bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of hypoxia on the expression of phosphoglycerate kinase and antitumor activity of troxacitabine and gemcitabine in non-small cell lung carcinoma
Authors: Lam Wing , Bussom Scott , Cheng Yung-Chi
Published: February 2009

β-l-Dioxolane-cytidine (l-OddC; BCH-4556; troxacitabine), a novel l-configuration deoxycytidine analogue, was under clinical trials for treating cancer. The cytotoxicity of l-OddC is dependent on its phosphorylation to l-OddCTP by phosphoglycerate kinase (PGK) and its subsequent addition into nuclear DNA. Because PGK is induced with hypoxia, the expression of hypoxia-inducible factor-1α and PGK of H460 cells (human non-small cell lung carcinoma) in vitro and in vivo was studied. In culture, hypoxic treatment induced the protein expression of PGK by 3-fold but had no effect on the protein expression of other l-OddC metabolism-associated enzymes such as apurinic/apyrimidinic endonuclease-1, deoxycytidine kinase, CMP kinase, and nM23 H1. Using a clonogenic assay, hypoxic treatment of H460 cells rendered cells 4-fold more susceptible to l-OddC but not to gemcitabine (dFdC) following exposure to drugs for one generation. Using hypoxia response element-luciferase reporter system, Western blotting, and immunohistochemistry, it was found that hypoxia-inducible factor-1α and PGK expression increased and could be correlated to tumor size. Despite dFdC being more toxic than l-OddC in cell culture, l-OddC (300 mg/kg i.p.) had a stronger antitumor activity than dFdC in H460 xenograft-bearing nude mice. Furthermore, l-OddC retained ∼50% of its antitumor activity with oral gavage compared with i.p. delivery. Oral administration of l-OddC (600 mg/kg p.o.) had a similar area under the curve value compared with i.p. injection of dFdC (300 mg/kg i.p.). In conclusion, the hypoxia, which commonly exists in non-small cell lung carcinoma or other solid tumors resistant to radiotherapy or chemotherapy, is a favorable determinant to enhance the antitumor activity of l-OddC in vivo. [Mol Cancer Ther 2009;8(2):415–23]
EFEMP1 Expression Promotes In vivo Tumor Growth in Human Pancreatic Adenocarcinoma
Authors: Seeliger Hendrik , Camaj Peter , Ischenko Ivan , Kleespies Axel , De Toni Enrico N. , Thieme Susanne E. , Blum Helmut , Assmann Gerald , Jauch Karl-Walter , Bruns Christiane J.
Published: February 2009

The progression of pancreatic cancer is dependent on local tumor growth, angiogenesis, and metastasis. EFEMP1, a recently discovered member of the fibulin family, was characterized with regard to these key elements of pancreatic cancer progression.

Differential gene expression was assessed by mRNA microarray hybridization in FG human pancreatic adenocarcinoma cells and L3.6pl cells, a highly metastatic variant of FG. In vivo orthotopic tumor growth of EFEMP1-transfected FG cells was examined in nude mice. To assess the angiogenic properties of EFEMP1, vascular endothelial growth factor (VEGF) production of tumor cells, endothelial cell proliferation and migration, and tumor microvessel density were analyzed in response to EFEMP1. Further, tumor cell apoptosis, cell cycle progression, and resistance to cytotoxic agents were quantitated by propidium iodide staining and flow cytometry. In microarray hybridization, EFEMP1 was shown to be significantly up-regulated in L3.6pl cells compared with FG cells. Concordantly, EFEMP1 transfection of FG cells stimulated orthotopic and metastatic tumor growth in vivo. EFEMP1 expression resulted in a stimulation of VEGF production by tumor cells and an increased number of CD31-positive microvessels. Endothelial cell proliferation and migration were not altered by EFEMP1, indicating an indirect angiogenic effect. Further, EFEMP1 expression decreased apoptosis and promoted cell cycle progression in response to serum starvation or exposure to gemcitabine, 5-fluorouracil, and irinotecan.

EFEMP1 has protumorigenic effects on pancreatic cancer in vivo and in vitro mediated by VEGF-driven angiogenesis and antiapoptotic mechanisms. Hence, EFEMP1 is a promising candidate for assessing prognosis and individualizing therapy in a clinical tumor setting. (Mol Cancer Res 2009;7(2):189–98)
Annexin-1 Regulates Growth Arrest Induced by High Levels of Estrogen in MCF-7 Breast Cancer Cells
Authors: Ang Emily Zhao-Feng , Nguyen Hung Thanh , Sim Hui-Ling , Putti Thomas C. , Lim Lina H.K.
Published: February 2009

