bluuebunny/crossref_metadata_2025 huggingface dataset:
Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non–small cell lung carcinoma
Authors: Frederick Barbara A. , Helfrich Barbara A. , Coldren Christopher D. , Zheng Di , Chan Dan , Bunn Paul A. , Raben David
Published: June 2007

The modest response of patients with head and neck squamous cell carcinoma (HNSCC) and non–small cell lung carcinoma (NSCLC) to epithelial growth factor receptor tyrosine kinase inhibitors such as gefitinib and erlotinib indicates the need for the development of biomarkers to predict response. We determined gefitinib sensitivity in a panel of HNSCC cell lines by a 5-day 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and confirmed these responses with analysis of downstream signaling by immunoblotting and cell cycle arrest. Basal gene expression profiles were then determined by microarray analysis and correlated with gefitinib response. These data were combined with previously reported NSCLC microarray results to generate a broader predictive index. Common markers of resistance between the two tumor types included genes associated with the epithelial to mesenchymal transition. We confirmed that increased protein expression of vimentin combined with the loss of E-cadherin, claudin 4, and claudin 7 by immunoblotting was associated with gefitinib resistance in both HNSCC and NSCLC cell lines. In addition, the loss of the Ca2+-independent cell-cell adhesion molecules EpCAM and TROP2 in resistant lines was confirmed by immunofluorescence. Tumor xenografts derived from the gefitinib-sensitive UM-SCC-2 were growth-delayed by gefitinib, whereas the gefitinib-resistant 1483 xenografts were unaffected. These data support a role for epithelial to mesenchymal transition in establishing gefitinib resistance for both HNSCC and NSCLC, and indicate that clinical trials should address whether these biomarkers will be useful for patient selection. [Mol Cancer Ther 2007;6(6):1683–91]
Membrane-Type 1 Matrix Metalloproteinase Stimulates Cell Migration through Epidermal Growth Factor Receptor Transactivation
Authors: Langlois Stéphanie , Nyalendo Carine , Di Tomasso Geneviève , Labrecque Lyne , Roghi Christian , Murphy Gillian , Gingras Denis , Béliveau Richard
Published: June 2007

Proteolysis of extracellular matrix proteins by membrane-type 1 matrix metalloproteinase (MT1-MMP) plays a pivotal role in tumor and endothelial cell migration. In addition to its proteolytic activity, several studies indicate that the proinvasive properties of MT1-MMP also involve its short cytoplasmic domain, but the specific mechanisms mediating this function have yet to be fully elucidated. Having previously shown that the serum factor sphingosine 1-phosphate stimulates MT1-MMP promigratory function through a process that involves its cytoplasmic domain, we now extend these findings to show that this cooperative interaction is permissive to cellular migration through MT1-MMP–dependent transactivation of the epidermal growth factor receptor (EGFR). In the presence of sphingosine 1-phosphate, MT1-MMP stimulates EGFR transactivation through a process that is dependent upon the cytoplasmic domain of the enzyme but not its catalytic activity. The MT1-MMP–induced EGFR transactivation also involves Gi protein signaling and Src activities and leads to enhanced cellular migration through downstream extracellular signal-regulated kinase activation. The present study, thus, elucidates a novel role of MT1-MMP in signaling events mediating EGFR transactivation and provides the first evidence of a crucial role of this receptor activity in MT1-MMP promigratory function. Taken together, our results suggest that the inhibition of EGFR may represent a novel target to inhibit MT1-MMP–dependent processes associated with tumor cell invasion and angiogenesis. (Mol Cancer Res 2007;5(6):569–83)
Detection and Monitoring of Cytomegalovirus Infection in Renal Transplant Patients by Quantitative Real-Time PCR
Authors: Madi Nada , Al-Nakib Widad , Mustafa Abu Salim , Saeed Tarek , Pacsa Alexander , Nampoory M.R. Narayanan
Published: June 2007

Objectives: To establish a sensitive and specific real-time PCR for quantitation of cytomegalovirus (CMV) DNA in clinical specimens.Subjects and Methods: In a prospective study, CMV DNA was quantified in blood samples of 255 kidney recipients with and without CMV-related symptoms between the years 2000 and 2005 in Kuwait. In a selected group of patients, the effect of anti-CMV chemotherapy was monitored by quantitative real-time PCR (qRT-PCR). Results: The established qRT-PCR assay had a sensitivity to detect 30 CMV DNA copies. CMV DNA was detected in 54/255 (24%) patients; of these, 17 (31.5%) were asymptomatic, and 37 patients (68.5%) had symptomatic CMV infection. Sequential blood specimens were collected from all CMV-positive patients and tested by CMV pp65 antigenemia and qRT-PCR assays. There was a moderate positive correlation between the two assays (Pearson’s correlation = 0.52). The median CMV viral load measured by qRT-PCR was higher in symptomatic (6.5 × 104 copies/ml) than in asymptomatic (185copies/ml) patients (p = 0.001). The estimated cut-off value of CMV DNA for CMV symptoms/disease was ≧800 copies/ml of blood. Testing of sequential samples from patients treated with symptomatic CMV infection showed that the viral load was significantly reduced after 3 weeks of anti-CMV chemotherapy (p = 0.001). Conclusion: The reported qRT-PCR is a sensitive method for quantitation of CMV DNA in the blood of kidney recipients and can be useful in monitoring the efficacy of anti-CMV therapy.
Kuwaiti Parents’ Knowledge of First-Aid Measures of Avulsion and Replantation of Teeth
Authors: Al-Jame Qumasha , Andersson Lars , Al-Asfour Adel
Published: June 2007

