bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymorphisms in the IL-4, IL-4 Receptor α Chain, TNF-α, and Lymphotoxin-α Genes and Risk of Asthma in Hong Kong Chinese Adults
Authors: Mak Judith C.W. , Ko Fanny W.S. , Chu Chung M. , Leung Helen C.M. , Chan Henry W. , Cheung Amy H.K. , Ip Mary S.M. , Chan-Yeung Moira
Published: May 2007

Background: Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components. However, association studies with interleukin-4 (IL-4), IL-4 receptor α subunit (IL-4Rα), tumor necrosis factor-α (TNF-α) and lymphotoxin-α (LT-α) genes were inconclusive, as both positive and negative results were obtained in several populations studied. We aimed to investigate the association of the polymorphisms for IL-4 (C–589T), IL-4Rα (Gln576Arg), TNF-α (G–308A) and LT-α (A252G) genes as candidates and asthma in adult Hong Kong Chinese population. Methods: The association study was conducted in an age- and smoking status-matched case-control design in asthma patients (n = 292) and healthy controls (n = 292) using polymerase chain reaction and restriction fragment length polymorphism. Results: No significant differences were found in allele and genotype frequencies of all four genes between patients and controls. After stratification by atopic status, the heterozygous AG genotype of LT-α (A252G) was found to increase risk of asthma in atopic population [odds ratio (OR) = 2.00, 95% CI 1.09–3.67, p = 0.024]. When stratified by smoking status, we found increased risk of asthma with subjects carrying the heterozygous AG and homozygous GG genotypes of LT-α in ever-smokers (OR = 2.73, 95% CI 1.11–6.69, p = 0.028 for heterozygotes; OR = 3.34, 95% CI 1.16–9.62, p = 0.026 for homozygotes). Conclusion: Our results suggest that the variability of LT-α genotypes may have potential implications for individual susceptibility to asthma in atopic or in ever-smoking Chinese adults in Hong Kong.
Balance of Vascular Endothelial Growth Factor and Pigment Epithelial Growth Factor prior to Development of Proliferative Vitreoretinopathy
Authors: Dieudonné Suzanne C. , La Heij Ellen C. , Diederen Roselie M.H. , Kessels Alfons G.H. , Liem Albert T.A. , Kijlstra Aize , Hendrikse Fred
Published: May 2007

Background: Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) are imbalanced in eyes with proliferative diabetic retinopathy or proliferative vitreoretinopathy (PVR). It is not known whether such an imbalance is already present in early PVR stages. We therefore analyzed VEGF and PEDF concentrations in subretinal fluids prior to PVR development. Methods: A large number (n = 137) of subretinal fluid samples were obtained at the time of scleral buckling surgery for rhegmatogenous retinal detachment (RRD). Thirty patients developed PVR within 6 months after surgery. One hundred and seven patients undergoing the same surgery but without complications served as controls. Furthermore, vitreous from 16 patients with macular hole or pucker (MHP) served as reference for baseline intraocular concentrations. PEDF and VEGF concentrations were measured by commercial ELISAs. Results: PEDF levels were substantially higher (9.6 µg/ml) compared to MHP vitreous (0.3 µg/ml, p < 0.001). VEGF levels were also higher (RRD: 0.07 ng/ml; MHP: 0.01 ng/ml, p < 0.05). Subretinal concentrations were not significantly different between PVR and control RRD patients. Conclusions: Although both VEGF and PEDF are increased at first surgery for RRD, they do not predict PVR development later on. The high PEDF concentrations and its known antiangiogenic activity suggest a protective role against neovascularization.
Modulation of Ku70/80, Clusterin/ApoJ Isoforms and Bax Expression in Indocyanine-Green-Mediated Photo-Oxidative Cell Damage
Authors: Ricci Federico , Pucci Sabina , Sesti Fabiola , Missiroli Filippo , Cerulli Luciano , Spagnoli Luigi Giusto
Published: May 2007

Purpose: In order to characterize the biological effects and molecular mechanism underlying indocyanine-green (ICG)-mediated photo-oxidative cell damage, human cultured retinal pigmented epithelium (RPE) cells preloaded with ICG were exposed to 810-nm laser irradiation. Cell viability and death induction were examined, as well as the modulation of proteins involved in cell death and DNA repair. Methods: ARPE-19 cells preloaded with 100 µM ICG were irradiated using continuous and micropulsed 810-nm laser for the dye photoactivation, and cell viability and apoptosis were evaluated. The expression and subcellular localization of Bax, Ku70, Ku80 and clusterin/ApoJ were analyzed by immunocytochemistry and Western blot. Results: ICG photoactivation induced apoptosis in RPE cells. The micropulsed laser irradiation induced a higher percentage of cell killing as compared to continuous wave. Cell killing was inhibited by sodium azide, suggesting the involvement of reactive oxygen species in the laser-induced cell damage. Bax was strongly induced after 4 and up to 24 h of treatment. The nuclear proapoptotic isoform of clusterin/ApoJ was selectively upregulated after 24 h of treatment. The DNA repair machinery was upregulated after 4 and up to 24 h. Conclusion: These data elucidate some molecular mechanisms involved in cell death induced by ICG photosensitization. The increase and relocalization of Bax into the mitochondria and the upregulation and translocation of the proapoptotic isoform of clusterin/ApoJ in the nucleus demonstrated the involvement of these proteins in the photo-oxidative cell death pathway. These data point out new molecular targets and suggest potential applications in the therapy of the retinal diseases that could benefit by selective RPE treatment.
Preventing Falls in Physically Active Community-Dwelling Older People: A Comparison of Two Intervention Techniques
Authors: Freiberger Ellen , Menz Hylton B. , Abu-Omar Karim , Rütten Alfred
Published: May 2007