Estrogen, a naturally occurring female steroid growth hormone, has been implicated as a major risk factor for the development of breast cancer. Recent research into this disease has also correlated Annexin-1 (ANXA1), a glucocorticoid-inducible protein, with the development of breast tumorigenesis. ANXA1 is lost in many cancers, including breast cancer, and this may result in a functional promotion of tumor growth. In this study, we investigated the expression of ANXA1 in MCF-7 cells treated with estrogen and the regulation of estrogen functions by ANXA1. Exposure of MCF-7 breast cancer cells to high physiologic levels (up to 100 nmol/L) of estrogen leads to an up-regulation of ANXA1 expression partially through the activation of cyclic AMP-responsive element binding protein and dependency on activation of the estrogen receptor. In addition, treatment of MCF-7 cells with physiologic levels of estrogen (1 nmol/L) induced proliferation, whereas high pregnancy levels of estrogen (100 nmol/L) induced a growth arrest of MCF-7 cells, associated with constitutive activation of extracellular signal-regulated kinase 1/2 and up-regulation of cell cycle arrest proteins such as p21waf/cip. Silencing of ANXA1 with specific small interfering RNA reverses the estrogen-dependent proliferation as well as growth arrest and concomitantly modulates extracellular signal-regulated kinase 1/2 phosphorylation. We confirm that ANXA1 is lost in clinical breast cancer, indicating that the antiproliferative protective function of ANXA1 against high levels of estrogen may be lost. Finally, we show that ANXA1-deficient mice exhibit faster carcinogen-induced tumor growth. Our data suggest that ANXA1 may act as a tumor suppressor gene and modulate the proliferative functions of estrogens. (Mol Cancer Res 2009;7(2):266–74)
CD44 Variant Isoforms Promote Metastasis Formation by a Tumor Cell-Matrix Cross-talk That Supports Adhesion and Apoptosis Resistance
Authors: Klingbeil Pamela , Marhaba Rachid , Jung Thorsten , Kirmse Robert , Ludwig Thomas , Zöller Margot
Published: February 2009

CD44 designates a large family of proteins with a considerable structural and functional diversity, which are generated from one gene by alternative splicing. As such, the overexpression of CD44 variant isoform (CD44v) has been causally related to the metastatic spread of cancer cells. To study the underlying mechanism, stable knockdown clones with deletion of exon v7 containing CD44 isoforms (CD44vkd) of the highly metastatic rat adenocarcinoma line BSp73ASML (ASMLwt) were established. ASML-CD44vkd clones hardly form lung metastases after intrafootpad application and the metastatic load in lymph nodes is significantly reduced. Rescuing, albeit at a reduced level, CD44v expression in ASML-CD44vkd cells (ASML-CD44vrsc) restores the metastatic potential. The following major differences in ASMLwt, ASML-CD44vkd, and ASML-CD44vrsc clones were observed: (a) ASMLwt cells produce and assemble a matrix in a CD44v-dependent manner, which supports integrin-mediated adhesion and favors survival. This feature is lost in the ASML-CD44vkd cells. (b) CD44v cross-linking initiates phosphatidylinositol 3-kinase/Akt activation in ASMLwt cells. Accordingly, apoptosis resistance is strikingly reduced in ASML-CD44vkd cells. The capacity to generate an adhesive matrix but not apoptosis resistance is restored in ASML-CD44vrsc cells. These data argue for a 2-fold effect of CD44v on metastasis formation: CD44v-mediated matrix formation is crucial for the settlement and growth at a secondary site, whereas apoptosis resistance supports the efficacy of metastasis formation. (Mol Cancer Res 2009;7(2):168–79)
Yin Yang 1 Modulates Taxane Response in Epithelial Ovarian Cancer
Authors: Matsumura Noriomi , Huang Zhiqing , Baba Tsukasa , Lee Paula S. , Barnett Jason C. , Mori Seiichi , Chang Jeffrey T. , Kuo Wen-Lin , Gusberg Alison H. , Whitaker Regina S. , Gray Joe W. , Fujii Shingo , Berchuck Andrew , Murphy Susan K.
Published: February 2009

Survival of ovarian cancer patients is largely dictated by their response to chemotherapy, which depends on underlying molecular features of the malignancy. We previously identified YIN YANG 1 (YY1) as a gene whose expression is positively correlated with ovarian cancer survival. Herein, we investigated the mechanistic basis of this association. Epigenetic and genetic characteristics of YY1 in serous epithelial ovarian cancer were analyzed along with YY1 mRNA and protein. Patterns of gene expression in primary serous epithelial ovarian cancer and in the NCI60 database were investigated using computational methods. YY1 function and modulation of chemotherapeutic response in vitro was studied using small interfering RNA knockdown. Microarray analysis showed strong positive correlation between expression of YY1 and genes with YY1 and transcription factor E2F binding motifs in ovarian cancer and in the NCI60 cancer cell lines. Clustering of microarray data for these genes revealed that high YY1/E2F3 activity positively correlates with survival of patients treated with the microtubule-stabilizing drug paclitaxel. Increased sensitivity to taxanes, but not to DNA cross-linking platinum agents, was also characteristic of NCI60 cancer cell lines with a high YY1/E2F signature. YY1 knockdown in ovarian cancer cell lines results in inhibition of anchorage-independent growth, motility, and proliferation but also increases resistance to taxanes, with no effect on cisplatin sensitivity. These results, together with the prior demonstration of augmentation of microtubule-related genes by E2F3, suggest that enhanced taxane sensitivity in tumors with high YY1/E2F activity may be mediated by modulation of putative target genes with microtubule function. (Mol Cancer Res 2009;7(2):210–20)
Inactivation of the MAL Gene in Breast Cancer Is a Common Event That Predicts Benefit from Adjuvant Chemotherapy
Authors: Horne Hisani N. , Lee Paula S. , Murphy Susan K. , Alonso Miguel A. , Olson John A. , Marks Jeffrey R.
Published: February 2009