Objective: The aim of this study was to assess the knowledge level of emergency measures for tooth avulsion among Kuwaiti parents. Subjects and Methods: Sixty-three parents completed an Arabic language questionnaire about their first-aid knowledge. The following fields of knowledge were assessed: general body injury treatment principles, tooth avulsion and replantation principles, avulsed permanent/primary teeth, cleaning of an avulsed tooth before replantation, extra-alveolar time and storage media. For each category, a score ranging from 0 to 3 was possible. Results: Experience of first-aid information or training was seen in 12 (19%) except for dental injuries, which had not been included in such first-aid information. Knowledge was demonstrated in 52 (82%) about first aid of minor body injuries, yet the knowledge of how to manage avulsed teeth was poor, as 50–54 (79–86%) parents had no knowledge of how to manage an avulsed tooth in the specific modes of treatment measured. There was no difference in knowledge between mothers and fathers, young or old, nor was knowledge greater in parents with an academic education. Conclusion: First-aid knowledge in Kuwaiti parents is lacking for avulsion and replantation of teeth despite a high level of knowledge of how to manage simple body injuries. Knowledge of first-aid measures regarding avulsion and replantation of teeth should be increased by intervention programs.
Hemoglobin F Concentration as a Function of Age in Kuwaiti Sickle Cell Disease Patients
Authors: Adekile Adekunle , Al-Kandari Mohammed , Haider Mohammad , Rajaa Marouf , D’Souza Mark , Sukumaran Jalaja
Published: June 2007

Objective: This study aimed to document the transition of hemoglobin (Hb) F levels from early childhood to adulthood in Kuwaiti sickle cell disease patients, investigating its relationship to sex, Hb genotype and coexistence of α-thalassemia trait. Subjects and Methods: The following parameters were extracted from the patients’ records: age, sex, Hb, mean corpuscular volume, mean corpuscular Hb, red blood cell count, Hb F, Hb S, Hb A2 and α-globin genotype. Hb quantitation was performed with cation exchange HPLC, while α-globin genotype was determined by PCR. Results: Records were available for 149 patients, made up of 94 SS and 55 Sβ⁰thal; 83 males and 66 females, aged 3 months to 60 years (mean 10.5 ± 1.8). The mean Hb F level in the whole population was 21.5 ± 8.1% and was not significantly different between males and females, and SS or Sβ⁰thal. When the age groups were analyzed, the Hb F level was highest (28.9 ± 10.9%) in those below 5 years. Indeed, patients ≤2 years had a mean level of 31.9 ± 13.0%. There was no significant difference in the Hb F levels in SS patients with or without coexistent α-thal trait. Conclusions: Kuwaiti sickle cell disease patients below 5 years of age have close to 30% Hb F and this is probably a major reason why they usually do not present before this age, unlike patients elsewhere who present within the first year of life.
Weight Loss Attempts among Kuwaiti Adults Attending the Central Medical Nutrition Clinic
Authors: Al-Qaoud Nawal , Prakash Prasanna , Jacob Susan
Published: June 2007

Objectives: To investigate the reasons for attempting to lose weight and identify weight loss perception and characteristics. Methods: A cross-sectional survey of a sample of 526 Kuwaiti adults was carried out at the Central Medical Nutrition Clinic, Kuwait, from August to December 2003. Heights and weights were measured and body mass index (BMI) was calculated and classified according to WHO grades of obesity. A structured questionnaire used for collecting data was analyzed using SPSS version 12.0. Results: Of the 526 subjects, the most commonly cited reasons for attempting to lose weight were to avoid health problems (n = 248, 47.1%) followed by improving personal appearance (n = 141, 26.8%). The weight loss perceptions of 263 (50%) of the subjects were within the accepted range (2–5 kg/month); 321 (61.0%)had previously attemptedto lose weight, among them 147 (45.8%) followed the advice of doctors and dieticians. The major reason mentioned for stopping the previous dietary regime was inability to resist sweets and traditional foods (n = 99, 31.0%) followed by dissatisfactionwith the dietary outcome (n = 79, 24.8%). Conclusion: The study confirms an awareness of the health risks of obesity,but an inability amongthe dieters to maintain a weight loss program. Hence, behavioral management techniques may be necessary to develop nutritional education approaches and effective weight management strategies.
Assessment of Anti-HBs Antigen in 6- to 9-Year-Old Children Routinely Vaccinated via Vaccination Program in Iran
Authors: Hadi Nahal , Hadi Negin
Published: June 2007

Objective: To determine persisting antibody levels to hepatitis B virus (HBV) antigen in healthy children, aged 6–9 years, vaccinated at birth. Methods: Blood samples were collected from 374 vaccinated children (178 girls and 196 boys) and 57 unvaccinated children, attending Shiraz Primary School, Shiraz, Iran from September 2002 to April 2003. An HBV surface antibody (anti-HBs) was determined using enzyme-linked immunosorbent assay. Results: The anti-HBs titer was detected in 17% of the 8-year-old children, 7.7% of the 7-year-old children and 46.6% of the 6-year-old children. The decrease was greatest in the 9-year-old children; more than half (54.3%) had a titer of less than 10 IU/ml, indicating a decrease in antibody levels with increasing age/time. Conversely, more than 35% of the 6-year-old children had a titer greater than 150 IU/ml compared with 24, 12 and 7% of children at the age of 7, 8 and 9, respectively, whose antibody titer was less than 150 IU/ml. Conclusion: Antibody titer declined with time. In comparison with other countries, the antibody titer in Iranian children was much lower.
Impact of Viral Hepatitis on Apo- and Lipoprotein Status in Blood
Authors: Irshad M. , Dube R. , Joshi Y.K.
Published: June 2007

