bluuebunny/crossref_metadata_2025 huggingface dataset:
Curing of DGEBA epoxy resin by low generation amino‐group‐terminated dendrimers
Authors: Xu Dong‐Mei , Zhang Ke‐Da , Zhu Xiu‐Lin
Published: June 2006

Low generation amino‐group‐terminated poly(ester‐amine) dendrimers PEA1.0 (NH2)3 and PEA1.5 (NH2)8, and poly(amido‐amine) dendrimer PAMAM1.0 (NH2)4 were used as diglycidyl ether of bisphenol A (DGEBA) epoxy resin hardeners. Thermal behavior and curing kinetics of dendrimer/DGEBA systems were investigated by means of differential scanning calorimetry (DSC). Compared with ethylene diamine (EDA)/DGEBA system, the dendrimer/DGEBA systems gradually liberated heat in two stages during the curing process, and the total heat liberated was less. Apparent activation energy and curing reaction rate constants for dendrimer and EDA/DGEBA systems were estimated. Thermal stabilities and mechanical properties of cured thermosetting systems were examined as well. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3902–3906, 2006
Antigenic targets and pathogenicity of anti–aortic endothelial cell antibodies in Takayasu arteritis
Authors: Chauhan Sunil Kumar , Tripathy Naresh Kumar , Nityanand Soniya
Published: June 2006

Objective

Anti–endothelial cell antibodies are considered to have an important role in the pathogenesis of Takayasu arteritis (TA). Previously, these antibodies were detected using human umbilical vein endothelial cells, which do not completely represent the antigenicity/functions of aortic endothelial cells, the specific targets in TA. To delineate the precise role of antigenic targets, we investigated such targets as well as the pathogenic mechanism of antibodies directed against aortic endothelial cells (AAECAs) in TA.

Methods

AAECAs were detected using a cellular enzyme‐linked immunosorbent assay (ELISA), and their antigenic targets were detected by immunoblotting. AAECA‐mediated induction of endothelial adhesion molecule expression and cytokine production was studied by ELISA, and apoptosis was studied using the TUNEL method.

Results

AAECAs were detected in 86% of patients with TA and in 9% of controls. Sera obtained from AAECA‐positive patients with TA recognized a total of 9 antigens ranging in size from 18 kd to 200 kd, of which the 60–65‐kd triplet was recognized most often. The aortic endothelial cell reactivity of Hsp60‐absorbed sera was reduced by ∼50% as compared with that of unabsorbed sera (mean ± SD 0.488 ± 0.08 versus 0.838 ± 0.116). Sera from AAECA‐positive patients with TA, compared with sera from AAECA‐negative patients with TA and that from controls, induced increased expression of E‐selectin (mean ± SD 0.833 ± 0.063 versus 0.217 ± 0.081 and 0.221 ± 0.101 optical density [OD] units, respectively) and vascular cell adhesion molecule 1 (0.620 ± 0.144 versus 0.165 ± 0.005 and 0.177 ± 0.055 OD units, respectively) and increased production of interleukin‐4 (IL‐4) (6.8 ± 2.4 versus 1.2 ± 1.6 and 1.3 ± 2.5 pg/ml, respectively), IL‐6 (24.3 ± 2.4 versus 4.5 ± 6.7 and 5.9 ± 5.1 pg/ml, respectively), and IL‐8 (36.8 ± 10.3 versus 10.1 ± 6.7 and 7.8 ± 2.1 pg/ml, respectively). Sera from AAECA‐positive patients with TA induced 29 ± 6% (median ± SEM) apoptosis of aortic endothelial cells.

Conclusion

Our data show that the AAECAs that are present in patients with TA are directed mainly against 60–65‐kd antigen(s) and may cause vascular dysfunction by inducing expression of endothelial adhesion molecules, cytokine production, and apoptosis.
Hemorheologic profile in systemic sclerosis: Role of NOS3 −786T>C and 894G>T polymorphisms in modulating both the hemorheologic parameters and the susceptibility to the disease
Authors: Fatini Cinzia , Mannini Lucia , Sticchi Elena , Rogai Veronica , Guiducci Serena , Conforti Maria Letizia , Cinelli Marina , Pignone Alberto Moggi , Bolli Paola , Abbate Rosanna , Cerinic Marco Matucci
Published: June 2006

Objective

Microvascular disorders are relevant in systemic sclerosis (SSc). Hyperviscosity, due to alterations of blood cells and plasma components, may play a role in the pathogenesis of microcirculatory disorders. An impaired availability of nitric oxide, related to polymorphisms in NOS3, the gene for endothelial cell nitric oxide synthase, might influence erythrocyte deformability. We undertook this study to investigate the hemorheologic profile in SSc and the role of NOS3 polymorphisms in modulating the hemorheologic status of SSc patients.

Methods

We studied 113 consecutive SSc patients (75 with limited cutaneous SSc [lcSSc] and 38 with diffuse cutaneous SSc [dcSSc]) and 113 healthy controls. The hemorheologic profile was obtained by assessing whole blood viscosity (WBV; at shear rates of 0.512 and 94.5 seconds−1), plasma viscosity (PLV; at a shear rate of 94.5 seconds−1), and erythrocyte deformability index (DI). We determined NOS3 polymorphisms by molecular analysis.

