca-SDKP bound to rat CFs and fractionated membranes with similar affinities and specificity in a concentration- and time-dependent fashion. Scatchard plot analyses revealed a single class of high-affinity Hpp-Aca-SDKP binding sites (maximal binding: 1,704 ± 198 fmol/mg protein; dissociation constant: 3.3 ± 0.6 nM).125I-labeled Hpp-Aca-SDKP binding in CFs was displaced by unlabeled native peptide Ac-SDKP (inhibition constant: 0.69 ± 0.15 nM) and the analog Hpp-Aca-SDKP (inhibition constant: 10.4 ± 0.2 nM) but not the unrelated peptide ANG II or ET-1 (10 μM). In vitro, both Ac-SDKP and Hpp-Aca-SDKP inhibited ET-1-stimulated collagen synthesis in CFs in a dose-dependent fashion, reaching a maximal effect at 1 nM (control: 7.5 ± 0.4, ET-1: 19.9 ± 1.2, ET-1+SDKP: 7.7 ± 0.4, ET-1+Hpp-Aca-SDKP: 9.7 ± 0.1 μg/mg protein; P < 0.001). Ac-SDKP also significantly attenuated ET-1-induced increases in intracellular calcium and MAPK ERK1/2 phosphorylation in CFs. In the rat heart, in vitro autoradiography revealed specific125I-labeled Hpp-Aca-SDKP binding throughout the myocardium, primarily interstitially. We believe that these results demonstrate for the first time that Hpp-Aca-SDKP is a functional ligand specific for Ac-SDKP receptor binding sites and that both Ac-SDKP and Hpp-Aca-SDKP exert antifibrotic effects by binding to Ac-SDKP receptors in rat CFs.
O2delivery and redox state are determinants of compartment-specific reactive O2species in myocardial reperfusion
Authors: Stoner Jason D. , Clanton Thomas L. , Aune Sverre E. , Angelos Mark G.
Published: October 2006

Reperfusion of the ischemic myocardium leads to a burst of reactive O2species (ROS), which is a primary determinant of postischemic myocardial dysfunction. We tested the hypothesis that early O2delivery and the cellular redox state modulate the initial myocardial ROS production at reperfusion. Isolated buffer-perfused rat hearts were loaded with the fluorophores dihydrofluorescein or Amplex red to detect intracellular and extracellular ROS formation using surface fluorometry at the left ventricular wall. Hearts were made globally ischemic for 20 min and then reperfused with either 95% or 20% O2-saturated perfusate. The same protocol was repeated in hearts loaded with dihydrofluorescein and perfused with either 20 or 5 mM glucose-buffered solution to determine relative changes in NADH and FAD. Myocardial O2delivery during the first 5 min of reperfusion was 84.7 ± 4.2 ml O2/min with 20% O2-saturated buffer and 354.4 ± 22.8 ml O2/min with 95% O2( n = 8/group, P < 0.001). The fluorescein signal (intracellular ROS) was significantly increased in hearts reperfused with 95% O2compared with 20% O2. However, the resorufin signal (extracellular ROS) was significantly increased with 20% O2compared with 95% O2during reperfusion. Perfusion of hearts with 20 mM glucose reduced the·NADH during ischemia ( P < 0.001) and the·ROS at reperfusion ( P < 0.001) compared with 5.5 mM-perfused glucose hearts. In conclusion, initial O2delivery to the ischemic myocardium modulates a compartment-specific ROS response at reperfusion such that high O2delivery promotes intracellular ROS and low O2delivery promotes extracellular ROS. The redox state that develops during ischemia appears to be an important precursor for reperfusion ROS production.
Notch-1 regulates pulmonary neuroendocrine cell differentiation in cell lines and in transgenic mice
Authors: Shan Lin , Aster Jon C. , Sklar Jeffrey , Sunday Mary E.
Published: October 2006

The notch gene family encodes transmembrane receptors that regulate cell differentiation by interacting with surface ligands on adjacent cells. Previously, we demonstrated that tumor necrosis factor-α (TNF) induces neuroendocrine (NE) cell differentiation in H82, but not H526, undifferentiated small cell lung carcinoma lines. We now test the hypothesis that TNF mediates NE cell differentiation in part by altering Notch gene expression. First, using RT-PCR, we determined that TNF treatment of H82, but not H526, transiently decreases notch-1 mRNA in parallel with induction of gene expression for the NE-specific marker DOPA decarboxylase (DDC). Second, we treated H82 and H526 with notch-1 antisense vs. sense oligodeoxynucleotides. Using quantitative RT-PCR and Western analyses we demonstrate that DDC mRNA and protein are increased in H82 by notch-1 antisense, whereas notch-1 mRNA and activated Notch-1 protein are decreased. mRNA for Hes1, a transcription factor downstream from activated Notch, is also decreased by Notch-1 antisense in H82 but not H526. After 7 days of Notch-1 antisense treatment, neural cell adhesion molecule (NCAM) immunoreactivity is induced in H82 but not H526. Third, we generated transgenic mice bearing notch-1 driven by the neural/NE-specific calcitonin promoter, which express activated Notch-1 in developing lung epithelium. Newborn NotchCal mouse lungs have high levels of hes1 mRNA, reflecting increased activated Notch, compared with wild-type. NotchCal lungs have decreased CGRP-positive NE cells, decreased protein gene product 9.5 (PGP9.5)-positive NE cells, and decreased gastrin-releasing peptide (GRP), CGRP, and DDC mRNA levels compared with normal littermates. Cumulatively, these observations provide further support for a role for Notch-1 signaling in regulating pulmonary NE cell differentiation.
Cell-based tissue engineering for lung regeneration
Authors: Andrade Cristiano F. , Wong Amy P. , Waddell Thomas K. , Keshavjee Shaf , Liu Mingyao
Published: October 2006

