bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stratigraphic evidence for a Late Devonian possible back‐bulge basin in the Appalachian basin, United States
Authors: Filer Jonathan K. 
Published: August 2003

AbstractIsopach and sedimentary facies maps of Upper Devonian (upper Frasnian and lower Famennian) strata deposited in a part of the central Appalachian foreland basin (eastern United States) during the Acadian orogeny show a significant change in depositional style over time. Maps of two successive upper Frasnian intervals show steady thickening to the east towards the hinterland. Coarser‐grained sediment was deposited in distinct tongues in front of the Augusta lobe, a previously recognized locus of sediment input in the central Appalachian basin. Maps of two subsequent lower Famennian stratigraphic intervals show distinct depocentres in the study area. Famennian strata thin eastward (by about 50%) over a distance of about 90 km from these depocentres to the limit of mapping at the Allegheny structural front. This is towards the Acadian sediment source and in contrast to general Upper Devonian thickening in that direction. The axes of these lower Famennian depocentres are stacked on top of each other. Also, coarser‐grained lower Famennian sediment is concentrated in strike trends just east of the axes of the depocentres, and no coarser tongues exist in front of the Augusta lobe, in contrast to the underlying (upper Frasnian) strata.The duration of each of the four study intervals is estimated to be between 0.5 and 3.0 Myr. The early Famennian depocentres may be in a back‐bulge basin, with a forebulge uplifted to the east of the study area. Earlier deposition may have occurred in a basin with a subtle, subdued, and longer wavelength forebulge (perhaps located west of the study area). Previously published regional isopachs of Upper Devonian strata suggest that the main axis of subsidence of the Acadian foreland basin (foredeep depozone) at this time was over 350 km east of the study area. Examination of published quantitative flexural models of other foreland basins with flexural rigidities close to published rigidities calculated for the Appalachian basin suggests that the proposed back‐bulge basin is in the correct location, relative to the suggested position of the foredeep at that time. Several previously recognized structural features of the northern Appalachian basin support the interpretations presented herein. Much of the Acadian foreland basin may be eroded in the central Appalachian basin. The present study demonstrates the difficulties in recognizing foreland basin depozones in partially preserved orogens.
Defective function of Fas in T cells from paediatric patients with autoimmune thyroid diseases
Authors: BONA G , DEFRANCO S , CHIOCCHETTI A , INDELICATO M , BIAVA A , DIFRANCO D , DIANZANI I , RAMENGHI U , CORRIAS A , WEBER G , DE SANCTIS V , IUGHETTI L , RADETTI G , DIANZANI U 
Published: August 2003

SUMMARYTriggering of the Fas receptor induces T cell apoptosis and is involved in shutting-off the immune response. Inherited defects impairing Fas function cause the autoimmune lymphoproliferative syndrome, and may play a role in other autoimmune diseases. The aim of this work was to analyse the Fas function in paediatric patients with thyroid autoimmunities. We found that T cells from 24/28 patients with Graves’ disease (GD) and 12/35 patients with Hashimoto's thyroiditis (HT) displayed defective Fas function. In HT, the defect was more frequent in patients requiring replacement therapy (11/20) than in those not requiring (1/15); moreover, in untreated HT the highest defect was displayed by patients with the highest levels of autoantibodies. Fas was always expressed at normal levels and no Fas mutations were detected. Analysis of the healthy parents of seven Fas-resistant patients showed that several of them were Fas-resistant, which suggests a genetic component. Fusion of Fas-resistant T cells with the Fas-sensitive HUT78 T cell line generated Fas-resistant hybrid cells, which suggests the presence of molecules exerting a dominant negative effect on Fas function. Analysis of Fas-induced activation of caspase-8 and -9 showed decreased activity of both caspases in HT, whereas activity of caspase-9 was increased and that of caspase-8 was decreased in GD. These data suggest that heterogeneous inherited defects impairing Fas function favour the development of thyroid autoimmunities.
Binding of live conidia of Aspergillus fumigatus activates in vitro-generated human Langerhans cells via a lectin of galactomannan specificity
Authors: PERSAT F , NOIREY N , DIANA J , GARIAZZO M-J , SCHMITT D , PICOT S , VINCENT C 
Published: August 2003