Background: Falls are common in physically active older people; however, most intervention studies have been targeted at frail older people. Objective: To evaluate the effectiveness of two intervention techniques for preventing falls in physically active community-dwelling older people. Methods: Two hundred and seventeen people (120 men and 97 women) aged between 70 and 90 years recruited from a health insurance company membership database were randomly allocated to receive either a psychomotor intervention focusing on body awareness, body experience and coordination, a fitness intervention focusing on functional skills, strength, endurance and flexibility, or no intervention (control group).The outcome measures wereprospective falls (number of fallers, number of multiple fallers, number of falls and falls rate) and measures of physical performance (Timed Up and Go Test, maximal step length, sit-to-stand time, normal and fast walking speed). Results: At the 4-month follow-up, significant improvements in the Timed Up and Go Test and sit-to-stand times were observed for both the psychomotor and fitness intervention groups. During the 12-month follow-up period, 39% of the participants fell at least once, and 19% fell on multiple occasions. The proportion of fallers in the fitness intervention group was 23% less than in the control group (RR = 0.77, 95% CI 0.60–0.97), but no significant reduction in falls was observed in the psychomotor intervention group. Conclusion: A fitness training program improves some aspects of physical performance and reduces falls by 23% in physically active older people.
Placement of Intraventricular Catheters Using Flexible Electromagnetic Navigation and a Dynamic Reference Frame: A New Technique
Authors: Rodt Thomas , Köppen Gregory , Lorenz Martin , Majdani Omid , Leinung Martin , Bartling Soenke , Kaminsky Jan , Krauss Joachim K.
Published: May 2007

Background: Catheterization of narrow ventricles may prove difficult resulting in misplacement or inefficient trials with potential damage to brain tissue. Material and Methods: The application of a new module for navigated ventricular catheterization using flexible electromagnetic navigation and a dynamic reference frame is presented. Results: Navigated catheter placement was successful and accurate in a pilot study. Electromagnetic interferences had to be taken into consideration. Conclusion: Flexible electromagnetic navigation with a dynamic reference frame is a useful tool for catheter placement as it reduces the risk of misplacement or repeated catheterization trials.
Indapamide Decreases Plasma Adiponectin Concentration in Patients with Essential Hypertension
Authors: Piecha Grzegorz , Adamczak Marcin , Chudek Jerzy , Wiecek Andrzej
Published: May 2007

Background/Aim: Adiponectin is an adipose tissue-specific protein with antiatherogenic and insulin-sensitizing properties. In patients with essential hypertension, plasma adiponectin concentrations are lower than in healthy subjects. Antihypertensive drugs do not uniformly influence components of the metabolic syndrome. Therefore, the aim of this study was to evaluate the influence of 6 months’ monotherapy with different antihypertensive drugs on plasma adiponectin concentration in essential hypertension patients. Methods: Forty essential hypertension patients were randomized to receive enalapril, metoprolol, amlodipine or indapamide. Plasma concentrations of adiponectin, insulin, glucose and body fat content were estimated twice: before and after 6 months of antihypertensive monotherapy. Results: Plasma adiponectin concentration did not change significantly after enalapril (11.5 ± 4.8 vs. 11.1 ± 4.1 mg/l), metoprolol (10.2 ± 4.2 vs. 9.8 ± 4.5 mg/l), and amlodipine (9.0 ± 6.0 vs. 8.5 ± 5.4 mg/l) treatment. However, a significant decrease of plasma adiponectin concentration (from 11.6 ± 4.6 to 10.2 ± 4.2 mg/l, p = 0.047) was observed in patients treated with indapamide. Additionally in these patients, a significant increase of the HOMA-IR index was found (p = 0.021). Conclusion: Treatment with indapamide was followed by a significant decrease of plasma adiponectin concentration. This may participate in the pathogenesis of carbohydrate metabolism disturbances often found in patients treated with thiazide-type diuretics.
Thrombotic Thrombocytopenic Purpura in Humans and Mice
Authors: Desch Karl C. , Motto David G.
Published: May 2007

Thrombotic thrombocytopenic purpura (TTP) is a disorder of blood coagulation that presents classically with the pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, renal dysfunction and mental status changes. However, the clinical presentation can be quite variable making the diagnosis difficult in many cases. “Hyaline” microthrombi composed primarily of platelets and Von Willebrand Factor (VWF) are found in the small vessels of affected organs and represent the pathological hallmark of the disease. The accompanying tissue ischemia is thought to explain the clinical TTP signs and symptoms. Pathogenesis of TTP has been linked to dysfunction of ADAMTS13, a metalloprotease whose only known substrate is VWF. Interestingly, further investigation into the natural history of TTP has demonstrated that ADAMTS13 deficiency likely is necessary, but not sufficient for the development of this disease, suggesting that additional genetic and/or environmental factors are required for TTP pathogenesis. Recently, a mouse model of TTP was established that recapitulates many of the key clinical features of this disease, including the requirement for further genetic and environmental factors in addition to ADAMTS13 deficiency. Therefore, in addition to being useful for the direct study of disease pathophysiology
in vivo
, this mouse model may also play a key role in elucidating some of the important environmental and genetic contributors to disease pathogenesis. Here we will review TTP in humans, and then discuss recent information gained from the analysis of ADAMTS13-deficient mice.
Enhancing Repair of the Mammalian Heart
Authors: Santini Maria Paola , Tsao Lana , Monassier Laurent , Theodoropoulos Catherine , Carter Janice , Lara-Pezzi Enrique , Slonimsky Esfir , Salimova Ekaterina , Delafontaine Patrice , Song Yao-Hua , Bergmann Martin , Freund Christian , Suzuki Ken , Rosenthal Nadia
Published: May 2007

