bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene transfer of hepatocyte growth factor by electroporation reduces bleomycin-induced lung fibrosis
Authors: Gazdhar Amiq , Fachinger Patrick , van Leer Coretta , Pierog Jaroslaw , Gugger Mathias , Friis Robert , Schmid Ralph A. , Geiser Thomas
Published: October 2006

Abnormal alveolar wound repair contributes to the development of pulmonary fibrosis after lung injury. Hepatocyte growth factor (HGF) is a potent mitogenic factor for alveolar epithelial cells and may therefore improve alveolar epithelial repair in vitro and in vivo. We hypothesized that HGF could increase alveolar epithelial repair in vitro and improve pulmonary fibrosis in vivo. Alveolar wound repair in vitro was determined using an epithelial wound repair model with HGF-transfected A549 alveolar epithelial cells. Electroporation-mediated, nonviral gene transfer of HGF in vivo was performed 7 days after bleomycin-induced lung injury in the rat. Alveolar epithelial repair in vitro was increased after transfection of wounded epithelial monolayers with a plasmid encoding human HGF, pCikhHGF [human HGF (hHGF) gene expressed from the cytomegalovirus (CMV) immediate-early promoter and enhancer] compared with medium control. Electroporation-mediated in vivo HGF gene transfer using pCikhHGF 7 days after intratracheal bleomycin reduced pulmonary fibrosis as assessed by histology and hydroxyproline determination 14 days after bleomycin compared with controls treated with the same vector not containing the HGF sequence (pCik). Lung epithelial cell proliferation was increased and apoptosis reduced in hHGF-treated lungs compared with controls, suggesting increased alveolar epithelial repair in vivo. In addition, profibrotic transforming growth factor-β1 (TGF-β1) was decreased in hHGF-treated lungs, indicating an involvement of TGF-β1 in hHGF-induced reduction of lung fibrosis. In conclusion, electroporation-mediated gene transfer of hHGF decreases bleomycin-induced pulmonary fibrosis, possibly by increasing alveolar epithelial cell proliferation and reducing apoptosis, resulting in improved alveolar wound repair.
High tidal volume ventilation induces lung injury after hepatic ischemia-reperfusion
Authors: Ota Shuhei , Nakamura Kyota , Yazawa Takuya , Kawaguchi Yosuke , Baba Yasuko , Kitaoka Ritsuko , Morimura Naoto , Goto Takahisa , Yamada Yoshitsugu , Kurahashi Kiyoyasu
Published: October 2006

Ischemia-reperfusion not only damages the affected organ but also leads to remote organ injuries. Hepatic inflow interruption usually occurs during hepatic surgery. To investigate the influence of liver ischemia-reperfusion on lung injury and to determine the contribution of tidal volume settings on liver ischemia-reperfusion-induced lung injury, we studied anesthetized and mechanically ventilated rats in which the hepatic inflow was transiently interrupted twice for 15 min. Two tidal volumes, 6 ml/kg as a low tidal volume (IR-LT) and 24 ml/kg as a high tidal volume (IR-HT), were assessed after liver ischemia-reperfusion, as well as after a sham operation, 6 ml/kg (NC-LT) and 24 ml/kg (NC-HT). Both the IR-HT and IR-LT groups had a gradual decline in the systemic blood pressure and a significant increase in plasma TNF-α concentrations. Of the four groups, only the IR-HT group developed lung injury, as assessed by an increase in the lung wet-to-dry weight ratio, the presence of significant histopathological changes, such as perivascular edema and intravascular leukocyte aggregation, and an increase in the bronchoalveolar lavage fluid TNF-α concentration. Furthermore, only in the IR-HT group was airway pressure increased significantly during the 6-h reperfusion period. These findings suggest that liver ischemia-reperfusion caused systemic inflammation and that lung injury is triggered when high tidal volume ventilation follows liver ischemia-reperfusion.
Surfactant protein D regulates the cell surface expression of alveolar macrophage β2-integrins
Authors: Senft Albert P. , Korfhagen Thomas R. , Whitsett Jeffrey A. , LeVine Ann Marie
Published: October 2006

The β2-integrin receptors (CD11a/CD18, CD11b/CD18, and CD11c/CD18) are expressed on the surface of alveolar macrophages and are important for the phagocytic clearance of pathogens. In the present study, we demonstrate that surfactant protein D (SP-D) modulates surface expression of CD11b and CD11c, but not CD11a or CD18, on alveolar macrophages. While cell surface receptors were reduced, CD11b and CD11c mRNAs were increased by SP-D deficiency. CCSP-rtTA+/(tetO)7-rSPD+/SP-D−/−mice, which conditionally express SP-D in the lung, were used to study the kinetics and reversibility of β2-integrin receptors in response to changes in alveolar SP-D. Surface CD11b and CD11c were reduced on the alveolar macrophages within 3 days of SP-D deficiency and were restored with 3 days for CD11b and 7 days for CD11c of repletion of SP-D. SP-D deficiency caused a loss of cellular CD11b and CD11c content, indicating that the decrease in total cell content of the receptors was related to degradation rather than to redistribution of the receptor within the macrophage. CD11b and CD11c staining colocalized with Lamp-1 during SP-D deficiency, supporting the concept that reduced macrophage receptor levels resulted from increased lysosomal trafficking. Hydroxychloroquine, a lysomotropic agent, prevented the reduction of cellular and surface CD11b and CD11c. SP-D regulates surface CD11b and CD11c levels on the alveolar macrophage by modulating receptor trafficking, providing a mechanism by which SP-D mediates phagocytic activity in the alveolar macrophage.
The Potential of BORIS Detected in the Leukocytes of Breast Cancer Patients as an Early Marker of Tumorigenesis
Authors: D'Arcy Vivien , Abdullaev Ziedulla K. , Pore Naresh , Docquier France , Torrano Verónica , Chernukhin Igor , Smart Melissa , Farrar Dawn , Metodiev Metodi , Fernandez Nelson , Richard Carlos , Delgado M. Dolores , Lobanenkov Victor , Klenova Elena
Published: October 2006

