bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenoviral Transduction ofMRP-1/CD9andKAI1/CD82Inhibits Lymph Node Metastasis in Orthotopic Lung Cancer Model
Authors: Takeda Takayuki , Hattori Noboru , Tokuhara Takahiro , Nishimura Yoshihiro , Yokoyama Mitsuhiro , Miyake Masayuki
Published: February 2007

Conventional therapies still remain less effective for metastasis of lung cancer, thus leading to a poor prognosis for this disorder. Although the processes involved in metastasis have not yet been clearly elucidated, our previous studies have shown that higher expression levels of MRP-1/CD9 and KAI1/CD82 in cancer cells are significantly correlated with less metastatic potency. To determine whether the gene transfer of these tetraspanins into lung tumor cells may be a useful strategy to regulate metastasis, we adopted an orthotopic lung cancer model produced by the intrapulmonary implantation of Lewis lung carcinoma (LLC) cells and evaluated the metastatic growth in the mediastinal lymph nodes using two different methods of gene delivery as follows: (a) the implantation of LLC cells preinfected with adenovirus encoding either MRP-1/CD9 cDNA, KAI1/CD82 cDNA, or LacZ gene into the mouse lung and (b) the intratracheal administration of these adenoviruses into the mice orthotopically preimplanted with LLC cells. In both cases, we found that the delivery of either MRP-1/CD9 or KAI1/CD82 cDNA dramatically reduced the metastases to the mediastinal lymph nodes in comparison with those of LacZ gene delivery, without affecting the primary tumor growth at the implanted site. These results reemphasize the important role of MRP-1/CD9 and KAI1/CD82 in the suppression of the metastatic process and also show the feasibility of gene therapy when using these tetraspanins for lung cancer to prevent metastasis to the regional lymph nodes. This strategy may therefore be clinically applicable as a prophylactic treatment to suppress the occurrence of lymph node metastasis. [Cancer Res 2007;67(4):1744–9]
Adaptation of Energy Metabolism in Breast Cancer Brain Metastases
Authors: Chen Emily I. , Hewel Johannes , Krueger Joseph S. , Tiraby Claire , Weber Martin R. , Kralli Anastasia , Becker Katja , Yates John R. , Felding-Habermann Brunhilde
Published: February 2007

Brain metastases are among the most feared complications in breast cancer, as no therapy exists that prevents or eliminates breast cancer spreading to the brain. New therapeutic strategies depend on specific knowledge of tumor cell properties that allow breast cancer cell growth within the brain tissue. To provide information in this direction, we established a human breast cancer cell model for brain metastasis based on circulating tumor cells from a breast cancer patient and variants of these cells derived from bone or brain lesions in immunodeficient mice. The brain-derived cells showed an increased potential for brain metastasis in vivo and exhibited a unique protein expression profile identified by large-scale proteomic analysis. This protein profile is consistent with either a selection of predisposed cells or bioenergetic adaptation of the tumor cells to the unique energy metabolism of the brain. Increased expression of enzymes involved in glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation pathways suggests that the brain metastatic cells derive energy from glucose oxidation. The cells further showed enhanced activation of the pentose phosphate pathway and the glutathione system, which can minimize production of reactive oxygen species resulting from an enhanced oxidative metabolism. These changes promoted resistance of brain metastatic cells to drugs that affect the cellular redox balance. Importantly, the metabolic alterations are associated with strongly enhanced tumor cell survival and proliferation in the brain microenvironment. Thus, our data support the hypothesis that predisposition or adaptation of the tumor cell energy metabolism is a key element in breast cancer brain metastasis, and raise the possibility of targeting the functional differentiation in breast cancer brain lesions as a novel therapeutic strategy. [Cancer Res 2007;67(4):1472–86]
Heat Shock Protein 90 and ErbB2 in the Cardiac Response to Doxorubicin Injury
Authors: Gabrielson Kathleen , Bedja Djahida , Pin Scott , Tsao Allison , Gama Lucio , Yuan Bibo , Muratore Nicole
Published: February 2007

A major drawback to doxorubicin as a cancer-treating drug is cardiac toxicity. To understand the mechanism of doxorubicin cardiac toxicity and the potent synergic effect seen when doxorubicin is combined with anti-ErbB2 (trastuzumab), we developed an in vivo rat model that exhibits progressive dose-dependent cardiac damage and loss of cardiac function after doxorubicin treatment. The hearts of these animals respond to doxorubicin damage by increasing levels of ErbB2 and the ErbB family ligand, neuregulin 1β, and by activating the downstream Akt signaling pathway. These increases in ErbB2 protein levels are not due to increased ErbB2 mRNA, however, suggesting post-transcriptional mechanisms for regulating this protein in the heart. Accordingly, levels of heat shock protein 90 (HSP90), a known ErbB2 protein stabilizer and chaperone, are increased by doxorubicin treatment, and coimmunoprecipitation reveals binding of HSP90 to ErbB2. Isolated cardiomyocytes are more susceptible to doxorubicin after treatment with HSP90 inhibitor, 17-(allylamino)-17-demethoxygeldanamycin, suggesting that the HSP90 is protective during doxorubicin treatment. Thus, our results provide one plausible mechanism for the susceptibility of the heart to anti-ErbB2 therapy post-doxorubicin therapy in subclinical and clinical conditions. Additionally, these results suggest that further testing is needed for HSP90 inhibitors under various conditions in the heart. [Cancer Res 2007;67(4):1436–41]
Nuclear Factor-κB Is Central to the Expression of Truncated Neurokinin-1 Receptor in Breast Cancer: Implication for Breast Cancer Cell Quiescence within Bone Marrow Stroma
Authors: Ramkissoon Shakti H. , Patel Prem S. , Taborga Marcelo , Rameshwar Pranela
Published: February 2007