Emphysema is a chronic lung disease characterized by alveolar enlargement and tissue loss. Tissue engineering represents an attractive potential for regeneration of several organ systems. The complex three-dimensional architectural structure of lung parenchyma requiring connections of alveolar units to airways and the pulmonary circulation makes this strategy less optimistic. In the present study, we used Gelfoam sponge as a scaffold material, supplemented with fetal rat lung cells as progenitors, to explore the potential application of cell-based tissue engineering for lung regeneration in adult rats. After injection into lung parenchyma, the sponge showed porous structures similar to alveolar units. It did not induce severe local inflammatory response. Fetal lung cells in the sponge were able to survive in the adult lung for at least 35 days, determined by CMTMR [5-(and-6)-{[(4-chloromethyl)benzoyl]amino}tetramethylrhodamine] labeling. Proliferation of cells within the sponge was demonstrated in vivo by bromodeoxyuridine (BrdU) labeling. Cells formed “alveolar-like structures” at the border between the sponge and the surrounding lung tissue with positive immunohistochemical staining for epithelial and endothelial cells. Neovascularization of the sponge was demonstrated with India ink perfusion. The sponge degraded after several months. This study suggests that cell-based tissue engineering possesses the potential to regenerate alveolar-like structures, an important step towards our ultimate goal of lung regeneration.
Diesel exhaust particulate-induced activation of Stat3 requires activities of EGFR and Src in airway epithelial cells
Authors: Cao Dongsun , Tal Tamara L. , Graves Lee M. , Gilmour Ian , Linak William , Reed William , Bromberg Philip A. , Samet James M.
Published: October 2006

In vivo exposure to diesel exhaust particles (DEP) elicits acute inflammatory responses in the lung characterized by inflammatory cell influx and elevated expression of mediators such as cytokines and chemokines. Signal transducers and activators of transcription (STAT) proteins are a family of cytoplasmic transcription factors that are key transducers of signaling in response to cytokine and growth factor stimulation. One member of the STAT family, Stat3, has been implicated as a regulator of inflammation but has not been studied in regard to DEP exposure. The results of this study show that DEP induces Stat3 phosphorylation as early as 1 h following stimulation and that phosphorylated Stat3 translocates into the nucleus. Inhibition of epidermal growth factor receptor (EGFR) and Src activities by the inhibitors PD-153035 and PP2, respectively, abolished the activation of Stat3 by DEP, suggesting that Stat3 activation by DEP requires EGFR and Src kinase activation. The present study suggests that oxidative stress induced by DEP may play a critical role in activating EGFR signaling, as evidenced by the fact that pretreatment with antioxidant prevented the activation of EGFR and Stat3. These findings demonstrate that DEP inhalation can activate proinflammatory Stat3 signaling in vitro.
Prostaglandin E2inhibits collagen expression and proliferation in patient-derived normal lung fibroblasts via E prostanoid 2 receptor and cAMP signaling
Authors: Huang Steven , Wettlaufer Scott H. , Hogaboam Cory , Aronoff David M. , Peters-Golden Marc
Published: October 2006

Uncontrolled fibroblast activation is one of the hallmarks of fibrotic lung disease. Prostaglandin E2(PGE2) has been shown to inhibit fibroblast migration, proliferation, collagen deposition, and myofibroblast differentiation in the lung. Understanding the mechanisms for these effects may provide insight into the pathogenesis of fibrotic lung disease. Previous work has focused on commercially available fibroblast cell lines derived from tissue whose precise origin and histopathology are often unknown. Here, we sought to define the mechanism of PGE2inhibition in patient-derived fibroblasts from peripheral lung verified to be histologically normal. Fibroblasts were grown from explants of resected lung, and proliferation and collagen I expression was determined following treatment with PGE2or modulators of its receptors and downstream signaling components. PGE2inhibited fibroblast proliferation by 33% and collagen I expression by 62%. PGE2resulted in a 15-fold increase in intracellular cAMP; other cAMP-elevating agents inhibited collagen I in a manner similar to PGE2. These effects were reproduced by butaprost, a PGE2analog selective for the cAMP-coupled E prostanoid (EP) 2 receptor, but not by selective EP3 or EP4 agonists. Fibroblasts expressed both major cAMP effectors, protein kinase A (PKA) and exchange protein activated by cAMP-1 (Epac-1), but only a selective PKA agonist was able to appreciably inhibit collagen I expression. Treatment with okadaic acid, a phosphatase inhibitor, potentiated the effects of PGE2. Our data indicate that PGE2inhibits fibroblast activation in primary lung fibroblasts via binding of EP2 receptor and production of cAMP; inhibition of collagen I proceeds via activation of PKA.
Epithelial repair is inhibited by an α1,6-fucose binding lectin
Authors: Adam Elizabeth C. , Holgate Stephen T. , Lackie Peter M.
Published: October 2006