Results

A marked alteration of hemorheologic parameters was found both in patients with lcSSc and in those with dcSSc compared with controls (P < 0.0001). In multivariate analysis, rheologic variables were significantly associated with the disease (for WBV at a shear rate of 94.5 seconds−1, odds ratio [OR] 5.4, 95% confidence interval [95% CI] 1.4–19.9, P = 0.01; for PLV, OR 2.8, 95% CI 1.2–6.5, P = 0.01; for DI, OR 3.9, 95% CI 1.4–10.8, P = 0.007), and NOS3 −786C and 894T alleles significantly affected the DI (for −786C allele, OR 2.3, 95% CI 1.01–5.4, P = 0.04; for 894T allele, OR 2.2, 95% CI 1.01–4.8, P = 0.04). The simultaneous presence of the −786C and 894T alleles represented a susceptibility factor for SSc (OR 2.8, 95% CI 1.4–5.7, P = 0.004).

Conclusion

Our findings document an altered rheologic profile in SSc and demonstrate a relationship between this alteration and NOS3 polymorphisms, thus shedding light on a potential novel mechanism influencing the microcirculation in this disease.
Salivary gland epithelial cells: A new source of the immunoregulatory hormone adiponectin
Authors: Katsiougiannis Stergios , Kapsogeorgou Efstathia K. , Manoussakis Menelaos N. , Skopouli Fotini N.
Published: June 2006

Objective

Adiponectin is an adipocytokine that displays insulin‐sensitizing and immunoregulatory properties. Adipocyte development in association with fibrosis is frequently detected in primary Sjögren's syndrome lesions, connoting a healing process. The aim of this study was to examine the expression of adiponectin in minor salivary gland biopsy specimens obtained from patients with primary SS and controls.

Methods

The expression of adiponectin in minor salivary gland biopsy specimens and in long‐term–cultured non‐neoplastic salivary gland epithelial cell (SGEC) lines obtained from patients with primary SS and control subjects was examined, using immunohistochemistry and immunoblotting, respectively. The expression of adiponectin, adiponectin receptor 1 (AdipoR1), and AdipoR2 messenger RNA (mRNA) by SGECs was investigated by reverse transcription–polymerase chain reaction.

Results

Immunohistochemical analysis for adiponectin revealed positive staining of adipocytes from primary SS lesions as well as ductal epithelial cells from both patients with primary SS and controls. All of the SGEC lines tested were shown to express adiponectin, AdipoR1, and AdipoR2 mRNA, whereas adiponectin protein expression was detected by immunoblotting in SGECs from patients with primary SS but not in those from controls. The analysis of concentrated culture supernatants also revealed increased adiponectin expression by SGECs from patients with SS compared with controls.

Conclusion

Our findings provide novel evidence that adiponectin is produced by SGECs. The high constitutive expression of adiponectin by SGECs from patients with primary SS is likely attributable to aberrant activation of these cells. Although the significance of adiponectin expression remains unknown, it is possible that adiponectin functions in an autocrine manner, as suggested by concurrent expression of the relevant receptors.
Impaired salivary gland function in NOD mice: Association with changes in cytokine profile but not with histopathologic changes in the salivary gland
Authors: Jonsson Malin V. , Delaleu Nicolas , Brokstad Karl A. , Berggreen Ellen , Skarstein Kathrine
Published: June 2006

Objective

To characterize the chronologic disease course and possible interrelationships between salivary gland inflammation, hyposalivation, and cytokine levels in NOD mice, a model for Sjögren's syndrome (SS).

Methods

NOD mice of different ages were used to mimic different disease stages of SS. Histopathologic findings and rates of salivary secretion were compared between 8‐week‐old, 17‐week‐old, and 24‐week‐old female mice. In addition, 10 cytokines were analyzed in serum and saliva obtained from NOD and BALB/c mice.

Results

In NOD mice, the salivary flow rate did not change between 8 weeks and 17 weeks of age, while a significant decrease in the salivary flow rate occurred between 17 weeks and 24 weeks of age (P < 0.001). In contrast, significant histopathologic changes in the salivary glands occurred before 17 weeks of age. Chronic inflammatory cell infiltrates were characterized by T and B cell infiltration. Interestingly, in one‐third of the mice, proliferating cells were observed in the focal infiltrates. Significant changes in the levels of interleukin‐2 (IL‐2), IL‐5, and granulocyte–macrophage colony‐stimulating factor in serum, and in the levels of IL‐4 and tumor necrosis factor α (TNFα) in saliva occurred contemporarily with the decrease in salivary flow. Correlation analyses revealed a negative association between salivary secretion and the levels of IL‐4, interferon‐γ, and TNFα in saliva obtained from NOD mice, while the correlation with inflammatory changes in the glands was consistently weak.

Conclusion

Consistent with previous findings, our results indicate at least 2 phases of SS‐like disease in NOD mice. Hyposalivation was preceded by inflammatory changes in the salivary glands, whereas abrupt changes in secretion occurred without significant progression of inflammation. Changes in cytokine levels are an indication of the mechanisms involved in the adaptive immune response in the transition from early to overt disease.
Induction of apoptosis and fibrillin 1 expression in human dermal endothelial cells by scleroderma sera containing anti–endothelial cell antibodies
Authors: Ahmed S. Sohail , Tan Filemon K. , Arnett Frank C. , Jin Li , Geng Yong‐Jian
Published: June 2006

Objective

Sera from patients with scleroderma (systemic sclerosis [SSc]) contain anti–endothelial cell antibodies (AECAs) capable of inducing endothelial cell apoptosis. We sought to determine whether SSc sera containing anticentromere antibodies (ACAs) or anti–topoisomerase I antibodies (or, anti–Scl‐70 antibodies) contain subsets of AECAs that trigger distinct pathways of apoptosis and gene expression in normal adult human dermal endothelial cells (HDECs).

Methods

Adult HDECs were grown to subconfluence and treated with control or SSc patient sera. Apoptosis was investigated by differential interference contrast (DIC) microscopy, microarrays of proapoptotic gene expression, caspase 3 protease activity, and flow cytometry for phosphatidyl serine translocation.