Objectives:To investigate the effect of viral hepatitis on serum levels of apo- and lipoproteins in different forms of liver diseases. Materials and Methods: One hundred and thirty adult patients and 100 healthy age- and gender-matched control individuals participated in this study. Patients were grouped according to four types of liver disease: acute viral hepatitis, chronic active hepatitis (CAH), cirrhosis of the liver and fulminant hepatic failure. Results: Hepatitis B virus, C virus and E virus (HEV) infections were recorded in different combinations in these patients, but viral infections of hepatitis A and D were not seen in any of the patient groups. The results of lipo- and apoprotein analysis showed different patterns. The low-density lipoprotein value was high in the CAH group. In the other three groups, low-density lipoprotein level was comparable to the control value. The high-density lipoprotein level (p = 0.02) was significantly low in all groups except in the cirrhosis group. Apo-A was significantly reduced in the acute viral hepatitis and fulminant hepatic failure groups, whereas Apo-B level was low in the CAH and cirrhosis groups. The lipoprotein (a) level in these groups was low, compared to control. Conclusion: No apparent relationship was observed between etiological viruses and ensuing changes in lipid/lipoprotein profile.
Supravalvular and Valvular Aortic Stenosis in Heterozygous Familial Hypercholesterolemia
Authors: Rafeiyian Sima , Mojtahedzadeh Saeed , Hekmat Manouchehr , Naderi Nasim , Nobahar Rezvan , Hashemi Mohammah Jafar , Kouhi Ali
Published: June 2007

Objectives: To report calcified aortic stenosis due to hypercholesterolemia in two siblings. Case Presentation and Intervention: A 13-year-old boy with a history of dyspnea on exertion and a systolic murmur of aortic stenosis was referred to our center. Echocardiography showed combined valvular and supravalvular aortic stenoses with a good left ventricle systolic function and severe left ventricular hypertrophy. Two years later his 17-year-old sister was referred to the clinic with similar symptoms. Severe valvular aortic stenosis was detected by echocardiography. Selective coronary angiography showed significant involvement. The father had a history of hypercholesterolemia and confirmed coronary artery disease involving 3 vessels. Angiography showed anterioapical and inferiobasal hypokinesis with preserved left ventricle systolic function. The mother and the other two siblings did not have hyperlipidemia, thereby indicating heterozygous familial hypercholesterolemia in the two affected siblings. The siblings were managed with atrovastatin and nicotinic acid and cholestyramine was added stepwise. The father was treated with lovostatin. Conclusion: This report shows thatsevere hyperlipidemia in very young patients may be a risk factor for valvulopathy.
Inferior Vena Cava Filter as a Preventive Device for Recurrent Pulmonary Embolism in a Patient with Nephrotic Syndrome
Authors: Tsai Yu-Che , Hsieh Yuan-Kai , Lee Chien-Te
Published: June 2007

Objective: This study describes a patient with nephrotic syndrome who experienced recurrent pulmonary emboli as renal disease relapsed frequently. Clinical Presentation: A 30-year-old male, who was diagnosed as having nephrotic syndrome at 12, presented with general edema, ascites and hypoalbuminemia. Although the patient responded well to steroid therapy, a common cold frequently caused flare-up of nephrotic syndrome. Histopathological examination of renal tissue revealed minimal disease change. At 17, the patient had a first pulmonary embolism attack with concurrent upper respiratory tract infection. Full-blown manifestations of nephrotic syndrome with low antithrombin III levels were identified at that time. Anticoagulant therapy was administered to treat the pulmonary embolism. Since the first attack, several episodes of pulmonary emboli occurred, which, combined with kidney disease, triggered refractory nephrotic syndrome. The nephrotic syndrome did not remit, and a secondary renal biopsy identified glomerular pathological changes similar to previous biopsy results. To prevent recurrent pulmonary emboli, a Greenfield inferior vena cava filter was implanted in April 2002. No further pulmonary embolism events occurred after interventional filter deployment. Conclusion: The results of this study suggest that inferior vena cava filter implantation can be effective for preventing recurrent pulmonary embolism complicating refractory nephrotic syndrome.
Bronchoscopic Measurement of Collateral Ventilation in a Sheep Model of Emphysema
Authors: Tsai Larry W. , Hoffman Andrew M. , Mazan Melissa R. , Ingenito Edward P.
Published: June 2007

Background: The development of bronchoscopic therapies for emphysema has renewed interest in collateral ventilation. The success or failure of bronchoscopically placed valves or biologic glues may be determined by collateral ventilation, which is exaggerated in emphysema. Furthermore, the validity of various animal models of emphysema for testing such techniques must be understood in the context of their species-specific collateral ventilation. Objectives: To quantify collateral ventilation in a sheep model of emphysema using a simple in vivo bronchoscopic method. Methods: Collateral ventilation was measured in 8 anesthetized sheep using a simple method which measured pressure and flow through the working channel of a bronchoscope wedged in a segmental lung orifice. Animals then underwent nebulized papain treatments to generate emphysema, followed by repeat bronchoscopic measurements. Results: There was a 33% decrease in resistance to collateral ventilation following papain treatment. Changes in collateral resistance were closely correlated with disease severity as measured by changes in segmental compliance, which increased 267%. Conclusions: Collateral ventilation is significantly increased in sheep following nebulized papain. Bronchoscopic measurement of collateral ventilation may be useful for evaluating other animal models of emphysema and for predicting the response to bronchoscopic therapies in human emphysema patients.
Nitric Oxide in the Pulmonary Vasculature
Authors: Coggins Matthew P. , Bloch Kenneth D.
Published: June 2007

