bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Interleukin‐6 levels in pituitary‐deficient patients are independently related to their carotid intima‐media thickness
Authors: Leonsson M. , Hulthe J. , Johannsson G. , Wiklund O. , Wikstrand J. , Bengtsson B. Å. , Oscarsson J. 
Published: July 2003

Summaryobjective Increased cardiovascular morbidity and mortality has been observed in patients with pituitary deficiency and untreated growth hormone deficiency (GHD). We investigated peripheral inflammatory and fibrinolytic markers and their associations with arterial intima‐media thickness (IMT) in GHD.design Cross‐sectional study.patients Thirty‐four patients with GHD, but without cardiovascular disease, were compared to healthy controls matched for age, sex, body mass index (BMI) and smoking habits.measurements IMT of the common carotid artery, C‐reactive protein (CRP), interleukin‐6 (IL‐6), fibrinogen, plasminogen activator inhibitor‐1 (PAI‐1) activity and tissue plasminogen activator antigen (tPA‐ag) were measured.results Median IL‐6 concentrations were increased by 208% and 248% in GHD patients compared to BMI‐matched and nonobese controls, respectively. Median CRP and tPA‐ag levels were increased by 237% and 167% in patients compared to nonobese controls, but not significantly different compared to BMI‐matched controls. Plasma levels of fibrinogen and PAI‐1 activity did not differ between groups. Age, low‐density lipoprotein (LDL) cholesterol, tPA‐ag and IL‐6 were positively correlated, and IGF‐I was negatively correlated to IMT in the patient group, but only age and IL‐6 were independently related to IMT.conclusions IL‐6 concentrations were increased in GHD patients compared to controls and independently related to IMT in patients. This finding may help to explain the variance in IMT and the increased vascular morbidity and mortality in hypopituitary patients with GHD.
The effectiveness of arginine + GHRH test compared with GHRH + GHRP‐6 test in diagnosing growth hormone deficiency in adults
Authors: Popovic Vera , Pekic Sandra , Doknic Mirjana , Micic Dragan , Damjanovic Svetozar , Zarkovic Milos , Aimaretti Gianluca , Corneli Ginerva , Ghigo Ezio , Deiguez Carlos , Casanueva Felipe F. 
Published: July 2003

Summaryobjective The objective of this study is to investigate the performance of two novel tests in diagnosing growth hormone deficiency in adults.patients Fifty patients presenting with long‐standing hypopituitarism and two control groups consisting of 50 healthy subjects in each group [age‐, sex‐ and body mass index (BMI)‐matched] participated in a multicentre study. All underwent two provocative tests on different days within 3 months apart: (i) a combined GHRH + GHRP‐6 test and (ii) arginine + GHRH test. Main outcome measures were sensitivity, specificity and areas under reciever operating characteristic curves (ROC) for GHRH + GHRP‐6 and arginine + GHRH tests in the diagnosis of GH deficiency in adults.results A peak GH level after GHRH + GHRP‐6, under 15·0 µg/l had a sensitvity of 94·4% and specificity of 98·8% for diagnosing GHD and area under the ROC curve was 0·99 (95% confidence interval 0·95–0·99). For peak GH levels after arginine + GHRH, a level under 9·6 µg/l had a sensitivity of 88·4% and specficity of 95% and area under the ROC curve of 0·96 (95% confidence interval 0·91–0·98). The relationship between the increment in serum GH following GHRH + GHRP‐6 and arginine + GHRH test was positive, i.e. r = 0·749, P = 0·001.Thus, there was high concordance between both tests.conclusion Both GHRH + GHRP‐6 and/or arginine + GHRH test may serve as an alternative to the ITT in diagnosing GHD in adults.
High‐risk clinical features predict increased post‐infarction myocardial apoptosis and the benefits as a result of an open infarct‐related artery
Authors: Abbate A. , Biondi‐Zoccai G. G. L. , Bussani R. , Camilot D. , Dobrina A. , Leone A. M. , Baldi F. , Silvestri F. , Biasucci L. M. , Baldi A. 
Published: July 2003