SUMMARY
Aspergillus fumigatus is the most common aetiological fungus responsible for human pulmonary aspergilloses. This study investigated the primary contact between Langerhans cells (LC), corresponding to dendritic cells present in pulmonary mucosa and live conidia of A. fumigatus. LC play a key role in antigen presentation for initiation of the primary T cell response. In vitro-generated LC (iLC) were differentiated from cultured human cord blood CD34+ cells and incubated at 4°C or 37°C with fluorescein-isothiocyanate (FITC)-stained conidia or control latex beads. In vitro, conidia were shown by microscopy and cytometry to adhere to iLC in a dose- and time-dependent manner. This adhesion was not limited to iLC because interstitial dendritic and other cells also fluoresced in the presence of conidia-FITC. A lectin other than mannose receptor-type lectin was demonstrated to be responsible of conidial binding. Inhibition of binding was observed with heterologous galactomannan and EDTA, indicating a C-lectin-like receptor with galactomannan structure specificity. After binding only a few conidia were internalized in acidic vesicles, as indicated by the cessation of conidial fluorescence. Conidial binding was followed by activation and maturation of iLC, suggesting that LC present in the lung may play a role in cellular host defence against aspergilloses.
Marked increase in vascular endothelial growth factor concentrations during Escherichia coli endotoxin‐induced acute inflammation in humans
Authors: Mittermayer F. , Pleiner J. , Schaller G. , Weltermann A. , Kapiotis S. , Jilma B. , Wolzt M. 
Published: August 2003

AbstractBackground  Bacterial endotoxins can induce the synthesis and release of vascular endothelial growth factor (VEGF), which may alter vascular permeability and cause vascular leakage.Materials and methods  The effect of acute systemic inflammation on VEGF concentration was measured in healthy males after an intravenous bolus infusion of Escherichia coli endotoxin (lipopolysaccharide, LPS, 20 IU kg−1) in a double‐blind, placebo‐controlled parallel group study. LPS administration was followed by an infusion of lepirudin (bolus 0·1 mg kg−1, continuous infusion of 0·1 mg kg−1 h−1, n= 12) or saline (n = 12).Results  Plasma VEGF increased from a mean of 15·1 pg mL−1 to 74·6 pg mL−1 5 h after LPS (P < 0·003). Body temperature, pulse rate, leukcytes, prothrombin fragment 1 + 2 (F1 + 2) and lactoferrin increased and platelets decreased after LPS (P < 0·05). The LPS‐induced increase in VEGF was paralleled by the neutrophil cell degranulation marker lactoferrin but not by F1 + 2, and was not affected by lepirudin, which blunted F1 + 2 formation (P < 0·05).Conclusions  Inflammation‐induced activation of leukcytes rather than platelets plays a role in the marked increase in VEGF, which cannot be abrogated by antithrombotic therapy.
Are elevated homocysteine plasma levels related to peripheral arterial disease? Results from a cross‐sectional study of 6880 primary care patients
Authors: Darius H. , Pittrow D. , Haberl R. , Trampisch H. J. , Schuster A. , Lange S. , Tepohl H. G. , Allenberg J. R. , Diehm C. 
Published: August 2003

AbstractBackground  It is still unclear whether the strength of the association between elevated plasma homocysteine (HC) levels and peripheral arterial disease (PAD), coronary artery disease (CAD) and cerebrovascular disease (CVD) is similar.Methods  Fasting homocysteine plasma levels were measured in 6880 unselected primary care patients aged 65 years or older. Presence of PAD was determined with the ankle brachial index, and both CAD and CVD were recorded according to patient history.Results  Median homocysteine levels in the total sample (58·0% females, mean age 72·5 years, mean body mass index 27·3 kg m−2) differed between patients with and without PAD: 15·2 µmol L−1 (95% confidence interval [CI] 14·8; 15·7, vs. 13·9 µmol L−1 (CI: 13·8; 14·1; P < 0·001). Peripheral arterial disease prevalence moderately increased from 13·0% in the lowest HC quintile to 24·3% in the highest quintile (crude odds ratio [OR], 2·1 [CI: 1·7; 2·6]). The frequency of atherothrombotic manifestations in the patients’ history increased nearly linearly across the homocysteine quintiles in the univariate analysis. However, the association diminished substantially after adjusting for known interfering variables: the ORs between the HC highest fifth vs. lowest fifth (adjusted for age, gender, smoking status, diabetes, hypertension lipid disorders, and estimated glomerular filtration rate levels) for PAD decreased to 1·4, for CAD to 1·0 (NS), and for CVD to 1·1. (NS).Conclusions  Elevated HC is only slightly more related to PAD than to CAD and CVD. After adjustment for known risk factors, the effect size is small, and an association can no longer be observed between homocysteine and CAD and CVD.
On the mechanism of post‐splenectomy leukocytosis in mice
Authors: Djaldetti M. , Bergman M. , Salman H. , Cohen A. M. , Fibach E. , Bessler H. 
Published: August 2003