Results

Flow cytometry and DIC microscopy demonstrated that HDECs exposed to SSc sera containing either SSc autoantibody underwent apoptosis at much higher levels than those treated with control sera. While unique gene expression profiles were induced in HDECs by stimulation with SSc sera containing the respective autoantibody, similar patterns of increased gene expression of transcripts for the proapoptotic protease caspase 3 as well as the SSc autoantigen fibrillin 1 were demonstrated. Caspase 3 gene expression correlated with increased protease activity, and targeted inhibition of this protease partly blocked SSc serum–induced apoptosis. Immunohistochemistry studies of serum‐stimulated HDECs demonstrated the aberrant expression of fibrillin 1 protein only in apoptotic endothelial cells treated with SSc sera containing AECAs.

Conclusion

There are distinct AECA subsets in the sera of patients with limited SSc (with ACAs) and diffuse SSc (with anti–Scl‐70) that induce unique patterns of HDEC gene expression in the setting of apoptosis associated with increased caspase 3 activity and the reexpression of endothelial cell fibrillin 1.
Prospective study of fetal DNA in serum and disease activity during pregnancy in women with inflammatory arthritis
Authors: Yan Zhen , Lambert Nathalie C. , ØStensen Monika , Adams Kristina M. , Guthrie Katherine A. , Nelson J. Lee
Published: June 2006

Objective

Rheumatoid arthritis (RA) usually improves during pregnancy and recurs postpartum. Fetal cells and cell‐free DNA reach the maternal circulation during normal pregnancy. The present study investigated dynamic changes in levels of fetal DNA in serum from women with RA and inflammatory arthritis during and after pregnancy to test the hypothesis that the levels of circulating fetal DNA correlate with arthritis improvement.

Methods

Twenty‐five pregnant patients were prospectively studied. A real‐time quantitative polymerase chain reaction panel targeting unshared, paternally transmitted HLA sequences, a Y chromosome–specific sequence, or an insertion sequence within the glutathione S‐transferase M1 gene was used to measure cell‐free fetal DNA. Results were expressed as fetal genomic equivalents per milliliter (gE/ml) of maternal serum. Physical examinations were conducted during and after pregnancy.

Results

Levels of fetal DNA in women with improvement in or remission of arthritis were higher than those in women with active disease, especially in the third trimester. Overall, an inverse relationship between serum fetal DNA levels and disease activity was observed (P < 0.001). Serum fetal DNA increased with advancing gestation, reaching median levels of 24 gE/ml (range 0–334), 61 gE/ml (range 0–689), and 199 gE/ml (range 0–2,576) in the first, second, and third trimesters, respectively, with fetal DNA clearance observed postpartum. Arthritis improvement was initially noted in the first trimester for most patients, increased further or was sustained with advancing gestation, and was active postpartum.

Conclusion

Changes in serum fetal DNA levels correlated with arthritis improvement during pregnancy and recurrence postpartum. Immunologic mechanisms by which pregnancy might modulate RA activity are described.
Increased extracellular levels of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 in minor salivary glands of patients with Sjögren's syndrome
Authors: Ek Monica , Popovic Karin , Erlandsson Harris Helena , Söderberg Nauclér Cecilia , Wahren‐Herlenius Marie
Published: June 2006

Objective

To investigate the expression of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 (HMGB‐1) in the salivary glands of patients with Sjögren's syndrome (SS) and patients with sicca symptoms.

Methods

Biopsy samples from the minor labial salivary glands of patients with SS, patients with sicca symptoms but no diagnosis of SS, and healthy controls were investigated. Expression of HMGB‐1, tumor necrosis factor (TNF), and interleukin‐1β (IL‐1β) was analyzed using immunohistochemical staining on consecutive cryosections.

Results

Increased expression of HMGB‐1 was observed among the large infiltrates of mononuclear cells found in biopsy samples from patients with SS, and the degree of extracellular HMGB‐1 was significantly higher in patients with SS compared with patients with sicca symptoms and with healthy controls (P < 0.05 and P < 0.01, respectively). Cellular expression of TNF was increased in patients with SS and in patients with sicca symptoms. In addition, the level of secreted TNF was significantly higher in patients with SS than in healthy controls (P < 0.05). Intracellular expression of IL‐1β was detected in all groups, while extracellular IL‐1β was observed almost exclusively among the infiltrating mononuclear cells of patients with SS.

Conclusion

The increased amount of extracellular HMGB‐1 observed in salivary glands of patients with SS indicates that HMGB‐1 is involved in the inflammatory process of the disease. This cytokine, along with TNF and IL‐1β, may form a proinflammatory loop that promotes the chronic features of the glandular inflammation in SS.
Evidence of a flip‐flop phenomenon in acamprosate pharmacokinetics: an in vivo study in rats
Authors: Zornoza T. , Cano‐Cebrián M. J. , Hipólito L. , Granero L. , Polache A.
Published: June 2006