AbstractBackground Infarct‐related artery (IRA) patency after acute myocardial infarction (AMI) is associated with a more favourable clinical course, in particular in patients with high‐risk features. As it has been recently reported that IRA patency is associated with a reduced postinfarction apoptotic rate (AR), the aim of our study was to assess whether IRA status late after AMI had a different impact on AR in high‐ vs. low‐risk patients.Methods and results Co‐localization of TUNEL and caspase‐3 was used to calculate the AR at the site of infarction at the time of death in 30 subjects. The Norris coronary prognostic index (NI) was calculated (computing age, presence of pulmonary congestion, heart size and history of previous additional AMI) in order to define the patients’ individual risk at the time of hospitalization. According to the NI (≤ 7 vs. > 7), subjects were divided into low and high risk, as NI > 7 carries an approximate threefold higher risk of death. The NI was significantly correlated with the AR at the time of death both in infarct and remote areas. Twenty subjects had IRA occlusion at the time of death, and in these patients AR was significantly higher both in infarct and remote areas (P < 0·001 and P= 0·009 vs. the others, respectively). However the impact of IRA occlusion on AR was significantly different comparing high‐ vs. low‐risk subjects. In particular, AR at the infarct site was 10‐fold higher in the high‐risk subjects with IRA occlusion (26·1%[20·4–28·7%]) vs. those with open IRA (2·3%[0·6–3·5%]; P = 0·002) and was nonsignificantly different in the low‐risk subjects vs. those without IRA occlusion (8·2%[2·5–17·5%] vs. 5·4%[1·5–7·9%]; P = 0·48). Similarly, in the high‐risk subjects, AR in remote areas was significantly greater in cases with occluded vs. open IRA (0·7%[0·4–0·9%] vs. 0·3%[0·3–0·32%]; P= 0·009).Conclusion A significantly higher AR is associated with IRA occlusion late post AMI in subjects with high‐risk clinical features, and not in low‐risk patients. The diverse impact of IRA occlusion on AR in subjects with different risk profiles may explain the greater benefit associated with coronary reperfusion in high‐risk subjects. The overall lower AR in low‐risk subjects, independently from the IRA status, may be correlated with the better long‐term prognosis after AMI in this case.
Interleukins 1 beta and 6 induce functional alteration of rat colonic motility: an in vitro study
Authors: Natale L. , Piepoli A. L. , De Salvia M. A. , De Salvatore G. , Mitolo C. I. , Marzullo A. , Portincasa P. , Moschetta A. , Palasciano G. , Mitolo‐Chieppa D. 
Published: July 2003

AbstractBackground In rodents, interleukins administration induces intestinal changes similar to those found in inflammatory bowel disease. We investigated the effects of in vivo subchronic treatment with IL‐1 beta and IL‐6 on rat colonic mucosa and circular smooth muscle.Materials and method We evaluated transmucosal electrical parameters (Ussing chambers) and early changes of in vitro direct contractility induced by carbachol and tachykinins. Alterations in excitatory and inhibitory neurotransmission were studied with electrical field stimulation (EFS).Results Treatment with interleukins induces inflammation proved by fever, early signs of colonic histological damage and changes in mucosal ion transport. Concentration response‐curve to carbachol was significantly lower in treated rats (P < 0·02) with significant difference in Emax between control (1·67 ± 0·17 g) and treated preparations (1·20 ± 0·13 g) (P < 0·05). Concentration response‐curve to NK2 agonist was significantly lower in the treated rats (P < 0·005) with a significant difference in Emax between the control (0·26 ± 0·04 g) and treated preparations (0·12 ± 0·02 g) (P < 0·02). None of the drugs used induces changes in EC50. The contractile reflex response to electrically induced distension was significantly higher in the treated rats and more reduced after administration of atropine. Adding NK2 receptor antagonist resulted in a further reduction being observed in the treated and control rats (P = NS). Relaxation by EFS on cholinergic tone was not different between treatments, although pretreatment with L‐NNA resulted in greater relaxation in the treated (−21·7%) than in the control rats (−14·8%).Conclusion Early inflammation induced by a subchronic treatment with ILs causes changes in mucosal ionic transport parameters, a reduction in the direct contractile response, and an alteration in the neurotransmission (by an enhancing cholinergic component) that may affect the physiological pattern of colonic motility and the sensory reflex.
Super‐marathon race increases serum and urinary nitrotyrosine and carbonyl levels
Authors: Radák Z. , Ogonovszky H. , Dubecz J. , Pavlik G. , Sasvari M. , Pucsok J. , Berkes I. , Csont T. , Ferdinandy P. 
Published: July 2003