AbstractBackground  Increased number of peripheral white blood cells (PWBCs) has been noted after removal of the spleen.Design  To clarify the possible mechanisms by which splenectomy affects the PWBC number, the percentage of apoptotic PWBCs, the number and migration rate of peritoneal cells, as well as the 3H‐TdR incorporation into PWBCs, were examined in splenectomized, sham‐operated and control mice. In addition, the effect of control plasma injected to splenectomized animals on the number of PWBCs was examined.Results  One and two months after splenectomy the PWBC counts significantly increased, whereas the percentage of apoptotic PWBCs and the number of cells in the peritoneal cavity decreased in comparison with that of the control and sham‐operated mice. Seventeen days after injection of carboxy‐fluorescein diacetate succinimidyl ester (CFSE)‐labelled peritoneal cells into the peritoneal cavity of the animals, their number was significantly higher in the peripheral blood and lower in the peritoneal cavity of the splenectomized animals in comparison with that of the control and sham‐operated mice. Injection of control plasma into the splenectomized mice prevented the development of postsplenectomy leukocytosis. Finally, 3H‐TdR incorporation into nonstimulated and Con A stimulated PBMCs from the splenectomized mice was higher as compared with cells from the control and sham‐operated mice.Conclusions  The results of the study present several mechanisms that may clarify the cause of postsplenectomy leukocytosis.
Enterohepatic cycling of bilirubin as a cause of ‘black’ pigment gallstones in adult life
Authors: Vítek L. , Carey M. C. 
Published: August 2003

AbstractIn contrast to bile salts, which undergo a highly efficient enterohepatic circulation with multiple regulatory and physiologic functions, glucuronic acid conjugates of bilirubin are biliary excretory molecules that in health do not have a continuing biologic life. Intestinal absorptive cells are devoid of recapture transporters for bilirubin conjugates, and their large size and polarity prevent absorption by passive diffusion. However, unconjugated bilirubin, the β‐glucuronidase hydrolysis product of bilirubin glucuronides can be absorbed passively from any part of the small and large intestines. This can occur only if unconjugated bilirubin is kept in solution and does not undergo rapid bacterial reduction to form urobilinoids. Here we collect, and in some cases reinterpret, experimental and clinical evidence to show that in addition to the well‐known occurrence in newborns, enterohepatic cycling of unconjugated bilirubin can reappear in adult life. This happens as a result of several common conditions, particularly associated with bile salt leakage from the small intestine, the most notable ileal dysfunction resulting from any medical or surgical cause. We propose that when present in excess, colonic bile salts solubilize unconjugated bilirubin, delay urobilinoid formation, prevent calcium complexing of unconjugated bilirubin and promote passive absorption of unconjugated bilirubin from the large intestine. Following uptake, reconjugation, and resecretion into bile, this source of ‘hyperbilirubinbilia’ may be the important pathophysiological risk factor for ‘black’ pigment gallstone formation in predisposed adult humans.
Low plasma aldosterone despite normal plasma renin activity in uncomplicated type 1 diabetes mellitus: effects of RAAS stimulation
Authors: Luik P. T. , Kerstens M. N. , Hoogenberg K. , Navis G. J. , Dullaart R. P. F. 
Published: August 2003

AbstractBackground  Data on levels and responsiveness of PRA and aldosterone in type 1 diabetes mellitus are conflicting. Earlier studies were not standardized with respect to the type of diabetes mellitus, the presence of diabetic complications or sodium intake. Therefore, we studied plasma renin activity and plasma aldosterone in uncomplicated type 1 diabetes mellitus by evaluating the effects of endogenous (sodium restriction) and exogenous (angiotensin I infusion) stimulation.Design  Twenty‐four type 1 diabetic patients and 24 matched healthy subjects were studied after 1 week of liberal sodium diet (200 mmol 24 h−1) and 1 week of low sodium diet (50 mmol 24 h−1). Angiotensin (Ang)I was infused at 4 and 8 ng kg−1 min−1 during both study days.Results  During liberal and low sodium intake, plasma aldosterone was lower in type 1 diabetic patients compared with healthy subjects both at 08:00 h (P < 0·05) and after a 2‐h euglycaemic clamp (P < 0·05), despite similar PRA levels. The correlations between changes in PRA and changes in plasma aldosterone when shifting sodium intake were similar in both groups. During liberal sodium intake, the aldosterone levels after AngI infusion were lower in type 1 diabetic patients, whereas during low sodium they were not different.Conclusions  Plasma aldosterone was deceased relative to PRA in uncomplicated type 1 diabetic patients, irrespective sodium intake. The responsiveness to sodium restriction was adequate and sodium restriction was able to overcome the decreased plasma aldosterone response to exogenous AngI, which was observed during liberal sodium in diabetic patients. The lower aldosterone is not secondary to diabetic complications and does not depend on the level of sodium intake.
Cellular characterization of the tropism of recombinant adenovirus for the adrenal glands
Authors: Wang Y. , Groot‐Wassink T. , Lemoine N. R. , Vassaux G. 
Published: August 2003

