bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small intestine capsule endoscopy in the diagnostics of coeliac disease
Authors: Kovács Márta , Pák Péter , Pák Gábor , Fehér János 
Published: October 2008

A coeliakia olyan autoimmun enteropathia, amelyet a genetikailag prediszponált egyénekben a gabonafélék gluténje indít el. A betegséget sokáig gyermekkori betegségnek tartották, mivel a klinikai tünetek a glutén étrendbe való beépítésekor jelentkeztek. A coeliakiára specifikus szerológiai markerek elterjedése megváltoztatta a kórkép epidemiológiájával és tünettanával kapcsolatos ismereteket. A diagnosztika nehézsége abból adódik, hogy a gluténszenzitív enteropathiás betegek több mint 50%-ának tünetei atípusosak, és az extragastrointestinalis manifesztációjú coeliakiában szenvedő betegek 90%-ának nincs gastrointestinalis tünete. Jelenleg a coeliakia diagnosztikája a specifikus autoantitestek kimutatásán és a duodenum szövettani értékelésén alapszik. Kezeletlen betegek esetén a felső standard endoszkópia során a nyombélben jól láthatók a boholyatrophia makroszkópos eltérései (Kerking-redőzet elsimulása, a nyálkahártyán áttűnő érrajzolat, a mucosa mozaikszerű rajzolata vagy granuláltsága és a fésűfogszerű redőzet kialakulása). A kapszulás endoszkópia (CE) a hagyományos endoszkópos módszerekkel szemben a teljes vékonybél noninvazív, fájdalmatlan vizsgálatát teszi lehetővé. A vizsgálatok során a vékonybél-nyálkahártya 8:1 arányú nagyításban válik láthatóvá, ami gyakorlott vizsgáló számára lehetővé teszi a boholyatrophia megítélését. Az első tapasztalatok alapján úgy tűnik, hogy a standard felső endoszkópia és a kapszulás endoszkópia szenzitivitása és specificitása azonos coeliakiában. A CE előnyét a felső endoszkópiával szemben a vékonybél teljes értékelhetősége jelenti, mert így a betegség kiterjedése és súlyossága is megítélhető. Hátránya a hisztológiai mintavétel hiánya. Bizonyítottan coeliakiában szenvedő betegek esetében, „alarm” tünetek jelentkezésekor a CE „first line” módszerként javasolható.
Extrapolation concepts for dealing with multiple contamination in environmental risk assessment
Authors: Altenburger Rolf , Greco William R 
Published: October 2008

AbstractMixture exposure against several stressors is what organisms in the environment typically experience, and combined effects resulting from this are well documented. Risk management often still focuses on the assessment of individual priority compounds. Because of the large number of possible mixtures and their variability in time, experimental investigation of every conceivable mixture for their adverse effects is not a viable option. Instead, during the past decade, modeling approaches have been discussed in ecotoxicology that allow the prediction of expected combination effects based on the knowledge of the biological activity of the individual components. This contribution summarizes mixture exposure situations where consensus has been achieved about extrapolation techniques. In particular, for simultaneous exposure and for sequential exposure with no intervening recovery, currently available evidence demonstrates reasonable predictability of combined effects from the information of the individual mixture components. By contrast, when organisms are exposed to pulsed exposure with recovery periods or when nonchemical stressors interfere, there is still an open research field as how to account for these types of interaction.
The Acquisition and Processing of Vertical Seismic Profile in Horizontal Wells Erb West Field, Sabah, Malaysia
Authors: Hocker C. , Track A. , Cao D. , Williams R. , Dupal L. , Shapiro B. 
Published: October 2008