Dysregulation of MAL (myelin and lymphocyte protein) has been implicated in several malignancies including esophageal, ovarian, and cervical cancers. The MAL protein functions in apical transport in polarized epithelial cells; therefore, its disruption may lead to loss of organized polarity characteristic of most solid malignancies. Bisulfite sequencing of the MAL promoter CpG island revealed hypermethylation in breast cancer cell lines and 69% of primary tumors analyzed compared with normal breast epithelial cells. Differential methylation between normal and cancer DNA was confined to the proximal promoter region. In a subset of breast cancer cell lines including T47D and MCF7 cells, promoter methylation correlated with transcriptional silencing that was reversible with the methylation inhibitor 5-aza-2′-deoxycytidine. In addition, expression of MAL reduced motility and resulted in a redistribution of lipid raft components in MCF10A cells. MAL protein expression measured by immunohistochemistry revealed no significant correlation with clinicopathologic features. However, in patients who did not receive adjuvant chemotherapy, reduced MAL expression was a significant predictive factor for disease-free survival. These data implicate MAL as a commonly altered gene in breast cancer with implications for response to chemotherapy. (Mol Cancer Res 2009;7(2):199–209)
p53 Mutant Human Glioma Cells Are Sensitive to UV-C-Induced Apoptosis Due to Impaired Cyclobutane Pyrimidine Dimer Removal
Authors: Batista Luis F.Z. , Roos Wynand P. , Kaina Bernd , Menck Carlos F.M.
Published: February 2009

The p53 protein is a key regulator of cell responses to DNA damage, and it has been shown that it sensitizes glioma cells to the alkylating agent temozolomide by up-regulating the extrinsic apoptotic pathway, whereas it increases the resistance to chloroethylating agents, such as ACNU and BCNU, probably by enhancing the efficiency of DNA repair. However, because these agents induce a wide variety of distinct DNA lesions, the direct importance of DNA repair is hard to access. Here, it is shown that the induction of photoproducts by UV light (UV-C) significantly induces apoptosis in a p53-mutated glioma background. This is caused by a reduced level of photoproduct repair, resulting in the persistence of DNA lesions in p53-mutated glioma cells. UV-C-induced apoptosis in p53 mutant glioma cells is preceded by strong transcription and replication inhibition due to blockage by unrepaired photolesions. Moreover, the results indicate that UV-C-induced apoptosis of p53 mutant glioma cells is executed through the intrinsic apoptotic pathway, with Bcl-2 degradation and sustained Bax and Bak up-regulation. Collectively, the data indicate that unrepaired DNA lesions induce apoptosis in p53 mutant gliomas despite the resistance of these gliomas to temozolomide, suggesting that efficiency of treatment of p53 mutant gliomas might be higher with agents that induce the formation of DNA lesions whose global genomic repair is dependent on p53. (Mol Cancer Res 2009;7(2):237–46)
Efficacy of Antibiotic Prophylaxis Before the Implantation of Pacemakers and Cardioverter-Defibrillators
Authors: de Oliveira Julio Cesar , Martinelli Martino , Nishioka Silvana Angelina D'Orio , Varejão Tânia , Uipe David , Pedrosa Anísio Alexandre Andrade , Costa Roberto , Danik Stephan B.
Published: February 2009

Background—

Although routinely administered, definitive evidence for the benefits of prophylactic antibiotics before the implantation of permanent pacemakers and implantable cardioverter-defibrillators from a large double-blinded placebo-controlled trial is lacking. The purpose of this study was to determine whether prophylactic antibiotic administration reduces the incidence of infection related to device implantation.

Methods and Results—

This double blinded study included 1000 consecutive patients who presented for primary device (Pacemaker and implantable cardioverter-defibrillators) implantation or generator replacement randomized in a 1:1 fashion to prophylactic antibiotics or placebo. Intravenous administration of 1 g of cefazolin (group I) or placebo (group 2) was done immediately before the procedure. Follow-up was performed 10 days, 1, 3, and 6 months after discharge. The primary end point was any evidence of infection at the surgical incision (pulse generator pocket), or systemic infection related to be procedure. The safety committee interrupted the trial after 649 patients were enrolled due to a significant difference in favor of the antibiotic arm (group I: 2 of 314 infected patients—0.63%; group II: 11 of 335 to 3.28%; RR=0.19
; P
=0.016). The following risk factors were positively correlated with infection by univariate analysis: nonuse of preventive antibiotic (
P
=0.016); implant procedures (versus generator replacement:
P
=0.02); presence of postoperative hematoma (
P
=0.03) and procedure duration (
P
=0.009). Multivariable analysis identified nonuse of antibiotic (
P
=0.037) and postoperative hematoma (
P
=0.023) as independent predictors of infection.

Conclusions—

Antibiotic prophylaxis significantly reduces infectious complications in patients undergoing implantation of pacemakers or cardioverter-defibrillators.
Burst Stimulation Improves Hemodynamics During Resuscitation After Prolonged Ventricular Fibrillation
Authors: Walcott Gregory , Melnick Sharon , Killingsworth Cheryl , Ideker Raymond
Published: February 2009

Background—

Although return of spontaneous circulation is frequently achieved during resuscitation for sudden cardiac arrest, systolic blood pressure can then decrease, requiring additional myocardial support. Previous studies have shown that a series of 1-ms electric pulses delivered through the defibrillation patches during ventricular fibrillation can stimulate the autonomic nervous system to increase myocardial function after defibrillation. We hypothesized that a similar series of electric pulses could increase myocardial function and blood pressure during the early postresuscitation period.

Methods and Results—

Six swine were studied that underwent 6 to 7 minutes of fibrillation. Each animal received 5, 10, 15, or 20 pulse packets consisting of six 10-A, 1-ms pulses every 3 to 4 s in random order whenever systolic blood pressure became <50 mm Hg. All 4 sets of pulse packets were delivered to each animal. Systolic blood pressure and cardiac function (left ventricular+dP/dt) were increased to above prestimulation levels or above by all 4 sets of pulse packets. The increases were significantly greater for the longer than the shorter number of pulse packets. The mean�SD duration of the time that the systolic pressure remained above 50 mm Hg after pulse delivery was 4.2�2.5 minutes.