The pharmacokinetics of acamprosate were examined in the rat after oral and intravenous administration in order to detect the possible presence of a flip‐flop phenomenon. Rats received 9.3 or 73.3 mg/kg of the drug as an intravenous bolus. The same doses were orally administered via gastric intubation. Plasma samples were taken from the jugular vein for determination of acamprosate concentration by liquid scintillation counting. The drug content was also quantified in urine and faeces. The acamprosate bioavailability was close to 20%, the amount recovered in the faeces being around 80% of the administered dose. The terminal slope of the oral plasma curve was significantly lower than that obtained after intravenous administration of the drug at both doses tested (p<2 × 10−6 in both cases). Moreover, the downward slope after oral administration (λ2=0.006 ± 0.001 min−1) practically coincided with the first‐order absorption rate constant, previously reported by us, obtained using an in situ rat gut technique. It is concluded that the acamprosate absorption rate is considerably slower than its elimination rate so that the drug exhibits flip‐flop pharmacokinetics after oral administration. The lower intrinsic first‐order absorption rate constant, ka, is responsible for this phenomenon. Copyright © 2006 John Wiley & Sons, Ltd.
Decreased levels of mucosal detoxification enzymes in the pouch of patients with familial adenomatous polyposis
Authors: Friederich P , Berkhout M , Roelofs H M J , van Goor H , van Krieken J H J M , Peters W H M , Nagengast F M
Published: June 2006

Background

Adenomas can develop in the pouch after colectomy with ileal pouch–anal anastomosis (IPAA) in patients with familial adenomatous polyposis (FAP). Glutathione S-transferases (GSTs) have a protective role in carcinogenesis. GST activity is much higher in the ileum than in the colon. The present study examined the hypothesis that the protective capacity of GSTs may be lowered as a result of colonic metaplasia of the ileal pouch.

Methods

Levels of GSTs, glutathione and cysteine, and the degree of inflammation and colonic metaplasia were quantified in biopsies from the pouch and afferent loop of 26 patients with FAP.

Results

GST enzyme activity, and levels of GST alpha, glutathione and cysteine in the pouch were significantly lower than those in the afferent loop (308 versus 398 nmol per min per mg protein (P < 0·001), 4604 versus 5286 ng per mg protein (P = 0·010), 27·1 versus 34·8 nmol per mg protein (P = 0·023) and 0 versus 4·8 nmol per mg protein (P = 0·009) respectively). No correlation was found between inflammation or colonic metaplasia of the pouch and GST enzyme activity in the pouch.

Conclusion

After IPAA, GST detoxification activity in the pouch is significantly lower than that in the afferent ileal loop, which may promote tumorigenesis.
Incidence and patterns of recurrence after resection for cure of colonic cancer in a well defined population
Authors: Manfredi S , Bouvier A M , Lepage C , Hatem C , Dancourt V , Faivre J
Published: June 2006

Background

The aim of this study was to determine the incidence and patterns of failure following potentially curative surgery of colonic cancer.

Methods

Data were obtained from the cancer registry of the Côte-d'Or (France). Data on 2657 patients who had resection for cure of colonic cancer between 1976 and 2000 were analysed. Local and distant failure rates were calculated using the actuarial method and multivariable analysis was performed using a Cox model.

Results

The 5-year cumulative rate was 12·8 per cent for local recurrence and 25·6 per cent for distant metastases. Five-year cumulative local recurrence rates were 4·9 per cent for stage I, 11·0 per cent for stage II and 23·5 per cent for stage III tumours (P < 0·001). The corresponding rates for distant metastases were 6·4, 21·4 and 48·0 per cent (P < 0·001). The 5-year cumulative rates for distant metastases were 31·7 per cent for the period 1976–1980 and 21·1 per cent for 1996–2000, and the local recurrence rates were 17·6 and 9·0 per cent respectively. The decreases in rates of local recurrence and distant metastases were significant in multivariable analysis. Cancer extension and presenting features were related to patterns of failure. Tumour location was significantly associated with risk of local recurrence, whereas age and gross features were associated with risk of distant metastasis.

Conclusion

Recurrence following resection of colonic cancer remains a substantial problem. Follow-up is of particular importance in the 3 years after surgery.
A meta-analysis comparing suprapubic and transurethral catheterization for bladder drainage after abdominal surgery
Authors: McPhail M J W , Abu-Hilal M , Johnson C D
Published: June 2006

Background

Although bladder drainage is widely used for general surgical patients undergoing laparotomy, there is little consensus on whether suprapubic or transurethral catheterization is better.

Method

A systematic database search was undertaken to find all studies of suprapubic catheterization. Randomized controlled trials were identified for inclusion. Endpoints for analysis were bacteriuria, patient satisfaction and recatheterization rates. A meta-analysis was performed using fixed-effect or random-effect models as appropriate, depending on heterogeneity.

Results

After abdominal surgery, transurethral catheterization is associated with significant bacteriuria (relative risk (RR) = 2·02, P < 0·001, 95 per cent confidence interval (c.i.) 1·34 to 3·04) and pain or discomfort (RR = 2·94, P = 0·004, 95 per cent c.i. 1·41 to 6·14). Recatheterization rates using the transurethral method were not increased significantly (RR = 1·97, P = 0·213, 95 per cent c.i. 0·68 to 5·74) with heterogeneity between studies.

Conclusion

The suprapubic route for bladder drainage in general surgery is more acceptable to patients and reduces microbiological morbidity.
Accessibility and functionality of the corporate web site: implications for sustainability reporting
Authors: Adams Carol A. , Frost Geoffrey R.
Published: June 2006

This paper explores the development of the corporate web site as a medium for sustainability reporting. Drawing upon survey data of corporate web sites in Australia, Germany and the United Kingdom and the experiences of six companies, it seeks to identify how issues of accessibility and functionality of the web site affect web based sustainability reporting. The study highlights the diversity of approaches to sustainability reporting on the internet and identifies a number of hurdles faced by managers responsible for sustainability reporting. Copyright © 2006 John Wiley & Sons, Ltd and ERP Environment.
Waste management, the challenges of the PFI and ‘sustainability reporting’
Authors: Ball Amanda , Broadbent Jane , Jarvis Tony
Published: June 2006