The injured mammalian heart is particularly susceptible to tissue deterioration, scarring, and loss of contractile function in response to trauma or sustained disease. We tested the ability of a locally acting insulin-like growth factor-1 isoform (mIGF-1) to recover heart functionality, expressing the transgene in the mouse myocardium to exclude endocrine effects on other tissues. supplemental mIGF-1 expression did not perturb normal cardiac growth and physiology. Restoration of cardiac function in post-infarct mIGF-1 transgenic mice was facilitated by modulation of the inflammatory response and increased antiapoptotic signaling. mIGF-1 ventricular tissue exhibited increased proliferative activity several weeks after injury. The canonical signaling pathway involving Akt, mTOR, and p70S6 kinase was not induced in mIGF-1 hearts, which instead activated alternate PDK1 and SGK1 signaling intermediates. The robust response achieved with the mIGF-1 isoform provides a mechanistic basis for clinically feasible therapeutic strategies for improving the outcome of heart disease.
Subannual, Seasonal, and Interannual Variability of the North Atlantic Meridional Overturning Circulation
Authors: Hirschi Joël J-M. , Killworth Peter D. , Blundell Jeffrey R.
Published: May 2007

An eddy-permitting numerical ocean model is used to investigate the variability of the meridional overturning circulation (MOC). Both wind stress and fluctuations of the seawater density contribute to MOC changes on subannual and seasonal time scales, whereas the interannual variability mainly reflects changes in the density field. Even on subannual and seasonal time scales, a significant fraction of the total MOC variability is due to changes of the density field in the upper 1000 m of the ocean. These changes reflect perturbations of the isopycnal structure that travel westward as Rossby waves. Because of a temporally changing phase difference between the eastern and western boundaries, the Rossby waves affect the MOC by modifying the basinwide east–west density gradient. Both the numerical model used in this study and calculations based on Rossby wave theory suggest that this effect can account for an MOC variability of several Sverdrups (Sv ≡ 106 m3 s−1). These results have implications for the interpretation of variability signals inferred from hydrographic sections and might contribute to the understanding of the results obtained from the Rapid Climate Change (RAPID) monitoring array deployed at 26°N in the North Atlantic Ocean.
Deodorization of Ethyl Mercaptan by Cotton Fabrics Mordant Dyed with a Direct Dye and Copper Sulfate
Authors: Kobayashi Yasuko , Kamimaru Mayuka , Tsuboyama Kaori , Nakanishi Tadashi , Komiyama Jiro
Published: May 2007

Six cotton samples obtained from appropriate market sources were dyed with C. I. Direct Blue 200, a copper complex direct dye, and pre-and post-mordanted with Cu(II) sulfate. Dye and copper ion uptake, carboxylic acid contents and deodorization of ethyl mercaptan were measured for the samples appropriately treated. The uptake of the dye by four differently mordant-dyed specimens from a single cotton sample was the same to within ± 10%: the uptake by respective specimens was in the range 10—15 mg/g, except for that of a scoured and mercerized sample, which had uptake in the range of 20 mg/g. The copper ion uptake by pre-mordanted specimens was found not to be correlated with the carboxylic acid contents. It was inferred that the differences in the nature and the scouring treatment of the cotton sample were responsible for the unexpected copper ion uptake. The uptake was most enhanced by the successive pre-mordanting, dyeing, and post-mordanting treatment for all the six cotton samples. The uptake of dyed and post-mordanted samples came next and the rest of the treatments showed that uptake varied within three times the copper ion uptake. The deodorizing abilities of ethyl mercaptan by the dyed and mordanted cotton specimens were compared. It was found that the deodorization rates can be classified into three groups, one group almost null, the second one intermediate and the third one fast in comparison with activated carbon. All the deodorization effects plotted against the copper ion uptakes were found to increase quadratically with the copper ion uptake, regardless of the dyeing and mordanting conditions.
Basilar Artery Thrombosis in a Child Heterozygous for Prothrombin Gene G20210A Mutation
Authors: Hüdaoğlu Orkide , Kurul Semra , Yiş Uluç , Dirik Eray , Çakmakçi Handan , Men Süleyman
Published: May 2007

Prothrombin G20210A mutation is an important prothrombotic condition for venous thrombosis. Recently, some studies have also considered it to be a risk factor for arterial ischemic stroke in children. A 10-year-old boy with basilar artery thrombosis who was heterozygous for prothrombin G20210A mutation is described. In concordance with the previous literature, the present case suggests that prothrombin G20210A mutation may be a risk factor for arterial ischemic stroke in childhood.
Global repeat discovery and estimation of genomic copy number in a large, complex genome using a high-throughput 454 sequence survey
Authors: Swaminathan Kankshita , Varala Kranthi , Hudson Matthew E
Published: May 2007

Background

Extensive computational and database tools are available to mine genomic and genetic databases for model organisms, but little genomic data is available for many species of ecological or agricultural significance, especially those with large genomes. Genome surveys using conventional sequencing techniques are powerful, particularly for detecting sequences present in many copies per genome. However these methods are time-consuming and have potential drawbacks. High throughput 454 sequencing provides an alternative method by which much information can be gained quickly and cheaply from high-coverage surveys of genomic DNA.