Conclusions—

Electric stimulation during regular rhythm after prolonged ventricular fibrillation and resuscitation can increase blood pressure and cardiac function to above prestimulation levels.
Association of Cystatin C With Left Ventricular Structure and Function
Authors: Patel Parag C. , Ayers Colby R. , Murphy Sabina A. , Peshock Ronald , Khera Amit , de Lemos James A. , Balko Jody A. , Gupta Sachin , Mammen Pradeep P.A. , Drazner Mark H. , Markham David W.
Published: February 2009

Background—

Cystatin C, a novel marker of renal function, has been associated with heart failure and cardiovascular mortality in older individuals. We tested the hypothesis that cystatin C is associated with preclinical cardiac structural and functional abnormalities in a younger population-based sample.

Methods and Results—

The study included participants in the Dallas Heart Study (ages 30 to 65 years) who had measurements of cystatin C and cardiac MRI. The associations of cystatin C with left ventricular (LV) mass, LV end-systolic and -diastolic volumes, concentricity (LV mass/LV end-diastolic volume), LV wall thickness, and LV ejection fraction were evaluated. Cystatin C levels ranged from 0.46 to 6.55 mg/L. In univariable analyses, increasing levels of cystatin C correlated with higher LV mass, concentricity, and wall thickness (
P
<0.001), but not with LV end-systolic volume, LV end-diastolic volume, or LV ejection fraction. After adjustment with traditional covariates and estimated glomerular filtration rate by the modification of diet in renal disease formula, log-transformed cystatin C remained independently associated with LV mass (
P
<0.001), concentricity (
P
=0.027), and wall thickness (
P
<0.001). These associations persisted when creatinine or estimated glomerular filtration rate by the Cockcroft-Gault formula were included in the models.

Conclusions—

Higher levels of cystatin C were associated with increased LV mass and a concentric LV hypertrophy phenotype. These findings were independent of potential confounding variables including standard measurements of renal function, supporting the hypothesis that cystatin C may be useful to identify individuals with preclinical structural heart abnormalities.
Pheochromocytoma-Induced Cardiomyopathy is Modulated by the Synergistic Effects of Cell-Secreted Factors
Authors: Mobine Hector R. , Baker Aaron B. , Wang Libin , Wakimoto Hiroko , Jacobsen Kurt C. , Seidman Christine E. , Seidman J.G. , Edelman Elazer R.
Published: February 2009

Background—Pheochromocytomas are rare tumors derived from the chromaffin cells of the adrenal medulla. Although these tumors have long been postulated to induce hypertension and cardiomyopathy through the hypersecretion of catecholamines, catecholamines alone may not fully explain the profound myocardial remodeling induced by these tumors. We sought to determine whether changes in myocardial function in pheochromocytoma-induced cardiomyopathy result solely from catecholamines secretion or from multiple pheochromocytoma-derived factors.

Methods and Results—Isolated cardiomyocytes incubated with pheochromocytoma-conditioned growth media contracted at a higher frequency than cardiomyocytes incubated with norepinephrine (NE) only. Sprague-Dawley rats and black-6 mice were implanted with agarose-encapsulated pheochromocytoma (PC12) cells, dihydroxyphenylalanine decarboxylase knock-out PC12 cells deficient in NE (PC12-KO), or NE-secreting pumps. PC12 cell implantation increased left ventricular dilation by 35�6% and 9.6�1.4% and reduced left ventricular fractional shortening by 20�3% and 28�4% in rats and mice compared with animals dosed only with NE, respectively. Elimination of NE secretion in PC12-KO cells induced neither cardiac dilation (3.9%�1.8% increase versus control) nor changes in (1.9%�0.4% reduction) fractional shortening compared to controls.

Conclusions—Pheochromocytomas induce a greater degree of cardiomyopathy than equivalent doses of NE, suggesting pheochromocytoma-induced cardiomyopathy is not solely mediated by NE, rather pheochromocytoma secretory factors in combination with catecholamines act synergistically to induce greater cardiac damage than catecholamines alone.
Randomized Comparison of Coronary Bifurcation Stenting With the Crush Versus the Culotte Technique Using Sirolimus Eluting Stents
Authors: Erglis Andrejs , Kumsars Indulis , Niemelä Matti , Kervinen Kari , Maeng Michael , Lassen Jens F. , Gunnes Pål , Stavnes Sindre , Jensen Jan S. , Gall�e Anders , Narbute Inga , Sondore Dace , Mäkikallio Timo , Ylitalo Kari , Christiansen Evald H. , Ravkilde Jan , Steigen Terje K. , Mannsverk Jan , Thayssen Per , Hansen Knud N�rregaard , Syvänne Mikko , Helqvist Steffen , Kjell Nikus , Wiseth Rune , Aar�e Jens , Puhakka Mikko , Thuesen Leif
Published: February 2009

Background—

In a number of coronary bifurcation lesions, both the main vessel and the side branch need stent coverage. Using sirolimus eluting stents, we compared 2 dedicated bifurcation stent techniques, the crush and the culotte techniques in a randomized trial with separate clinical and angiographic end-points.