Purpose: Brother of the regulator of imprinted sites (BORIS) is a novel member of the cancer-testis antigen gene family. These genes are normally expressed only in spermatocytes but abnormally activated in different malignancies, including breast cancer. The aim of this study was to investigate the expression of BORIS in the leukocytes of breast cancer patients and the correlation between BORIS levels and clinical/pathologic variables.

Experimental Design: Leukocytes were obtained from whole blood of 87 breast cancer patients and 52 donors not diagnosed with cancer. BORIS protein was detected in leukocytes by immunohistochemical staining; the immunoreactivity score (IRS) of each sample was determined. Additionally, BORIS expression was assessed by Western blot analysis and real-time reverse transcription-PCR.

Results: We describe significantly high levels of BORIS (IRS = 4.25 ± 0.034) in a subpopulation of leukocytes, the neutrophil polymorphonuclear granulocytes, in 88.5% of breast cancer patients. Increased IRS for BORIS in these patients correlated with increased tumor size. In comparison, 19.2% samples from the control group were BORIS positive with only very low levels of BORIS (IRS = 0.25 ± 0.009).

Conclusion: We report here the novel finding of BORIS expression in polymorphonuclear granulocytes of breast cancer patients. This tumor-related occurrence is a phenomenon not observed in donors with injuries and immune and inflammatory diseases. Detection of BORIS in a high proportion of patients with various types of breast tumors indicates that BORIS can be a valuable early blood marker of breast cancer. We conclude that BORIS represents a new class of cancer biomarkers different from those currently used in medical practice.
The Novel p21 Polymorphism p21G251A Is Associated with Locally Advanced Breast Cancer
Authors: Staalesen Vidar , Knappskog Stian , Chrisanthar Ranjan , Nordgard Silje H. , Løkkevik Erik , Anker Gun , Østenstad Bjørn , Lundgren Steinar , Risberg Terje , Mjaaland Ingvil , Gram Inger Torhild , Kristensen Vessela N. , Børresen-Dale Anne-Lise , Lillehaug Johan Richard , Lønning Per Eystein
Published: October 2006

Purpose: p21 is a main effector of growth arrest induced by p53. In addition, a second transcript from the same gene (p21B) has been linked to apoptosis. We previously analyzed p21 status in breast cancer and reported two novel polymorphisms of the p21 gene. In the present study, we present a larger study designed to explore a possible association between these novel polymorphisms and breast cancer.

Experimental Design: The p21/p21B polymorphisms were analyzed in 507 breast cancer patients and 1,017 healthy individuals using cDNA or genomic DNA from tumor and/or blood samples.

Results: We detected five polymorphisms of the p21 gene. Three of these polymorphisms are earlier reported by others, whereas two were reported for the first time in a recent study by us. The presence of the A allele of the p21G251A polymorphism was observed more frequently among patients with primary stage III breast cancer (4.5%) compared with stage I and II tumors (1.5%) and healthy female controls (1.4%; P = 0.007, comparing the three groups; P = 0.0049 and P = 0.0057, comparing locally advanced to stage I/II and healthy controls, or to healthy controls alone, respectively). The allele frequencies of the remaining four polymorphisms were evenly distributed among patients and healthy individuals.

Discussion: The finding of an association between locally advanced breast cancer and one particular polymorphism of the p21 gene suggests this polymorphism to be related to tumor behavior, including enhanced growth rate. If confirmed in other studies, this may add significant information to our understanding of the biology as well as of the clinical behaviour of locally advanced breast cancers.
Functional Plasminogen Activator Inhibitor-1 Gene Variants and Breast Cancer Survival
Authors: Zhang Xianglan , Shu Xiao-Ou , Cai Qiuyin , Ruan ZhiXian , Gao Yu-Tang , Zheng Wei
Published: October 2006

Purpose: Plasminogen activator inhibitor-1 (PAI-1) plays an important role in cancer invasion and metastasis. A common polymorphism (4G/5G) in the promoter region of the PAI-1 gene has been reported to influence transcription and plasma levels of PAI-1. We evaluated the association between PAI-1 4G/5G polymorphism and breast cancer survival in a population-based cohort of breast cancer patients.

Experimental Design: Included in this analysis were 1,083 Chinese women diagnosed with stage 0 to III primary breast cancer at age 25 to 64 years who were recruited between 1996 and 1998 for the Shanghai Breast Cancer Study and followed for a median of 5.2 years. The Kaplan-Meier method and Cox model were used to evaluate the genotype and survival association.