Homeostasis in the pulmonary vasculature is maintained by the actions of vasoactive compounds, including nitric oxide (NO). NO is critical for normal development of the pulmonary vasculature and continues to mediate normal vasoregulation in adulthood. Loss of NO bioavailability is one component of the endothelial dysfunction and vascular pathology found in pulmonary hypertension (PH). A broad research effort continues to expand our understanding of the control of NO production and NO signaling and has generated novel theories on the importance of pulmonary NO production in the control of the systemic vasculature. This understanding has led to exciting developments in our ability to treat PH, including inhaled NO and phosphodiesterase inhibitors, and to several promising directions for future therapies using nitric oxide-donor compounds, stimulators of soluble guanylate cyclase, progenitor cells expressing NO synthase (NOS), and NOS gene manipulation.
Heme Oxygenase-1
Authors: Wenzel Philip , Oelze Matthias , Coldewey Meike , Hortmann Marcus , Seeling Andreas , Hink Ulrich , Mollnau Hanke , Stalleicken Dirk , Weiner Henry , Lehmann Jochen , Li Huige , Förstermann Ulrich , Münzel Thomas , Daiber Andreas
Published: June 2007

Objective—

Nitrate tolerance is likely attributable to an increased production of reactive oxygen species (ROS) leading to an inhibition of the mitochondrial aldehyde dehydrogenase (ALDH-2), representing the nitroglycerin (GTN) and pentaerythrityl tetranitrate (PETN) bioactivating enzyme, and to impaired nitric oxide bioactivity and signaling. We tested whether differences in their capacity to induce heme oxygenase-1 (HO-1) might explain why PETN and not GTN therapy is devoid of nitrate and cross-tolerance.

Methods and Results—

Wistar rats were treated with PETN or GTN (10.5 or 6.6 μg/kg/min for 4 days). In contrast to GTN, PETN did not induce nitrate tolerance or cross-tolerance as assessed by isometric tension recordings in isolated aortic rings. Vascular protein and mRNA expression of HO-1 and ferritin were increased in response to PETN but not GTN. In contrast to GTN therapy, NO signaling, ROS formation, and the activity of ALDH-2 (as assessed by an high-performance liquid chromatography–based method) were not significantly influenced by PETN. Inhibition of HO-1 expression by apigenin induced “tolerance” to PETN whereas HO-1 gene induction by hemin prevented tolerance in GTN treated rats.

Conclusions—

HO-1 expression and activity appear to play a key role in the development of nitrate tolerance and might represent an intrinsic antioxidative mechanism of therapeutic interest.
Age Moderates the Short-Term Effects of Transdermal 17β-Estradiol on Endothelium-Dependent Vascular Function in Postmenopausal Women
Authors: Sherwood Andrew , Bower Julie K. , McFetridge-Durdle Judith , Blumenthal James A. , Newby L. Kristin , Hinderliter Alan L.
Published: June 2007

Objective—

We evaluated age and coronary heart disease (CHD) as potential moderators of the effects of 17β-estradiol on vascular endothelial function in postmenopausal women.

Methods and Results—

In a double-blind crossover design, 100 postmenopausal women aged 50 to 80 years were randomized to each of 3 transdermal patches, releasing 17β-estradiol (0.05 mg/d), 17β-estradiol (0.05 mg/d)+ norethindrone acetate (NETA, 0.14 mg/d), and placebo. Flow-mediated dilation (FMD) and response to 400 μg sublingual glyceryl trinitrate (GTN-D) were assessed approximately 18 hours after patch placement. Age, but not CHD, moderated the FMD response to treatment (
P
=0.01). For women in their fifties, the estradiol patch was associated with improved FMD (7.69±4.79%) compared with placebo (4.81±5.97%,
P
<0.05), but the estradiol+norethindrone patch response (5.81±4.85%) was not significantly different from placebo. Women in their sixties and seventies showed no alterations in FMD response to either active patch. GTN-D response declined with advancing age (
P
<0.01), with women in their seventies exhibiting blunted GTN-D response compared with younger women.

Conclusions—

The cardiovascular benefits of natural estrogen supplementation on vascular endothelial function may be dependent on postmenopausal age, with improved vascular function evident only in the early postmenopausal years. Short-term FMD response to estradiol might help stratify individual differences in risks versus benefits of HRT.
In Vivo Reverse Cholesterol Transport From Macrophages Lacking ABCA1 Expression Is Impaired
Authors: Wang Ming-Dong , Franklin Vivian , Marcel Yves L.
Published: June 2007

Background—

ATP-binding cassette transporter A1 (ABCA1) is a key mediator of cholesterol efflux to apoA-I in cholesterol loaded macrophages, a first step of reverse cholesterol transport (RCT) in vivo. Macrophage specific
abca1
inactivation or overexpression, respectively, accelerated or suppressed the development of atherosclerosis in mouse models. However, it is yet to be established that the ABCA1 effect is related to specific changes in RCT from the macrophages in vivo.