Breast cancer is a leading cause of mortality among women in the United States. Tac1 and neurokinin-1 (NK1) are involved in autocrine stimulation of breast cancer cells (BCCs). The single NK1 gene produces full-length (NK1-FL) and truncated (NK1-Tr) forms. NK1-Tr mediates malignancy in breast cells. We now report a critical role for nuclear factor-κB (NF-κB) in the expression of NK1-Tr, but not NK1-FL, in human BCCs. By Western and Northern blot analyses, NK1-FL and NK1-Tr were coexpressed in BCCs but were undetectable in nontumorigenic cells. Loss of repressive activity within the 5′ flanking region of the NK1 partly accounts for constitutive expression of NK1 in BCCs but could not account for the presence of NK1-Tr. Transient transfections with dominant-negative and wild-type IκB show that activation of NF-κB is required for the expression of NK1-Tr. Tac1 gene was linked to the generation of NK1-Tr because its overexpression in BCCs led to the production of multiple cytokines that can activate NF-κB to mediate NK1-Tr expression. Studies with Tac1 knockdown BCCs and Tac1-expressing nontumorigenic breast cells verified a role for NF-κB in the expression of NK1-Tr. The quiescent phenotype of BCCs on contact with bone marrow stroma was partly explained by decreased NF-κB activation and undetectable NK1-Tr. In summary, this study shows a role for NF-κB in the expression of NK1-Tr in BCCs, which seems to be reversed by bone marrow stromal cells. [Cancer Res 2007;67(4):1653–9]
Lapatinib induces apoptosis in trastuzumab-resistant breast cancer cells: effects on insulin-like growth factor I signaling
Authors: Nahta Rita , Yuan Linda X.H. , Du Yi , Esteva Francisco J.
Published: February 2007

The majority of breast cancer patients who achieve an initial therapeutic response to the HER2-targeted antibody trastuzumab will show disease progression within 1 year. Thus, the identification of novel agents that effectively inhibit survival of cancer cells that have progressed on trastuzumab is critical. In the current study, we show that the dual epidermal growth factor receptor (EGFR)/human EGFR-2 (HER2) kinase inhibitor lapatinib induces apoptosis in trastuzumab-resistant cells derived from the HER2-overexpressing SKBR3 breast cancer line. Lapatinib inhibited EGFR and HER2 signaling in resistant cells, blocking activation of downstream Akt, mitogen-activated protein kinase, and S6 kinases and inducing expression of p27kip1. Importantly, lapatinib also inhibited insulin-like growth factor I (IGF-I) signaling and growth-promoting effects in parental and resistant cells, and the cytotoxic effects of lapatinib were further enhanced by the IGF-I receptor–blocking antibody αIR3. As increased IGF-I receptor signaling has been implicated in trastuzumab resistance, our data strongly support further study of lapatinib as a potential therapeutic in breast cancers that have progressed on trastuzumab. [Mol Cancer Ther 2007;6(2):667–74]
Potent cytotoxicity of the phosphatase inhibitor microcystin LR and microcystin analogues in OATP1B1- and OATP1B3-expressing HeLa cells
Authors: Monks Noel R. , Liu Shuqian , Xu Yongsheng , Yu Hui , Bendelow Adam S. , Moscow Jeffrey A.
Published: February 2007

Microcystins are a family of cyclic peptides that are potent inhibitors of the protein phosphatase families PP1 and PP2A. Only three human proteins are thought to be able to mediate the hepatic uptake of microcystins (the organic anion-transporting polypeptides OATP1B1, OATP1B3, and OATP1A2), and the predominant hepatic expression of these transporters accounts for the liver-specific toxicity of microcystins. A significant obstacle in the study of microcystins as anticancer drugs is the requirement of specific transport proteins for cellular uptake. We report that OATP1B3 mRNA is up-regulated in non–small cell lung cancer tumors in comparison with normal control tissues. This finding led to the exploration of microcystins as potential anticancer agents. We have developed a HeLa cell model with functional OATP1B1 and OATP1B3 activity. Transiently transfected HeLa cells are over 1,000-fold more sensitive to microcystin LR than the vector-transfected control cells, showing that transporter expression imparts marked selectivity for microcystin cytotoxicity. In addition, microcystin analogues showed variable cytotoxicities in the OATP1B1- and OATP1B3-transfected cells, including two analogues with IC50 values <1 nmol/L. Cytotoxicity of microcystin analogues seems to correlate to the inhibition of PP2A in these cells and induces rapid cell death as seen by chromatin condensation and cell fragmentation. These studies show that microcystin-induced phosphatase inhibition results in potent cytotoxicity when microcystin compounds can gain intracellular access and are a potent novel class of therapeutic agents for tumors expressing these uptake proteins. [Mol Cancer Ther 2007;6(2):587–98]
Combining radiotherapy with AZD2171, a potent inhibitor of vascular endothelial growth factor signaling: pathophysiologic effects and therapeutic benefit
Authors: Williams Kaye J. , Telfer Brian A. , Shannon Aoife M. , Babur Muhammad , Stratford Ian J. , Wedge Stephen R.
Published: February 2007