Results: After adjustment for known prognostic factors for breast cancer, patients homozygous for the 4G allele had significantly poorer disease-free survival [hazard ratio (HR), 1.7; 95% confidence interval (95% CI), 1.1-2.4] and overall survival (HR, 1.5; 95% CI, 1.0-2.3) than those homozygous for the 5G allele. The association was more evident in patients with advanced disease. The HRs (95% CI) were 3.5 (1.4-9.0) for disease-free survival and 3.1 (1.1-8.3) for overall survival in stage III patients.

Conclusions: The PAI-1 4G/5G polymorphism may be a prognostic marker for young and middle-aged Chinese breast cancer patients.
Effect of Simultaneous Inhibition of Epidermal Growth Factor Receptor and Cyclooxygenase-2 in HER-2/Neu-Positive Breast Cancer
Authors: Lanza-Jacoby Susan , Burd Randy , Rosato Francis E. , McGuire Kandace , Little James , Nougbilly Noel , Miller Sheldon
Published: October 2006

Purpose: HER-2/erbB2/neu is overexpressed in 25% to 30% of all invasive breast cancers and is associated with an aggressive course and reduced survival. HER-2/erbB2/neu breast tumors are frequently associated with up-regulation of cyclooxygenase (COX)-2 and activation of the epidermal growth factor receptor (EGFR) pathway, which promote enhanced cell growth and resistance to apoptosis. This study investigated whether simultaneously blocking both EGFR and COX-2 pathways with ZD1839 and celecoxib, respectively, would be more effective in inhibiting cell growth and inducing apoptosis than either agent alone.

Experimental Design: The effects of ZD1839, celecoxib, and their combination on cell survival, cell cycle progression, and apoptosis were determined in NMF11.2 mouse mammary tumor cells. We also investigated the potential downstream EGFR-activated pathways that are altered by simultaneous inhibition of COX-2 and EGFR.

Results: Celecoxib alone and ZD1839 alone produced a concentration- and time-dependent inhibition of cell survival. Both agents combined produced supra-additive inhibitory effects on cell survival and apoptosis compared with either agent alone. This effect was associated with increased cleaved poly(ADP-ribose)polymerase and reduced protein expression of bcl-2. Phosphorylation of extracellular signal-regulated kinase 1/2 was partially blocked by ZD1839 and celecoxib alone and was completely blocked by the combination of both agents. The enhanced proapoptotic effects of the combined agents were also associated with decreased phosphorylation of Akt and increased phosphorylation of p38.

Conclusions: These findings show that both COX-2 and EGFR are important targets for inhibiting survival and inducing apoptosis in breast cancer. The data suggest a potential cross-talk between COX-2 and EGFR signaling in breast cancer cells overexpressing HER-2/erbB2/neu.
Reverse Transcription-PCR for t(11;18)(q21;q21) Staging and Monitoring in Mucosa-Associated Lymphoid Tissue Lymphoma
Authors: Streubel Berthold , Huber Daniela , Wöhrer Stefan , Chott Andreas , Raderer Markus
Published: October 2006

Purpose: Subclinical dissemination as well as persistence after therapy may be difficult to assess on clinical and histologic examinations in patients with mucosa-associated lymphoid tissue (MALT) lymphoma. We have analyzed the use of reverse transcription-PCR (RT-PCR) for the detection of t(11;18)(q21;q21) in histologically infiltrated and normal biopsies at diagnosis and during follow-up to determine its clinical and prognostic effect.

Experimental Design: Twenty-one patients with t(11;18)(q21;q21)+ MALT lymphoma were included in this retrospective study. Presence of t(11;18)(q21;q21) was determined by RT-PCR done on 316 biopsies of various tissues obtained during staging and follow-up.

Results: Infiltration with lymphoma was histologically detected in 67 of 316 biopsies, whereas molecular infiltration was established in 104 of 316 biopsies. All histologically positive specimens were also positive in RT-PCR. There was a good concordance (P = 0.0001) between histology and RT-PCR at the time of disease presentation with only one further infiltration site identified by RT-PCR. In 8 of 12 patients with persistent lymphoma, RT-PCR revealed tumor infiltration in histologically unsuspected sites. Eight of nine treated patients with histologic and clinical complete remission (CR) remained RT-PCR positive. CR on RT-PCR was achieved later than histologic CR (between 13-59 months) without any further therapy in five of these eight patients; only one patient with persistent t(11;18)(q21;q21) relapsed histologically.

Conclusions: This study shows the potential of RT-PCR for t(11;18)(q21;q21) done on routine paraffin-embedded specimens to identify disseminated disease in tissues otherwise not diagnostic of MALT lymphoma involvement. T(11;18)(q21;q21) persistence in patients with clinical and histologic CR does not necessarily require therapeutic intervention.
Carcinoembryonic Antigen Messenger RNA Expression in Blood Predicts Recurrence in Esophageal Cancer
Authors: Setoyama Tetsuro , Natsugoe Shoji , Okumura Hiroshi , Matsumoto Masataka , Uchikado Yasuto , Ishigami Sumiya , Owaki Tetsuhiro , Takao Sonshin , Aikou Takashi
Published: October 2006

Purpose: The clinical significance of isolated tumor cells (ITC) in blood has not been clearly established, particularly during follow-up in cancer patients. We conducted a longitudinal analysis of the relationship between ITC in blood during follow-up and clinicopathologic findings in patients with esophageal squamous cell carcinoma.

Experimental Design: Blood samples obtained from 106 patients were examined by real-time RT-PCR assay targeting carcinoembryonic antigen (CEA) mRNA. Follow-up examination every 3 months after surgery included testing for CEA mRNA and tumor markers, as well as imaging.