Results

We sequenced 78 million base-pairs of randomly sheared soybean DNA which passed our quality criteria. Computational analysis of the survey sequences provided global information on the abundant repetitive sequences in soybean. The sequence was used to determine the copy number across regions of large genomic clones or contigs and discover higher-order structures within satellite repeats. We have created an annotated, online database of sequences present in multiple copies in the soybean genome. The low bias of pyrosequencing against repeat sequences is demonstrated by the overall composition of the survey data, which matches well with past estimates of repetitive DNA content obtained by DNA re-association kinetics (Cot analysis).

Conclusion

This approach provides a potential aid to conventional or shotgun genome assembly, by allowing rapid assessment of copy number in any clone or clone-end sequence. In addition, we show that partial sequencing can provide access to partial protein-coding sequences.
A first step in understanding an invasive weed through its genes: an EST analysis of invasive Centaurea maculosa
Authors: Broz Amanda K , Broeckling Corey D , He Ji , Dai Xinbin , Zhao Patrick X , Vivanco Jorge M
Published: May 2007

Background

The economic and biological implications of plant invasion are overwhelming; however, the processes by which plants become successful invaders are not well understood. Limited genetic resources are available for most invasive and weedy species, making it difficult to study molecular and genetic aspects that may be associated with invasion.

Results

As an initial step towards understanding the molecular mechanisms by which plants become invasive, we have generated a normalized Expressed Sequence Tag (EST) library comprising seven invasive populations of Centaurea maculosa, an invasive aster in North America. Seventy-seven percent of the 4423 unique transcripts showed significant similarity to existing proteins in the NCBI database and could be grouped based on gene ontology assignments.

Conclusion

The C. maculosa EST library represents an initial step towards looking at gene-specific expression in this species, and will pave the way for creation of other resources such as microarray chips that can help provide a view of global gene expression in invasive C. maculosa and its native counterparts. To our knowledge, this is the first published set of ESTs derived from an invasive weed that will be targeted to study invasive behavior. Understanding the genetic basis of evolution for increased invasiveness in exotic plants is critical to understanding the mechanisms through which exotic invasions occur.
Estrogen Signaling via a Linear Pathway Involving Insulin-Like Growth Factor I Receptor, Matrix Metalloproteinases, and Epidermal Growth Factor Receptor to Activate Mitogen-Activated Protein Kinase in MCF-7 Breast Cancer Cells
Authors: Song Robert X.-D. , Zhang Zhenguo , Chen Yucai , Bao Yongde , Santen Richard J.
Published: May 2007

We present an integrated model of an extranuclear, estrogen receptor-α (ERα)-mediated, rapid MAPK activation pathway in breast cancer cells. In noncancer cells, IGF-I initiates a linear process involving activation of the IGF-I receptor (IGF-IR) and matrix metalloproteinases (MMP), release of heparin-binding epidermal growth factor (HB-EGF), and activation of EGF receptor (EGFR)-dependent MAPK. 17β-Estradiol (E2) rapidly activates IGF-IR in breast cancer cells. We hypothesize that E2 induces a similar linear pathway involving IGF-IR, MMP, HB-EGF, EGFR, and MAPK. Using MCF-7 breast cancer cells, we for the first time demonstrated that a sequential activation of IGF-IR, MMP, and EGFR existed in E2 and IGF-I actions, which was supported by evidence that the selective inhibitors of IGF-IR and MMP or knockdown of IGF-IR all inhibited E2- or IGF-I-induced EGFR phosphorylation. Using the inhibitors and small inhibitory RNA strategies, we also demonstrated that the same sequential activation of the receptors occurred in E2-, IGF-I-, but not EGF-induced MAPK phosphorylation. Additionally, a HB-EGF neutralizing antibody significantly blocked E2-induced MAPK activation, further supporting our hypothesis. The biological effects of sequential activation of IGF-IR and EGFR on E2 stimulation of cell proliferation were also investigated. Knockdown or blockade of IGF-IR significantly inhibited E2- or IGF-I-stimulated but not EGF-induced cell growth. Knockdown or blockade of EGFR abrogated cell growth induced by E2, IGF-I, and EGF, indicating that EGFR is a downstream molecule of IGF-IR in E2 and IGF-I action. Together, our data support the novel view that E2 can activate a linear pathway involving the sequential activation of IGF-IR, MMP, HB-EGF, EGFR, and MAPK.
Long-Term Survival is Possible After Stenting for Malignant Ureteric Obstruction in Colorectal Cancer
Authors: Jones Oliver M , John Solomon KP , Lawrance Richard J , Fozard J Basil J
Published: May 2007

INTRODUCTION

Ureteric obstruction is a potentially terminal event in patients with irresectable or recurrent colorectal cancer. Urinary tract obstruction is easily relieved by either two stage antegrade stenting or one stage retrograde stenting. However, there is little in the literature about outcomes after this procedure and it is unclear which, if any, patients should be offered this intervention.

PATIENTS AND METHODS

This was a retrospective review of a prospectively collected database of patients diagnosed with colorectal cancer. This database comprised 1428 cases (operative and non-operative) diagnosed at a single institution. This was cross-checked with databases for patients undergoing nephrostomy and/or antegrade stenting and by clinical coding for those patients having retrograde stenting between January 1996 and October 2004.