This paper examines the potential for ‘sustainability reporting’ in the context of waste management contracts let under the Private Finance Initiative (PFI). Whilst issues relating to the use of the PFI as a source of funding have been discussed at length, this paper takes the PFI as a ‘given’ in the context of the funding of waste management. The paper concentrates instead on the implications of using PFI and how, if it is to be used, it might be used constructively. There are two somewhat contradictory implications. The first is that the impetus to the funding of the creation of infrastructure assets has been a factor in driving the agenda towards chemico‐energy modernization, which may not be the ideal long‐term solution to creating sustainability. The second, however, is that PFI contracts create an opportunity to ensure that ‘sustainability reporting’ must be undertaken as a condition. Based on empirical work in the field, we argue this can provide the foundation for a discourse that might eventually lead to the promotion of a more embedded attitude to sustainability. Drawing on our fieldwork, we also identify possible sustainability reporting models and identify reasons why such approaches may be worthwhile in the context of waste management and other PFI contracts with significant environmental impact. Copyright © 2006 John Wiley & Sons, Ltd and ERP Environment.
From sustainable management to sustainable development: a longitudinal analysis of a leading New Zealand environmental reporter
Authors: Tregidga Helen , Milne Markus J.
Published: June 2006

This paper reports the results of an interpretive textual analysis of New Zealand's most consistent and arguably leading reporter on environmental and social impacts. Since 1995, Watercare Services Ltd, an Auckland‐based water utility, has been an award winning environmental reporter. The paper works with all of the organization's reports since 1993 through 2003 identifying and analysing the emergence and development of a sustainable development discourse. Focusing on the language and images used to construct meanings, and the context in which the reports emerged, the paper traces the organization's reporting developments. The paper illustrates how, in evolving from environmental reports to sustainable development reports, the organization has (re)constructed itself from one that sustainably manages resources to one that practises sustainable development. The implications of these developments are explored in terms of the literature on ‘capture’ and organizational change. Copyright © 2006 John Wiley & Sons, Ltd and ERP Environment.
A closed‐form expression for computing the sensitivity in second‐order bilinear calibration
Authors: Olivieri Alejandro C. , Faber Nicolaas (Klaas) M.
Published: June 2006

A general expression is derived for estimating the sensitivity of second‐order bilinear calibration models, particularly parallel factor analysis (PARAFAC) and bilinear least‐squares (BLLS), whether the second‐order advantage is required or not. In the latter case, the sensitivity is correctly estimated either if the advantage is achieved by processing the unknown sample together with the calibration set (PARAFAC), or by post‐calibration residual bilinearization (BLLS). The expression includes, as special cases, the sensitivity expressions already discussed by Messick, Kalivas and Lang (MKL) and by Ho, Christian and Davidson (HCD). The former one is the maximum achievable sensitivity in a given calibration situation, where all components are present in the calibration set of samples. The latter approach gives the lowest possible sensitivity, corresponding to only calibrating the analyte of interest, leaving the remaining components as uncalibrated constituents of the unknown sample. In intermediate situations, that is more than one calibrated analyte and presence of unexpected components in the unknown sample, only the present approach is able to provide a satisfactory sensitivity parameter, in close agreement with previously described Monte Carlo numerical simulations. Copyright © 2006 John Wiley & Sons, Ltd.
Randomized phase II study of carboplatin/gemcitabine versus vinorelbine/gemcitabine in patients with advanced nonsmall cell lung cancer
Authors: Yamamoto Nobuyuki , Nakagawa Kazuhiko , Uejima Hisao , Sugiura Takahiko , Takada Yoshiki , Negoro Shun‐ichi , Matsui Kaoru , Kashii Tatsuhiko , Takada Minoru , Nakanishi Yoichi , Kato Terufumi , Fukuoka Masahiro
Published: June 2006

BACKGROUND.

Combined gemcitabine and carboplatin (GC) and combined gemcitabine and vinorelbine (GV) are active and well tolerated chemotherapeutic regimens for patients with advanced nonsmall cell lung cancer (NSCLC). The authors conducted a randomized Phase II study of GC versus GV to compare them in terms of efficacy and toxicity.

METHODS.

One hundred twenty‐eight patients with Stage IIIB or IV NSCLC were randomized to receive either carboplatin at an area under the curve of 5 on Day 1 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) or vinorelbine 25 mg/m2 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) every 3 weeks.

RESULTS.

Response rates were 20.3% for the GC patients and 21.0% for the GV patients. In the GC arm, the median survival was 432 days, and the a 1‐year survival rate was 57.6%; in the GV arm, the median survival was 385 days, and the 1‐year survival rate was 53.3% in the GV arm. The median progression‐free survival was 165 days in the GC arm and 137 days in the GV arm. Severe hematologic toxicity (Grade 4) was significantly more frequent in the GC arm (45.3% vs. 25.8% in the GV arm; P = .022). Most notably, the incidence of Grade 3 or 4 thrombocytopenia was significantly higher in the GC arm (81.3% vs. 6.5% in the GV arm; P < .001). Conversely, severe nonhematologic toxicity (Grade 3 or 4) was more common in the GV arm (7.8% vs. 19.4% in the GC arm; P = .057).

CONCLUSIONS.

Although the GV and GC regimens had different toxicity profiles, there was no significant difference in survival among patients with NSCLC in the current study. Cancer 2006. © 2006 American Cancer Society.
Epithelioid sarcoma: Still an only surgically curable disease
Authors: de Visscher Sebastiaan A. H. J. , van Ginkel Robbert J. , Wobbes Theo , Veth René P. H. , ten Heuvel Suzanne E. , Suurmeijer Albert J. H. , Hoekstra Harad J.
Published: June 2006

BACKGROUND.