Abstract
Three Vertical Seismic Profiles and one well shoot mere acquired as pari of the EWDP-A revisit-3 horizontal drilling campaign in the Erb West field. The main objective in acquiring this data was to derive a reliable velocity model for the overburden in the main part of the field. By positioning the geophones in the horizontal section, and below the heavily faulted overburden, allowed for correct imaging of reservoirs immediaiely belozu the wellbore and the dipping horizons that subcrop the Shallow Regional Unconformity. Also an attempt will be made to integrate the VSP rcsults with the newly acquired surface 3D seismic to help identify multiple patiems, and to guide the derivation of velocities for stacking and migration.
The acquisition involves the deployment of, a 3- component, gimbal-mounted seismic geophone that is drill pipe conveyed into the well. As the tool is pushed into the hole, it is siopped at pre-determined stations, rigidly coupled to the casing, and acoustically isolated from the drillpipe to provide a good signal-to-noise ratio. The seismic source is positioned directly over the sensor, and a serie.s of shots are recorded at euch Station.
The main problem with processing VSP data acquired in a horizontal well is the Separation of the upgoing from the downgoing wavefields. In conventional VSP Processing this is accomplished by the geophone being vertically displaced in the wellbore. In the Erb West field, this was accomplished by using the downgoing wavefield obtained over the build up section together with differences in moveout betzoeen the direct arrivals and reflected events from structurally tilted reflectors beneath the horizontal part of the hole. This all ozo ed for the creation of a high resolution seismic image in the vicinity of the well.
Effect of Endothelium-Specific Insulin Resistance on Endothelial Function In Vivo
Authors: Duncan Edward R. , Crossey Paul A. , Walker Simon , Anilkumar Narayana , Poston Lucilla , Douglas Gillian , Ezzat Vivienne A. , Wheatcroft Stephen B. , Shah Ajay M. , Kearney Mark I. 
Published: October 2008

OBJECTIVE—Insulin resistance is an independent risk factor for the development of cardiovascular atherosclerosis. A key step in the development of atherosclerosis is endothelial dysfunction, manifest by a reduction in bioactivity of nitric oxide (NO). Insulin resistance is associated with endothelial dysfunction; however, the mechanistic relationship between these abnormalities and the role of impaired endothelial insulin signaling versus global insulin resistance remains unclear.
RESEARCH DESIGN AND METHODS—To examine the effects of insulin resistance specific to the endothelium, we generated a transgenic mouse with endothelium-targeted overexpression of a dominant-negative mutant human insulin receptor (ESMIRO). This receptor has a mutation (Ala-Thr1134) in its tyrosine kinase domain that disrupts insulin signaling. Humans with the Thr1134 mutation are insulin resistant. We performed metabolic and vascular characterization of this model.
RESULTS—ESMIRO mice had preserved glucose homeostasis and were normotensive. They had significant endothelial dysfunction as evidenced by blunted aortic vasorelaxant responses to acetylcholine (ACh) and calcium ionophore. Furthermore, the vascular action of insulin was lost in ESMIRO mice, and insulin-induced endothelial NO synthase (eNOS) phosphorylation was blunted. Despite this phenotype, ESMIRO mice demonstrate similar levels of eNOS mRNA and protein expression to wild type. ACh-induced relaxation was normalized by the superoxide dismutase mimetic, Mn(III)tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride. Endothelial cells of ESMIRO mice showed increased superoxide generation and increased mRNA expression of the NADPH oxidase isoforms Nox2 and Nox4.
CONCLUSIONS—Selective endothelial insulin resistance is sufficient to induce a reduction in NO bioavailability and endothelial dysfunction that is secondary to increased generation of reactive oxygen species. This arises independent of a significant metabolic phenotype.
Obesity-Related Upregulation of Monocyte Chemotactic Factors in Adipocytes
Authors: Jiao Ping , Chen Qiu , Shah Suketu , Du Jing , Tao Bo , Tzameli Iphigenia , Yan Weiqun , Xu Haiyan 
Published: October 2008

