bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deficient UDP‐glucuronosyltransferase detoxification enzyme activity in the small intestinal mucosa of patients with coeliac disease
Authors: GOERRES M. , ROELOFS H. M. J. , JANSEN J. B. M. J. , PETERS W. H. M. 
Published: December 2005

SummaryBackground  Small intestinal malignancies in humans are rare; however, patients with coeliac disease have a relatively high risk for such tumours. Intestinal UDP‐glucuronosyltransferases are phase II drug metabolism enzymes also involved in the detoxification of ingested toxins and carcinogens. As many toxins and carcinogens are ingested via food, the human gastrointestinal tract not only has an important role in the uptake of essential nutrients, but also acts as a first barrier against such harmful constituents of the food. Therefore, the gastrointestinal mucosa contains high levels of detoxification enzymes such as cytochromes‐P450, glutathione S‐transferases and UDP‐glucuronosyltransferases.Aim  To compare the UDP‐glucuronosyltransferase detoxification capacity in small intestinal mucosa of patients with coeliac disease vs. that in normal controls.Methods  We assessed UDP‐glucuronosyltransferase enzyme activities towards 4‐methylumbelliferone in small intestinal biopsies of patients with coeliac disease (n = 22) and age‐ and sex‐matched controls (n = 27).Results  Small intestinal UDP‐glucuronosyltransferase enzyme activity in controls was significantly higher than in patients with coeliac disease: 0.55 ± 0.27 vs. 0.35 ± 0.16 nmol/min mg protein, respectively (mean ± s.d., P = 0.005).Discussion  The low small intestinal UDP‐glucuronosyltransferase detoxification activity in patients with coeliac disease may result in a deficient detoxification of potential carcinogens, and thus could explain in part the relatively high small intestinal cancer risk in these patients.
Pharmacokinetics of ruboxistaurin are significantly altered by rifampicin‐mediated CYP3A4 induction
Authors: Yeo Kwee Poo , Lowe Stephen L. , Lim Ming Tung , Voelker James R. , Burkey Jennifer L. , Wise Stephen D. 
Published: December 2005

AimsThe aim of this study was to evaluate the effect of rifampicin co‐administration on the pharmacokinetics of ruboxistaurin and its active metabolite, N‐desmethyl ruboxistaurin and, in addition, to compare the changes in pharmacokinetics of ruboxistaurin and N‐desmethyl ruboxistaurin with the urinary 6β‐hydroxycortisol : cortisol ratio. Ruboxistaurin is a specific protein‐kinase‐C β inhibitor in clinical development for the treatment of diabetic microvascular complications.MethodsThis was a two‐period, one‐sequence study. Sixteen healthy male subjects completed both study periods. In period one, a single 64 mg oral dose of ruboxistaurin was administered. In period two, 600 mg rifampicin was administered daily for 9 days, during which another single 64 mg ruboxistaurin dose was administered on day 7. Blood samples were collected and assayed for ruboxistaurin and N‐desmethyl ruboxistaurin. CYP3A4 induction was assessed by ratios of urinary 6β‐hydroxycortisol : cortisol (6β‐OHC : C) obtained via 24 h and morning‐spot sampling techniques.ResultsFollowing repeated doses of rifampicin, both the mean Cmax and AUC(0,∞) of ruboxistaurin were significantly reduced by approximately 95% (P ≤ 0.001). For the metabolite, the mean Cmax decreased by 68% (P ≤ 0.001), and AUC(0,∞) decreased by 77% (P ≤ 0.001). The tmax values did not appear affected. The 6β‐OHC : C ratios from both 24 h and morning spot methods increased significantly, consistent with CYP3A4 induction.ConclusionsThe effect of rifampicin co‐administration on the exposure of ruboxistaurin is consistent with ruboxistaurin being a substrate of CYP3A4. Therefore, co‐administration with known CYP3A4 inducing agents (rifampicin, carbamazepine, phenobarbital, etc.) may decrease the concentrations of ruboxistaurin and N‐desmethyl‐ruboxistaurin. In this study, 6β OHC : C ratios substantially underestimated the impact of rifampicin on ruboxistaurin.
Animal models of allergen‐induced tolerance in asthma: are T‐regulatory‐1 cells (Tr‐1) the solution for T‐helper‐2 cells (Th‐2) in asthma?
Authors: Tournoy K. G. , Van Hove C. , Grooten J. , Moerloose K. , Brusselle G. G. , Joos G. F. 
Published: December 2005