AbstractBackground In normal conditions, proteins are not present in the urine, however, exercise of long duration could result in proteinurea. Increased levels of reactive oxygen and nitrogen species (RONS) are formed during exhaustive physical exercise and causes alterations to cellular proteins.Materials In the present study serum and urinary nitrotyrosine and protein carbonyl levels were measured before and after each run of a 4‐day super‐marathon race.Result Serum nitrotyrosine and protein carbonyl levels increased after the first (93 km) day running and reached a plateau on the second (120 km), third (56 km) and forth (59 km) days of the competition. A significant correlation was found between urinary and serum protein carbonyl and nitrotyrosine levels (r = 0·78, r = 0·71, respectively). A large percentage of urinary proteins were carbonylated and nitrated. Therefore, it appears that clearance of oxidized proteins in certain conditions occurs not only by the proteolytic pathways but also by filtration and urination.Conclusion Data reveals that exhaustive aerobic exercise causes oxidative stress and increases the nitration and carbonylation of serum proteins. The presence of carbonyl and nitrotyrosine in proteins of the urine might reflect oxidative stress and could serve as a noninvasive diagnostic tool for exercise physiology.
Effects of homocysteine on l‐arginine transport and nitric oxide formation in human platelets
Authors: Leoncini G. , Pascale R. , Signorello M. G. 
Published: July 2003

AbstractBackground Recent evidence indicates that hyperhomocysteinaemia is an independent risk factor for atherosclerosis, thrombosis and other cardiovascular diseases. This may be secondary to impaired fibrinolysis or increased platelet reactivity. Nitric oxide (NO), a product from l‐arginine by NOS and potent antiaggregating agent, plays an important role in the regulation of platelet function.Design The present study aimed to define the effect of homocysteine on the l‐arginine/NO pathway in human platelets. l‐arginine uptake, NO formation and Ca2+ levels were measured. Moreover the homocysteine effect on platelet activation induced by thrombin was tested.Results Homocysteine causes a concentration‐dependent inhibition of l‐arginine transport. Results show that homocysteine does not modify the Km parameter, but it significantly decreases the Vmax value. The nitrite and nitrate formation, strictly correlated with the l‐arginine transport, also significantly decreased. In contrast, cNOS activity remained unchanged upon homocysteine treatment. In addition homocysteine in a dose dependent manner increased the intracellular Ca2+ concentration and platelet response to thrombin.Conclusions Results indicate that the l‐arginine/NO pathway is one of the various targets of homocysteine in human platelets. The increased Ca2+ levels associated with reduced NO formation may generate hyperactivation and may contribute to the thrombogenic processes.
Stochastic modelling of nutrient loading and lake ecosystem response in relation to submerged macrophytes and benthivorous fish
Authors: Portielje R. , Rijsdijk R. E. 
Published: July 2003

SUMMARY 1. The strong stabilising effect of increased submerged macrophytes (charophytes) and benthivorous fish reduction on the clear water state was shown for shallow Lake Veluwe and Lake Wolderwijd.2. The first two links in the chain of relationships from external phosphorus (P) loading to in‐lake total‐P concentrations to chlorophyll a concentrations to water transparency, showed a significant correlation with the areal fraction of coverage with charophytes. Higher coverages lead to (i) lower ratios of the in‐lake total‐P concentration compared with the volume weighted average concentration in the inlet water, indicating a higher retention of P in the presence of charophytes (ii) lower chlorophyll a to total‐P ratios, indicating a positive effect of charophytes on top‐down control of algae, and (iii) higher water transparency because of lower algal turbidity. Transparency further improved as a result of benthivorous fish reduction and a significant positive correlation between non‐algal turbidity and benthivorous fish biomass.3. A model was developed taking into account the inherent variability in precipitation and uncertainties in the empirical relationships determining phosphorus export from stream catchments and other sources and eutrophication variables in the receiving lakes. The model was used to compute (i) probability distributions for in‐lake total‐P, chlorophyll a and Secchi Disc transparency in relation to the coverage with charophytes and benthivorous fish biomass, and (ii) exceedence probabilities with respect to critical values for in‐lake total‐P and water transparency for several management scenarios.4. The effects of an expected rise in external nutrient loading on the in‐lake total‐P and chlorophyll a concentrations and on water transparency can be compensated for by two proposed control measures: (i) extended treatment at a waste water treatment plant directly discharging into Lake Veluwe, and (ii) diverting the outlet of a stream draining a catchment with high fertilisation. The minimal internal charophyte coverage needed to sufficiently stabilise the clear water state and to meet with the objective of a summer mean water transparency of at least 1 m was estimated at well over 30% of the lake area, while the benthivorous fish stock should be maintained at the present level of c. 20 kg ha−1.
Negative effects of UVB‐irradiated phytoplankton on life history traits and fitness of Daphnia magna
Authors: De Lange Hendrika J. , Van Reeuwijk Paul L. 
Published: July 2003