AZD2171 is a highly potent, orally active inhibitor of vascular endothelial growth factor receptor signaling. The potential for AZD2171 to enhance the antitumor effects of radiotherapy was investigated in lung (Calu-6) and colon (LoVo) human tumor xenograft models. Combined treatment resulted in a significantly enhanced growth delay compared with either modality alone. The enhancement was independent of whether chronic once daily AZD2171 treatment was given 2 h prior to each radiation fraction (2 Gy daily for 3 or 5 consecutive days), and daily thereafter, or commenced immediately following the course of radiotherapy. Histologic assessments revealed that 5 days of radiation (2 Gy) or AZD2171 (3 or 6 mg/kg/d) reduced vessel density and perfusion. Concomitant AZD2171 and radiation enhanced this effect and produced a significant increase in tumor hypoxia. Concomitant AZD2171 (6 mg/kg/d) was also found to reduce tumor growth significantly during the course of radiotherapy (5 × 2 Gy). However, the extent and duration of tumor regression observed postradiotherapy was similar to sequentially treated tumors, suggesting that preirradiated tumors were sensitized to AZD2171 treatment. An enhanced antivascular effect of administering AZD2171 postradiotherapy was observed in real-time in Calu-6 tumors grown in dorsal window chambers. Collectively, these data support the clinical development of AZD2171 in combination with radiotherapy. [Mol Cancer Ther 2007;6(2):599–606]
Impact of Sleep and Sleep Loss on Neuroendocrine and Metabolic Function
Authors: van Cauter Eve , Holmbäck Ulf , Knutson Kristen , Leproult Rachel , Miller Annette , Nedeltcheva Arlet , Pannain Silvana , Penev Plamen , Tasali Esra , Spiegel Karine
Published: February 2007

Background: Sleep exerts important modulatory effects on neuroendocrine function and glucose regulation. During the past few decades, sleep curtailment has become a very common behavior in industrialized countries. This trend toward shorter sleep times has occurred over the same time period as the dramatic increases in the prevalence of obesity and diabetes. Aims: This article will review rapidly accumulating laboratory and epidemiologic evidence indicating that chronic partial sleep loss could play a role in the current epidemics of obesity and diabetes. Conclusions: Laboratory studies in healthy young volunteers have shown that experimental sleep restriction is associated with a dysregulation of the neuroendocrine control of appetite consistent with increased hunger and with alterations in parameters of glucose tolerance suggestive of an increased risk of diabetes. Epidemiologic findings in both children and adults are consistent with the laboratory data.
Genetics of Hypogonadotropic Hypogonadism
Authors: Simoni Manuela , Nieschlag Eberhard
Published: February 2007

Background: Idiopathic hypogonadotropic hypogonadism (HH) results from a defect in the normal pulsatile secretion pattern of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Clinically it can be categorized as one of two types: HH associated with anosmia, known as Kallmann syndrome, and isolated HH. The anatomical explanation for Kallmann syndrome stems from incomplete or total failure of GnRH-secreting neurons to migrate from the olfactory epithelium to their final destination in the mediobasal hypothalamus. Several genes are involved in the migration of the GnRH neurons. Conclusions: Mutations of the KAL1 gene, encoding for anosmin 1, and of the FGFR1 (or KAL2) gene, encoding for fibroblast growth factor receptor 1, can be found in familial cases of Kallmann syndrome. KAL1 mutations are responsible for X-linked recessive inheritance, and FGFR1 mutations are the autosomal dominant form. Moreover, mutations of the gonadotropin-releasing hormone receptor gene and G-protein-coupled receptor 54 gene are found in over 50% of familial cases of isolated HH with autosomal recessive inheritance.
Novel Germline Mutations in the SDHB and SDHD Genes in Japanese Pheochromocytomas
Authors: Isobe Kazumasa , Minowada Shigeru , Tatsuno Ichiro , Suzukawa Kazumi , Nissato Sumiko , Nanmoku Toru , Hara Hisato , Yashiro Toru , Kawakami Yasushi , Takekoshi Kazuhiro
Published: February 2007

The SDHA, SDHB, SDHC, and SDHD genes code for subunits of succinate dehydrogenase (SDH), which forms part of the mitochondrial respiratory chain. Germline mutations in the genes encoding SDHB and SDHD have been reported in familial paragangliomas/pheochromocytomas and in apparently sporadic pheochromocytomas. SDHB and SDHD mutations are widely distributed along the genes with no apparent hot spots. SDHB mutations are often detected in malignant and extra-adrenal pheochromocytomas. SDHD mutations are also detected frequently in head and neck paragangliomas. We sequenced the entire coding regions of the SDHB and SDHD genes in 17 pheochromocytomas. Weidentified novel heterozygous G to A point mutations at the first base of intron 3 of the SDHB gene in a malignant extra-adrenal abdominal pheochromocytoma patient, and at the first base of codon 111 of the SDHD gene in an adrenal pheochromocytoma patient. Further, we confirmed the SDHD mutation by DHPLC. The prevalence of SDHB and SDHD mutations in pheochromocytomas we examined was 12% (2/17). Thus, we identified two novel SDH mutations in Japanese pheochromocytomas. Further studies will investigate the oncogenic potential of these mutations.
Antileukemic and Cytogenetic Activity by Triple Administration of Three Modified Steroidal Derivatives of Nitrogen Mustards
Authors: Fousteris M.A. , Papageorgiou A. , Arsenou E.S. , Koutsourea A.I. , Karaberis E. , Mourelatos D. , Onyango D.O. , Nikolaropoulos S.S.
Published: February 2007