The effective repair of damage to the airway epithelium is essential to maintain the ability to exclude airborne particulates and protect against potential pathogens. Carbohydrates on the cell surface have an important role in cell-cell and cell substrate interactions. Using a model of repair with airway epithelial-derived cells of the 16HBE 14o−cell line, we have examined the effect of the Aleuria aurantia lectin (AAL), which binds very selectively to α1,6-linked fucose residues. Addition of unconjugated or FITC-labeled AAL reduced the rate of epithelial repair to approximately one-third of control values as measured by image analysis while cell viability was maintained. Pulse labeling with AAL-FITC for 30 min followed by incubation in AAL-free medium caused similar inhibition of repair but could be reversed by addition of fucose up to 7 h after AAL removal. By confocal microscopy, AAL binding was found to be on the apical, but not basolateral, surfaces of cells, and internalization of the labeled lectin was seen. Preincubation of the lectin with fucose prevented this effect. Ulex europeaus I lectin, which is also fucose specific, resulted in similar binding to the cells and internalization, but it did not affect the speed of the repair process. We conclude that α1,6-fucose binding sites play an important role in epithelial repair. Better understanding of this process will provide a deeper insight into the crucial mechanisms of epithelial repair.
A Phase I Study ofIn vitroExpanded Natural Killer T Cells in Patients with Advanced and Recurrent Non–Small Cell Lung Cancer
Authors: Motohashi Shinichiro , Ishikawa Aki , Ishikawa Eiichi , Otsuji Mizuto , Iizasa Toshihiko , Hanaoka Hideki , Shimizu Naomi , Horiguchi Shigetoshi , Okamoto Yoshitaka , Fujii Shin-ichiro , Taniguchi Masaru , Fujisawa Takehiko , Nakayama Toshinori
Published: October 2006

Purpose: Human Vα24 natural killer T (Vα24 NKT) cells bearing an invariant Vα24JαQ antigen receptor are activated by a glicolipid ligand α-galactosylceramide (αGalCer; KRN7000) in a CD1d-dependent manner. The human Vα24 NKT cells activated with αGalCer and interleukin-2 have been shown to produce large amounts of cytokines, such as IFN-γ, and also exerting a potent killing activity against various tumor cell lines. We did a phase I study with autologous activated Vα24 NKT cell therapy.

Experimental Design: Patients with advanced or recurrent non–small cell lung cancer received i.v. injections of activated Vα24 NKT cells (level 1: 1 × 107/m2 and level 2: 5 × 107/m2) to test the safety, feasibility, and clinical response of this therapeutic strategy. Immunomonitoring was also done in all cases.

Results: Six patients were enrolled in this study. No severe adverse events were observed during this study in any patients. After the first and second injection of activated Vα24 NKT cells, an increased number of peripheral blood Vα24 NKT cells was observed in two of three cases receiving a level 2 dose of activated Vα24 NKT cells. The number of IFN-γ-producing cells in peripheral blood mononuclear cells increased after the administration of activated Vα24 NKT cells in all three cases receiving the level 2 dose. No patient was found to meet the criteria for either a partial or a complete response.

Conclusions: The clinical trial with activated Vα24 NKT cell administration was well tolerated and carried out safely with minor adverse events even in patients with advanced diseases.
Clinicopathological Features of Patients with Biochemical Recurrence after Radical Prostatectomy without Progressive Rise in Serum Prostate-Specific Antigen
Authors: Miyake Hideaki , Hara Isao , Kurahashi Toshifumi , Muramaki Mototsugu , Yamanaka Kazuki , Inoue Taka-aki , Fujisawa Masato
Published: October 2006