Results: Thirty-nine (36.8%) patients were positive for CEA mRNA expression. CEA mRNA positivity significantly correlated with tumor depth, lymph node metastasis, stage, and venous invasion. Recurrent disease was found in 34 of 106 (32.1%) cases. CEA mRNA was found in 28 (76.5%) patients experiencing relapse. Of these 28 patients, the number positive of CEA mRNA before detection by imaging, at the same time of detection by imaging, and after detection by imaging was 18 (52.9%), 8 (23.5%), and 2 (5.9%), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for CEA mRNA were higher than those for serum CEA or squamous cell carcinoma. Patients positive for CEA mRNA experienced significantly shorter disease-free interval than those with negative CEA mRNA (P < 0.001). According to multivariate analysis, CEA mRNA positivity was an independent factor for disease-free interval.

Conclusions: Examination of CEA mRNA in peripheral blood during follow-up is useful for early detection of occult recurrence. We believe that CEA mRNA in blood will be a new marker for recurrence in esophageal squamous cell carcinoma.
Targeting Factors Involved in Bone Remodeling as Treatment Strategies in Prostate Cancer Bone Metastasis
Authors: Vessella Robert L. , Corey Eva
Published: October 2006

Prostate cancer is the most commonly diagnosed cancer in men within the western world and the third leading cause of cancer-related deaths. Even if the cancer is considered localized to the prostate, there is a 15% to 20% incidence of subsequent metastatic disease. Prostate cancer has a very high proclivity for metastasizing to bone, with ∼90% of men with advanced disease having skeletal lesions. The prostate cancer metastases are characteristically osteoblastic, with extensive new bone deposition, unlike other tumors that metastasize to bone and cause an osteolytic response reflective of bone degradation. There are a considerable number of studies relating to inhibition of the osteoblastic response, including interference with endothelin-1, bone morphogenetic proteins, and Wnt signaling pathways. Within the past few years, several studies showed that increased osteolytic activity also occurs in the background of the prostate cancer skeletal metastases. Because growth factors are being released from the bone matrix during degradation, it suggests that inhibition of osteolysis might be effective in slowing tumor growth. Several strategies are being developed and applied to affect directly the osteolytic events, including use of bisphosphonates and targeting the critical biological regulators of osteoclastogenesis, receptor activator of nuclear factor-κB and receptor activator of nuclear factor-κB ligand. This review focuses on several of the clinical and preclinical strategies to inhibit the growth of prostate cancer cells in bone and to alleviate the multitude of associated skeletal-related events.
Molecular Mechanisms of Action of Bisphosphonates: Current Status
Authors: Roelofs Anke J. , Thompson Keith , Gordon Sharon , Rogers Michael J.
Published: October 2006

Purpose: Bisphosphonates are currently the most important class of antiresorptive agents used in the treatment of metabolic bone diseases, including tumor-associated osteolysis and hypercalcemia. These compounds have high affinity for calcium ions and therefore target bone mineral, where they are internalized by bone-resorbing osteoclasts and inhibit osteoclast function.

Experimental Design: This article reviews the pharmacology of bisphosphonates and the relationship between chemical structure and antiresorptive potency. We also describe new insights into their intracellular molecular mechanisms of action, methods for assessing the effects of bisphosphonates on protein prenylation, and their potential as direct antitumor agents.

Results: Nitrogen-containing bisphosphonates act intracellularly by inhibiting farnesyl diphosphate synthase, an enzyme of the mevalonate pathway, thereby preventing prenylation of small GTPase signaling proteins required for normal cellular function. Inhibition of farnesyl diphosphate synthase also seems to account for their antitumor effects observed in vitro and for the activation of γ,δ T cells, a feature of the acute-phase response to bisphosphonate treatment in humans. Bisphosphonates that lack a nitrogen in the chemical structure do not inhibit protein prenylation and have a different mode of action that seems to involve primarily the formation of cytotoxic metabolites in osteoclasts.

Conclusions: Bisphosphonates are highly effective inhibitors of bone resorption that selectively affect osteoclasts in vivo but could also have direct effects on other cell types, such as tumor cells. After >30 years of clinical use, their molecular mechanisms of action on osteoclasts are finally becoming clear but their exact antitumor properties remain to be clarified.
Genomics and Proteomics of Bone Cancer
Authors: Marguiles Aaron G. , Klimberg V. Suzanne , Bhattacharrya Sudeepa , Gaddy Dana , Suva Larry J.
Published: October 2006