Combination chemotherapy is widely and routinely used for most cancer patients. The main objective of this study is an effort to develop new anticancer drugs and procedures with enhanced antitumor activity and reduced toxicity. This study was designed to determine the antileukemic and cytogenetic activity of five mixtures of three specific steroidal esters of aromatic nitrogen mustards in different proportions. This is the next step of two previous studies where the combination of two such esteric analogues was investigated with promising results. All of the five mixtures used proved active against leukemia P388 and in the induction of sister chromatid exchanges, indicating that the combination of the same class of compounds can be successful, especially when a highly potent agent is combined with another less active but probably mechanistically supplementary one. These results can be used in future experiments in order to further scout the specific role of the steroidal part of these molecules in the antileukemic potency of them.
Care Management of Poststroke Depression
Authors: Williams Linda S. , Kroenke Kurt , Bakas Tamilyn , Plue Laurie D. , Brizendine Edward , Tu Wanzhu , Hendrie Hugh
Published: February 2007

Background and Purpose—

Poststroke depression is a prevalent and disabling disorder, yet evidence regarding the effectiveness of treating poststroke depression is inconclusive. Our objective was to determine the effectiveness of the Activate-Initiate-Monitor care management program for the treatment of poststroke depression.

Methods—

We conducted a prospective, randomized, outcome-blinded trial in 188 ischemic stroke survivors identified at the time of admission to one of 4 Indianapolis hospitals. Depression screening and enrollment occurred between 1 and 2 months poststroke. The Activate-Initiate-Monitor intervention was a care management program that included
A
ctivation of the patient to recognize depression symptoms and accept treatment,
I
nitiation of an antidepressant medication, and
M
onitoring and adjusting treatment. Usual care subjects received nondepression-related education and were prescribed antidepressants at the discretion of their provider. The primary outcome measure was depression response, defined as a Hamilton Depression Inventory score <8 (remission) or a decrease from baseline of at least 50% at 12 weeks.

Results—

Intervention and usual care groups did not differ on any key baseline measures. Both depression response (51% versus 30%,
P
=0.005) and remission (39% versus 23%,
P
=0.01) were more likely in the Activate-Initiate-Monitor intervention than in the usual care group. This difference in depression scores was present by 6 weeks and persisted through the 12-week assessment. Serious adverse events did not differ between the 2 groups.

Conclusion—

The Activate-Initiate-Monitor care management model is significantly more effective than usual care in improving depression outcomes in patients with poststroke depression.
Associations of Fine and Ultrafine Particulate Air Pollution With Stroke Mortality in an Area of Low Air Pollution Levels
Authors: Kettunen Jaana , Lanki Timo , Tiittanen Pekka , Aalto Pasi P. , Koskentalo Tarja , Kulmala Markku , Salomaa Veikko , Pekkanen Juha
Published: February 2007

Background and Purpose—

Daily variation in outdoor concentrations of inhalable particles (PM
10
<10 μm in diameter) has been associated with fatal and nonfatal stroke. Toxicological and epidemiological studies suggest that smaller, combustion-related particles are especially harmful. We therefore evaluated the effects of several particle measures including, for the first time to our knowledge, ultrafine particles (<0.1 μm) on stroke.

Methods—

Levels of particulate and gaseous air pollution were measured in 1998 to 2004 at central outdoor monitoring sites in Helsinki. Associations between daily levels of air pollutants and deaths caused by stroke among persons aged 65 years or older were evaluated in warm and cold seasons using Poisson regression.

Results—

There was a total of 1304 and 1961 deaths from stroke in warm and cold seasons, respectively. During the warm season, there were positive associations of stroke mortality with current- and previous-day levels of fine particles (<2.5 μm, PM
2.5
) (6.9%; 95% CI, 0.8% to 13.8%; and 7.4%; 95% CI, 1.3% to 13.8% for an interquartile increase in PM
2.5
) and previous-day levels of ultrafine particles (8.5%; 95% CI, −1.2% to 19.1%) and carbon monoxide (8.3; 95% CI, 0.6 to 16.6). Associations for fine particles were mostly independent of other pollutants. There were no associations in the cold season.

Conclusions—

Our results suggest that especially PM
2.5
, but also ultrafine particles and carbon monoxide, are associated with increased risk of fatal stroke, but only during the warm season. The effect of season might be attributable to seasonal differences in exposure or air pollution mixture.
Adipose Tissue and Atherosclerosis
Authors: Fantuzzi Giamila , Mazzone Theodore
Published: February 2007