OBJECTIVE—We sought to evaluate the entire picture of all monocyte chemotactic factors that potentially contribute to adipose tissue macrophage accumulation in obesity.
RESEARCH DESIGN AND METHODS—Expression and regulation of members in the entire chemokine superfamily were evaluated in adipose tissue and isolated adipocytes of obese versus lean mice. Kinetics of adipose tissue macrophage infiltration was characterized by fluorescence-activated cell sorting. The effects of fatty acids on stimulation of chemokine expression in adipocytes and underlying mechanisms were investigated.
RESULTS—Six monocyte chemotactic factors were found to be predominantly upregulated in isolated adipocytes versus stromal vascular cells in obese mice for the first time, although most of them were previously reported to be upregulated in whole adipose tissue. In diet-induced obese mice, adipose tissue enlargement, increase of adipocyte number, and elevation of multiple chemokine expression precede the initiation of macrophage infiltration. Free fatty acids (FFAs) are found to be inducers for upregulating these chemokines in 3T3-L1 adipocytes, and this effect can be partially blunted by reducing Toll-like receptor 4 expression. FFAs induce expression of monocyte chemotactic factors in adipocytes via both transcription-dependent and -independent mechanisms. In contrast to the reported role of JNK as the exclusive mediator of FFA-induced monocyte chemoattractant protein-1 (MCP-1) expression in macrophages, we show a novel role of inhibitor of κB kinase-β (IKKβ) in mediating FFA-induced upregulation of all six chemokines and a role of JNK in FFA-induced upregulation of MCP-1 and MCP-3.
CONCLUSIONS—Multiple chemokines derived from adipocytes might contribute to obesity-related WAT macrophage infiltration with FFAs as potential triggers and involvement of both IKKβ and JNK pathways.
Resistance to High-Fat Diet–Induced Obesity but Exacerbated Insulin Resistance in Mice Overexpressing Preadipocyte Factor-1 (Pref-1)
Authors: Villena Josep A. , Choi Cheol Soo , Wang Yuhui , Kim Sheene , Hwang Yu-Jin , Kim Young-Bum , Cline Gary , Shulman Gerald I. , Sul Hei Sook 
Published: October 2008

OBJECTIVE—White adipose tissue is a critical regulator of whole-body glucose metabolism. Preadipocyte factor-1 (Pref-1) is a secreted protein that inhibits adipocyte differentiation, both in vitro and in vivo. In this study, we have investigated the effects of Pref-1 overexpression on whole-body glucose homeostasis and its contribution to the development of insulin resistance.RESEARCH DESIGN AND METHODS—To gain insight into the role of Pref-1 on the onset of insulin resistance and type 2 diabetes, we measured body composition and whole-body insulin-stimulated glucose metabolism during a hyperinsulinemic-euglycemic clamp in Pref-1 transgenic and wild-type control mice fed a high-fat diet.RESULTS—Mice overexpressing Pref-1 were resistant to high-fat diet–induced obesity, as reflected by a marked reduction in adipose tissue mass. However, Pref-1–overexpressing mice were severely insulin resistant, mainly because of a reduction in insulin-stimulated glucose uptake in skeletal muscle and adipose tissue. The aggravated insulin resistance was associated with impaired insulin signaling and increased diacylglycerol content in skeletal muscle.CONCLUSIONS—Mice overexpressing Pref-1 are insulin resistant despite being protected from diet-induced obesity and may provide a new rodent model for the study of lipodystrophic disorders.
Genome-Wide Linkage Scan in Gullah-Speaking African American Families With Type 2 Diabetes
Authors: Sale Michèle M. , Lu Lingyi , Spruill Ida J. , Fernandes Jyotika K. , Lok Kerry H. , Divers Jasmin , Langefeld Carl D. , Garvey W. Timothy 
Published: October 2008