Although the control of bone metastasis has been the focus of intensive investigation, relatively little is known about the molecular mechanisms that regulate or predict the process, even though widespread skeletal dissemination is an important step in the progression of many tumors. As a result, understanding the complex interactions contributing to the metastatic behavior of tumor cells is essential for the development of effective therapies. Using a state-of-the-art combination of gene expression profiling and functional annotation of human tumor cells, and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry of patient serum, we have shown that changes in tumor biochemistry correlate with disease progression and help to define the aggressive tumor phenotype. Based on these approaches, it is apparent that the metastatic phenotype of tumor cells is extremely complex. The identification of the phenotype of tumor cells has benefited greatly from the application of gene expression profiling (microarray analysis). This technology has been used by many investigators to identify changes in gene expression and cytokine and growth factor elaboration (such as interleukin 8). The tumor phenotype(s) presumably also include changes in the cell surface carbohydrate profile (via altered glycosyltransferase expression) and heparan sulfate expression (via increased heparanase activity), to name but a few. These specific alterations in gene expression, identified by functional annotation of accumulated microarray data, have been validated using a variety of approaches. Collectively, the data described here suggest that each of these activities is associated with distinct aspects of the aggressive tumor cell phenotype. Collectively, the data suggest that multiple factors constitute the complex phenotype of metastatic tumor cells. In particular, the differences observed in gene expression profiles and serum protein biomarkers play a critical role in defining the mechanisms responsible for bone-specific colonization and growth of tumors in bone. Future studies will identify the mechanisms that participate in the formation of secondary tumor growths of cancers in bone.
Hoosier Oncology Group Randomized Phase II Study of Docetaxel, Vinorelbine, and Estramustine in Combination in Hormone-Refractory Prostate Cancer with Pharmacogenetic Survival Analysis
Authors: Hahn Noah M. , Marsh Sharon , Fisher William , Langdon Robert , Zon Robin , Browning Mark , Johnson Cynthia S. , Scott-Horton Tiffany J. , Li Lang , McLeod Howard L. , Sweeney Christopher J.
Published: October 2006

Purpose: To determine the safety and efficacy of two docetaxel doublets in hormone-refractory prostate cancer (HRPC) patients and to examine the prognostic role of polymorphisms in host genes important to docetaxel metabolism and transport.

Experimental Design: Sixty-four chemotherapy-naive patients with HRPC were randomized to docetaxel and vinorelbine (D, 20 mg/m2 i.v. days 1 and 8; V, 25 mg/m2 i.v. days 1 and 8) or docetaxel and estramustine phosphate (D, 60-70 mg/m2 i.v. day 1; E, 280 mg oral thrice daily days 1-5) administered q21d. Primary end point was clinically significant toxicity. A pharmacogenetic analysis of host genes was done in patients who received at least one cycle of docetaxel therapy.

Results: Grade 3/4 toxicity occurred in 15.6% of DV patients and in 28.6% DE patients. Neither arm exceeded the threshold of clinically significant toxicity. In the DV arm, objective response rate was 33%, prostate-specific antigen response rate was 20%, and median survival was 16.2 months. In the DE arm, objective response rate was 67%, prostate-specific antigen response rate was 43%, and median survival was 19.7 months. Pharmacogenetic analyses showed a significant association between survival beyond 15 months and the ABCG2 421 C>A (Q141K) polymorphism compared with the wild-type (C/C) genotype (66% versus 27%; P = 0.05).

Conclusions: DV and DE doublets are active with a tolerable toxicity profile in patients with HRPC; however, efficacy does not seem superior to standard single-agent docetaxel. The ABCG2 421 C>A (Q141K) polymorphism may be an important predictor of response and survival in HRPC patients treated with docetaxel-based chemotherapy.
NO Synthase Uncoupling in the Kidney of Dahl S Rats
Authors: Taylor Norman E. , Maier Kristopher G. , Roman Richard J. , Cowley Allen W.
Published: October 2006

NO synthase (NOS) can paradoxically contribute to the production of reactive oxygen species when
l
-arginine or the cofactor R-tetrahydrobiopterin (BH
4
) becomes limited. The present study examined whether NOS contributes to superoxide production in kidneys of hypertensive Dahl salt-sensitive (SS) rats compared with an inbred consomic control strain (SS-13
BN
) and tested the hypothesis that elevated dihydrobiopterin (BH
2
) levels are importantly involved in this process. This was assessed by determining the effects of
l
-nitroarginine methyl ester (
l
-NAME) inhibition of NOS on superoxide production and by comparing tissue concentrations of BH
4
and BH
2
. A reverse-phase high-performance liquid chromatography method was applied for direct measurements of BH
4
and BH
2
using (S)-tetrahydrobiopterin as an internal standard. Superoxide concentrations were measured in vivo from medullary microdialysis fluid using dihydroethidine and in vitro using lucigenin. The results indicate the following: (1) that superoxide levels were elevated in the outer medulla of SS rats fed a 4% salt diet and could be inhibited by
l
-NAME. In contrast,
l
-NAME resulted in elevated superoxide production in consomic SS-13
BN
rats because of higher NOS activity; (2) SS rats showed a reduced ratio of BH
4
/BH
2
in the outer medulla that was driven by increased concentrations of BH
2
; and (3) lower superoxide dismutase and catalase activities contributed to elevated reactive oxygen species in SS samples. Based on the shift of BH
4
to BH
2
and the observation of
l
-NAME inhibitable superoxide production, we conclude that NOS uncoupling occurs in the renal medulla of hypertensive SS rats fed a high-salt diet.
Effects of Angiotensin II on NO Bioavailability Evaluated Using a Catheter-Type NO Sensor
Authors: Imanishi Toshio , Kobayashi Katsunobu , Kuroi Akio , Mochizuki Seiichi , Goto Masami , Yoshida Kiyoshi , Akasaka Takashi
Published: October 2006