The prevalence of obesity, especially among the young, is dramatically increasing in the United States. Obesity is associated with accelerated atherosclerosis and increased rates of cardiovascular death. There are many plausible mechanisms by which an increase in adipose tissue could adversely affect the vessel wall. These include the changes in blood pressure, glucose level, lipid/lipoprotein metabolism, and systemic inflammation. In addition, factors secreted by adipose tissue may directly influence vessel wall homeostasis by influencing the function of endothelial cells, arterial smooth muscle cells, and macrophages in the vessel wall. There is general agreement that central, as opposed to peripheral, adipose tissue confers the most cardio-metabolic risk. Although the basis of this differential risk has not been not established, the pattern of gene expression and secretory products in visceral fat would be predicted to be more atherogenic compared with that in subcutaneous peripheral fat. Numerous studies have shown the beneficial effects of weight loss on markers of cardiovascular risk but fewer have demonstrated improvement in direct measures of large vessel disease. The unfolding role of adipose tissue as an important metabolic and secretory organ provides new opportunities for developing more effective approaches for preventing obesity and its atherosclerotic complications.
High-Density Lipoprotein Attenuates Inflammation and Coagulation Response on Endotoxin Challenge in Humans
Authors: Birjmohun Rakesh S. , van Leuven Sander I. , Levels Johannes H.M. , van ‘t Veer Cornelis , Kuivenhoven Jan Albert , Meijers Joost C.M. , Levi Marcel , Kastelein John J.P. , van der Poll Tom , Stroes Erik S.G.
Published: February 2007

Objective—

Low high-density lipoprotein (HDL) cholesterol is a strong independent cardiovascular risk factor, which has been attributed to its role in reverse cholesterol transport. Whereas HDL also has potent antiinflammatory effects, the relevance of this property remains to be established in humans. In the present study, we evaluated whether there is a relation between HDL and sensitivity toward a low-dose endotoxin challenge.

Methods and Results—

Thirteen healthy men with genetically determined isolated low HDL cholesterol (averaging 0.7±0.1 mmol/L) and 14 age- and body weight-matched healthy men with normal/high HDL cholesterol levels (1.9±0.4 mmol/L) were challenged with low-dose endotoxin intravenously (1 ng/kg body weight). The incidence and severity of endotoxin-associated clinical symptoms was increased in the low HDL group. Accordingly, both the inflammatory response (tumor necrosis factor-α, IL-1β, IL-6, IL-8, and monocyte chemoattractant protein-1) as well as thrombin generation (prothrombin activation fragments F
1+2
) were significantly increased in the low HDL group on endotoxin challenge.

Conclusions—

Low HDL in healthy males is associated with increased sensitivity toward inflammatory stimuli as reflected by enhanced inflammatory and coagulation responses on endotoxin challenge. These antiinflammatory effects of HDL in humans may lend further support to HDL-increasing interventions, particularly in proinflammatory conditions, such as acute coronary syndromes.
Genetic Etiology of Isolated Low HDL Syndrome
Authors: Kiss Robert S. , Kavaslar Nihan , Okuhira Kei-ichiro , Freeman Mason W. , Walter Stephanie , Milne Ross W. , McPherson Ruth , Marcel Yves L.
Published: February 2007

Objective—

We have used a multitiered approach to identify genetic and cellular contributors to high-density lipoprotein (HDL) deficiency in 124 human subjects.

Methods and Results—

We resequenced 4 candidate genes for HDL regulation and identified several functional nonsynonymous mutations including 2 in apolipoprotein A-I (
APOA1
), 4 in lecithin:cholesterol acyltransferase (
LCAT
), 1 in phospholipid transfer protein (
PLTP
), and 7 in the ATP-binding cassette transporter
ABCA1
, leaving 88% (110/124) of HDL deficient subjects without a genetic diagnosis. Cholesterol efflux assays performed using cholesterol-loaded monocyte-derived macrophages from the 124 low HDL subjects and 48 control subjects revealed that 33% (41/124) of low HDL subjects had low efflux, despite the fact that the majority of these subjects (34/41) were not carriers of dysfunctional
ABCA1
alleles. In contrast, only 2% of control subjects presented with low efflux (1/48). In 3 families without
ABCA1
mutations, efflux defects were found to cosegregate with low HDL.

Conclusions—

Efflux defects are frequent in low HDL syndromes, but the majority of HDL deficient subjects with cellular cholesterol efflux defects do not harbor
ABCA1
mutations, suggesting that novel pathways contribute to this phenotype.
DNA Vaccination Against VEGF Receptor 2 Reduces Atherosclerosis in LDL Receptor–Deficient Mice
Authors: Petrovan Ramona J. , Kaplan Charles D. , Reisfeld Ralph A. , Curtiss Linda K.
Published: February 2007

Objective—

Similarities between neovascular ingrowth in atherosclerotic plaques and angiogenesis in tumors suggest that antiangiogenic factors that target tumor expansion may prove efficacious in the treatment of atherosclerosis. This study examined whether an oral DNA vaccine against the murine VEGF receptor 2 (Flk-1) with demonstrated antitumor effect through inhibition of pathological neovascularization can prevent or retard progression of atherosclerosis in hyperlipidemic low density lipoprotein receptor–deficient (LDLr
−/−
) mice.

Methods and Results—

Vaccination against Flk-1 resulted in T cell activation, suppression of neoangiogenesis, and a marked reduction in atherosclerosis which was independent of hypercholesterolemia in both male and female mice. Immunohistochemical characterization of aortic sinus lesions showed that the decreased lesion area was not associated with reduced plaque stability and had a lower density of microvessels.