Methods and Results—

A total of 424 patients with a bifurcation lesion were randomized to crush (n=209) and culotte (n=215) stenting. The primary end point was major adverse cardiac events; cardiac death, myocardial infarction, target vessel revascularization, or stent thrombosis after 6 months. At 6 months there were no significant differences in major adverse cardiac event rates between the groups; crush 4.3%, culotte 3.7% (
P
=0.87). Procedure and fluoroscopy times and contrast volumes were similar in the 2 groups. The rates of procedure-related increase in biomarkers of myocardial injury were 15.5% in crush versus 8.8% in culotte group (
P
=0.08). A total of 324 patients had a quantitative coronary assessment at the index procedure and after 8 months. The angiographic end-points of in-segment and in-stent restenosis of main vessel and/or side branch after 8 months were found in 12.1% versus 6.6% (
P
=0.10) and in 10.5% versus 4.5% (
P
=0.046) in the crush and culotte groups, respectively.

Conclusions—

Both the crush and the culotte bifurcation stenting techniques were associated with similar and excellent clinical and angiographic results. Angiographically, there was a trend toward less in-segment restenosis and significantly reduced in-stent restenosis following culotte stenting.
Effect of Length and Diameter of Drug-Eluting Stents Versus Bare-Metal Stents on Late Outcomes
Authors: Applegate Robert J. , Sacrinty Matthew T. , Kutcher Michael A. , Santos Renato M. , Gandhi Sanjay K. , Little William C.
Published: February 2009

Background—

The risk of restenosis and other adverse cardiac events with bare-metal stents (BMS) is increased with smaller stent diameters and longer stent lengths. Drug-eluting stents (DES) may reduce this effect in select patients; however, whether this benefit occurs in high-risk lesions and patients in routine practice is not clear.

Methods and Results—

Clinical outcomes (target-vessel revascularization [TVR], stent thrombosis, nonfatal myocardial infarction [MI], and cardiac death) at 2 years stratified by stented length and diameter were compared in 949 consecutive patients who received BMS and 1236 consecutive and comparable patients who received DES for single lesions. The longest tertile of BMS (>23 mm) was associated with increased hazard of TVR, ST, and nonfatal MI or death compared with shorter tertiles of BMS, which was abolished by DES. DES compared with BMS was independently associated with a lower hazard of TVR (HR, 0.34 [0.20 to 0.58]) and nonfatal MI or death (HR, 0.60 [0.39 to 0.92]) in the longest length tertile (>23 mm). No clear association of stented tertile diameter and clinical outcomes for either stent type was observed. However, DES compared with BMS was independently associated with a lower hazard of TVR for all diameter tertiles, and a lower hazard of nonfatal MI or death (0.66 [0.44 to 0.99]) in the largest diameter tertile (>3.4 mm).

Conclusions—

Independent of adverse patient and lesion characteristics, DES demonstrated significantly lower hazard of TVR and nonfatal MI or death at 2 years compared with BMS within the longest stented lengths (>23 mm) and largest diameters (>3.4 mm).
The Risk of Aneurysmal Subarachnoid Hemorrhage During Pregnancy, Delivery, and the Puerperium in the Utrecht Population
Authors: Tiel Groenestege Andreas T. , Rinkel Gabriel J.E. , van der Bom Johanna G. , Algra Ale , Klijn Catharina J.M.
Published: February 2009

Background and Purpose—

It is unclear whether the risk of aneurysmal subarachnoid hemorrhage (aSAH) is increased during pregnancy, labor, and the puerperium. We compared the risk of aSAH during this period with the risk outside this period.

Methods—

We included women with aSAH between 18 and 42 years of age (n=244) from our prospectively collected database of patients with subarachnoid hemorrhage treated in the University Medical Center Utrecht, the provincial referral center, between January 1987 and April 2006. We estimated the relative risk of aSAH during pregnancy, delivery, or the puerperium by a case-crossover design and calculated a standardized incidence ratio, dividing the observed number of patients with aSAH during pregnancy, delivery, or puerperium by the expected number based on the incidence in the general population of women of the same age during the study period.

Results—

Of the 244 women, 4 were pregnant, 3 in the puerperium and none in labor. The relative risk of aSAH during pregnancy, delivery, or the puerperium was 0.4 (95% CI, 0.2 to 0.9). Based on the number of women aged 18 to 42 years within the catchment area of our hospital and the number of pregnancies within the study period, the expected number of patients with aSAH during pregnancy, delivery, or the puerperium was 12, resulting in a standardized incidence ratio of 0.6 (95% CI, 0.2 to 1.1).

Conclusions—

The risk of aSAH is not increased during pregnancy, labor, and the puerperium. There is no need to advise against pregnancy in women with an increased risk of subarachnoid hemorrhage and no evidence to advise against vaginal delivery in such women.
Does Sex Matter? Thirty-Day Stroke and Death Rates After Carotid Artery Stenting in Women Versus Men
Authors: Howard Virginia J. , Voeks Jenifer H. , Lutsep Helmi L. , Mackey Ariane , Milot Genevieve , Sam Albert D. , Tom MeeLee , Hughes Susan E. , Sheffet Alice J. , Longbottom Mary , Avery Jason B. , Hobson Robert W. , Brott Thomas G.
Published: February 2009

Background and Purpose—

Several carotid endarterectomy randomized, controlled trials and series have reported higher perioperative stroke and death rates for women compared with men. The potential for this same relationship with carotid artery stenting was examined in the lead-in phase of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST).

Methods—

CREST compares efficacy of carotid endarterectomy and carotid artery stenting in preventing stroke, myocardial infarction, and death in the periprocedural period and ipsilateral stroke over the follow-up period. CREST included a “lead-in” phase of symptomatic (≥50% stenosis) and asymptomatic (≥70% stenosis) patients. Patients were examined by a neurologist preprocedure, at 24 hours, and at 30 days. Review of stroke and death was by an independent events committee. The association of sex with periprocedural stroke and death was examined in 1564 patients undergoing carotid artery stenting (26.5% symptomatic).