Introduction: The objective of this study was to characterize clinicopathological features of patients with biochemical recurrence after radical prostatectomy who did not exhibit a progressive rise in serum prostate-specific antigen (PSA) during the follow-up period. Materials and Methods: We analyzed data from 162 consecutive patients who underwent radical prostatectomy for clinically organ-confined prostate cancer without neoadjuvant hormonal therapy and were followed postoperatively for at least 1 year. The serum PSA value was measured using an ultrasensitive PSA assay system (Roche Diagnostics, Mannheim, Germany), and biochemical recurrence was defined as a serum PSA of ≧0.1 ng/ml. Results: A total of 32 patients (19.8%) were diagnosed as having biochemical recurrence. Among these patients, we identified 10 (31.3%) with a serum PSA >0.1 ng/ml who had not shown PSA or clinical progression during a median follow-up of 34 months after radical prostatectomy. In these 10 patients, the median time to biochemical recurrence was 17 months, the median PSA velocity after biochemical recurrence was 0.034 ng/ml/year, and there was no patient whose serum PSA value became >0.4 ng/ml. There were no clinicopathological parameters except for PSA velocity that were significantly associated with the features of these 10 patients. Conclusion: Because of the presence of a subset of patients with biochemical recurrence after radical prostatectomy who will not show a progressive increase in serum PSA value, the indication for adjuvant therapy for such patients should be cautiously determined considering several factors, such as PSA kinetics.
Upper Urothelial Tumors in Emigrants from Balkan Endemic Nephropathy Areas in Serbia
Authors: Nikolic Jovan , Djokic Milan , Ignjatovic Ivan , Stefanovic Vladisav
Published: October 2006

Aim: The aim of the study was to investigate upper urothelial tumors (UUT) in emigrants from Balkan endemic nephropathy (BEN) areas in Serbia and compare them with UUT from both endemic and nonendemic areas. Materials and Methods: A total of 1,121 patients from the state cancer database, between 1960 and 1998, were investigated. Sixty of them were emigrants from BEN areas. Results: UUT in emigrants from BEN areas occurred after 21.7 ± 9.9 years (median 20) spent in a rural environment. The time spent outside of the BEN regions was 33.2 ± 12.8 years (median 31, range 10–72). Age at surgery was 55 years (range 31–89). In emigrants from BEN areas, there was a significant association of other diseases with UUT: renal failure in 63%, bladder tumors in 23.3% and bilateralism in 6.7% of the patients. Bilateralism was statistically more frequent in emigrants from BEN areas (p = 0.04), as were low-grade tumors (p = 0.03). There was no statistical difference in tumor stage between patients from BEN areas and from outside of them. Relatives of the emigrants from BEN areas were also affected by BEN, UUT and both of them (33%). Conclusions: It is concluded that hereditary as well as environmental factors are important for the expression and evolution of the disease. An early period of life spent in the endemic region seems important for the later development of UUT in emigrants from BEN regions. Different time spans spent in the endemic region have no effect on the age of appearance of UUT.
Effects of Propylthiouracil on Testicular Tissue in Undescended Testes of Newborn Rats
Authors: Karabulut Ramazan , Türkyılmaz Zafer , Sönmez Kaan , Demiroğulları Billur , Özen İ. Onur , Poyraz Aylar , Başaklar A. Can , Kale Nuri
Published: October 2006

Aim: The most important goal in the treatment of cryptorchidism is to preserve the potential for fertility. This experimental study was performed to investigate the effect of propylthiouracil (PTU) on the undescended testes (UTs) of newborn rats. Materials and Methods: The experimental cryptorchidism model in newborn male rats consisted of 4 groups. The groups A (control) and B (PTU) underwent no surgical intervention, whereas in groups C (UT only) and D (treatment) UTs were produced by dissecting and suturing the future right scrotal area. In groups D and B, 0.1% (w/v) PTU was added to the drinking water of mother rats between 2 and 24 days. At the end of the 90th day rat body weights, testicular weights, Johnsen tubular biopsy scores (JTBSs), seminiferous tubule diameters (STDs), testosterone, and thyroid hormone levels were measured. Mann-Whitney U test was used for statistical analysis. Results: Mean testicular weight was similar between groups A, B and D, and statistically lowest in group C. Mean body weight was statistically higher in groups A and C compared with groups B and D. Mean testosterone levels showed no statistical difference between the groups. Mean JTBSs were statistically higher in groups A and B compared with groups C and D. The value in treatment group D was statistically higher compared to group C (p < 0.05). Mean STDs were statistically lowest in group C compared to other groups (p < 0.05). No difference was found between groups A, B, and D (p > 0.05). Both the mean free triiodothyronine and free thyroxine values between groups A and C and between groups B and D were similar. The values in groups A and C were statistically higher than those of groups B and D (p < 0.05). Conclusion: PTU-induced transient hypothyroidism in the newborn rat UT model shows protective effects on testicular growth parameters.
Anti-Tumor Necrosis Factor Alpha-Induced Psoriasiform Eruptions: Three Further Cases and Current Overview
Authors: Pirard D. , Arco D. , Debrouckere V. , Heenen M.
Published: October 2006