SummaryNon‐specific anti‐inflammatory medication is actually the treatment of choice for controlling the T‐helper type 2 (Th‐2) cell‐driven airway inflammation in asthma. The induction of counterbalancing Th‐1 cell clones, long considered a promising approach for immunotherapy, has failed to fulfil its promise because of potentially detrimental side‐effects. This is therefore probably not a valid option for the treatment of asthma.With the increasing awareness that active immune mechanisms exist to control inflammatory responses, interest rises to investigate whether these can be exploited to control allergen‐induced airway disease. The induction of antigen‐specific T cells with suppressive characteristics (regulatory T cells) is therefore a potentially interesting approach. These regulatory T cells mediate tolerance in healthy, non‐atopic individuals and have the potential of becoming an effective means of preventing allergen‐induced airway inflammation and possibly of suppressing ongoing allergic immune responses. Here we review the available knowledge about allergen‐induced suppressive immunity obtained from animal models taking into account the different developmental stages of allergic airway disease.
Exhaled breath condensate levels of eotaxin and macrophage‐derived chemokine in stable adult asthma patients
Authors: Ko F. W. S. , Lau C. Y. K. , Leung T. F. , Wong G. W. K. , Lam C. W. K. , Lai C. K. W. , Hui D. S. C. 
Published: December 2005

SummaryBackground
Asthma is associated with esoinophilic airway inflammation and overproduction of T‐helper type 2 (Th2) lymphocyte‐related cytokines.Objective
This study assessed the eosinophil chemoattractant eotaxin and Th2‐specific macrophage‐derived chemokine (MDC) in the adult asthmatic airway. Eotaxin and MDC levels were determined in exhaled breath condensate (EBC) obtained from adult patients with asthma.Methods
Fifty‐four asthmatics (20 male, mean (SD) age 40 (12) years and percentage predicted forced expiratory volume in 1 s (FEV1) 81.7 (20.8)) and 20 age‐ and sex‐matched controls were studied. EBC was collected using EcoScreen by 10 min of tidal breathing with a nose clip. Concentrations of eotaxin and MDC were measured by ELISA.Results
Asthma patients on inhaled corticosteroid (ICS) had a higher median interquartile range (IQR) level of eotaxin than the steroid‐naïve asthmatics (18.5 (17.7–20.1) vs. 17.9 (17.0–18.6) pg/mL, P=0.02) and controls (18.5 (17.7–20.1) pg/mL vs 17.4 (16.3–18.0) pg/mL, P=0.001). Eotaxin level in EBC had a significant negative correlation with the FEV1/forced vital capacity ratio (r=−0.43, P=0.03) in steroid‐naïve asthmatics. EBC MDC level was higher in subjects on ICS than the steroid naïve asthmatics (120 (118–125) vs. 117 (116–119) pg/mL, P=0.01) and the controls (120 (118–125) vs. 117 (116–120) pg/mL, P=0.02).Conclusions
Eotaxin and MDC could be measured in EBC of adults with asthma. EBC eotaxin and MDC levels were higher in asthmatics on ICS than the steroid‐naïve asthmatics or controls. Exhaled chemokines may be potential non‐invasive markers for assessing airway inflammation in asthmatics.
T cell‐mediated hypersensitivity to quinolones: mechanisms and cross‐reactivity
Authors: Schmid D. A. , Depta J. P.H. , Pichler W. J. 
Published: December 2005

SummaryBackground
Quinolones are widely used, broad spectrum antibiotics that can induce immediate‐ and delayed‐type hypersensitivity reactions, presumably either IgE or T cell mediated, in about 2–3% of treated patients.Objective
To better understand how T cells interact with quinolones, we analysed six patients with delayed hypersensitivity reactions to ciprofloxacin (CPFX), norfloxacin (NRFX) or moxifloxacin (MXFX).Methods
We confirmed the involvement of T cells in vivo by patch test and in vitro by means of the lymphocyte proliferation test (LTT). The nature of the drug–T cell interaction as well as the cross‐reactivity with other quinolones were investigated through the generation and analysis (flow cytometry and proliferation assays) of quinolone‐specific T cell clones (TCC).Results
The LTT confirmed the involvement of T cells because peripheral blood mononuclear cells (PBMC) mounted an enhanced in vitro proliferative response to CPFX and/or NRFX or MXFX in all patients. Patch tests were positive after 24 and 48 h in three out of the six patients. From two patients, CPFX‐ and MXFX‐specific CD4+/CD8+ T cell receptor (TCR) αβ+ TCC were generated to investigate the nature of the drug‐T cell interaction as well as the cross‐reactivity with other quinolones. The use of eight different quinolones as antigens (Ag) revealed three patterns of cross‐reactivity: clones exclusively reacting with the eliciting drug, clones with a limited cross‐reactivity and clones showing a broad cross‐reactivity. The TCC recognized quinolones directly without need of processing and without covalent association with the major histocompatability complex (MHC)–peptide complex, as glutaraldehyde‐fixed Ag‐presenting cells (APC) could present the drug and washing quinolone‐pulsed APC removed the drug, abrogating the reactivity of quinolone‐specific TCC.Conclusion
Our data show that T cells are involved in delayed immune reactions to quinolones and that cross‐reactivity among the different quinolones is frequent.
Non‐haem iron transport in the rat proximal colon
Authors: Johnston K. L. , Johnson D. M. , Marks J. , Srai S. K. , Debnam E. S. , Sharp P. A. 
Published: December 2005