RESULTS

Thirteen patients were identified (median age, 69 years: range, 35–85 years; 9 male). The aetiology of obstruction was recurrent tumour in 6 patients and irresectable tumour in the remaining 7 patients. Two patients were discussed at a urology multidisciplinary meeting before stenting and a further two were discussed with colorectal surgeons. One patient received a palliative cystectomy and ileal conduit for a vesicovaginal fistula followed by radiotherapy. Four patients received chemotherapy after stenting. Overall median survival was 210 days (range, 13–927 days).

CONCLUSIONS

Long-term survival is possible in selected patients with recurrent or irresectable colorectal cancer and malignant ureteric obstruction. This appears to be more likely in those patients in whom other treatments, particularly chemotherapy, are available.
Conference Reports
Authors: Saad Mohammed , Ame Abdurahman , Etzkowitz Henry
Published: May 2007

Conference on the Triple Helix Paradigm for Development: Strategies for Co-operation and Exchange of Good Practice

University and Development: The Triple Helix Conference in Addis Ababa
Suicide Acceptability is Related to Suicide Planning in U.S. Adolescents and Young Adults
Authors: Joe Sean , Romer Daniel , Jamieson Patrick E.
Published: May 2007

The association between adolescents' and young adults' attitudes toward suicide and their own suicidality across five racial‐ethnic classifications was studied in a nationally representative sample of 3,301 youth ages 14 to 22 years from the National Annenberg Risk Survey of Youth. Results indicate that adolescents and young adults who most strongly believe that it is acceptable to end one's life are more than fourteen times more likely to make a plan to kill themselves as those who do not have such beliefs (p< .001). Future behavioral prevention and intervention research should take into consideration adolescents' and young adults' approval of suicide as a risk factor for taking their own lives.0
Self‐Mutilation and Coping Strategies in a College Sample
Authors: Andover Margaret S. , Pepper Carolyn M. , Gibb Brandon E.
Published: May 2007

The goal of this study was to examine the use of specific coping strategies among self‐mutilating college students. The self‐mutilating group (n = 44) reported utilizing avoidance strategies more often than did a control group (n = 44) matched for general psychological distress but with no history of self‐mutilation. In addition, female, but not male, self‐mutilators endorsed using problem‐solving and social support seeking strategies less often than nonmutilators. These findings suggest that coping strategies in general and avoidance‐based strategies in particular may be important targets for the treatment of self‐mutilative behaviors.
MIO-M1 Cells and Similar Müller Glial Cell Lines Derived from Adult Human Retina Exhibit Neural Stem Cell Characteristics
Authors: Lawrence Jean M. , Singhal Shweta , Bhatia Bhairavi , Keegan David J. , Reh Thomas A. , Luthert Philip J. , Khaw Peng T. , Limb Gloria Astrid
Published: May 2007

Growing evidence suggests that glial cells may have a role as neural precursors in the adult central nervous system. Although it has been shown that Müller cells exhibit progenitor characteristics in the postnatal chick and rat retinae, their progenitor-like role in developed human retina is unknown. We first reported the Müller glial characteristics of the spontaneously immortalized human cell line MIO-M1, but recently we have derived similar cell lines from the neural retina of several adult eye donors. Since immortalization is one of the main properties of stem cells, we investigated whether these cells expressed stem cell markers. Cells were grown as adherent monolayers, responded to epidermal growth factor, and could be expanded indefinitely without growth factors under normal culture conditions. They could be frozen and thawed without losing their characteristics. In the presence of extracellular matrix and fibroblast growth factor-2 or retinoic acid, they acquired neural morphology, formed neurospheres, and expressed neural stem cell markers including βIII tubulin, Sox2, Pax6, Chx10, and Notch 1. They also expressed markers of postmitotic retinal neurons, including peripherin, recoverin, calretinin, S-opsin, and Brn3. When grafted into the subretinal space of dystrophic Royal College of Surgeons rats or neonatal Lister hooded rats, immortalized cells migrated into the retina, where they expressed various markers of retinal neurons. These observations indicate that adult human neural retina harbors a population of cells that express both Müller glial and stem cell markers and suggest that these cells may have potential use for cell-based therapies to restore retinal function.

Disclosure of potential conflicts of interest is found at the end of this article.
Isolation and Characterization of Neural Crest Progenitors from Adult Dorsal Root Ganglia
Authors: Li Hong-Yun , Say Evonne Hwee Min , Zhou Xin-Fu
Published: May 2007

After peripheral nerve injury, the number of sensory neurons in the adult dorsal root ganglia (DRG) is initially reduced but recovers to a normal level several months later. The mechanisms underlying the neuronal recovery after injury are not clear. Here, we showed that in the DRG explant culture, a subpopulation of cells that emigrated out from adult rat DRG expressed nestin and p75 neurotrophin receptor and formed clusters and spheres. They differentiated into neurons, glia, and smooth muscle cells in the presence or absence of serum and formed secondary and tertiary neurospheres in cloning assays. Molecular expression analysis demonstrated the characteristics of neural crest progenitors and their potential for neuronal differentiation by expressing a set of well-defined genes related to adult stem cells niches and neuronal fate decision. Under the influence of neurotrophic factors, some of these progenitors gave rise to neuropeptide-expressing cells and protein zero-expressing Schwann cells. In a 5-bromo-2′-deoxyuridine chasing study, we showed that these progenitors likely originate from satellite glial cells. Our study suggests that a subpopulation of glia in adult DRG is likely to be progenitors for neurons and glia and may play a role in neurogenesis after nerve injury.