We investigated the acute or chronic effects of angiotensin (Ang) II on the bioavailability of NO in Ang II–infused rabbits using the catheter-type NO sensor. Male New Zealand White rabbits were infused with vehicle (sham), Ang II at a rate of 200 ng/kg per minute, either alone or in combination with hydralazine, Ang II type I receptor antagonist (valsartan), or an antioxidant (tempol) for 24 hours or 14 days. Plasma NO concentration was measured using the catheter-type NO sensor located in the aorta. We then infused saline (vehicle) and acetylcholine (ACh) into the aortic arch with or without pretreatment with N
G
-methyl-
l
-arginine. An increase in plasma NO levels in response to ACh was significantly attenuated in the Ang II group compared wit the control group. The decrease in the basal plasma NO concentration was significantly lower in the Ang II group than in the control group. Plasma peroxynitrite concentrations in Ang II group were significantly higher than in the control group. The negative effects of Ang II, that is, the decrease in basal and ACh-induced NO production and the increase in oxidative stress, were significantly suppressed by the cotreatment with either valsartan or tempol. Short-term treatment with Ang II significantly increased the ACh-induced increase in plasma NO concentration, as well as basal NO release. Although Ang II stimulates release of NO in the short term, chronic treatment with Ang II elicits the decreased NO bioavailability in the aorta of the Ang II–infusion rabbit model.
Intracoronary ST-Segment Shift Soon After Elective Percutaneous Coronary Intervention Accurately Predicts Periprocedural Myocardial Injury
Authors: Balian Vruyr , Galli Michele , Marcassa Claudio , Cecchin Gianni , Child Maurice , Barlocco Fabio , Petrucci Ettore , Filippini Giulia , Michi Riccardo , Onofri Marco
Published: October 2006

Background—

Elevation of cardiac biomarkers after coronary angioplasty (percutaneous coronary intervention [PCI]) reflects periprocedural myocardial damage and is associated with adverse cardiac events. We assessed whether periprocedural myocardial damage that occurs despite successful PCI could be rapidly and easily identified by intracoronary ST-segment recording with the use of a catheter guidewire.

Methods and Results—

In 108 consecutive stable patients undergoing elective single-vessel PCI, we recorded unipolar ECG from the intracoronary guidewire in the distal coronary before PCI and 2 minutes after the last balloon inflation. After PCI, intracoronary ST-segment shift ≥1 mm from baseline was considered significant. Troponin I levels were measured at baseline and at 8 and 24 hours after intervention, and myocardial damage was defined as troponin I increase above the upper normal value after intervention. All patients had normal cardiac marker values before PCI, and PCI was successful in all (residual stenosis <20%, Thrombolysis in Myocardial Infarction grade 3 flow). After PCI, long-term follow-up data were collected; myocardial damage was detected in 50 patients (46%), although abnormal creatine kinase-MB values were documented in only 11 (10%). Significant intracoronary ST-segment shift after PCI was present in 40 patients (37%; group A) and absent in the remaining 68 (63%; group B). Procedural myocardial damage was documented in 37 group A patients (93%) and in 13 group B patients (19%;
P
<0.001); significant ECG changes were found on standard ECG after intervention in only 5 patients (13%) and 1 patient (1%) (
P
<0.05). Sensitivity of intracoronary ST-segment shift for predicting myocardial damage was 74%, and specificity was 95%, with positive and negative predictive values of 93% and 81%, respectively. On multivariate analysis, intracoronary ST-segment shift was the sole independent predictor of myocardial damage (odds ratio, 54.1; 95% confidence interval, 12.1 to 240;
P
<0.0001). At a median follow-up of 12±5 months, major coronary event–free survival was significantly worse in group A patients (log-rank test χ
2
=4.0;
P
<0.05).

Conclusions—

After successful single-vessel PCI, intracoronary ST-segment shift allows the prompt and inexpensive identification of patients developing myocardial injury, who may require adjunctive therapy and longer in-hospital stay.
Age-Dependent Effect of Abciximab in Patients With Acute Coronary Syndromes Treated With Percutaneous Coronary Interventions
Authors: Ndrepepa Gjin , Kastrati Adnan , Mehilli Julinda , Neumann Franz-Josef , ten Berg Jurriën , Bruskina Olga , Dotzer Franz , Seyfarth Melchior , Pache Jürgen , Dirschinger Josef , Ulm Kurt , Berger Peter B. , Schömig Albert
Published: October 2006

Background—

No studies have specifically performed an age-based analysis of the efficacy of abciximab in patients with non–ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention (PCI). The aim of the study was to assess whether there are age-dependent differences in the clinical benefit of abciximab in patients with acute coronary syndrome treated with PCI.

Methods and Results—

We performed this retrospective analysis of 2022 patients with acute coronary syndrome enrolled in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 2) study and randomized to receive abciximab or placebo during a PCI procedure. The incidence of major adverse cardiac events (MACE) during the 30 days after PCI was the primary end point of the study. On the basis of the cutoff age value provided by logistic regression in connection with bootstrap resampling, patients were divided into those younger (n=1220) and older (n=802) than 70 years. Among younger patients, the incidence of MACE was 7.7% in the abciximab group versus 13.3% in the placebo group (relative risk 0.57, 95% confidence interval 0.40 to 0.80,
P
=0.001). In contrast, no difference was observed among older patients: The incidence of MACE was 10.9% in the abciximab group versus 9.9% in the placebo group (relative risk 1.10, 95% confidence interval 0.72 to 1.69,
P
=0.65). After adjustment for other variables, including cardiac troponin, there was a significant interaction between age and abciximab (
P
=0.04) with respect to MACE reduction, with abciximab being more effective in younger patients.