The increasing use of anti-TNF-α agents led to a better knowledge of their side effects. Among the cutaneous reactions, psoriasiform eruptions are increasingly described. We encountered 3 further psoriasiform eruptions during anti-TNF-α treatment for rheumatologic conditions and review the literature in order to identify the common characteristics of these cases. We found 30 case reports by using a comprehensive search of the 1966–2005 Medline database with a wild variety concerning the psoriasis type of eruption, the anti-TNF-α agent, the treatment duration and the presence or absence of a personal or familial history of psoriasis. We conclude that a psoriasiform eruption during anti-TNF-α treat- ment seems to be a class effect, without any as yet known identified predisposing factors, but it is more often self-limited and does not require treatment discontinuation.
Detection of Melanoma Relapse: First Comparative Analysis on Imaging Techniques versus S100 Protein
Authors: Beyeler Mirjam , Waldispühl Severa , Strobel Klaus , Joller-Jemelka Helen I. , Burg Günter , Dummer Reinhard
Published: October 2006

Background: Early detection of melanoma recurrence is essential for the patient’s prognosis. The serum S100 level may be a useful tool to detect relapse early. Objective: To compare the efficacy of imaging techniques and serum S100 in the early detection of melanoma progression. This is the first report of a comparison of a serum marker with an imaging tool in the follow-up of melanoma patients. Methods: From 1992 to 2003, we screened 192 patients suffering from melanoma recurrence after a disease-free interval. Of those, 127 patients were identified whose S100 levels had been assessed parallel to imaging procedures. Results: Serum S100 was elevated in 37% of patients at the time of relapse. In stage III, 32% of the patients had elevated S100 levels whereas in case of progression to stage IV, 48% of the patients presented with increased S100. In 5.5% of patients, S100 was the first indicator of disease progression. Imaging procedures lead to detection of melanoma recurrence in 26.8%. Conclusion: A rising level of serum S100 is a specific and sensitive marker of melanoma progression.
Meta-Analysis of 5% Imiquimod and 0.5% Podophyllotoxin in the Treatment of Condylomata Acuminata
Authors: Yan Jun , Chen Sheng-Li , Wang Hai-Na , Wu Tai-Xiang
Published: October 2006

Background: Genital warts are a common sexually transmitted disease caused by human papillomaviruses. Podophyllotoxin 0.5%, approved for patient self-administration, has been used most extensively in the treatment of genital warts. Imiquimod, a novel immune response modifier capable of inducing interferon-α and a variety of cytokines, has been examined as a potential treatment for genital warts. But 0.5% podophyllotoxin and 5% imiquimod have not been compared in any extensive and formal studies, although they are the common topical agents for genital warts. Objective: To evaluate the efficacy and safety of topical 5% imiquimod and 0.5% podophyllotoxin in the treatment of genital warts. Methods: We searched Medline (1966 to June 2005), Embase (1974 to June 2005) and the Cochrane Controlled Trials Register (issue 3, 2005). Randomized controlled trials of 5% imiquimod or 0.5% podophyllotoxin in the treatment of genital warts were collected. Two reviewers extracted the data and independently assessed the quality of the included medical literature. Then, meta-analysis was conducted. Results: Twelve studies including 3 placebo-controlled trials of imiquimod and 9 placebo-controlled trials of podophyllotoxin were included. The clinical cure rates of imiquimod and podophyllotoxin were 50.34 and 56.41%, respectively, without statistically significant differences between the two (p > 0.05). A combined analysis of the 3 studies on imiquimod showed a statistically significant difference to the placebo group [pooled odds ratio (OR) 11.65, 95% confidence interval (CI) 6.05–22.44], as did a combined analysis of the 9 studies on podophyllotoxin (pooled OR 16.70, 95% CI 7.06–39.48). The most common adverse events of imiquimod were erythema, erosion, excoriation, itching and burning; those of podophyllotoxin were burning, pain, erosion, itching and inflammation. Conclusion: Imiquimod and podophyllotoxin possess similar curative effects on condylomata acuminata but podophyllotoxin has more serious adverse effects.
Antimicrobial Silk Clothing in the Treatment of Atopic Dermatitis Proves Comparable to Topical Corticosteroid Treatment
Authors: Senti G. , Steinmann L.S. , Fischer B. , Kurmann R. , Storni T. , Johansen P. , Schmid-Grendelmeier P. , Wüthrich B. , Kündig T.M.
Published: October 2006

Background: Atopic dermatitis (AD) is aggravated by mechanical irritation and bacterial colonization. Objective: This study compared the efficacy of an antimicrobial silk fabric (DermaSilk®) with that of a topical corticosteroid in the treatment of AD. Methods: Fifteen children were enrolled and wore a dress, where the left side was made of DermaSilk and the right side was made of cotton. The right arm and leg were treated daily with the corticosteroid mometasone for 7 days. The treatment efficacy was measured with a modified EASI (Eczema Area and Severity Index) and with an assessment by the patients/parents and by a physician. All patients were evaluated at baseline, as well as 7 and 21 days after the initial examination. Results: All parameters showed that, irrespective of the treatment, there was a significant decrease of eczema after 7 days. No significant difference between DermaSilk-treated and corticosteroid-treated skin could be observed. Conclusion: DermaSilk showed potential to become an effective treatment of AD.
Creeping Hair: An Isolated Hair Burrowing in the Uppermost Dermis Resembling Larva Migrans
Authors: Sakai Rie , Higashi Kushio , Ohta Miyuki , Sugimoto Yasushi , Ikoma Yukiko , Horiguchi Yuji
Published: October 2006