SUMMARY 1. We tested the effect of ultraviolet‐B (UVB)‐irradiated phytoplankton on life history characteristics of Daphnia magna. Two phytoplankton species were used, Chlamydomonas reinhardtii and Cryptomonas pyrenoidifera. The phytoplankton species were cultured under photosynthetically active radiation (PAR) conditions, and under PAR supplemented with ultraviolet‐A and ultraviolet‐B radiation, and fed to Daphnia.2. Life history traits of Daphnia were negatively affected when fed on UVB‐irradiated Cryptomonas. Size at maturity was depressed and fewer juveniles with lower fitness were produced in the UVB treatments. In the Chlamydomonas experiment, no significant effects were found.3. The cause of the observed UVB effects is likely to be constraints in food quality. Ultraviolet‐B radiation thus has the potential of inhibiting energy transfer from the first to the second trophic level.
Microhabitat selection by the invasive amphipod Echinogammarus ischnus and native Gammarus fasciatus in laboratory experiments and in Lake Erie
Authors: Van Overdijk Colin D. A. , Grigorovich Igor A. , Mabee Tracy , Ray William J. , Ciborowski Jan J. H. , Macisaac Hugh J. 
Published: July 2003

SUMMARY1. The amphipod Echinogammarus ischnus was first reported in the Laurentian Great Lakes during 1995. However, analysis of archived samples revealed the presence of the species from western Lake Erie in 1994 and possibly as early as 1993.2. Surveys conducted in Lake Erie between 1995 and 1998 revealed that Echinogammarus was the dominant amphipod on rocks covered by Dreissena molluscs compared with those fouled by the filamentous alga Cladophora, while Gammarus fasciatus used both Dreissena and Cladophora substrata extensively.3. In laboratory habitat selection studies, Echinogammarus chose Dreissena‐ over Cladophora‐encrusted rocks and bare rocks, while Gammarus occupied the more complex substrata equally.4. Field colonisation experiments demonstrated that the densities of Echinogammarus and Gammarus were positively correlated when the total density of the species was low, in contrast to the large‐scale natural distribution of the species that revealed a strong inverse relationship.5. The on‐going replacement of Gammarus by Echinogammarus in the Laurentian Great Lakes may be related to the stronger affinity of the latter for substrata fouled by Dreissena, a genus with which it co‐evolved.
Structure and evolution of the luciferin‐regenerating enzyme (LRE) gene from the firefly Photinus pyralis
Authors: Day J. C. , Bailey M. J. 
Published: July 2003

AbstractTo study the structural features of genes for the luciferin‐regenerating enzyme (LRE), the entire gene along with 524 bp of upstream sequence was determined from Photinus pyralis (Coleoptera: Lampyridae). The LRE gene revealed an open reading frame composed of five exons divided by four introns ranging in size from 47 to 904 bp. The deduced LRE amino acid sequence showed identity to senescence marker protein‐30 (SMP30) from a number of insects and mammals including four putative SMP30 sequences from Anopheles gambiae. Gene structure comparisons showed some intron/exon site conservation with A. gambiae and mammalian SMP30 proteins but not Drosophila. LRE and luciferase sequence comparisons revealed two conserved putative luciferin‐binding sites. The evolution of LRE was discussed in relation to its function.
RNase G of Escherichia coli exhibits only limited functional overlap with its essential homologue, RNase E
Authors: Ow Maria C. , Perwez Tariq , Kushner Sidney R. 
Published: July 2003

SummaryRNase G (rng) is an E. coli endoribonuclease that is homologous to the catalytic domain of RNase E (rne), an essential protein that is a major participant in tRNA maturation, mRNA decay, rRNA processing and M1 RNA processing. We demonstrate here that whereas RNase G inefficiently participates in the degradation of mRNAs and the processing of 9S rRNA, it is not involved in either tRNA or M1 RNA processing. This conclusion is supported by the fact that inactivation of RNase G alone does not affect 9S rRNA processing and only leads to minor changes in mRNA half‐lives. However, in rng rne double mutants mRNA decay and 9S rRNA processing are more defective than in either single mutant. Conversely, increasing RNase G levels in an rne‐1 rng::cat double mutant, proportionally increased the extent of 9S rRNA processing and decreased the half‐lives of specific mRNAs. In contrast, variations in the amount of RNase G did not alter tRNA processing under any circumstances. Thus, the failure of RNase G to complement rne mutations, even when overproduced at high levels, apparently results from its inability to substitute for RNase E in the maturation of tRNAs.
Leptospira spp. possess a complete haem biosynthetic pathway and are able to use exogenous haem sources
Authors: Guégan Rozenn , Camadro Jean‐Michel , Saint Girons Isabelle , Picardeau Mathieu 
Published: July 2003