Conclusions—

These findings demonstrate for the first time that a DNA vaccine targeting activated endothelial cells in atherosclerotic lesions provides direct atheroprotective effects.
Circulating Secretory Phospholipase A2 Activity and Risk of Incident Coronary Events in Healthy Men and Women
Authors: Mallat Ziad , Benessiano Joelle , Simon Tabassome , Ederhy Stéphane , Sebella-Arguelles Carla , Cohen Ariel , Huart Virginie , Wareham Nicholas J. , Luben Robert , Khaw Kay-Tee , Tedgui Alain , Boekholdt S. Matthijs
Published: February 2007

Objective—

To assess the association between secretory phospholipase A2 (sPLA2) activity, which encompasses several types of sPLA2, and cardiovascular disease (CAD) in healthy individuals.

Methods and Results—

We investigated this association in a nested case-control study among the 25 663 participants in EPIC-Norfolk cohort. Cases (n=991) were subjects in whom CAD developed during the 6 years of mean follow-up. Controls (n=1806) matched by age, sex, and enrollment time remained free of any CAD during follow-up. The risk of incident CAD was associated with increasing quartiles of sPLA2 activity (
P
<0.001). After adjustment for risk factors, C-reactive protein and sPLA2 type IIA concentration, the odds ratios of incident CAD in the second, third, and fourth quartiles of sPLA2 activity were 1.41, 1.33, and 1.56 (
P
=0.003), compared with the lowest quartile. sPLA2 activity and CRP were poorly correlated (
r
=0.15), and their combined values were more informative for incident risk of CAD than either biomarker alone. Subjects in the highest quartiles of sPLA2 activity and CRP had an adjusted odds ratio of 2.89 (95% confidence interval, 1.78 to 4.68;
P
<0.001) for CAD compared with those with the lowest quartiles of both markers.

Conclusions—

Measurement of serum sPLA2 activity provides additive prognostic value to traditional risk factors and CRP levels, and identifies a subgroup of individuals at high risk for incident CAD. Measurement of sPLA2 type II concentration had little added prognostic utility.
The Rise and Fall of Popular Mass Movements
Authors: Tranvik Tommy , Selle Per
Published: February 2007

This article is about the erosion of the Norwegian democratic infrastructure, with particular emphasis on the causes and effects of the transformation of the voluntary sector and the decline of social movements. We are seeing a turning away from large-scale ideological mass movements and an increase in smaller and nimbler associations that are better at catering for individual needs and wishes, but poorer in plugging members into the central decision-making institutions. This is putting increasing pressure on the Norwegian social contract, which has been characterized by high levels of institutional centralization balanced by high levels of citizen control. We relate these important changes in the democratic infrastructure to the impact of globalization, highlighting structural similarities between globalization and the new organizational forms of political or civic participation. Our argument is that globalization is a process that has particular structural characteristics, and that these characteristics are giving shape to the new forms of civic participation that are now emerging in Norway (and probably also in the rest of Scandinavia).
The Cato Manor Development Project in Durban, South Africa
Authors: Odendaal Nancy
Published: February 2007

Cato Manor, located on the outskirts of Durban, South Africa, was the focus of massive development efforts led by the Cato Manor Development Association (CMDA)—an agency that partnered with community-based organizations in facilitating redevelopment of this poor, underserviced area—from 1993 to 2003. The aim of the project was to create an area spatially and functionally integrated with metropolitan Durban in ensuring that poor urban residents have access to employment as well as social and infrastructure services. Implementation of the project was beset with enormous difficulties, many of which related to the massive transformational changes that the country was experiencing during this time. Innovation was often contextually driven, but some argue that the nature of the CMDA, as an independent agency free of the institutional constraints of government, as well as the nature of the collaboration with local community organizations together with the vision and commitment of the development team, led to innovative practice. This article aims to understand the extent to which innovation was achieved and uncovers the dynamics underpinning this.
Ideological Success, Educational Failure?
Authors: Apple Michael W.
Published: February 2007

Most educators in the United States have had to confront the changed reality brought about by the federal reauthorization of the Elementary and Secondary Education Act, commonly known as No Child Left Behind (NCLB). This represents a set of initiatives that can radically transform the federal role in policing and controlling core aspects of education in general and teacher education. Using a number of key volumes that have been written to either criticize or support major components of NCLB, I provide a critical reading of the assumptions behind NCLB and point to a number of its key negative implications for educational policy and practice. In the process, I point to areas where educators might look for more critically democratic alternatives.
The Relationship of Statistical and Psychological Risk Markers to Sexual Reconviction in Child Molesters
Authors: Craig Leam A. , Thornton David , Beech Anthony , Browne Kevin D.
Published: February 2007

This study examines the integration of statistical and psychological risk factors using psychometric markers of psychopathology and psychosexual characteristics from the Static-99 in 119 sexual offenders. Psychological risk markers are combined to approximate four deviancy domains: sexual interests, distorted attitudes, socio-affective functioning, and self-management. The sexual interests domain predicts sexual reconviction independent of Static-99. The four deviancy domains are used to calculate the Psychological Deviance Index, which was also found to predict sexual reconviction independent of Static-99. Organizing the Static-99 risk items into three subscales (sexual deviance, general criminality, and immaturity) reveals a distinct pattern of correlations within the psychological markers and risk domains. The Static-99 sexual deviance and general criminality subscales make modest predictions. Results support the use of integrating statistical and psychological markers within a risk domains framework in predicting sexual reconviction.
Computer Equivalency of the Psychopathic Personality Inventory-Revised in a Nonincarcerated Population
Authors: Sandler Jeffrey C.
Published: February 2007