AbstractBackground  Recombinant adenoviruses are widely used in gene therapy clinical trials. A particular tropism for the adrenal glands has been reported but the precise cellular base for this tropism has not been determined.Materials and methods  Recombinant adenoviruses were injected intravenously into Balb/c nu/nu or C57BL/6 mice. Seventy‐two hours later, the animals were sacrificed and the adrenal glands and livers collected. The glands were sectioned and analyzed using immunohistochemical methods to detect adenoviral epitopes and transgene expression. Total RNA were extracted from the liver and adrenal glands of some animals and subjected to real‐time RT‐PCR.Results  The only cell type infected in the adrenal glands of Balb/c nu/nu or C57BL/6 mice is the adrenocortical cells in the zona fasciculata. Quantitatively, the relative level of gene expression in the adrenal gland is comparable but lower than that measured in the liver.Conclusions  Systemic injection of recombinant adenovirus could be used as a procedure to restore adrenal steroidogenesis in clinical gene therapy protocols. In addition, our study suggest that adrenal dysfunction should be considered when criteria are established to assess the safety of gene therapy formulations administered systemically.
Effects of bosentan on neointimal response following coronary angioplasty
Authors: Sanmartín M. , Fernández‐Ortiz A. , Fantidis P. , Aragoncillo P. , Fernández‐Durango R. , Rollín R. , Alfonso F. , Hernández R. , Escaned J. , Macaya C. 
Published: August 2003

AbstractBackground  Endothelins are important vasoconstrictors and cellular‐growth promoters. ETA‐specific antagonists have been shown to reduce neointimal response to injury in some experimental angioplasty models. However, there is little information on the effects of dual ETA/ETB receptor blockers, such as bosentan, on neointimal proliferation following experimental coronary angioplasty.Materials and methods  Coronary injury was achieved by directional atherectomy in the left anterior descending artery of 20 pigs. Animals were randomly assigned to receive a daily dose of oral bosentan (30 mg kg−1) (group I, n= 10) or no treatment (group II, n= 10). At 4 weeks, arteries were processed for histomorphometry and endothelin characterization.Results  Vessel injury score was similar among the two groups. Overall, a linear correlation was found between injury and neointimal development (r = 0·57, P= 0·01). This correlation had a lower slope in group I compared with group II (P < 0·001), indicating a smaller amount of neointimal development for a similar degree of injury in bosentan‐treated animals. Multivariate regression showed that neointimal response was reduced by oral treatment with bosentan (beta: –0·59 mm2, 95% CI: −1·11/−0·06 mm2). In addition, immunostaining revealed fewer positive endothelin areas in group I arteries.Conclusions  Oral treatment with bosentan reduces neointimal development following coronary angioplasty in this experimental model.
Controlled, randomized trial in maintenance treatment of intravenous buprenorphine dependence with naltrexone, methadone or buprenorphine: a novel study
Authors: Ahmadi J. , Ahmadi K. , Ohaeri J. 
Published: August 2003

AbstractAims  To test the effect of a 50‐mg day−1 dose of naltrexone in the maintenance treatment of intravenous‐buprenorphine dependence in comparison with a 50‐mg day−1 dose of methadone and also a 5‐mg day−1 dose of buprenorphine over a 24‐week treatment period.Participants  Two hundred and four intravenous‐buprenorphine‐dependent patients who met the DSM‐IV criteria for opioid dependence were randomized to three equal groups and were treated in a clinic in Iran where they were also offered a weekly 0·5‐h counselling session, in 2002.Findings  The mean age was 31·2 years (range 17–53). The majority [63·2%] was between 20 and 34 years of age. The educational level of most of them [55·4%] was between 6 and 12 years of study. Completion rates by groups were 83·8% for the 50‐mg dose methadone group, 58·8% for the 5‐mg dose buprenorphine group and 20·6% for the 50‐mg dose naltrexone group (P = 0·000). Retention in the 50‐mg methadone group was significantly better than in the 5‐mg dose buprenorphine group (P = 0·001) and the 50‐mg dose naltrexone group (P = 0·000). Retention in the 5‐mg buprenorphine group was significantly better than in the 50‐mg naltrexone dose group (P = 0·000).Conclusions  Evaluation of the Iranian experience on this subject may be useful for other countries.
Resveratrol modulates apoptosis and oxidation in human blood mononuclear cells
Authors: Losa G. A. 
Published: August 2003