A 55-year-old Japanese male presented with a slowly moving linear erythema that looked like an eruption of creeping disease, or cutaneous larva migrans. The eruption extended linearly along Langer’s line of the lateral side of the abdomen to the lower back, leaving wave-like erythema. In the top third of the erythematous eruption, close examination demonstrated a black thin line, which was revealed to be a hair shaft by a shallow incision of the skin. After removal of the hair, the eruption diminished immediately, leaving a slight pigmentation. An ingrown pubic hair seemed to have migrated with the lower end forward along Langer’s line, because of the arrangement of hair cuticle and the force of body motion. Linearly moving erythematous eruptions that look like that of larva migrans should be differentiated from creeping hair by close examination detecting burrowing hair.
Adaptation to Distorted Frequency-to-Place Maps: Implications of Simulations in Normal Listeners for Cochlear Implants and Electroacoustic Stimulation
Authors: Faulkner Andrew
Published: October 2006

The ideal cochlear implant electrode array positioning enables stimulation over a range of cochlear positions whose characteristic frequencies cover the frequency range of speech and match the speech processor filter frequencies. However, the electrode positions achieved in practice may not meet this specification. Users of conventional monaural cochlear implants seem able to perceptually adapt to a mismatch of speech processor filters to electrode positions. In electroacoustic stimulation, it is important to consider possible inconsistencies between acoustic and electrical frequency-to-place mapping. Two simulation studies are outlined that address normal listeners’ ability to perceive speech presented through distorted frequency maps. The first presented a map that is spectrally warped around a 10-mm medial cochlear area. Listeners were able to adapt to this map after a few hours of training. The second study presented a binaural mapping in which one ear was subject to a 6-mm basalward shift. Here listeners were unable to learn to integrate speech information across the two mismatched ears, rather they seem to learn to ignore the shifted information. Frequency-to-place mapping is likely to be an important factor in the successful use of a combination of electrical and acoustic hearing.
Inhibition of Restenosis Development after Mechanical Injury: A New Field of Application for Malononitrilamides?
Authors: Schrepfer Sonja , Deuse Tobias , Sultan Karim R. , Haddad Munif , Böger Rainer , Münzel Thomas , Schäfer Hansjörg , Pelletier Marc P. , Robbins Robert C. , Reichenspurner Hermann
Published: October 2006

Objective: To investigate the efficacy of the malononitrilamide FK778 to prevent vascular smooth muscle cell (SMC) migration/proliferation, and vascular fibrosis, the key events in restenosis development using in vivo and in vitro studies. Background: Since the high rate of restenosis after percutaneous transluminal coronary angioplasty limited its long-term success, the implementation of locally delivered antiproliferative/immunosuppressive agents became advantageous. Methods: Rats underwent balloon denudation of the abdominal aorta and received sirolimus, tacrolimus, or FK778 for 28 days in varying doses. Aortas were harvested for histologic evaluation, profibrotic gene expression, and organ chamber studies. Antifibrotic, antiproliferative and antimigratory effects of the immunosuppressants were further evaluated in vitro. Results: Histology of untreated animals revealed marked intimal hyperplasia with moderate luminal obliteration. Neointima formation was dose-dependently attenuated by all three agents with FK778 and sirolimus being most efficacious. Organ chamber relaxation studies showed a leftward shift of the nitroglycerin and the acetylcholine dose-responses in all treatment groups, indicating diminished endothelial dysfunction. In vivo, only FK778 treatment revealed a significant downregulation of the TGF-β/vasorin system which could be explained by upregulation of the TGF-β-inhibitory mediator SMAD7. In vitro, FK778 showed most potent antiproliferative and antimigratory effects on SMC compared with sirolimus and tacrolimus. Only the antiproliferative effect of FK778 was due to pyrimidine synthesis blockade and could be reversed by uridine supplementation. Conclusions: The malononitrilamide FK778 proved highly efficacious against restenosis development by targeting two major components of intimal hyperplasia: SMC proliferation/migration and vascular fibrosis. Thus, the introduction of malononitrilamide-loaded stents may be a promising effort for future strategies.
The Quail Mesonephros: A New Model for Renal Senescence?
Authors: Nacher Víctor , Carretero Ana , Navarro Marc , Armengol Clara , Llombart Cristina , Rodríguez Alfonso , Herrero-Fresneda Immaculada , Ayuso Eduard , Ruberte Jesús
Published: October 2006