This study is designed to test the equivalency of the paper format of the Psychopathic Personality Inventory-Revised (PPIR) with a computerized (online) version. It is hypothesized that the psychometric properties of the PPI-R would continue to hold when the administration format was changed from paper to computer. A total of 124 respondents participate in the study. Participant scores on all 15 of the PPI-R scales are found to be similar, as are all internal scale consistencies. Test-retest reliabilities for scores on the PPI-R Overall Total, Factors, and Content scales range from r = .76 (Coldheartedness) to r = .93 (PPI-R Total). The computerized format also allows for both more efficient scoring (i.e., no hand coding) and more complete responding (i.e., less missing data).
Development and Initial Examination of a Brief Intervention for Heightened Anxiety Sensitivity Among Heroin Users
Authors: Tull Matthew T. , Schulzinger David , Schmidt Norman B. , Zvolensky Michael J. , Lejuez C. W.
Published: February 2007

Anxiety sensitivity (AS) recently has been identified as a potential cognitive vulnerability underlying substance use problems, with some evidence specifically indicating its relevance to heroin. Focusing on the potential utility of interventions centered on increasing willingness to have anxiety-related sensations reduce vulnerability for relapse following substance use treatment, the current article describes the development of a brief (6 session) behavioral treatment for heightened AS among heroin users. The treatment consists of the following components: (a) psychoeducation about anxiety; (b) interoceptive exposure exercises; and (c) skills-training focused on heightening emotional acceptance, tolerance, and nonevaluative awareness (to facilitate willingness). Preliminary data on this treatment are provided in the form of a case study with a 46-year-old African American man in an inner-city residential substance use treatment facility. Results indicate reductions in AS (especially physical concerns), as well as corresponding decreases in heroin cravings and improvements in emotion regulation.
Adorno's aesthetic concept of aura
Authors: Sherratt Yvonne
Published: February 2007

Philosophers within the discipline of the history of philosophy have long since demonstrated a preoccupation with the history of aesthetic ideas. However, not all aesthetic concepts in 19th- and 20th-century thought have been given an adequate analysis. One concept which, while attracting interest in literary theory debates, has rarely been mentioned in history of philosophy debates, is that of aura. The reason for the marginal role of aura in present debates is due no doubt to the difficult and sometimes utterly obscure nature of Adorno's texts, which often veils their underlying philosophical content. Aura concept is important because it represents a still rather neglected strand of Adorno's Aesthetische Theorie, which has often been regarded as solely an avocation of the aesthetics of the ‘New’. This article offers an original and in-depth analysis of this key concept showing how significant it is to Adorno's overall project.
The ethical residue of language in Levinas and early Wittgenstein
Authors: Overgaard Søren
Published: February 2007

Using the later Levinas as a point of departure, this article tries to provide an account of the ethics of Wittgenstein's Tractatus. Although there has not been written much on this topic, there seems to be an increasing awareness among philosophers that there are interesting points of convergence between Levinas and the early Wittgenstein. In contrast to most (if not all) other accounts of the relation, however, this article argues that the truly significant convergence emerges only when one abandons the received interpretation of the early Wittgenstein, and instead opts for something more akin to the ‘new Wittgenstein’ interpretation introduced by Cora Diamond and James Conant, among others. On the received interpretation, Wittgenstein places ethics in a realm of ineffable being and truth, and thus remains within what Levinas calls ontology. But on Conant's and Diamond's reading of Wittgenstein, there really are no profound ethical truths that we cannot state, but only ‘show’; all the sentences of the Tractatus that appear to claim otherwise are ultimately completely nonsensical. This article argues that the Tractatus has an ‘ethical point’ in a quite Levinasian sense, precisely because of the way it unveils its sentences as utterly nonsensical; for this can be seen as a Wittgensteinian attempt to ‘unsay’ the ‘said’, in order to let the ‘saying’ itself be heard.
Questioning and the materiality of crisis
Authors: Jackson Jeffrey M.
Published: February 2007

The theme of the possibility or impossibility of the compatibility between Heideggerian philosophy and Freudian metapsychology has been taken up in various ways. Without going into the details of this body of commentary, it is argued that there is a clear difference between the ways in which Heidegger and Freud think cultural crisis. By examining texts of both thinkers from the early 1930s, it is shown that whereas Freud conceives of the possibility of amelioration of crisis in terms of a grappling with material necessity, Heidegger's philosophical conception of crisis seeks to bring about freedom's performative coincidence with ontological necessity. Heidegger's approach, it is claimed, is blind to the confrontation with material necessity that is its own condition of possibility. This blindness is evident in his ontological understanding of suffering.
The unexpected side-effects of dissonance
Authors: Bodner Ehud , Gilboa Avi , Amir Dorit
Published: February 2007

The effects of dissonant and consonant music on cognitive performance were examined. Situational dissonance and consonance were also tested and determined as the state where one’s opinion is contrasted or matched with the majority’s opinion, respectively. Subjects performed several cognitive tasks while listening to a melody arranged dissonantly, consonantly or under silence. Prior to hearing the music, subjects were given ‘worldwide opinions’ of the music they were about to hear: adequate information (e.g. positive evaluation of consonant music), inadequate information (e.g. positive evaluation of dissonant music) or neutral information. Results showed that dissonant situations (musical as well situational) improved cognitive abilities. This was found under different cognitive loads. A possible explanation involves recalibration of the dissonance-consonance continuum with arousal. It may be that dissonance brings arousal to optimal levels, thus sharpening concentration. Ways to expand the understanding of dissonance and its effects on performance and cognition are discussed.
Law and Life: Leviticus 18.5 in the Literary Framework of Ezekiel
Authors: Sprinkle Preston
Published: February 2007