AbstractBackground  Only 10% of dietary iron is absorbed in the duodenum which implies that 90% (approximately 9 mg day−1) reaches the lower small intestine and colon. Therefore the purpose of this study was to assess the iron transport capacity of the rat proximal colon and to determine whether iron absorption is regulated by changes in dietary iron content.Materials and methods  Rats were fed for 14 days on either iron adequate (44 mg Fe kg−1 diet) or iron‐deficient (< 0·5 mg Fe kg−1 diet) diets. The 59Fe transport across the colonic epithelium and its subsequent appearance in the blood were measured in vivo. In separate studies the colon was excised and used to measure divalent metal transporter expression.Results  Divalent metal transporter (DMT1) was expressed at the apical membrane of the surface epithelium in rat proximal colon. In animals fed an iron‐deficient diet, DMT1 mRNA and protein expression were increased. This was accompanied by a significant increase in tissue 59Fe uptake.Conclusions  The proximal colon can absorb non‐haem iron from the intestinal lumen. The purpose of this mechanism remains to be elucidated.
BNP and N‐terminal proBNP are both extracted in the normal kidney
Authors: Goetze J. P. , Jensen G. , Møller S. , Bendtsen F. , Rehfeld J. F. , Henriksen J. H. 
Published: December 2005

AbstractBackground  Increased plasma concentrations of cardiac‐derived B‐type natriuretic peptide (BNP) and N‐terminal pro‐B‐type natriuretic peptide (proBNP) are both associated with left ventricular dysfunction. Information on the regional elimination of the peptides is, however, still scarce. We therefore examined the renal and peripheral extraction of N‐terminal proBNP and BNP.Materials and methods  The study comprised 18 patients with essential arterial hypertension, 51 with cirrhosis, and 18 control patients without kidney or liver disease. All patients underwent a haemodynamic investigation with catheterization of the femoral artery and femoral and renal veins. Blood sampling from the catheters allowed determination of the arteriovenous extraction ratio of N‐terminal proBNP and BNP.Results  Neither the peripheral N‐terminal proBNP (13, 11, 19 pmol L−1, NS) nor the BNP plasma concentrations (4, 12, 9 pmol L−1, NS) differed between the patient groups. In addition, similar renal extractions were observed in the groups. The renal extraction of N‐terminal proBNP (0·16) was not different from that of BNP (0·16). In contrast, the N‐terminal proBNP extraction in the lower extremity was markedly lower compared with BNP (0·00 vs. 0·125, P = 0·007).Conclusions  A comparable renal elimination of N‐terminal proBNP and BNP is contrasted by a selective extraction of BNP in the lower extremity. Our results suggest a different elimination mechanism in the renal and peripheral circulation, which partly may explain the higher N‐terminal proBNP compared with BNP concentrations in normal plasma.
Interleukin‐4 can induce interleukin‐4 production in dendritic cells
Authors: Maroof Asher , Penny Michelle , Kingston Rosetta , Murray Clare , Islam Sabita , Bedford Penelope A. , Knight Stella C. 
Published: December 2005

SummaryThe presence of interleukin‐4 (IL‐4) during the generation of dendritic cells (DC) from precursor cells results in measurable increases of IL‐12 in supernatants but IL‐4 secretion has not been reported. However, DC have IL‐4 receptors and are able to make IL‐4. We therefore sought evidence for autocrine effects of IL‐4 on DC. IL‐4 gene expression was low in DC generated from bone‐marrow stem cells in the presence of granulocyte–macrophage colony‐stimulating factor but was up‐regulated by exposure of the developing DC to IL‐4. Exposure to IL‐4 also induced intracellular IL‐4 production in DC. The intracellular IL‐4 induced in the presence of IL‐4 was increased following further DC maturation with tumour necrosis factor‐α. By contrast, in supernatants of DC, IL‐4 was rarely detected and only at late culture periods. However, after exposure of DC to IL‐4, cell‐bound IL‐4 was detected transiently, which suggested binding and internalization of the cytokine. Binding via IL‐4 receptor‐α was indicated from phosphorylation of the signal transducer and activator of transcription (STAT) protein 6, which is known to mediate IL‐4 function. Cytokine persisting within the supernatants of the cells may therefore be unrepresentative of the actual production and function of IL‐4 in the cells; IL‐4 may be produced in DC in response to exposure to IL‐4 but may then be lost from the supernatants during cell binding and activation of the cells.
Molecular cloning of several rat ABC transporters including a new ABC transporter,Abcb8, and their expression in rat testis
Authors: Melaine Nathalie , Satie Anne‐Pascale , Lassurguère Julie , Desmots Sophie , Jégou Bernard , Samson Michel 
Published: December 2005