Conclusions—

In patients with non–ST-elevation acute coronary syndromes undergoing PCI, the efficacy of abciximab appears to be age-dependent, with greater benefit among younger patients.
Pretreatment With Angiotensin Receptor Blockade Prevents Left Ventricular Dysfunction and Blunts Left Ventricular Remodeling Associated With Acute Myocardial Infarction
Authors: Thai Hoang , Castellano Lisa , Juneman Elizabeth , Phan Huy , Do Rose , Gaballa Mohamed A. , Goldman Steven
Published: October 2006

Background—

This study was designed to determine the effects of pretreatment with an angiotensin receptor blocker on left ventricular (LV) function and remodeling during acute myocardial infarction (MI).

Methods and Results—

Sprague-Dawley rats were pretreated with candesartan (10 mg · kg
−1
· d
−1
) for 2 weeks and studied at 1, 3, and 6 minutes after MI. Compared with untreated rats, pretreatment with candesartan lowered (
P
<0.05) LV systolic pressure and the first derivative of LV pressure with respect to time but did not change LV end-diastolic pressure or improve LV regional function. With candesartan pretreatment, LV fractional shortening and ejection fraction increased (
P
<0.05) by 37% and 28%, and LV chamber dilation was attenuated (
P
<0.05). At 6 minutes after MI, LV endothelial nitric oxide synthase decreased in the infarcted and noninfarcted wall 47% (
P
=0.04) and 70% (
P
=0.002), and constitutive microtubulin increased 260% (
P
=0.0005) and 111% (
P
=0.003). Candesartan had no effect on LV tissue endothelial nitric oxide synthase levels but attenuated the increase in constitutive microtubulin by 77% (
P
=0.004) and 37% (
P
<0.05).

Conclusions—

Pretreatment with candesartan before an acute MI improves global LV function, prevents LV dilation, and blunts the increase in constitutive microtubulin, with minimal effects on LV hemodynamics, regional function, or tissue endothelial nitric oxide synthase. Thus, candesartan given before an MI attenuates LV remodeling and alters the cytoskeleton matrix of the left ventricle.
Extra-pair copulations in common murres I: a mate attraction strategy?
Authors: Cameron-Macmillan Maureen L. , Walsh Carolyn J. , Wilhelm Sabina I. , Storey Anne E.
Published: October 2006

We investigated the behavioural context of pair (PCs) and extra-pair copulations (EPCs) in individually-marked socially-monogamous, long-lived seabirds, common murres (Uria aalge). Since forced EPCs have been documented for this species, we first examined which sex controls successful (cloacal contact achieved) copulation. The finding that all successful copulations required female cooperation and crouching suggested that benefits of successful EPCs accrue primarily to females. In a group of murres for which paternity analyses indicated no extra-pair paternity, behavioural observations over five breeding seasons showed that individual females engaged in EPCs primarily under two circumstances: (1) before they were reunited with their mates, and (2) when they were in the process of re-pairing. There was no such relationship between EPCs and re-pairing for males. Successful EPCs occurred with familiar neighboring males of apparent high quality, indicated by their high ledge attendance and prior reproductive success rates. Thus, EPCs may be used by females to attract potential high quality mates in situations where females are attempting to re-pair as a result of divorce or mate death.
Use of chemical cues during shell fights in the hermit crab Pagurus bernhardus
Authors: Briffa Mark , Williams Rebecca
Published: October 2006

Chemical communication is likely to play an important role during agonistic encounters in aquatic crustaceans but the use of chemical signals is difficult to observe. An alternative approach to direct observation is to collect water that has contained fighting animals and then expose a focal animal of the same species to the cue water and monitor its behaviour. Here we investigate the possibility of the use of chemical cues during 'shell fights' in the hermit crab Pagurus bernhardus. Focal crabs exposed to the fighting cue spent more time withdrawn into their gastropod shell, less time on locomotion and less time searching for food than did those exposed to cues from non-fighting hermit crabs or those treated with plain sea water. At the end of the observation period we used a novel stimulus to induce a startle response in order to probe the focal crab's motivational state for this exploratory behaviour. Those exposed to the fighting cue water took longer to recover than crabs in the other groups, indicating that their motivation was lower. These findings provide clear evidence that chemical cues are a feature of these contests.
Risk factors and escape strategy in the grasshopper Dissosteira carolina
Authors: Cooper William E.
Published: October 2006

To determine aspects of escape strategy by the Carolina grasshopper, Dissosteira carolina, and applicability of models of escape behavior applied primarily to vertebrates, I conducted three field experiments by simulating an approaching predator. Escape theory predicts that flight initiation distance (distance from predator when escape begins) and distance fled increase as predation risk increases. Some aspects of escape are not predicted, and theory does not identify escape strategies including several components. I examined effects of risk factors (predator approach speed, directness of approach, and repeated approach) on flight initiation distance, distance fled, and the initial direction of escape. Flight initiation distance and distance fled were predicted to increase with approach speed. Because predators approaching directly may bypass prey without detecting it, probability of fleeing and flight initiation distance were predicted to increase with directness of approach. Because a persistent predator poses greater threat, flight initiation distance and distance fled were predicted to be greater for the second of two successive approaches. All findings were consistent with predictions of the Ydenberg & Dill (1986) model, suggesting that risk assessment and escape decisions by visually oriented insects may be similar to those of vertebrates. Although escape directly away from the predator might be expected to minimize risk, most grasshoppers escaped by flying at nearly right angles to the approach path. Lateral escape may be part of an escape strategy in which dark wing colour during flight rapidly disappears upon landing. With sudden change in colour and movement, the grasshopper becomes cryptic and difficult to relocate. Lateral escape may increase difficulty of maintaining visual contact with the grasshopper until it lands. It also avoids need for further escape from a predator that continues in its initial direction.
Amplification and Suppression of Internal Waves by Tides over Variable Bottom Topography
Authors: Vlasenko Vasiliy , Stashchuk Nataliya
Published: October 2006