Results—

Women comprised 37% of the lead-in cohort and did not differ from men by age, symptomatic status, or characteristics of the internal carotid artery. The 30-day stroke and death rate for women was 4.5% (26 of 579; 95% CI, 3.0% to 6.5%) compared with 4.2% (41 of 985; 95% CI, 3.0% to 5.6%) for men. The difference in stroke and death rate was not significant nor were there any significant differences by sex after adjustment for age, arterial characteristics, or cardiovascular risk factors.

Conclusions—

These results do not provide evidence that women have a higher carotid artery stenting stroke and death rate compared with men. The potential differential periprocedural risk by sex will be prospectively addressed in the randomized phase of CREST.
Prey chemical discrimination by a diploglossine lizard, the giant Hispaniolan galliwasp (Celestus warreni)
Authors: Cooper William , Bradley Kelly
Published: February 2009

Prey chemical discrimination, the ability to respond differentially to prey chemicals and control stimuli, enables many squamate reptiles to locate and identify prey using chemical cues sampled by tongue-flicking and analyzed by vomerolfaction. Among lizards this ability is limited to species that are active foragers having insectivorous/carnivorous diets and to omnivores and herbivores, even those derived from ancestral ambush foragers. We experimentally studied responses by hatchlings of giant Hispaniolan galliwasps, Celestus warreni, which appear to have a strict animal diet and are putatively active foragers, to prey chemicals and control substances. More individuals tongue-flicked in the cricket condition than the water condition. Response strength indicated by the tongue-flick attack score, a composite index of response strength based on number of tongue-flicks, biting (one lizard) and latency to bite, was greater in response to cricket stimuli than plant (lettuce) stimuli, cologne or distilled water. Thus, the galliwasps exhibited prey chemical discrimination. Celestus warreni, the first representative of Diploglossinae to be tested, exhibits chemosensory behavior similar to that of other anguids. Although no quantitative data on foraging mode are available, another diploglossine, Diploglossus vittatus, is an active forager. The limitation of prey chemical discrimination to active foragers among lizards with animal diets lend further support to the likelihood that C. warreni is an active forager. The galliwasps did not exhibit plant chemical discrimination.
Preferred temperatures of Podarcis vaucheri from Morocco: intraspecific variation and interspecific comparisons
Authors: Veríssimo Carla V. , Carretero Miguel A.
Published: February 2009

Preferred body temperatures (Tp) were analysed in the lacertid Podarcis vaucheri, from S. Iberia and N. Africa which has been recently revalidated as a full species within the P. hispanica complex. Adult lizards from a Moroccan population were exposed to a thermal gradient and Tp was measured at ten time intervals. Intraspecific Tp variation due to sex and reproductive condition (Tp: non-pregnant females ≥ males ≥ pregnant females) and time of the day (Tp: early morning > rest of the day) was detected. Pregnant females tended to increase their Tp after egg-laying. This dependence on the reproductive condition parallels findings in other lacertids. Class-by-class comparisons between P. vaucheri and P. (hispanica) liolepis from NE Iberia, analysed with the same methodology, revealed higher Tp values in P. vaucheri (non-pregnant females). Although further research is needed to determine the evolutionary pattern of the Tp divergence in this group, these results are compatible with the thermal rigidity hypothesis reinforcing the view of P. hispanica s.l. as an artificial assemblage.
Studies on specialized epidermal derivatives in iguanian lizards: II. New data on the scalation of the Malagasy iguanas of the genus Oplurus (Sauria: Iguanidae)
Authors: Dujsebayeva Tatjana , Ananjeva Natalia , Böhme Wolfgang , Wagner Philipp
Published: February 2009

The details of the ventral scalation were examined in adult and young
specimens of seven species of the Malagasy iguanids of the genera Chalarodon
Peters, 1854 and Oplurus Cuvier, 1829, both visually and using light
microscopy. For the first time, we report data on the topography, morphology
and histology of epidermal glandular structures of the genus Oplurus. The
modified swollen scales, callous-like in appearance, were described in the
abdominal, pre-cloacal and femoral integument. Histological investigation
confirmed a presence of the epidermal generation glands of the escutcheon
type. In the lizards of the genus Oplurus the epidermal glands are mainly
male characteristic, although partially modified ventral scales of the
females suggest that they also have a potential capability to production of
epidermal gland generation. A biological role of these scales is unclear, as
well as their possible relations to lizard's ecology and behaviour.
Ontogenetic and sexual variation in the coloration of the lacertid lizards Iberolacerta monticola and Podarcis bocagei. Do the females prefer the greener males?
Authors: Galán Pedro
Published: February 2009

Changes in the coloration of the lacertid lizards Iberolacerta monticola and Podarcis bocagei with age in populations from NW Spain are described. The onset of sexual maturity in P. bocagei males involves a change in the ventral (yellow) and dorsal (green) colorations, which is different from immature males (dorsally brownish in color). In I. monticola males, the ventral coloration also changes to a deep green when they reach maturity, while the dorsal coloration remains brownish as in the immature specimens. In this species, the green dorsal coloration is acquired gradually after maturity. Only the oldest individuals have a predominantly green dorsal coloration. The differences between the two species in the time males take to acquire the green dorsal coloration could be related to their different longevity. The coloring is acquired gradually in the most long-lived species (I. monticola). A field study was carried out on the behaviour of adult males of I. monticola during the reproductive period. The males with green dorsal coloration were seen to pair with females significantly more frequently than those with the brownish dorsal color. The increase in the green dorsal coloration (conspicuous) with the size and age of the males of this species would appear to have a clear function as an intersexual or intrasexual signal.
Species genetic ID card in animal conservation
Authors: Ruan Xiang-Dong , Wan Qiu-Hong
Published: February 2009