Methods And Results—

Bone marrow–derived macrophages from
abca1
−/−
or
abca1
+/−
mice were labeled with
3
H-cholesterol-AcLDL or
3
H-cholesterol-LDL and injected into
abca1
+/+
abca1
+/−
or
abca1
−/−
mice. When injected into
abca1
+/+
mice, return of
3
H-cholesterol from labeled
abca1
−/−
macrophages to serum, liver, bile, and feces was reduced by 50% (
P
=0.01) compared with control. When labeled wild-type macrophages were injected into
abca1
−/−
mice, as compared with wild-type mice, the return of
3
H-cholesterol to serum, liver, bile, and feces was also reduced.

Conclusions—

ABCA1 expression in macrophages contributes significantly to in vivo macrophage RCT. The important residual RCT observed from
abca1
−/−
macrophages highlight the functionality of transporters that efflux to HDL.
Angiopoietin-2 Impairs Revascularization After Limb Ischemia
Authors: Reiss Yvonne , Droste Jasmin , Heil Matthias , Tribulova Silvia , Schmidt Mirko H.H. , Schaper Wolfgang , Dumont Daniel J. , Plate Karl H.
Published: June 2007

Angiopoietins play important roles in the formation of neovessels and complex vascular networks. Angiopoietin (Ang)-1 and Ang-2 belong to a family of growth factors that display opposing effects on the activation of Tie2 (tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2). Endothelial Ang-2 expression is associated with vessel destabilization and regulates a balance between vascular regression and growth. To elucidate, in particular, the role of Ang-2 after arterial artery occlusion in the mouse limb, we applied a transgenic animal model with targeted Ang-2 expression in endothelial cells. We show here that restoration of blood flow in Ang-2:Tie1 transgenic mice is dramatically impaired when Ang-2 expression is induced in the vasculature. The defective restoration of perfusion in Ang-2 transgenic mice is evidenced by reduced collateral artery growth, which typically occurs to compensate for flow deficits after occlusion of the large conductance artery. Furthermore, reduced movement capacities and higher incidents of necrosis are consequently observed in the transgenic limbs as compared with controls. Mechanistically, the observed effects are attributed to defective smooth muscle cell recruitment in Ang-2 transgenic mice. Moreover, distinct Ang-2 levels in the genetically modified animals clearly correlated with the magnitude of reduced perfusion. In conclusion, our studies define Ang-2 as an important molecule for the progression of collateral artery growth and angiogenesis during ischemia and suggest precise Ang-2 dosage activities to accomplish blood vessel growth.
Organization of Ventricular Fibrillation in the Human Heart
Authors: Ten Tusscher Kirsten H.W.J. , Hren Rok , Panfilov Alexander V.
Published: June 2007

Sudden cardiac death is a major cause of death in the industrialized world, claiming approximately 300 000 victims annually in the United States alone. In most cases, sudden cardiac death is caused by ventricular fibrillation (VF). Experimental studies in large animal hearts have shown that the uncoordinated contractions during VF are caused by large numbers of chaotically wandering reentrant waves of electrical activity. However, recent clinical data on VF in the human heart seem to suggest that human VF may have a markedly different organization. Here, we use a detailed model of the human ventricles, including a detailed description of cell electrophysiology, ventricular anatomy, and fiber direction anisotropy, to study the organization of human VF. We show that characteristics of our simulated VF are qualitatively similar to the clinical data. Furthermore, we find that human VF is driven by only approximately 10 reentrant sources and thus is much more organized than VF in animal hearts of comparable size, where VF is driven by approximately 50 sources. We investigate the influence of anisotropy ratio, tissue excitability, and restitution properties on the number of reentrant sources driving VF. We find that the number of rotors depends strongest on minimum action potential duration, a property that differs significantly between human and large animal hearts. Based on these findings, we suggest that the simpler spatial organization of human VF relative to VF in large animal hearts may be caused by differences in minimum action potential duration. Both the simpler spatial organization of human VF and its suggested cause may have important implications for treating and preventing this dangerous arrhythmia in humans.
Role of Dicer and Drosha for Endothelial MicroRNA Expression and Angiogenesis
Authors: Kuehbacher Angelika , Urbich Carmen , Zeiher Andreas M. , Dimmeler Stefanie
Published: June 2007

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by binding to the cellular transcript leading to translational repression or degradation of the target mRNA. Dicer and Drosha are the miRNA processing enzymes that are required for the maturation of miRNAs. Here, we investigated the role of Dicer and Drosha for angiogenesis. Endothelial cells were transfected with siRNA against Dicer and Drosha to inhibit miRNA biogenesis. Genetic silencing of Dicer and Drosha significantly reduced capillary sprouting of endothelial cells and tube forming activity. Migration of endothelial cells was significantly decreased in Dicer siRNA–transfected cells, whereas Drosha siRNA had no effect. Silencing of Dicer but not of Drosha reduced angiogenesis in vivo. Next, we attempted to identify miRNAs expressed in endothelial cells. A screening analysis of 168 human miRNAs using real-time PCR revealed that members of the let-7 family, mir-21, mir-126, mir-221, and mir-222 are highly expressed in endothelial cells. Dicer and Drosha siRNA reduced lef-7f and mir-27b expression. Inhibitors against let-7f and mir-27b also reduced sprout formation indicating that let-7f and mir-27b promote angiogenesis by targeting antiangiogenic genes. In silico analysis of predicted targets for let-7 cluster identified the endogenous angiogenesis inhibitor thrombospondin-1. Indeed, Dicer and Drosha siRNA significantly increased the expression of thrombospondin-1. Taken together, transient reduction of the miRNA-regulating enzyme Dicer impairs angiogenesis in vitro and in vivo, whereas Drosha siRNA induced a minor antiangiogenic effect in vitro and was not effective in vivo. The let-7 family and mir-27b appear to be attractive targets for modulating angiogenesis.
Gender Differences in Outcomes Among Patients With Symptomatic Intracranial Arterial Stenosis
Authors: Williams Janice E. , Chimowitz Marc I. , Cotsonis George A. , Lynn Michael J. , Waddy Salina P.
Published: June 2007