OBJECTIVE—The Gullah-speaking African American population from the Sea Islands of South Carolina is characterized by a low degree of European admixture and high rates of type 2 diabetes and diabetic complications. Affected relative pairs with type 2 diabetes were recruited through the Sea Islands Genetic African American Registry (Project SuGAR).
RESEARCH DESIGN AND METHODS—We conducted a genome-wide linkage scan, genotyping 5,974 single nucleotide polymorphisms in 471 affected subjects and 50 unaffected relatives from 197 pedigrees. Data were analyzed using a multipoint engine for rapid likelihood inference and ordered subsets analyses (OSAs) for age at type 2 diabetes diagnosis, waist circumference, waist-to-hip ratio, and BMI. We searched for heterogeneity and interactions using a conditional logistic regression likelihood approach.
RESULTS—Linkage peaks on chromosome 14 at 123–124 cM were detected for type 2 diabetes (logarithm of odds [LOD] 2.10) and for the subset with later age at type 2 diabetes diagnosis (maximum LOD 4.05). Two linkage peaks on chromosome 7 were detected at 44–45 cM for type 2 diabetes (LOD 1.18) and at 78 cM for type 2 diabetes (LOD 1.64) and the subset with earlier age at type 2 diabetes diagnosis (maximum LOD 3.93). The chromosome 14 locus and a peak on 7p at 29.5 cM were identified as important in the multilocus model. Other regions that provided modest evidence for linkage included chromosome 1 at 167.5 cM (LOD 1.51) and chromosome 3 at 121.0 cM (LOD 1.61).
CONCLUSIONS—This study revealed a novel type 2 diabetes locus in an African American population on 14q that appears to reduce age of disease onset and confirmed two loci on chromosome 7.
Ang-1 Gene Therapy Inhibits Hypoxia-Inducible Factor-1α (HIF-1α)-Prolyl-4-Hydroxylase-2, Stabilizes HIF-1α Expression, and Normalizes Immature Vasculature in db/db Mice
Authors: Chen Jian-Xiong , Stinnett Amanda 
Published: October 2008

OBJECTIVE— Diabetic impaired angiogenesis is associated with impairment of hypoxia-inducible factor-1α (HIF-1α) as well as vasculature maturation. We investigated the potential roles and intracellular mechanisms of angiopoietin-1 (Ang-1) gene therapy on myocardial HIF-1α stabilization and vascular maturation in db/db mice.
RESEARCH DESIGN AND METHODS— db/db mice were systemically administrated adenovirus Ang-1 (Ad-CMV-Ang-1). Myocardial HIF-1α, vascular endothelial growth factor (VEGF), hemeoxygenase-1 (HO-1), endothelial nitric oxide synthase (eNOS), Akt, and HIF-1α–prolyl-4-hydroxylase-2 (PHD)2 expression were measured. Vasculature maturation, capillary and arteriole densities, and cardiac interstitial fibrosis were analyzed in the border zone of infarcted myocardium.
RESULTS— Systemic administration of Ad-CMV-Ang-1 results in overexpression of Ang-1 in db/db mice hearts. Ang-1 gene therapy causes a significant increase in Akt and eNOS expression and HIF-1α stabilization. This is accompanied by a significant upregulation of VEGF and HO-1 expression. Intriguingly, Ang-1 gene therapy also leads to a significant inhibition of PHD2 expression. Smooth muscle recruitment and smooth muscle coverage in the neovessels of the border zone of infarcted myocardium are severely impaired in db/db mice compared with wild-type mice. Ang-1 gene therapy rescues these abnormalities, which leads to a dramatic increase in capillary and arteriole densities and a significant reduction of cardiac hypertrophy and interstitial fibrosis at 14 days after ischemia. Taken together, our data show that Ang-1 increases myocardial vascular maturation and angiogenesis together with suppression of PHD2 and the upregulation of HIF-1α signaling.
CONCLUSIONS— Normalization of immature vasculature by Ang-1 gene therapy may represent a novel therapeutic strategy for treatment of the diabetes-associated impairment of myocardial angiogenesis.
Lower Metabolic Rate in Individuals Heterozygous for Either a Frameshift or a Functional Missense MC4R Variant
Authors: Krakoff Jonathan , Ma Lijun , Kobes Sayuko , Knowler William C. , Hanson Robert L. , Bogardus Clifton , Baier Leslie J. 
Published: October 2008