The energy exchange between internal waves and barotropic currents over inclined bottom topography is studied theoretically and in the framework of the numerical model. The energy balance equation derived for a continuously stratified fluid predicts that energy can either be transferred toward or away from the internal wave depending on the direction of propagation of both the wave and current. Four scenarios of wave–flow interaction over the inclined bottom were identified. An internal wave extracts energy from the background tidal flow during its propagation upslope–upstream or downslope–downstream and its amplitude grows. The wave loses energy propagating downslope–upstream or upslope–downstream and reduces in amplitude. This mechanism of suppression or amplification of internal waves by a current over an inclined bottom is verified numerically. When applied to the area of the Knight Inlet sill, a high-resolution fully nonlinear, nonhydrostatic model reproduces the packets of internal waves generated by supercritical tidal flow over the sill. Careful inspection of the wave fields revealed the presence of an irregular wave structure within wave packets—namely, internal waves are not arranged by amplitude. This phenomenon, obtained numerically and observed in situ, is treated in terms of the mechanism of wave–flow interaction: the energy exchange between the tidal current and generated internal waves over the inclined bottom topography is the reason for the absence of traditional rank-ordered waves in the packet.
Public Violence and State Building in Central America
Authors: Thies Cameron G.
Published: October 2006

This article examines the role played by war, and public violence more generally, in the state-building experiences of Central America. Bellicist theory expects that wars provide a stimulus to extractive efforts, thus enhancing the autonomy and capacity of the state over time, though recent qualitative studies of South America find the opposite. I expand the reach of bellicist theory to Central America through the broader concept of public violence, which captures the long-term impact of external and internal rivals on the state. The quantitative tests demonstrate that Central American interstate and civil wars reduce the extractive ability of states, consistent with the South American evidence. Interstate rivals stimulate extractive efforts among governments, whereas intrastate rivals detract from those efforts. Incorporating the concept of public violence into bellicist theory thus helps to increase our understanding of Central American state building.
Employee characteristics and participation in a worksite wellness programme
Authors: Joslin Beth , Lowe John B , Peterson N Andrew
Published: October 2006

Objective The purpose of this study was to explore the underlying structure of participation in a worksite wellness programme, and to examine the relationship between the demographic and quality of life (QOL) characteristics of employees, and the wellness programme offerings in which they choose to participate.

Design The cross-sectional design of this study involved gathering data from individuals at one point in time, following their decision to participate (or not participate) in a worksite wellness programme.

Setting This study involved county government employees in a Midwestern United States community.

Method Surveys were mailed to a random sample of 329 county government employees. The survey included demographics and measured QOL via the Short Form-36 (SF-36). One-week and three-week follow-ups were conducted in attempt to increase the survey response rate.

Results Two dimensions of wellness programme participation were identified to exist among wellness programme participants: (1) medical offerings; and (2) health education offerings. Certain employee characteristics were associated with participation in each of the two dimensions of participation.

Conclusion Findings suggest demographic and QOL characteristics may predict the type of employees a programme might expect to participate in wellness offerings. Results may be useful for worksite wellness programme coordinators regarding tailoring programme offerings, participant recruitment, and education efforts, based on the characteristics of the employee population.
Interventions to promote young people’s physical activity: Issues, implications and recommendations for practice
Authors: Cale Lorraine , Harris Jo
Published: October 2006

There has been increased interest in the development and implementation of physical activity interventions designed to increase young people’s physical activity participation in recent years. This is perhaps founded on concerns over youngsters’ physical activity levels and the possible health consequences. School-based interventions are the most common form of intervention but, given that the majority of young people’s physical activity occurs outside school, there is now growing recognition of the importance of community-based programmes and the involvement of the community at all levels if interventions are to be effective. Based on previous reviews of the findings of formally evaluated interventions, this article considers the evidence base for the effectiveness of school and community-based physical activity interventions. Despite limitations in the literature, it reveals that physical activity interventions with young people can be effective and achieve positive outcomes. The interventions are discussed and a number of issues and observations are highlighted concerning the programme types, target populations, and their design and implementation. Based on this discussion, a number of recommendations for physical activity promotion practice are then made. The article concludes that, until a stronger evidence base becomes available, health professionals, physical educators and other practitioners should be encouraged to plan, implement and evaluate physical activity programmes for young people and draw on such recommendations to inform their practice.
Morphology of Extruded PP/HDPE Foam Blends
Authors: Sahagún C. Zepeda , González-Núñez R. , Rodrigue D.
Published: October 2006

A complete three-dimensional morphological analysis is performed to determine the size and deformation of both foam cells and dispersed phase particles in the extrusion foaming of HDPE/PP blends. Each dimension is carefully measured to determine interaction between blending and foaming on the final foam morphology. In this study, blends of 0, 10, 30, 50, 70, 90, and 100% PP in HDPE are foamed using azodicarbonamide (ACA). The effect of using a compatibilizing agent (Kraton D 1102) is also included.