Background and Purpose—

There are limited and conflicting data on gender differences in clinical outcomes among patients with symptomatic intracranial arterial stenosis. This study examined gender differences in patients enrolled in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) Study.

Methods—

Participants were 569 men and women with symptomatic intracranial arterial stenosis. They were followed-up for the occurrence of ischemic stroke and the combined end point of stroke or vascular death from February 1999 through July 2003 (mean follow-up, 1.8 years).

Results—

Two-year rates of the primary end point were 28.4% and 16.6% for women and men, respectively. Cumulative probabilities of the outcomes over time were estimated by the Kaplan-Meier product-limit method and were compared between men and women with the use of the log-rank test. Cox proportional hazards regression analyses were used to estimate the hazard ratio of gender (women to men) for ischemic stroke and for the primary end point. The probabilities of ischemic stroke (
P
=0.005) and of the combined end point of stroke or vascular death (
P
=0.017) over time were significantly higher in women than men. Women had a greater multivariate-adjusted risk for ischemic stroke (HR, 1.85; 95% CI, 1.14 to 3.01;
P
=0.013) and for the combined end point of stroke or vascular death (HR, 1.58; 95% CI, 1.01 to 2.48;
P
=0.045).

Conclusions—

Women with symptomatic intracranial arterial stenosis are at significantly greater risk for ischemic stroke and for the combined end point of stroke or vascular death. These findings suggest the need for vigorous screening of risk factors and for aggressive management of risk factors and stroke in women. They also suggest the need to ensure adequate numbers of women in clinical trials designed to explore new and promising therapies for intracranial arterial stenosis.
Motor and Functional Recovery After Stroke
Authors: De Wit Liesbet , Putman Koen , Schuback Birgit , Komárek Arnošt , Angst Felix , Baert Ilse , Berman Peter , Bogaerts Kris , Brinkmann Nadine , Connell Louise , Dejaeger Eddy , Feys Hilde , Jenni Walter , Kaske Christiane , Lesaffre Emmanuel , Leys Mark , Lincoln Nadina , Louckx Fred , Schupp Wilfried , Smith Bozena , De Weerdt Willy
Published: June 2007

Background and Purpose—

Outcome after first stroke varies significantly across Europe. This study was designed to compare motor and functional recovery after stroke between four European rehabilitation centers.

Methods—

Consecutive stroke patients (532 patients) were recruited. They were assessed on admission and at 2, 4, and 6 months after stroke with the Barthel Index, Rivermead Motor Assessment of Gross Function, Rivermead Motor Assessment of Leg/Trunk, Rivermead Motor Assessment of Arm, and Nottingham Extended Activities of Daily Living (except on admission). Data were analyzed using random effects ordinal logistic models adjusting for case-mix and multiple testing.

Results—

Patients in the UK center were more likely to stay in lower Rivermead Motor Assessment of Gross Function classes compared with patients in the German center (ΔOR, 2.4; 95% CI, 1.3 to 4.3). In the Swiss center, patients were less likely to stay in lower Nottingham Extended Activities of Daily Living classes compared with patients in the UK center (ΔOR, 0.7; 95% CI, 0.5 to 0.9). The latter were less likely to stay in lower Barthel Index classes compared with the patients in the German center (ΔOR, 0.6; 95%CI, 0.4 to 0.8). Recovery patterns of Rivermead Motor Assessment of Leg/Trunk and Rivermead Motor Assessment of Arm were not significantly different between centers.

Conclusions—

Gross motor and functional recovery were better in the German and Swiss centers compared with the UK center, respectively. Personal self-care recovery was better in the UK compared with the German center. Previous studies in the same centers indicated that German and Swiss patients received more therapy per day. This was not the result of more staff but of a more efficient use of human resources. This study indicates potential for improving rehabilitation outcomes in the UK and Belgian centers.
Predicting Functional Gains in a Stroke Trial
Authors: Cramer Steven C. , Parrish Todd B. , Levy Robert M. , Stebbins Glenn T. , Ruland Sean D. , Lowry David W. , Trouard Theodore P. , Squire Scott W. , Weinand Martin E. , Savage Cary R. , Wilkinson Steven B. , Juranek Jenifer , Leu Szu-Yun , Himes David M.
Published: June 2007

Background and Purpose—

A number of therapies in development for patients with central nervous system injury aim to reduce disability by improving function of surviving brain elements rather than by salvaging tissue. The current study tested the hypothesis that, after adjusting for a number of clinical assessments, a measure of brain function at baseline would improve prediction of behavioral gains after treatment.