The state governments in China have laid down laws for protecting rare and endangered species, but the effective protection depends on accurate species identification. In this study, we developed one new Felidae-specific probe, pta1 probe and tested 138 skin samples from 14 species and subspecies. The results revealed that the pta1 probe succeeded in identifying all feline species in China due to species-specific “fingerprints”. As a result, we constructed a fingerprint management archives for Felidae family in China. It can provide forensic evidence of poaching for judicial organization, which have a profound effect on criminal activities of poachers, and therefore help to protect wild animals and conserve biodiversity.
Hepatic pigment cells of Proteidae (Amphibia, Urodela): A comparative histochemical and ultrastructural study
Authors: Prelovšek Petra-Maja , Mali Lilijana Bizjak , Bulog Boris
Published: February 2009

Amphibian liver pigment cells, also known as Kupffer cells, contain various amounts of melanin, haemosiderin and lipofuscin. We used different histochemical and ultrastructural methods to analyse and compare the level of hepatic pigmentation and the structure of hepatic pigment cells in the livers of three representatives of the family Proteidae; two subspecies of the hypogean Proteus anguinus (depigmented Proteus a. anguinus and pigmented Proteus a. parkelj) and the epygean Necturus maculosus. Our analysis revealed differences at histological and ultrastructural level. While the percentage of the pigmented area and ultrastructural characteristics are similar in both subspecies of P. anguinus, great differences occur in the amount and structure of the pigment cells between P. anguinus and N. maculosus. Pigment cells are more numerous and compose larger pigmented clusters in P. anguinus. They are structurally more heterogeneous and contain a larger amount of haemosiderin when compared to N. maculosus. Our results confirm a high degree of variation in hepatic pigmentation among different amphibian species. Because many factors influence the level of hepatic pigmentation in poikilotherms, differences among species from different habitats and also among individuals of the same species are expected but are not easily explained. We propose two possible explanations for the large amount of iron present in Proteus anguinus: (1) accumulation of pigments due to the very low metabolic rate and extended lifetime; (2) large iron storage capacity as an adaptation to a low and discontinuous food supply in caves.
Academic freedom and the discovery of electroreception in catfish and dogfish
Authors: Peters Robert
Published: February 2009

A brief sketch is given of the changing interpretation of Academic Freedom at the universities in The Netherlands during the last half of the twentieth century, by discussing the discoveries of electroreception in catfish, Ameiurus nebulosus, and dogfish, Scyliorhinus canicula. It is concluded that science is no longer hypothesis-driven, but money-driven. Whereas innovation and discoveries belong typically to the domain of the individual scientist and flourish in a bottom-up organisation, the funding agencies of today advocate a top-down approach to stimulate creativity. Apparently the resultant institutionalization has not the desired result.
Evoked bradycardia as response criterion for the detection of electrical stimuli in catfish
Authors: Peters Robert , Veeneklaas Robert , Schoenhage Albert , Eeuwes Lonneke
Published: February 2009

Heart rate deceleration (HRD) after exposure to novel stimuli is part of the orienting reflex, and can be used as a tool to investigate the susceptibility of various organisms to sensory stimuli. HRD as response criterion was used in unrestrained catfish, Ameiurus (Ictalurus) nebulosus (Lesueur, 1819) to investigate its susceptibility to electrical stimuli. HRD in catfish occurs after stimulation with light, mechanical stimuli, and electrical stimuli. HRD shows habituation and correlates with stimulus strength. The response to sinusoidal electrical stimuli from 70 to 700 μV/cm p-p was determined in the range from 0.1 to 1000 Hz. Using HRD as response criterion we found that at 85 μV/cm catfish react to stimuli from 0.1 to 3 Hz. In the absence of stimuli, the heart rate develops an ultradian rhythm with periods of 7 to 15 min. About twice a day cardiac arrest of 1 min occurs. During anaesthesia oscillations with a period of about 1 min are recorded. Comparison of this study with others supports the notion that there exist at least two neural channels for processing electrical stimuli. One channel is involved in predation, namely processing the fast potential changes accompanying the passage of a bioelectric dipole; another is involved in processing uniform DC fields used for navigation.
Spontaneous firing in primary afferent neurons of ampullary electroreceptor organs as attribute of bandwidth, threshold, and topology
Authors: Peters Robert , Bretschneider Franklin , Eeuwes Lonneke
Published: February 2009

Spontaneous firing of neurons plays an essential part in the detection of sensory stimuli. Spontaneous firing of primary afferents of ampullary electroreceptor organs in the catfish Ameiurus nebulosus (Lesueur, 1819) was studied in relation to the distribution, thresholds, and frequency characteristics of the electroreceptor organs. The spontaneous firing rate was correlated with the place on the skin. The mean inter-spike interval in 55 dorsal and 49 ventral ampullary organs in five specimens was 16.8 ms +/- 0.41 SEM and 20.5 ms +/- 0.48 SEM, corresponding to firing rates of 59.5 and 48.7 s-1 respectively. The concomitant coefficients of variation were 0.33 and 0.29. Approximately half of the dorsal ampullae were innervated by two fibres. The firing rates of each of the two fibres was lower than the firing rate of organs innervated by a single neuron. Responses to stimuli as weak as 10 pA could be recovered from the noisy average firing level provided the number of averaging sweeps was sufficiently large. This was equivalent to a stimulus of 0.025 μV/cm and was lower than the behavioural threshold of 1 μV/cm. The gain of the frequency response was enhanced at the carrier frequency, at twice the carrier frequency, and in the range from 75-90 Hz. The results revealed that the occurrence of spontaneous activity improved the signal to noise ratio of responses to electrical stimuli by reduction of the coefficient of variation, absence of a threshold, and phase locking.
Open lumina of microampullary electroreceptor organs in the transparent catfish, Kryptopterus bicirrhis (Valenciennes 1840), contain 50 mM potassium: why?
Authors: Peters Robert , Bretschneider Franklin , Eeuwes Lonneke
Published: February 2009