Epithelioid sarcoma is a rare soft tissue sarcoma with a known high propensity for locoregional recurrence and distant metastases. The clinical behavior and prognostic factors that influence the survival of patients with epithelioid sarcoma were studied.

METHODS.

Twenty‐three patients, including 16 men (70%) and 7 women (30%), who were treated for epithelioid sarcoma between 1979–2003 at the University Medical Center Groningen and Radboud University Nijmegen Medical Center, were reviewed retrospectively. The median age at diagnosis was 22 years (range, 1–54 years). At the time of diagnosis, 11 patients (48%) had metastases. Six patients with distant metastasis and 1 patient with an unresectable tumor received palliative treatment (30%). The remaining 16 patients underwent surgical treatment of local disease (11 patients) or locoregional disease (5 patients). Five patients in that group received isolated limb perfusion with tumor necrosis factor and melphalan.

RESULTS.

The 5‐year and 10‐year disease‐free survival rates for all patients were 34% and 17%, respectively; for the 16 patients who received curative treatment, both rates were 56%. In the latter group, 8 patients developed local recurrence (50%) after a median follow‐up of 4 months (range, 1–14 months). Nine patients were disease free after a median follow‐up of 50 months (range, 6–290 months). Tumor size >5 cm (P < .0026) at diagnosis and local recurrence (P<.0008) were significant predictors of survival.

CONCLUSIONS.

The prognosis for patients with epithelioid sarcoma is poor, because a substantial number of patients present with extensive disease, lymph node metastases, and/or distant metastases. Treatment consists of radical surgical excision of the tumor and, if indicated, therapeutic lymph node dissection. In patients who have large tumors, isolated limb perfusion may be useful. Cancer 2006. © 2006 American Cancer Society.
Proton beam therapy for hepatocellular carcinoma with limited treatment options
Authors: Hata Masaharu , Tokuuye Koichi , Sugahara Shinji , Fukumitsu Nobuyoshi , Hashimoto Takayuki , Ohnishi Kayoko , Nemoto Keiko , Ohara Kiyoshi , Matsuzaki Yasushi , Akine Yasuyuki
Published: June 2006

BACKGROUND.

The authors conducted a retrospective review to define the usefulness of proton beam therapy for patients who had hepatocellular carcinoma (HCC) with limited treatment options.

METHODS.

Twenty‐one patients with HCC for whom other treatment modalities either were contraindicative or were unfeasible because of coexisting diseases and unfavorable conditions received proton beam therapy. Four patients had renal failure, 2 patients had severe heart disease, 9 patients had severe cirrhosis, 1 patient had aplastic anemia, 1 patient had a dissecting abdominal aortic aneurysm before treatment, and 4 patients had bleeding tendency or unresectable tumors. Moreover, 2 of the latter 4 patients were allergic to iodine, and 2 other patients were unable to be catheterized for transcatheter arterial chemoembolization. Hepatic tumors were solitary in 14 patients and multiple in 7 patients, and the tumors ranged in greatest dimension from 25 mm to 100 mm (median, 40 mm). No patient had regional lymph node or distant metastasis. Total doses of 63 grays (Gy) to 84 Gy (median, 73 Gy) in 13 to 27 fractions (median, 18 fractions) were used for tumor treatments.

RESULTS.

All but 1 of the irradiated tumors were controlled at a median follow‐up of 3.3 years. The objective response rate was 81%, and the primary site‐control rate was 93% at 5 years. Eleven patients had intrahepatic recurrences, and 2 patients had distant metastases in the lungs. Four of 11 patients with intrahepatic recurrences received a second course of proton beam therapy, and all recurrent tumors were controlled. The overall and cause‐specific survival rates were 62% and 82% at 2 years, respectively, and 33% and 67% at 5 years, respectively. Grade ≥3 therapy‐related toxicities were not observed.

CONCLUSIONS.

Proton beam therapy was safe and effective for a variety of patients with HCC. The current results suggested that this method was tolerable and effective, even for patients with HCC who had limited treatment options. Cancer 2006. © 2006 American Cancer Society.
Randomized phase II study of atrasentan alone or in combination with zoledronic acid in men with metastatic prostate cancer
Authors: Michaelson M. Dror , Kaufman Donald S. , Kantoff Philip , Oh William K. , Smith Matthew R.
Published: June 2006

BACKGROUND.

Metastatic prostate cancer is characterized by the presence of osteoblastic bone metastases. Bone metastases account for most of the morbidity from this disease. Inhibition of osteoclast activity with the potent bisphosphonate zoledronic acid reduces skeletal complications and decreases serum levels of biochemical bone turnover markers compared with placebo. Atrasentan is an investigational agent that inhibits endothelin‐1 receptor, resulting in decreased osteoblast activity.

METHODS.

The effects of atrasentan alone versus combination therapy with atrasentan and zoledronic acid were investigated on bone turnover markers in men with bone metastases from prostate cancer. Forty‐four men were randomized to receive either atrasentan alone or combination therapy, and 33 completed at least 12 weeks of treatment and were included in the primary analysis.

RESULTS.

Treatment with the combination resulted in significantly lower serum levels of N‐telopeptide, a marker of bone resorption, compared with treatment with atrasentan alone. There was no difference between groups in serum levels of bone‐specific alkaline phosphatase, a marker of bone formation, at 12 weeks. Commonly observed adverse effects were edema, rhinitis, fatigue, and shortness of breath, most of which were NCI CTC (version 3.0) Grade 1. No Grade 4 or 5 treatment‐related toxicities were observed. There was minimal clinical efficacy, with no objective responses and only 1 prostate‐specific antigen (PSA) response.