OBJECTIVE—Humans with functional variants in the melanocortin 4 receptor (MC4R) are obese, hyperphagic, and hyperinsulinemic but have been reported to have no difference in energy expenditure.
RESEARCH DESIGN AND METHODS—We investigated the association of two MC4R variants, Arg165Gln (R165Q) and A insertion at nucleotide 100 (NT100), with adiposity in 3,074 full-heritage Pima Indians, a subset of whom had metabolic measures including 24-h energy expenditure (n = 252) and resting metabolic rate (RMR) (n = 364).
RESULTS—Among the 3,074 subjects, 43 were heterozygous for R165Q and 14 for NT100 (frequency = 0.007 and 0.002). Mean (± SD) BMI was higher among subjects with R165Q (39.3 ± 8.6 kg/m2) or NT100 (41.2 ± 7.8) than subjects without either variant (37.1 ± 8.4) (P = 0.04 and 0.02, adjusted for age, sex, and birth year and accounting for family membership). The 24-h energy expenditure (four with NT100; three with R165Q) or RMR (six with NT100; two with R165Q) was lower in heterozygous subjects but only met statistical significance when heterozygous subjects were combined and compared with subjects without either variant: least-squares means, 2,163 kcal/24 h (95% CI 2,035–2,291) vs. 2,307 kcal/24 h (2,285–2,328), P = 0.03 for 24-h energy expenditure, and 1,617 kcal/24 h (1,499–1,734) vs. 1,754 kcal/24 h (1,736–1,772), P = 0.02 for RMR; adjusted for age, sex, fat-free mass, and fat mass). For RMR, this difference persisted, even after accounting for family membership.
CONCLUSIONS—Pima Indians heterozygous for R165Q or NT100 in MC4R have higher BMIs and lower energy expenditure (by ∼140 kcal/day), indicating that lower energy expenditure was a component of the increased adiposity.
Atrial Natriuretic Peptide Induces Postprandial Lipid Oxidation in Humans
Authors: Birkenfeld Andreas L. , Budziarek Petra , Boschmann Michael , Moro Cedric , Adams Frauke , Franke Gabriele , Berlan Michel , Marques Marie A. , Sweep Fred C.G.J. , Luft Friedrich C. , Lafontan Max , Jordan Jens 
Published: October 2008

OBJECTIVE—Atrial natriuretic peptide (ANP) regulates arterial blood pressure. In addition, ANP has recently been shown to promote human adipose tissue lipolysis through cGMP-mediated hormone-sensitive lipase activation. We hypothesized that ANP increases postprandial free fatty acid (FFA) availability and energy expenditure while decreasing arterial blood pressure.
RESEARCH DESIGN AND METHODS—We infused human ANP (25 ng · kg−1 · min−1) in 12 men (age 32 ± 0.8 years, BMI 23.3 ± 0.4 kg/m2) before, during, and 2 h after ingestion of a standardized high-fat test meal in a randomized, double-blind, cross-over fashion. Cardiovascular changes were monitored by continuous electrocardiogram and beat-by-beat blood pressure recordings. Metabolism was monitored through venous blood sampling, intramuscular and subcutaneous abdominal adipose tissue microdialysis, and indirect calorimetry.
RESULTS—ANP infusion decreased mean arterial blood pressure by 4 mmHg during the postprandial phase (P &lt; 0.01 vs. placebo). At the same time, ANP induced lipolysis systemically (P &lt; 0.05 vs. placebo) and locally in subcutaneous abdominal adipose tissue (P &lt; 0.0001 vs. placebo), leading to a 50% increase in venous glycerol (P &lt; 0.01) and FFA (P &lt; 0.05) concentrations compared with placebo. The increase in FFA availability with ANP was paralleled by a 15% increase in lipid oxidation rates (P &lt; 0.05 vs. placebo), driving a substantial increase in postprandial energy expenditure (P &lt; 0.05 vs. placebo).
CONCLUSIONS—Our data identify the ANP system as a novel pathway regulating postprandial lipid oxidation, energy expenditure, and concomitantly arterial blood pressure. The findings could have therapeutic implications.
Combination Therapy With Glucagon-Like Peptide-1 and Gastrin Restores Normoglycemia in Diabetic NOD Mice
Authors: Suarez-Pinzon Wilma L. , Power Robert F. , Yan Yanhua , Wasserfall Clive , Atkinson Mark , Rabinovitch Alex 
Published: October 2008