Methods—

Twenty-four patients with chronic stroke underwent baseline clinical and functional MRI assessments, received 6 weeks of rehabilitation therapy with or without investigational motor cortex stimulation, and then had repeat assessments. Thirteen baseline clinical/radiological measures were evaluated for ability to predict subsequent trial-related gains.

Results—

Across all patients, bivariate analyses found that greater trial-related functional gains were predicted by (1) smaller infarct volume, (2) greater baseline clinical status, and (3) lower degree of activation in stroke-affected motor cortex on baseline functional MRI. When these 3 variables were further assessed using multivariate linear regression modeling, only lower motor cortex activation and greater clinical status at baseline remained significant predictors. Note that lower baseline motor cortex activation was also associated with larger increases in motor cortex activation after treatment.

Conclusions—

Lower motor cortex activity at baseline predicted greater behavioral gains after therapy, even after controlling for a number of clinical assessments. The boosts in cortical activity that paralleled behavioral gains suggest that in some patients, low baseline cortical activity represents underuse of surviving cortical resources. A measure of brain function might be important for optimal clinical decision-making in the context of a restorative intervention.
Further Reform of China’s Pension System: A Realistic Alternative Option to Fully Funded Individual Accounts
Authors: Zhang Wei
Published: June 2007

China's newly established three-pillar pension system consists of: basic pension; fully funded individual account; and voluntary commercial pension insurance. The second component faces immense financial difficulties caused by transitional costs in the short term and demographic changes in the long term. In addition, the inefficiency of the current capital market and the lack of fund management skills mean that these financial problems are unlikely to be solved within the existing framework of the fully funded individual account. This paper suggests another option—changing the fully funded individual account to a notional defined contribution individual account that operates on a pay-as-you-go basis. This change will keep the advantages of the individual account and avoid the huge risks caused by China's immature capital market.
Demographic Changes, Saving, and Current Account in East Asia
Authors: Kim Soyoung , Lee Jong-Wha
Published: June 2007

This paper analyzes the empirical relationships among demographic changes, saving, and current account balances in East Asia. The panel Vector-Auto Regressive (VAR) model shows that an increase in the dependency rate, especially the elderly dependency rate, significantly lowers saving rates and subsequently worsens current account balances. The result implies that the future aging of the population in East Asia would have a significant impact on global capital flows and current account imbalances.
Tax Policy Reform and Economic Performance in New Zealand
Authors: Claus Iris
Published: June 2007

New Zealand's tax system is relatively simple and transparent by international standards. But there may still be scope for reducing the costs of taxation. This paper develops a stylized model for New Zealand to evaluate the effects of reducing higher-income tax rates. The results suggest that a reduction in higher-income tax rates would improve New Zealand's long-run economic performance if it were financed by a decline in (non-productive) government spending and/or increases in revenue from other less distortional taxes. Despite the reductions in the higher-income tax rates, higher-income taxpayers would continue to pay a larger proportion of the tax burden than lower-income taxpayers.
Microcirculatory Effects of Viatromb® Spray Gel Heparin in Chronic Venous Insufficiency: Evaluation of TcPO2 and PCO2—A Product Evaluation Study
Authors: Rosaria Cesarone Maria , Belcaro Gianni , Errichi Silvia , Pellegrini Luciano , Ledda Andrea , Vinciguerra Giulia , Ricci Andrea , Gizzi Giuseppe , Ippolito Edmondo , Fano Filiberto , Dugall Mark , Acerbi Giovanni , Cacchio Marisa , Di Renzo Andrea , Hosoi Morio , Stuard Stefano , Corsi Marcello
Published: June 2007

The evolution of microcirculatory methods and the definition of the concept of venous microangiopathy allow the study in a quantitative way of microcirculatory changes produced by pharmacologic treatments at the areas most frequently and severely affected by chronic venous insufficiency (CVI), venous hypertensive microangiopathy, and venous ulcerations. This pilot study compares subjects with CVI, in the area most affected by venous hypertension in a 2-week registry. Elastic compression, compression plus Viatromb® (lyposomal spray gel heparin), Lioton® (gel including heparin), and Viatromb® alone were compared. Subjects were evaluated for laser Doppler flux, transcutaneous partial pressure of oxygen (TcPO2), and partial pressure of carbon dioxide (PCO2) and CVI analogic symptom scale. In the Viatromb® groups (B and D), significant decreases in laser Doppler flux, PCO2, and CVI score were observed. The decrease was proportionally more important in the elastic compression plus Viatromb ® group. Partial pressure of oxygen (PO2) was significantly increased. No significant changes were observed in the Lioton® group. There was a good effect for compression only. These differences are significant, as they can be observed even in small groups (10-15 patients). No treatment side effects were observed, and compliance and tolerability were very good.
Local Heparin, Superficial Vein Thrombosis
Authors: Cesarone Maria Rosaria , Belcaro Gianni , Corsi M. , Ippolito Edmondo , Errichi Silvia , Di Renzo Andrea , Ledda Andrea , Fano Filiberto , Cacchio Marisa , Adovasio Roberto
Published: June 2007