Background/Aims: Renal senescence during normal aging is associated with specific vascular alterations and tissue degeneration. Although the degenerative program executed during embryonic kidney development is known to include vascular alterations, studies yet have to examine whether it involves replicative senescence. In this study, we assessed the potential of the quail mesonephros, a transitory embryonic kidney, as a model of human renal senescence. Methods: Quail embryos with developing or degenerating mesonephros were studied on day 6 or day 11 of incubation, respectively. Senescence-associated β-galactosidase activity, a marker of replicative senescence, was examined on whole mounts and sections. Senescent vascular characterization was performed by the scanning electron-microscopic analysis of vascular corrosion casts. Results: Senescence-associated β-galactosidase activity was found only in old mesonephros. Moreover, at 11 days of incubation glomerular capillaries showed discontinuities and were thinner and more tortuous than those observed at 6 days, characteristics also reported for the aging human kidney. Conclusion: The degenerating quail mesonephros is a potential model of renal senescence, showing biochemical and morphological characteristics of the aging human kidney.
Mutation and Polymorphism Analyses of INSL3 and LGR8/GREAT in 62 Japanese Patients with Cryptorchidism
Authors: Yamazawa Kazuki , Wada Yuka , Sasagawa Isoji , Aoki Katsuya , Ueoka Katsuhiko , Ogata Tsutomu
Published: October 2006

Background/Aims: Although insulin-like factor 3 (INSL3) and its receptor leucine-rich repeat-containing G protein-coupled receptor 8/G protein-coupled receptor affecting testis descent (LGR8/GREAT) are essential for the gubernacular development, mutations of INSL3 and LGR8/GREAT are infrequent in patients with cryptorchidism (CO), and there is no report documenting a positive association of CO with a polymorphism in INSL3 or LGR8/GREAT. Here, we further examined the relevance of INSL3 and LGR8/GREAT mutations and polymorphisms to the development of CO. Methods: Sixty-two Japanese CO patients and 60 fertile males were studied. INSL3 was analyzed by direct sequencing and restriction enzyme digestion, and LGR8/GREAT was examined by denaturing high-performance liquid chromatography followed by direct sequencing for exons with abnormal chromatogram patterns. Results: No definitive mutation was identified in both genes. Six polymorphisms were detected in INSL3 or LGR8/GREAT and Thr/Thr genotype of Ala60Thr polymorphism in INSL3 was strongly associated with CO (p = 0.0024, odds ratio = 5.3, 95% confidence interval = 1.7–17). Conclusion: The results, in conjunction with the previous data, suggest that mutations of INSL3 and LGR8/GREAT remain rare, and that the Thr/Thr genotype of Ala60Thr polymorphism in INSL3 may constitute a susceptibility factor for the development of CO.
Tensile Residual Strains on the Elastic Lamellae along the Porcine Thoracic Aorta
Authors: Lillie M.A. , Gosline J.M.
Published: October 2006

Aims: This study determines the residual strains on the elastic lamellae in the porcine thoracic aorta to understand the distribution of strains amongst the components of the vascular wall. Methods: Residual strains in aortic rings were released by cutting and purifying the elastin. Strains were calculated from lamellar contour lengths based on lamellar waviness and from mechanical tests. Results: On the release of residual strains, waviness decreased 2–7%, the inner lamellae shortened 2.1 ± 0.6% and the outer lamellae shortened 7.1 ± 0.4% (p < 0.001), indicating that all lamellar elastin was under tension in fresh aortic tissue. Lamellar shortening was 3% greater in the distal than in the proximal tissue. Mechanical tests confirmed the morphological results and showed that the residual strains in fresh tissue required both the elastic tissue and the vascular smooth muscle. Tensile residual strains averaging 1.0% remained in the uncut elastin rings. Conclusion: When waviness is considered, the residual strains on the individual wall components can differ from the surface residual strains based only on the ring perimeter. The residual strains on the inner elastic lamellae are tensile, not compressive. The strain distribution amongst the individual components is non-uniform and not adequately understood to determine the physiological strains in the aortic wall.
Highlights in Cellular and Molecular Mechanisms of Allergic Diseases
Authors: Basinski T. , Ozdemir C. , Sackesen C. , Mantel P.-Y. , Barlan I. , Akdis M. , Jutel M. , Akdis C.A.
Published: October 2006

This year, the annual congress of the European Academy of Allergology and Clinical Immunology was held on 10–14 June in Vienna. More than 6,000 delegates, practicing bench or bedside work or both, gathered from over 50countries throughout the world. Health professionals, basic scientists and fellows in training could choose between a variety of activities in plenary, main, educational and workshop sessions, highlights of the past year, pros and cons, and oral abstract and poster sessions, and met with experts. A total of 1,713 abstracts, 31 symposia, and 54 workshops were presented, ranging from basic science to clinical trials and modern treatment of allergic diseases. Here, we summarize the highlights of cellular and molecular mechanisms of allergic disease.
Elevated Matrix Metalloproteinase-9 Associated With Stroke or Cardiovascular Death in Patients With Carotid Stenosis
Authors: Eldrup Nikolaj , Grønholdt Marie-Louise Moes , Sillesen Henrik , Nordestgaard Børge G.
Published: October 2006

Background—

Matrix metalloproteinase-9 could exhibit an important role in the destabilization of atherosclerotic carotid plaques. We hypothesized that in patients with carotid stenosis, elevated levels of plasma matrix metalloproteinase-9 are associated with ipsilateral stroke or cardiovascular death.