While it is often recognized that Ezekiel alludes to Lev. 18.5 throughout Ezekiel 20, this essay seeks to show that the Leviticus text is referred to in various other portions of the book. These allusions connect two major motifs in the book of Ezekiel: Israel’s disobedience to the ‘statutes and judgments’ of Yahweh and the lack of life therein. These motifs are climactically fulfilled in chs. 36-37 where Yahweh causes Israel to obey his ‘statutes and judgments’ and breathes life into the nation. This suggests that the text of Lev. 18.5 was selected to highlight the conditional nature of these covenant stipulations, which amplifies divine agency in the program of restoration.
Public Sector Compensation in Local Governments
Authors: Reilly Thom , Schoener Shaun , Bolin Alice
Published: February 2007

The purpose of this study was to examine local government compensation practices across the United States and to explore possible correlations of these practices to service delivery. One hundred twenty of the largest cities and counties responded to a mail survey, for a response rate of 40%. The data suggest a large percentage (86%) of local governments faced financial difficulties in the form of a budget shortfall since 2000. In response to these shortfalls, local governments were more likely to reduce their workforce, reduce or eliminate services, and/or raise taxes or user fees rather than scale back wages and benefits. Because of this reaction, more than one half of the respondents experienced a decrease in full-time equivalent employment per 1,000 residents. Collective bargaining status, geographical region, and type of government (county or city) were found to be significant factors in determining compensation practices. Implications for practice and policy are advanced.
The Changing Face of Public Employee Unionism
Authors: Riccucci Norma M.
Published: February 2007

This article provides a brief picture of the various unions that currently represent state and local government employees in the United States, including teachers and professors. It reviews the factors that have contributed to union decline in the private sector, and those factors explaining union growth in the public sector. Its purpose is purely descriptive, seeking to illustrate the ability of unions to seize opportunities to organize public employees, thereby increasing their “strength in numbers.”
Working Women Making It Work
Authors: Swanberg Jennifer , Macke Caroline , Logan TK
Published: February 2007

Partner violence may have significant consequences on women’s employment, yet limited information is available about how women cope on the job with perpetrators’ tactics and the consequences of her coping methods on employment status. This article investigates whether there is an association between workplace disclosure of victimization and current employment status; and whether there is an association between receiving workplace support and current employment status among women who disclosed victimization circumstances to someone at work. Using a sample of partner victimized women who were employed within the past year ( N = 485), cross-tabulation and ANOVA procedures were conducted to examine the differences between currently employed and unemployed women. Binary logistic regressions were conducted to examine whether disclosure and receiving workplace support were significantly associated with current employment. Results indicate that disclosure and workplace support are associated with employment. Implications for clinical practice, workplace policies, and future research are discussed.
Impossible Selves
Authors: Pizzolato Jane Elizabeth
Published: February 2007

Through study of 32 students’ narratives about coping with external threats to their career goals (e.g., denial of admission to the major of their choice), this study examines the following issues: (a) the coping mechanisms student use when faced with threats that loom large, (b) the relation between coping methods employed and whether the goal is retained, and (c) what seems to facilitate student use of coping strategies that support goal achievement. Findings suggest that threat attributions and coping strategies led to either exiting or recycling through the career development process. The ability to jointly consider career goals and goals unrelated to career, while allowing career goals to guide the coping process, was most strongly related to retention or revision (rather than abandonment) of the career-possible self. Implications for theory and practice are discussed
Impact Loads Identification in Standoff Metallic Thermal Protection System Panels
Authors: Hundhausen R. Jason , Adams Douglas E. , Derriso Mark
Published: February 2007

This article describes two experimental approaches for the identification of transient impact loads applied to a metallic composite thermal protection system (TPS) panel. The critical nature of the TPS to the survival of the vehicle and crew warrants the development of a technique that can detect, quantify, and locate transient impact loads. This information will provide an opportunity to identify specific panels that are more or less prone to damage from transient impacts. Furthermore, a historical database of impact loads encountered can be retained for use in the development of statistical models that relate impact loading to panel life. The two techniques presented herein are a physics-based approach, where the panel is assumed to behave as a rigid body at low frequencies, and an inverse frequency response approach, where the system impedance matrix is measured, from which the loads acting on the panel can be estimated using the measured response. The validity of approaches is verified experimentally, and it is shown that the inverse frequency response method is capable of detecting, locating, and quantifying transient impact loads to a high degree of accuracy.
Broadband Active Vibration Control of a Rectangular Flexible Wall of an Empty and a Water-filled Tank
Authors: Carra S. , Amabili M. , Ohayon R.
Published: February 2007

Broadband active vibration control of a rectangular plate representing a flexible wall of a thick Plexiglas container is experimentally investigated, for both empty and water-filled tanks, using five piezoelectric patches as control actuators. Preliminary dynamical analyses are carried out on the system in order to verify the influence of different water levels and different environment conditions (in particular, temperatures) on the system dynamics. Active vibration control is then experimentally applied to the plate with a single input—single output approach in the presence of broadband primary disturbance between 0 and 400 Hz, testing both filtered-x least mean square adaptive feedforward control and direct velocity feedback control. The time delay through the disturbance and control paths is measured.