Local, topical effects of heparins on the skin still need deeper investigations. The lack of evidence is mainly due to the lack of large investments in this field. Three main local actions of heparin on the skin can be defined: (1) the anticoagulant action, (2) the microcirculatorymodulatory action determining important control of the microcirculation in case of excessive vasoconstriction or vasodilatation, and (3) the “facilitatory action” on skin permeability, allowing other drugs to diffuse better and faster into the skin (producing a therapeutic effect). These aspects have to be evaluated more extensively both in experimental and in clinical conditions as they may be clinically very important. Recent experimental studies indicate these effects of locally applied heparin. Therefore, key questions on local heparin administration such as skin penetration and the action on the local thrombi have a promising answer. These observations suggest important clinical applications for local liposomal heparin. Both the potentials of local applications of heparin, particularly with new formulations, and some new aspects in the management of superficial vein thrombosis can focus on locally applied heparin. Superficial vein thrombosis is an important clinical condition considering its frequency and the potentially large use of local heparin in this clinical problem. Results from new studies and observations presented in this issue of Angiology could be a window for suggesting new significant clinical applications and therapeutic solutions.
Efficacy and Tolerability of Liposomal Heparin Spraygel as an Add-on Treatment in the Management of Superficial Venous Thrombosis
Authors: Katzenschlager Reinhold , Ugurlouglu Ara , Sipos Gyula , Bihari Imre , Anyova Eva B. , Hirschl Mirko , Maruszynski Marek , Noszczyk Wojciech , Rybak Zbigniew , Cencora Andrzej
Published: June 2007

Superficial venous thrombosis usually resolves spontaneously in a few weeks. In most cases, treatment includes peroral analgesics or nonsteroidal anti-inflammatory drugs accompanied by the recommendation to wear elastic stockings and perform regular mild ambulation. In contrast to this “standard treatment,” a recent ACCP guideline has recommended that patients affected by spontaneous superficial thrombophlebitis be treated with intermediate doses of unfractionated or low-molecular-weight heparin. This study was designed to assess the efficacy of topically applied heparin spraygel in terms of reduction of local symptoms and signs of superficial venous thrombosis.
Analysis of equivalence mapping for terminology services
Authors: McCulloch Emma , Macgregor George
Published: June 2007

This paper assesses the range of equivalence or mapping types required to facilitate interoperability in the context of a distributed terminology server. A detailed set of mapping types were examined, with a view to determining their validity for characterizing relationships between mappings from selected terminologies (AAT, LCSH, MeSH, and UNESCO) to the Dewey Decimal Classification (DDC) scheme. It was hypothesized that the detailed set of 19 match types proposed by Chaplan in 1995 is unnecessary in this context and that they could be reduced to a less detailed conceptually-based set. Results from an extensive mapping exercise support the main hypothesis and a generic suite of match types are proposed, although doubt remains over the current adequacy of the developing Simple Knowledge Organization System (SKOS) Core Mapping Vocabulary Specification (MVS) for inter-terminology mapping.
Grandparent—Grandchild Ties
Authors: Kemp Candace L.
Published: June 2007

Within the context of social, demographic, and historical change and informed by a life course perspective, this article examines patterns of relating between grandparents and grandchildren within families across and within generations. Using qualitative data from a study of 10 multigenerational families ( N = 86), the analysis assesses continuity and change in grandparent—grandchild ties across three generations of adults. Although findings reveal change in social and family circumstances over time, half the families experienced considerable continuity in grandparent—grandchild ties and whether close or distant, were characterized by distinct grand cultures. In the remaining families, different configurations of individual, family-related, and social factors led to intra- and intergenerational variations. Divorce and remarriage influenced grandparent—grandchild relationships in most families, yielding highly variable outcomes. Ultimately, the study families' experiences demonstrate how social, historical, familial, and individual circumstances merge to influence grandparent—grandchild ties, producing behaviors ranging from loving and supportive to indifferent and abusive.
Relational and Individual Well-Being Among Cohabitors and Married Individuals in Midlife
Authors: Hansen Thomas , Moum Torbjørn , Shapiro Adam
Published: June 2007

This study uses data from the Norwegian NorLAG study ( N = 2,455) to examine differences in relationship quality and psychological well-being between middle-aged cohabitors and married persons. The authors question whether previous results linking cohabitation as compared with marriage to lower well-being will replicate in Norway, where cohabitation is much more widespread and socially accepted and where the legal system increasingly treats cohabitation and marriage as equal. The authors find that never-married cohabitors but not formerly married cohabitors report lower levels of relational and subjective well-being compared with their married counterparts. In this way, cohabitation per se is not qualitatively different from marriage. The presence of children and union duration have previously been linked to greater discontentment among cohabitors, but this is not evinced in this study.
Variations in Parenting and Adolescent Outcomes Among African American and Latino Families Living in Low-Income, Urban Areas
Authors: Roche Kathleen M. , Ensminger Margaret E. , Cherlin Andrew J.
Published: June 2007

Drawing from social disorganization theory, this study examined how perceived neighborhood conditions modified associations between parenting and delinquency, depressive symptoms, and school problem behavior among more than 800 African American and Latino 10- to 14-year-olds participating in Welfare, Children, and Families: A Three-City Study. Permissive and disengaged parenting, maternal involvement, and punitive parenting were associated with youth outcomes in varying ways depending on perceived neighborhood context and a youth's race, ethnicity, and gender. Neighborhood-modifying influences on parenting were stronger for African Americans as compared to Latinos and for males as compared to females. Findings suggest that the stakes of uninvolved and permissive parenting for problematic youth outcomes are greater in higher risk neighborhoods. In addition, among African American males, punitive parenting is less strongly associated with poor youth outcomes when mothers perceive that the neighborhood poses more threats and offers fewer social resources.