Methods and Results—

We followed up 207 patients with ≥50% carotid stenosis initially for a mean of 4.4 years, during which time 53 patients developed ipsilateral stroke or died of cardiovascular causes. The cumulative incidence of ipsilateral stroke or cardiovascular death was higher in those with matrix metalloproteinase-9 above versus below the median of 41.9 ng/mL (log-rank
P
=0.002). Matrix metalloproteinase-9 above versus below the median had a hazard ratio for ipsilateral stroke or cardiovascular death of 1.9 (95% confidence interval [CI], 1.1 to 3.5); during extended follow-up, this remained significant until 10 years. The absolute risk of ipsilateral stroke or cardiovascular death at 4.4 years was 34% and 17% in those with matrix metalloproteinase-9 above and below the median, respectively. Elevated matrix metalloproteinase-9 and an echolucent plaque on B-mode ultrasound versus a low matrix metalloproteinase-9 and an echorich plaque had a hazard ratio for ipsilateral stroke or cardiovascular death of 4.4 (95% CI, 1.8 to 11.1) and for ipsilateral stroke of 3.3 (95% CI, 1.1 to 9.7).

Conclusions—

Elevated levels of matrix metalloproteinase-9 in patients with ≥50% carotid stenosis were associated with a 2-fold risk of ipsilateral stroke or cardiovascular death. Combining elevated matrix metalloproteinase-9 and plaque echolucency was associated with a 4-fold risk for ipsilateral stroke or cardiovascular death and a 3-fold risk for ipsilateral stroke.
Mothers, Wives, and Workers
Authors: Jordan Jason
Published: October 2006

Feminist criticism has uncovered significant differences in the approach of welfare states to women’s employment and the family not captured by more mainstream, class-based approaches. At the same time, a coherent explanation for gendered variation has been slow to develop. Exploring the French, German, and Swedish cases, this article develops a theory of welfare-state development that links the welfare state’s approach to women and the family to the state’s response to labor-market conditions during crucial periods of labor shortage. These three cases suggest a trade-off between the economy’s dependence on immigrant labor and the welfare state’s willingness to adapt to the specific interests of working mothers. This suggests a link between seemingly unrelated differences in immigration policy and the state’s support for working mothers.
Adolescents’ Perceptions of Parental Goals, Practices, and Styles in Relation to Their Motivation and Achievement
Authors: Spera Christopher
Published: October 2006

The current study examines research questions proposed by an expanded version of Darling and Steinberg’s contextual model of parenting. Using a sample of 184 adolescents, the analyses indicated that adolescents’ perceptions of parental educational goals and values were related positively and significantly to their reports of parental school involvement and parental monitoring. In turn, adolescents’ perceptions of parental involvement in schoolwork were related positively and significantly to their interest in school, internal academic self-regulation, and goal pursuit. Parental styles moderated the relationship between parental practices and student grades, with parental involvement and monitoring most effective under child-centered parenting styles. The implications of the study results on the parental socialization of school achievement and motivation are considered.
Similarities in Children’s and Early Adolescents’ Perceptions of Friendship Qualities Across Development, Gender, and Friendship Qualities
Authors: Simpkins Sandra D. , Parke Ross D. , Flyr Mary L. , Wild Margaret N.
Published: October 2006

Similarities between adolescents are often the cornerstone of a friendship; yet researchers know little about the similarities in friends’ perceptions of the relationship. In the current study, the authors examine similarities in friends’ perceived friendship qualities during the transition into early adolescence (n = 77 third graders, 110 fourth graders, 86 fifth graders, 81 sixth graders). The same study participants were assessed every year, but different self-selected friends of the study participants were assessed each year. Youth’s perceptions of conflict, help, disclosure, companionship, conflict resolution, and validation were measured with the Friendship Quality Questionnaire. Findings suggest that the study participants’ and their friends’ perceptions of friendship qualities were moderately similar. These similarities did not typically differ across development, gender, or the type of friendship quality. The importance of friendships for development during the transition into early adolescence is emphasized.
Stress in the Lives of College Women: “Lots to Do and Not Much Time”
Authors: Larson Elizabeth A.
Published: October 2006

This study examined how activity and engagement qualities were related to stress. Experience sampling using e-mail pagers collected simultaneous ratings of stress and qualities of activity for 30 college women during 14 days. Surveys included narrative questions about activity types, feelings, and experience and Likert-type scales rating activity qualities and stress. A total of 2,327 surveys were analyzed using descriptive, configural frequency, and qualitative analyses. Students rated 34% of all events as stressful. Most were academic tasks (41%), overrepresented compared to overall frequency. Finding an activity to be high in complexity was most likely to lead to perceptions of increased stress for students; however, there were also social circumstances and low complexity activities in which stress was experienced.