Disclosure of potential conflicts of interest is found at the end of this article.
A Tissue Engineering Approach to Progenitor Cell Delivery Results in Significant Cell Engraftment and Improved Myocardial Remodeling
Authors: Simpson David , Liu Hong , Fan Tai-Hwang Michael , Nerem Robert , Dudley Samuel C.
Published: May 2007

Cell replacement therapy has become an attractive solution for myocardial repair. Typical cell delivery techniques, however, suffer from poor cell engraftment and inhomogeneous cell distributions. Therefore, we assessed the hypothesis that an epicardially applied, tissue-engineered cardiac patch containing progenitor cells would result in enhanced exogenous cell engraftment. Human mesenchymal stem cells (hMSCs) were embedded into a rat tail type I collagen matrix to form the cardiac patch. Myocardial infarction was induced by left anterior descending coronary artery ligation in immunocompetent male cesarean-derived fischer rats, and patches with or without cells were secured to hearts with fibrin sealant. After patch formation, hMSCs retained a viability of >90% over 5 days in culture. In addition, >75% of hMSCs maintained a high degree of potency prior to patch implantation. After 4 days in culture, patches were applied to the epicardial surface of the infarct area and resulted in 23% ± 4% engraftment of hMSCs at 1 week (n = 6). Patch application resulted in a reduction in left ventricle interior diameter at systole, increased anterior wall thickness, and a 30% increase in fractional shortening. Despite this improvement in myocardial remodeling, hMSCs were not detectable at 4 weeks after patch application, implying that improvement did not require long-term cell engraftment. Patches devoid of progenitor cells showed no improvement in remodeling. In conclusion, pluripotent hMSCs can be efficiently delivered to a site of myocardial injury using an epicardial cardiac patch, and such delivery results in improved myocardial remodeling after infarction.

Disclosure of potential conflicts of interest is found at the end of this article.
Experimental investigation of EPS geofoam seismic buffers using shaking table tests
Authors: Zarnani S. , Bathurst R. J.
Published: May 2007

The paper reports the results of six shaking table tests using reduced-scale model walls constructed with expanded polystyrene (EPS) panels to reduce dynamic earth loads due to base shaking. The results are compared with a nominal identical rigid (control) wall constructed without a seismic buffer. The test results show that dynamic load attenuation increased with decreasing geofoam stiffness. The test with the highest buffer stiffness resulted in a 15% reduction in dynamic load and the test with lowest stiffness resulted in a 40% reduction in dynamic load compared with the control wall. The results of these experiments provide proof of the concept that EPS panels placed against rigid walls can act as seismic buffers to attenuate dynamic loads due to ground shaking (e.g. earthquake). Additional quantitative data related to load–deformation–time response, back-calculated elastic modulus values for the EPS seismic buffer configurations, dynamic interface shear properties, acceleration amplification in the backfill soil and post-excitation stress relaxation-creep behaviour are also reported.
Satisfaction and Quality of Life With Premeal Inhaled Versus Injected Insulin in Adolescents and Adults With Type 1 Diabetes
Authors: Testa Marcia A. , Simonson Donald C.
Published: May 2007

OBJECTIVE—We sought to compare and evaluate the impact of inhaled versus injected insulin on potential mediators of patient acceptance of insulin therapy while maintaining comparable A1C levels.

RESEARCH DESIGN AND METHODS—During a noninferiority efficacy trial conducted in 40 centers in the U.S., we surveyed treatment satisfaction, quality of life, and adherence barriers at weeks −4, −1, 6, 12, 20, and 24 in adolescents aged 12–17 years and adults with type 1 diabetes who received premeal regular plus twice-daily NPH insulin during a 4-week run-in; then, subjects were randomized to premeal inhaled human insulin plus twice-daily NPH (adults, n = 102; adolescents, n = 60) (inhaled) or remaining on run-in therapy (n = 105 and 60, respectively) (subcutaneous injection).

RESULTS—Overall treatment satisfaction (0–100) increased by 13.2 ± 1.1 units for inhaled insulin (baseline = 63.3 ± 1.2) compared with 1.7 ± 0.8 for subcutaneous insulin injection (baseline = 64.1 ± 1.2, P < 0.0001). All 12 satisfaction subscales favored inhaled insulin (all P < 0.01), and effects did not vary by age or sex. Despite similar baseline-adjusted end point A1C for inhaled (7.7 ± 0.1%) and subcutaneous (7.9 ± 0.1%) regimens, quality-of-life scales of mental health, symptoms, health status, cognitive functioning, and adherence barriers during treatment were more favorable for inhaled insulin (all P < 0.05). Greater satisfaction was associated with fewer barriers to insulin adherence (rho = −0.78, P < 0.0001) and a greater reduction in A1C (rho = −0.18, P < 0.001).

CONCLUSIONS—Treatment satisfaction was substantially more favorable, adherence barriers moderately lower, and quality of life moderately higher for inhaled compared with subcutaneous regimen. It remains to be demonstrated whether these patient-reported outcomes will translate into improved adherence and glycemic control.
Impact of Telmisartan Versus Ramipril on Renal Endothelial Function in Patients With Hypertension and Type 2 Diabetes
Authors: Schmieder Roland E. , Delles Christian , Mimran Albert , Fauvel Jean P. , Ruilope Luis M.
Published: May 2007

OBJECTIVE—One of the earliest signs of vascular change is endothelial dysfunction, which is also known to provoke albuminuria and to predict cardiovascular prognosis. The aim of this study was to analyze the effects of renin-angiotensin system (RAS) blockade on renal endothelial function.