CONCLUSIONS.

There is no evidence for additive or synergistic effects of combination therapy with atrasentan and zoledronic acid on bone turnover markers in men with metastatic prostate cancer. Cancer 2006. © 2006 American Cancer Society.
A shallow‐water approximation to the full water wave problem
Authors: Li Yi A.
Published: June 2006

We demonstrate that the system of the Green‐Naghdi equations as a two‐directional, nonlinearly dispersive wave model is a close approximation to the two‐dimensional full water wave problem. Based on the energy estimates and the proof of the well‐posedness for the Green‐Naghdi equations and the water wave problem, we compare solutions of the two systems, showing that without restrictions on the wave amplitude, any two solutions of the two systems remain close, at least in some finite time within the shallow‐water regime, provided that their initial data are close in the Banach space Hs × Hs+1 for some s > $3 \over 2$. As a consequence, we show that if the depth of the water compared with the wavelength is sufficiently small, the two solutions exist for the same finite time using the uniformly bounded energies defined in the paper. © 2006 Wiley Periodicals, Inc.
Fatty acid‐induced effect on glucagon secretion is mediated via fatty acid oxidation
Authors: Hong Jing , Jeppesen Per Bendix , Nordentoft Iver , Hermansen Kjeld
Published: June 2006

Background

While the effect of fatty acids and ectopic triglyceride storage in pancreatic beta cells has been well‐defined, only limited information is available on alpha cells. This study evaluates the long‐term impact of fatty acids on alpha cell function and proliferation as well as fatty acid oxidation.

Methods

Clonal alpha cells were cultured with fatty acids in the presence of high glucose for up to 3 days. The influence of fatty acids on glucagon secretion, glucagon content and triglyceride accumulation from 24 to 72 h was investigated. After a − 72 h culture, cell proliferation, carnitine palmitoyl transferase‐1 mRNA level and the effect of etomoxir were also elucidated.

Results

Fatty acids stimulated glucagon secretion and increased triglyceride accumulation in a time‐ and dose‐dependent manner, but inhibited alpha cell proliferation. Lower concentrations (0.125–0.25 mM) of fatty acids significantly increased glucagon secretion at 48 and 72 h, but did not affect triglyceride content. However, a marked increment in triglyceride accumulation occurred in the presence of 0.5 mM fatty acids. Fatty acids caused an up‐regulation of the expression of carnitine palmitoyl transferase‐1 gene. Etomoxir (1 µM) reversed fatty acid‐induced glucagon hypersecretion, but did not inhibit carnitine palmitoyl transferase‐1 mRNA level.

Conclusions

Our data indicates that compared with triglyceride accumulation, glucagon secretion is more sensitive to changes in fatty acid concentration. The effect of fatty acids on the glucagon response is mediated through their oxidation. The high carnitine palmitoyl transferase‐1 gene expression and the accumulation of triglyceride may initially be a compensatory oxidation reaction to elevated fatty acids. Copyright © 2006 John Wiley & Sons, Ltd.
Early temporal‐specific responses and differential sensitivity to lithium and Wnt‐3A exposure during heart development
Authors: Manisastry Shyam M. , Han Mingda , Linask Kersti K.
Published: June 2006

Members of both Wnt and bone morphogenetic protein (BMP) families of signaling molecules are important in heart development. We previously demonstrated that β‐catenin, a key downstream intermediary of the canonical Wnt signaling pathway, delineates the dorsal boundary of the cardiac compartments in an anteroposterior progression. We hypothesized the progression involves canonical Wnt signaling and reflects development of the primary body axis of the embryo. A similar anteroposterior signaling wave leading to cardiac cell specification involves inductive signaling by BMP‐2 synthesized by the underlying endoderm in anterior bilateral regions. Any molecule that disrupts the normal balance of Wnt and BMP concentrations within the heart field may be expected to affect early heart development. The canonical Wnt signaling step mimicked by lithium involves inactivation of glycogen synthase kinase‐3β (GSK‐3β; Klein and Melton [1996] Proc. Natl. Acad. Sci. U. S. A. 93:8455–8459). We show that lithium, Wnt‐3A, and an inhibitor of GSK‐3β, SB415286, affect early heart development at the cardiac specification stages. We demonstrate that normal expression patterns of key signaling molecules as Notch‐1 and Dkk‐1 are altered in the anterior mesoderm within the heart fields by a one‐time exposure to lithium, or by noggin inhibition of BMP, at Hamburger and Hamilton (HH) stage 3 during chick embryonic development. The severity of developmental defects is greatest with exposure to lithium or Wnt‐3A at HH stage 3 and decreases at HH stage 4. Taken together, our results demonstrate that there are temporal‐specific responses and differential sensitivities to lithium/Wnt‐3A exposure during early heart development. Developmental Dynamics 235:2160–2174, 2006. © 2006 Wiley‐Liss, Inc.
Transgenic Xenopus laevis strain expressing cre recombinase in muscle cells
Authors: Waldner Christoph , Sakamaki Kazuhiro , Ueno Naoto , Turan Gülüzar , Ryffel Gerhart U.
Published: June 2006