Administration of the cell impermeant fluorescent K+ and Na+ probes potassium-binding fluorescent indicator (PBFI) and sodium-binding fluorescent indicator (SBFI) to the lumina of ampullary electroreceptor organs in the transparent catfish Kryptopterus bicirrhis (Valenciennes 1840), demonstrated an unexpected high concentration of K+ ions: 50 mM. Since the lumina of the ampullary organs are in open contact with the surrounding water, such a high K+ concentration inside the lumen can be maintained only by heavy metabolic transport. The implications of this finding for stimulus transduction in freshwater ampullary electroreceptor cells are discussed.
Behavioural relevance of AC and DC in prey detection by the brown bullhead, Ameiurus nebulosus
Authors: Eeuwes Lonneke , Peters Robert , Bretschneider Franklin
Published: February 2009

A large range of aquatic vertebrates employs passive electroreception to detect the weak bioelectric fields that surround their prey. Bioelectric fields are dynamic in strength and frequency composition, but typically consist of a direct current (DC) and an alternating current (AC) component. We examined the biological relevance of these components for prey detection behaviour in the brown bullhead by means of a preference test. We gave each fish the choice between two small dipoles emitting a DC step or AC stimulus of variable strength, respectively. We used AC stimuli that were either representative for ventilatory movements by prey (1 Hz sine wave) or optimal for the ampullary electroreceptor cells (10 Hz sine wave). In an attempt to present a more complex stimulus, we also used slightly modified recordings of bioelectric prey fields, but this yielded no results. Brown bullheads prefer DC stimuli to 10 Hz sine waves if the stimulus intensity of either component is much larger. When the stimulus presentation consists of DC versus 1 Hz, most fish will choose randomly unless the stimulus intensities differ greatly. Then, they favour the component that had a higher amplitude during training. Our results suggest an intrinsic behavioural preference for very low frequency signals (<10 Hz) as well as plasticity in prey detection behaviour.
Energy and Enstrophy Spectra of Geostrophic Turbulent Flows Derived from a Maximum Entropy Principle
Authors: Verkley W. T. M. , Lynch Peter
Published: February 2009

The principle of maximum entropy is used to obtain energy and enstrophy spectra as well as average relative vorticity fields in the context of geostrophic turbulence on a rotating sphere. In the unforced-undamped (inviscid) case, the maximization of entropy is constrained by the constant energy and enstrophy of the system, leading to the familiar results of absolute statistical equilibrium. In the damped (freely decaying) and forced-damped case, the maximization of entropy is constrained by either the decay rates of energy and enstrophy or by the energy and enstrophy in combination with their decay rates. Integrations with a numerical spectral model are used to check the theoretical results for the different cases. Maximizing the entropy, constrained by the energy and enstrophy, gives a good description of the energy and enstrophy spectra in the inviscid case, in accordance with known results. In the freely decaying case, not too long after the damping has set in, good descriptions of the energy and enstrophy spectra are obtained if the entropy is maximized, constrained by the energy and enstrophy in combination with their decay rates. Maximizing the entropy, constrained by the energy and enstrophy in combination with their (zero) decay rates, gives a reasonable description of the spectra in the forced-damped case, although discrepancies remain here.
Disregarding Graduated Treatment: Why Transfer Aggravates Recidivism
Authors: Johnson Kristin , Lanza-Kaduce Lonn , Woolard Jennifer
Published: February 2009

These data merge correctional histories with official state and courthouse information for a sample of teenage offenders, some of whom had been transferred to the adult system. Previous research indicated that transfer aggravates recidivism after the age of 18. The correctional data allow the examination of the relationship between sanctions and recidivism for repeat offenders. The authors explored whether repeat offenders who received graduated sanctions had lower recidivism after age 18 than those who leapfrogged over graduated sanctions. Transfer often involves leapfrogging over treatment options; sometimes it leads to secure placement in adult facilities but sometimes it results in adult probation. Within the juvenile justice system, some repeat offenders jump over intermediate interventions to deep-end placements. Graduated sanctions lead to less recidivism. When measures of graduated sanctions are included in multivariate analyses, transfer no longer predicts recidivism.
Coping or Escaping?
Authors: Knobloch-Westerwick Silvia , Hastall Matthias R. , Rossmann Maik
Published: February 2009

A quasiexperiment tested competing hypotheses regarding escapist media use and alternative coping motivations in media selection behavior. For 287 participants, personal satisfaction levels for five life domains were assessed. In an ostensibly unrelated study, the participants browsed through online content in which some section topics corresponded to the life domains. Selective exposure was unobtrusively logged by software. Lower satisfaction with college and career situation and with personal financial situation was associated with longer exposure to information about college and career issues. Among respondents in a romantic relationship, higher satisfaction with personal romantic situation led to longer reading times for articles about romance issues, whereas among single respondents, lower satisfaction with one's romantic situation was connected to longer reading of such content. Satisfaction with own health and exposure to health information showed a curvilinear pattern, as low and high satisfaction produced lower exposure than moderate satisfaction.