RESEARCH DESIGN AND METHODS—In a multicenter, prospective, double-blind, forced-titration, randomized study, 96 patients with type 2 diabetes, hypertension, glomerular filtration rate >80 ml/min, and normo- or microalbuminuria were treated once daily with 40/80 mg telmisartan or 5/10 mg ramipril for 9 weeks.

RESULTS—The mean ± SE fall in renal plasma flow (RPF) in response to intravenous NG-monomethyl-l-arginine (l-NMMA), reflecting the magnitude of nitric oxide (NO) activity, increased with telmisartan from 71.9 ± 9.0 ml/min before therapy to 105.2 ± 9.7 ml/min at the end of treatment (P < 0.001). With ramipril, RPF response to l-NMMA increased from 60.1 ± 12.2 to 87.8 ± 9.2 ml/min (P = 0.018). The adjusted difference between treatments was −17.1 ± 13.7 ml/min (P = 0.214). In accordance, telmisartan increased RPF at rest (i.e., without l-NMMA) from 652.0 ± 27.0 to 696.1 ± 31.0 ml/min (P = 0.047), whereas ramipril produced no significant changes in RPF. The more the basal NO activity improved, the greater was the vasodilatory effect on renal vasculature (r = 0.47, P < 0.001).

CONCLUSIONS—In patients with type 2 diabetes, telmisartan and ramipril both increased NO activity of the renal endothelium significantly, which in turn may support the preservation of cardiovascular and renal function.
A Cohort Study of People With Diabetes and Their First Foot Ulcer
Authors: Ismail Khalida , Winkley Kirsty , Stahl Daniel , Chalder Trudie , Edmonds Michael
Published: May 2007

OBJECTIVE—The aim was to evaluate over 18 months whether depression was associated with mortality in people with their first foot ulcer.

RESEARCH DESIGN AND METHODS—A prospective cohort design was used. Adults with their first diabetic foot ulcer were recruited from foot clinics in southeast London, U.K. At baseline, the Schedules for Clinical Assessment in Neuropsychiatry 2.1 was used to define those who met DSM (Diagnostic and Statistical Manual of Mental Disorders)-IV criteria for minor and major depressive disorders. Potential covariates were age, sex, marital status, socioeconomic status, smoking, antidepressant use, A1C, macro- and microvascular complications, and University of Texas classification–based severity and size of ulcer. The main outcome was mortality 18 months later, and A1C was the secondary outcome. The proportion who had an amputation, had recurrence, and whose ulcer had healed was recorded.

RESULTS—A total of 253 people with their first diabetic foot ulcer were recruited. The prevalence of minor and major depressive disorder was 8.1% (n = 21) and 24.1% (n = 61), respectively. There were 40 (15.8%) deaths, 36 (15.5%) amputations, and 99 (43.2%) recurrences. In the adjusted Cox regression analysis, minor and major depressive disorders were associated with an approximately threefold hazard risk for mortality compared with no depression (3.23 [95% CI 1.39–7.51] and 2.73 [1.38–5.40], respectively). There was no association between minor and major depression compared with no depression and A1C (P = 0.86 and P = 0.43, respectively).

CONCLUSIONS—One-third of people with their first diabetic foot ulcer suffer from clinical depression, and this is associated with increased mortality.
Effects of Once-Weekly Dosing of a Long-Acting Release Formulation of Exenatide on Glucose Control and Body Weight in Subjects With Type 2 Diabetes
Authors: Kim Dennis , MacConell Leigh , Zhuang Dongliang , Kothare Prajakti A. , Trautmann Michael , Fineman Mark , Taylor Kristin
Published: May 2007

OBJECTIVE—In patients with type 2 diabetes, exenatide reduces A1C, postprandial and fasting glucose, and weight. In this study we investigated the effects of continuous exenatide administration from a long-acting release (LAR) formulation.

RESEARCH DESIGN AND METHODS—In this randomized, placebo-controlled phase 2 study, exenatide LAR (0.8 or 2.0 mg) was administered subcutaneously once weekly for 15 weeks to subjects with type 2 diabetes (n = 45) suboptimally controlled with metformin (60%) and/or diet and exercise (40%): 40% female, A1C (mean ± SD) 8.5 ± 1.2%, fasting plasma glucose 9.9 ± 2.3 mmol/l, weight 106 ± 20 kg, and diabetes duration 5 ± 4 years.

RESULTS—From baseline to week 15, exenatide LAR reduced mean ± SE A1C by −1.4 ± 0.3% (0.8 mg) and −1.7 ± 0.3% (2.0 mg), compared with +0.4 ± 0.3% with placebo LAR (P < 0.0001 for both). A1C of ≤7% was achieved by 36 and 86% of subjects receiving 0.8 and 2.0 mg exenatide LAR, respectively, compared with 0% of subjects receiving placebo LAR. Fasting plasma glucose was reduced by −2.4 ± 0.9 mmol/l (0.8 mg) and −2.2 ± 0.5 mmol/l (2.0 mg) compared with +1.0 ± 0.7 mmol/l with placebo LAR (P < 0.001 for both). Exenatide LAR reduced self-monitored postprandial hyperglycemia. Subjects receiving 2.0 mg exenatide LAR had body weight reductions (−3.8 ± 1.4 kg) (P < 0.05), whereas body weight was unchanged with both placebo LAR and the 0.8-mg dose. Mild nausea was the most frequent adverse event. No subjects treated with exenatide LAR withdrew from the study.