SummaryUnlike the spirochetes Borrelia burgdorferi and Treponema pallidum, Leptospira spp. contain genes encoding the enzymes for most biosynthetic pathways. In this study, we describe the first haem biosynthetic pathway genes in the order Spirochaetales. Sequence analysis of the L. interrogans genome shows that all haem biosynthetic genes (hemA, heml, hemB, hemC, hemE, hemN, hemY and hemH) are clustered in a 15 kb region of the CII secondary chromosome. Although no hemD homologue (encoding uroporphyrinogen III synthase) was found in the genome, the L. interrogans hemC gene (encoding porphobilinogen deaminase) was able to restore uroporphyrinogen III synthase activity in an Escherichia coliΔhemD mutant, suggesting that the L. interrogans hemC gene encodes a bifunctional enzyme. Similarly, we show that the L. interrogans hemH gene (encoding ferrochelatase, the terminal enzyme of the haem biosynthetic pathway) is able to complement a ferrochelatase‐defective E. coliΔhemH mutant. Further investigation of ferrochelatases was undertaken in both saprophytic and pathogenic species of Leptospira. Ferrochelatase activity of 2.3 ± 0.1 nmol h−1 mg−1 (in comparison with 0.25 ± 0.02 nmol h−1 mg−1 in E. coli) was found in membrane fractions of pathogenic and saprophytic species, suggesting that ferrochelatase is a membrane‐associated protein. Leptospira biflexa allelic exchange mutants containing an inactivated hemH gene were recovered only when exogenous haemin was present. The results indicate that haem is an essential growth factor for Leptospira, and that these spirochetes are capable of both de novo synthesis or uptake of haem. This may have implications in a better understanding of the pathogenesis of Leptospira.
Immunoreceptor tyrosine‐based activation motif phosphorylation during engulfment of Neisseria gonorrhoeae by the neutrophil‐restricted CEACAM3 (CD66d) receptor
Authors: McCaw Shannon E. , Schneider Jutta , Liao Edward H. , Zimmermann Wolfgang , Gray‐Owen Scott D. 
Published: July 2003

SummaryGonorrhea is characterized by a purulent urethral or cervical discharge consisting primarily of neutrophils associated with Neisseria gonorrhoeae. These interactions are facilitated by gonococcal colony opacity‐associated (Opa) protein binding to host cellular CEACAM receptors. Of these, CEACAM3 is restricted to neutrophils and contains an immunoreceptor tyrosine‐based activation motif (ITAM) reminiscent of that found within certain phagocytic Fc receptors. CEACAM3 was tyrosine phosphorylated by a Src family kinase‐dependent process upon infection by gonococci expressing CEACAM‐specific Opa proteins. This phosphorylation was necessary for efficient bacterial uptake; however, a less efficient uptake process became evident when kinase inhibitors or mutagenesis of the ITAM were used to prevent phosphorylation. Ligated CEACAM3 was recruited to a cytoskeleton‐containing fraction, intense foci of polymerized actin were evident where bacteria attached to HeLa‐CEACAM3, and disruption of polymerized actin by cytochalasin D blocked all bacterial uptake by these cells. These data support a model whereby CEACAM3 can mediate the Opa‐dependent uptake of N. gonorrhoeae via either an efficient, ITAM phosphorylation‐dependent process that resembles phagocytosis or a less efficient, tyrosine phosphorylation‐independent mechanism.
Complex regulation of csgD promoter activity by global regulatory proteins
Authors: Gerstel Ulrich , Park Chankyu , Römling Ute 
Published: July 2003

SummaryThe starvation‐induced csgD gene of Salmonella typhimurium encodes for the positive transcriptional regulator of extracellular matrix components curli fimbriae and cellulose. To analyse regulatory elements of csgD promoter (PcsgD) response genetic studies combined with in vitro experiments were performed. Six binding sites (D1 to D6) for OmpR, a transcriptional regulator, were identified by gel shifts and DNase I footprints. While ompR is required for PcsgD expression, binding of OmpR‐P to D2 centred immediately upstream of D1 at position −70.5 is proposed to repress PcsgD activity. The elevated expression of regulated and semiconstitutive PcsgD in response to microaerophilic conditions required integration host factor (IHF). Subsequently, two IHF‐binding sites were identified up‐ and downstream of PcsgD. IHF competes with OmpR‐P for binding at its upstream site IHF1, which overlaps with D3–D6 and thereby modulates the response to microaerophilic conditions. A complex regulatory network involving IHF, H‐NS and OmpR is proposed whereby the nucleo‐complex composition in the csgD–csgBA intergenic region is altered in response to oxygen tension.