For reproducible analyses of gene function in Xenopus, the use of transgenic strains is a promising approach but has limitations when investigating factors interfering with development. Therefore, inducible systems are attractive alternatives, and a binary system based on recombinases is a most versatile approach. We have shown previously that Cre and FLP recombinases are active in Xenopus laevis and can induce a silent reporter gene in a corresponding reporter strain. Here, we describe the establishment of the transgenic Xenopus laevis strain A7 expressing Cre recombinase under the control of the muscle‐specific cardiac actin promoter. Upon crossing to several distinct reporter strains, A7 is able to induce EYFP, DsRed2, or LacZ reporter genes in a muscle‐specific manner. This first Cre‐expressing strain allows conditional activation of any gene of interest in muscle cells and, thus, opens up the use of recombinases as a new experimental strategy in Xenopus. Developmental Dynamics 235:2220–2228, 2006. © 2006 Wiley‐Liss, Inc.
FGF‐4 signaling is involved in mir‐206 expression in developing somites of chicken embryos
Authors: Sweetman Dylan , Rathjen Tina , Jefferson Matthew , Wheeler Guy , Smith Terence G. , Wheeler Grant N. , Münsterberg Andrea , Dalmay Tamas
Published: June 2006

The microRNAs (miRNAs) are recently discovered short, noncoding RNAs, that regulate gene expression in metazoans. We have cloned short RNAs from chicken embryos and identified five new chicken miRNA genes. Genome analysis identified 17 new chicken miRNA genes based on sequence homology to previously characterized mouse miRNAs. Developmental Northern blots of chick embryos showed increased accumulation of most miRNAs analyzed from 1.5 days to 5 days except, the stem cell–specific mir‐302, which was expressed at high levels at early stages and then declined. In situ analysis of mature miRNAs revealed the restricted expression of mir‐124 in the central nervous system and of mir‐206 in developing somites, in particular the developing myotome. In addition, we investigated how miR‐206 expression is controlled during somite development using bead implants. These experiments demonstrate that fibroblast growth factor (FGF) ‐mediated signaling negatively regulates the initiation of mir‐206 gene expression. This may be mediated through the effects of FGF on somite differentiation. These data provide the first demonstration that developmental signaling pathways affect miRNA expression. Thus far, miRNAs have not been studied extensively in chicken embryos, and our results show that this system can complement other model organisms to investigate the regulation of many other miRNAs. Developmental Dynamics 235:2185–2191, 2006. © 2006 Wiley‐Liss, Inc.
Bladder tissue formation from cultured bladder urothelium
Authors: Oottamasathien Siam , Williams Karin , Franco Omar E. , Thomas John C. , Saba Katrina , Bhowmick Neil A. , Staack Andrea , Demarco Romano T. , Brock John W. , Hayward Simon W. , Pope John C.
Published: June 2006

Tissue recombination is a powerful method to evaluate the paracrine‐signaling events that orchestrate the development of organs using the in vivo environment of a host rodent. Studies have reported the successful generation of primary cultures of rodent bladder urothelium, but none have reported their use to recapitulate bladder tissue with tissue recombination. We propose that primary cultured bladder urothelium, when recombined with inductive embryonic bladder mesenchyme, will form bladder tissue in a recombination model. Adult rat bladders were isolated and urothelium obtained. Sheets of bladder urothelium were re‐suspended in collagen and maintained in tissue culture. After expansion (>20 passages), the urothelium was recombined with embryonic day‐14 mouse bladder mesenchyme, then grafted beneath the renal capsule of immunocompromised mouse hosts. Grafts were harvested after 28 days. Control grafts were performed with bladder mesenchyme alone, cultured bladder urothelium alone, and collagen matrix alone. Final tissues were evaluated with staining and immunohistochemistry (H&E, Gomori's trichrome, broad‐spectrum uroplakin, and smooth muscle actin α and γ). Immunocytochemistry on cultured urothelium for broad‐spectrum keratin, vimentin, and broad‐spectrum uroplakin confirmed pure populations, void of mesenchymal contaminants. Staining of recombinant grafts demonstrated bladder tissue with mature urothelium and stromal differentiation. Control tissues were void of bladder tissue formation. We have successfully demonstrated that a chimeric bladder is formed from primary cultured bladder urothelium recombined with embryonic bladder mesenchyme. This is a powerful new tool for investigating the molecular mechanisms of bladder development and disease. Future applications may include the in vitro genetic manipulation of urothelium and examining those effects on growth and development in an in vivo environment. Developmental Dynamics 235:2795–2801, 2006. © 2006 Wiley‐Liss, Inc.
Selective assembly of fibulin‐1 splice variants reveals distinct extracellular matrix networks and novel functions for perlecan/UNC‐52 splice variants
Authors: Muriel Joaquin M. , Xu Xuehong , Kramer James M. , Vogel Bruce E.
Published: June 2006

Fibulin‐1C and fibulin‐1D splice variants have been conserved throughout metazoan evolution and have distinct functions in Caenorhabditis elegans development. Both splice variants are required for the assembly of hemidesmosome‐mediated mechanosensory neuron and uterine attachments, although the molecular associations that underlie their distinct functions at these locations are not known. Here, we show that the assembly of fibulin‐1C and fibulin‐1D splice variants at these anchorages is dependent upon distinct components of the extracellular matrix (ECM): Fibulin‐1D assembly at uterine and mechanosensory neurons attachments is dependent upon a perlecan/ UNC‐52 splice variant that includes alternately spliced IG8‐IG10, whereas the assembly of fibulin‐1C at mechanosensory neuron attachments is dependent upon laminin/ EPI‐1. These data not only indicate that fibulin‐1C and fibulin‐1D are components of distinct networks of ECM but also demonstrates a novel function for a major class of perlecan splice variants found in C. elegans and mouse. In addition, we demonstrate that overexpression of another ECM protein, collagen XVIII, can suppress gonad morphogenesis defects associated with loss of fibulin‐1C, suggesting that some genetic defects that result in a weakened basement membrane can be compensated by overexpression of genes for ECM components that stabilize basement membranes. Developmental Dynamics 235:2632–2640, 2006. © 2006 Wiley‐Liss, Inc.