AbstractBackground  We examined the effect of resveratrol (RS), a nonflavonoid polyphenolic phytoalexin found in grapes and red wine, and RS coincubated with the oxidant 2‐deoxy‐D‐ribose (dR), on apoptosis and on the oxidative metabolic status of normal human peripheral blood mononuclear cells (PBMNCs) isolated ex vivo from healthy donors.Material and methods  Apoptosis was measured by changes of membrane permeability to propidium iodide (PI), plasma membrane exposure of phosphatidylserine (PS) and intracellular caspase activity. Oxidative status was assessed by recording the intracellular glutathione concentration (GSH), the activities of the enzymes y‐glutamyltransferase (y‐GT) and glutathione‐S‐transferase (GST), and intracellular lipid peroxidation (MDA).Results  Neither apoptotic nor oxidative parameters were affected by culturing PBMNCs in medium containing RS up to 20 µM for 5 days, while the frequency of cells with intermediate permeability to PI (17% ± 5) increased at 50 µM of RS. Thus resveratrol was slightly toxic, but there was little apoptosis in these cells. Peripheral blood mononuclear cells were also grown first in medium plus RS for 24 h and then for 96 h in medium containing RS plus 10 mM of dR, an oxidant sugar that is apoptogenic for human lymphocytes. The apoptotic changes triggered by dR were counteracted by the phytoalexin in a dose‐dependent manner, but RS activity was absent at the lowest concentration (5 µM) and significantly reduced at the highest concentration used (50 µM). In PBMNCs coincubated with 20 µM of RS and 10 mM of dR the antioxidant effect of RS manifested with a significant reduction of caspases‐3, ‐8, y‐GT, GST activities and MDA content.Conclusions  Peripheral blood mononuclear cells acquire antioxidant capacity when treated with RS. Grape resveratrol may make a useful dietary supplement for minimizing oxidative injury in immune‐perturbed states and human chronic degenerative diseases.
Experimental and interventional dietary study in humans on the role of HDL fatty acid composition in PGI2 release and Cox‐2 expression by VSMC
Authors: Escudero I. , Martínez‐González J. , Alonso R. , Mata P. , Badimon L. 
Published: August 2003

AbstractBackground  High‐density lipoproteins (HDLs) induce prostacyclin (PGI2) release in vascular smooth muscle cells (VSMCs) by up‐regulation of cyclooxygenase‐2 (Cox‐2). Our goal was to analyze the role of human HDL lipid moiety on Cox‐2‐dependent PGI2 synthesis in human VSMCs and to assess the impact that the intake of diets with different fatty acid composition exert on HDL‐induced PGI2 release.Materials and methods  Human VSMCs were treated with HDL or fatty acids in the presence or absence of different cell signalling inhibitors and PGI2 (by enzyme immunoassay) and Cox‐2 protein levels (by Western blot) were analyzed. High‐density lipoproteins were obtained from a plasma pool or from plasma of 12 volunteers subjected to a longitudinal dietary interventional study of three consecutive diets periods enriched in monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids n‐6 (PUFA n‐6) or n‐3 (PUFA n‐3).Results  High‐density lipoprotein delipidation attenuated the effect of HDL on both PGI2 synthesis and Cox‐2 up‐regulation, while arachidonic acid (AA) but not other fatty acids mimicked the effects of HDL. Arachidonic acid induced PGI2 synthesis and Cox‐2 expression through similar mechanisms to those activated by HDL [pertussis toxin‐sensitive G proteins, p42/44 mitogen‐activated protein kinase (MAPK), p38MAPK, and c‐Jun N‐terminal kinase‐1 (JNK‐1) pathways]. Finally, we observed that HDL from the PUFA n‐3 dietary period induced lower PGI2 release than that from the PUFA n‐6 period (64% vs. 100%).Conclusions  Our results suggest that lipid moiety modulates HDL‐induced PGI2 release/Cox‐2 up‐regulation in human VSMCs, and that changes in fatty acids as accomplished with the diet can modulate vascular PGI2 homeostasis.