OBJECTIVE—Glucagon-like peptide-1 (GLP-1) and gastrin promote pancreatic β-cell function, survival, and growth. Here, we investigated whether GLP-1 and gastrin can restore the β-cell mass and reverse hyperglycemia in NOD mice with autoimmune diabetes.
RESEARCH DESIGN AND METHODS—Acutely diabetic NOD mice were treated with GLP-1 and gastrin, separately or together, twice daily for 3 weeks. Blood glucose was measured weekly and for a further 5 weeks after treatments, after which pancreatic insulin content and β-cell mass, proliferation, neogenesis, and apoptosis were measured. Insulin autoantibodies were measured, and adoptive transfer of diabetes and syngeneic islet transplant studies were done to evaluate the effects of GLP-1 and gastrin treatment on autoimmunity.
RESULTS—Combination therapy with GLP-1 and gastrin, but not with GLP-1 or gastrin alone, restored normoglycemia in diabetic NOD mice. The GLP-1 and gastrin combination increased pancreatic insulin content, β-cell mass, and insulin-positive cells in pancreatic ducts, and β-cell apoptosis was decreased. Insulin autoantibodies were reduced in GLP-1–and gastrin-treated NOD mice, and splenocytes from these mice delayed adoptive transfer of diabetes in NOD-scid mice. Syngeneic islet grafts in GLP-1–and gastrin-treated NOD mice were infiltrated by leukocytes with a shift in cytokine expression from interferon-γ to transforming growth factor-β1, and β-cells were protected from apoptosis.
CONCLUSIONS—Combination therapy with GLP-1 and gastrin restores normoglycemia in diabetic NOD mice by increasing the pancreatic β-cell mass and downregulating the autoimmune response.
Rho Kinase Inhibition by Fasudil Ameliorates Diabetes-Induced Microvascular Damage
Authors: Arita Ryoichi , Hata Yasuaki , Nakao Shintaro , Kita Takeshi , Miura Muneki , Kawahara Shuhei , Zandi Souska , Almulki Lama , Tayyari Faryan , Shimokawa Hiroaki , Hafezi-Moghadam Ali , Ishibashi Tatsuro 
Published: October 2008

OBJECTIVE—Leukocyte adhesion in retinal microvasuculature substantially contributes to diabetic retinopathy. Involvement of the Rho/Rho kinase (ROCK) pathway in diabetic microvasculopathy and therapeutic potential of fasudil, a selective ROCK inhibitor, are investigated.
RESEARCH DESIGN AND METHODS—Localization of RhoA/ROCK and Rho activity were examined in retinal tissues of rats. Impact of intravitreal fasudil administration on retinal endothelial nitric oxide synthase (eNOS) and myosin phosphatase target protein (MYPT)-1 phosphorylation, intercellular adhesion molecule-1 (ICAM-1) expression, leukocyte adhesion, and endothelial damage in rat eyes were investigated. Adhesion of neutrophils from diabetic retinopathy patients or nondiabetic control subjects to cultured microvascular endothelial cells was quantified. The potential of fasudil for endothelial protection was investigated by measuring the number of adherent neutrophils and terminal transferase-mediated dUTP nick-end labeling–positive endothelial cells.
RESULTS—RhoA and ROCK colocalized predominantly in retinal microvessels. Significant Rho activation was observed in retinas of diabetic rats. Intravitreal fasudil significantly increased eNOS phosphorylation, whereas it reduced MYPT-1 phosphorylation, ICAM-1 expression, leukocyte adhesion, and the number of damaged endothelium in retinas of diabetic rats. Neutrophils from diabetic retinopathy patients showed significantly higher adhesion to cultured endothelium and caused endothelial apoptosis, which was significantly reduced by fasudil. Blockade of the Fas-FasL interaction prevented endothelial apoptosis. The protective effect of fasudil on endothelial apoptosis was significantly reversed by Nω-nitro-l-arginine methyl ester, a NOS inhibitor, whereas neutrophil adhesion remained unaffected.
CONCLUSIONS—The Rho/ROCK pathway plays a critical role in diabetic retinal microvasculopathy. Fasudil protects the vascular endothelium by inhibiting neutrophil adhesion and reducing neutrophil-induced endothelial injury. ROCK inhibition may become a new strategy in the management of diabetic retinopathy, especially in its early stages.