CONCLUSIONS—Exenatide LAR offers the potential of 24-h glycemic control and weight reduction with a novel once-weekly treatment for type 2 diabetes.
Exercise Capacity and Body Mass as Predictors of Mortality Among Male Veterans With Type 2 Diabetes
Authors: McAuley Paul A. , Myers Jonathan N. , Abella Joshua P. , Tan Swee Y. , Froelicher Victor F.
Published: May 2007

OBJECTIVE—To demonstrate the relation of exercise capacity and BMI to mortality in a population of male veterans with type 2 diabetes.

RESEARCH DESIGN AND METHODS—After excluding two underweight patients (BMI <18.5 kg/m2), the study population comprised 831 consecutive patients with type 2 diabetes (mean age 61 ± 9 years) referred for exercise testing for clinical reasons between 1995 and 2006. Exercise capacity was determined from a maximal exercise test and measured in metabolic equivalents (METs). Patients were classified both according to BMI category (18.5–24.9, 25.0–29.9, and ≥30 kg/m2) and by exercise capacity (<5.0 or ≥5.0 maximal METs). The association among exercise capacity, BMI, other clinical variables, and all-cause mortality was assessed by Cox proportional hazards. Study participants were followed for mortality up to 30 June 2006.

RESULTS—During a mean follow-up of 4.8 ± 3.0 years, 112 patients died, for an average annual mortality rate of 2.2%. Each 1-MET increase in exercise capacity conferred a 10% survival benefit (hazard ratio 0.90 [95% CI 0.82–0.98]; P = 0.01), but BMI was not significantly associated with mortality. After adjustment for age, ethnicity, examination year, BMI, presence of cardiovascular disease (CVD), and CVD risk factors, diabetic patients achieving <5 maximal METs were 70% more likely to die (1.70 [1.13–2.54]) than those achieving ≥5 maximal METs.

CONCLUSIONS—There was a strong inverse association between exercise capacity and mortality in this cohort of men with documented diabetes, and this relationship was independent of BMI.
Abnormal Left Ventricular Energy Metabolism in Obese Men With Preserved Systolic and Diastolic Functions Is Associated With Insulin Resistance
Authors: Perseghin Gianluca , Ntali Georgia , De Cobelli Francesco , Lattuada Guido , Esposito Antonio , Belloni Elena , Canu Tamara , Costantino Federica , Ragogna Francesca , Scifo Paola , Del Maschio Alessandro , Luzi Livio
Published: May 2007

OBJECTIVE—Perturbations in cardiac energy metabolism might represent early alterations in diabetes preceding functional and pathological changes. We evaluated left ventricular (LV) structure/geometry and function in relation to energy metabolism and cardiovascular risk factors in overweight/obese men using magnetic resonance techniques.

RESEARCH DESIGN AND METHODS—We studied 81 healthy men (aged 22–55 years, with BMI between 19 and 35 kg/m2) by means of cardiac magnetic resonance imaging and 31P-magnetic resonance spectroscopy in the resting and fasted conditions and stratified them in quartiles of BMI (cut offs: 23.2, 25.5 and 29.0 kg/m2).

RESULTS—LV mass increased across quartiles of BMI; meanwhile, the volumes did not differ. Parameters of LV systolic and diastolic function were not different among quartiles. The phosphocreatine-to-ATP ratio was reduced across increasing quartiles of mean ± SD BMI (2.25 ± 0.52, 1.89 ± 0.26, 1.99 ± 0.38, and 1.79 ± 0.29; P < 0.006) in association with insulin sensitivity (computer homeostasis model assessment 2 model); this relation was independent of age, BMI, blood pressure, wall mass, HDL cholesterol, triglycerides, smoking habits, and metabolic syndrome.

CONCLUSIONS—Abnormal LV energy metabolism was detectable in obese men in the presence of normal function, supporting the hypothesis that metabolic remodeling in insulin resistant states precedes functional and structural/geometrical remodeling of the heart regardless of the onset of overt hyperglycemia.
Is There a Single Underlying Factor for the Metabolic Syndrome in Adolescents?
Authors: Li Chaoyang , Ford Earl S.
Published: May 2007

OBJECTIVE—The lack of a universally applicable model for the metabolic syndrome in the pediatric population makes it difficult to define this syndrome and compare its prevalence across studies and diverse populations. We sought to assess whether a single underlying factor could represent the metabolic syndrome in adolescents.

RESEARCH DESIGN AND METHODS—Using data from the National Health and Nutrition Examination Survey (1999–2002), we conducted a confirmatory factor analysis to assess the validity of waist circumference, triglycerides, fasting insulin, and systolic blood pressure (SBP) as potential phenotypic traits for the metabolic syndrome in adolescents aged 12–17 years (n = 1,262). A multiple-group approach was used to test the invariance in factor loadings across sex and race/ethnicity.

RESULTS—The estimates of factor loadings for the total sample were 0.76, 0.46, 0.81, and 0.42 for waist circumference, triglycerides, fasting insulin, and SBP, respectively. The goodness-of-fit indexes were adequate for the total sample (comparative fit index, 0.99; standardized root mean square residual, 0.02), Caucasian boys (1.0; 0.01), African-American boys (0.99; 0.03), Mexican-American boys (1.0; 0.01), Mexican-American girls (1.0; 0.01), and Caucasian girls (0.95; 0.04) and acceptable for African-American girls (0.94; 0.05). There were no significant differences in factor loadings of the four measured variables between boys and girls and among the three racial or ethnic subgroups.

CONCLUSIONS—The metabolic syndrome as a single underlying factor for the four simple phenotypic traits may be plausible in adolescents. The proposed model appears to be generalizable across sex and race/ethnicity.