SummarySeveral members of the ABC transporter superfamily play an important role in testicular physiology and defence against anticancer drugs. Using a reverse transcription‐polymerase chain reaction strategy with degenerate primers and rat testis RNA as template, we have looked for the presence of other members of this superfamily. Of the six partial cDNA found, five corresponded to ABC transporters already known –Mdr1b, Mrp1, Tapl/Abcb9, Umat/Abcb6andSur2/Abcc9– and one presented a strong homology with mouse and humanABCB8. Using a 5′ and 3′ RACE approach, we cloned the full‐length cDNA and found that the predicted protein presented 92% and 80% homology with the mouse and human proteins respectively. Strong expression of rat abcb8 was found in heart, brain and testis when compared with liver, lung and spleen. In the testis, rat abcb8 was expressed both in the somatic Sertoli cells and peritubular cells and in the germline (spermatogonia and pachytene spermatocytes). Furthermore,Umat/Abcb6was very highly expressed in the testis (high amounts in meiotic pachytene spermatocytes and low amount in post‐meiotic early spermatids). In conclusion, we confirm the presence of several ABC transporters in the testis and also provide evidence of the presence of Abcb8 in the organ.
Real‐time three‐dimensional ultrasound visualization of erection and artificial coitus
Authors: DENG JING , HALL‐CRAGGS MARGARET A. , PELLERIN D. , LINNEY ALFRED D. , LEES WILLIAM R. , RODECK CHARLES H. , TODD‐POKROPEK ANDREW 
Published: December 2005

SummaryTo investigate the feasibility of imaging penile erection and coitus in real time and in three dimensions, a ‘Live’ three‐dimensional (3‐D) ultrasound system was used to acquire the volume of interest at 25 Hz from five healthy men. Water baths and gel‐made artificial vaginas were devised to facilitate the 3‐D scans without the probe being in direct contact with the penis. For the first volunteer scanned with the water bath alone, the penis failed to erect within 30 min. For the other four volunteers, the ‘vagina’ successfully initiated and maintained the erection and allowed artificial intercourse. Results have shown that the ‘Live’ 3‐D ultrasound and minimally compressive imaging techniques together can offer an objective means for visualizing erection and coitus in spatial totality and temporal reality. They can be further developed to reveal more reliable details about the dynamic morphology, improving scientific understanding of sexual activities and clinical management of related problems.
Small rodent winter survival: snow conditions limit access to food resources
Authors: KORSLUND LARS , STEEN HARALD 
Published: December 2005

Summary

In Fennoscandia during winter small rodents spend most of their time in the subnivean space, between the snow cover and the ground. The subnivean space is probably not a uniform habitat, but broken into accessible and inaccessible patches by ice covering the vegetation. This might reduce access to otherwise available food resources.
To test whether ice formations reduce access to food and thus limit winter survival of small rodents, we conducted an experiment where we increased subnivean space by adding corrugated aluminium sheets on the ground before onset of winter. The sheets prevented ice formation, thus mimicking natural occurring subnivean space, and providing more room for animals living in the subnivean space to forage.
During the experiment 142 Microtus oeconomus were passive induced transponder (PIT)‐tagged, and a system consisting of fixed tube‐shaped antennas and PIT‐tag readers were used to provide data to analyse winter survival and individual subnivean space use. The extent of winter grazing was measured after snow melt by examining percentage area grazed.
The treatment resulted in increased survival which corresponded well with significantly higher space use and more grazing under the sheets.
Females showed a positive correlation between probability of survival and body mass while no such effect was observed in males.
The results suggest that the snow cover reduces survival in winter by physically enclosing the vegetation in ice and thus reducing access to otherwise available food resources. The amount of ice and its configuration might vary between years due to changing weather patterns. Our results offer a mechanistic explanation for variations in winter survival and suggest incorporating climate variables in future small rodent models.
Directional and long‐term changes in climate might result in increased ice formation in the subnivean system. Such deterioration may lead to reduced winter survival and act by stabilizing population dynamics and dampening vole cyclicity.
Syndrome specificity and behavioural disorders in young adults with intellectual disability: cultural differences in family impact
Authors: Blacher J. , McIntyre L. L. 
Published: December 2005

AbstractBackground  This study examined whether behaviour problems and adaptive behaviour of low functioning young adults, and well‐being of their families, varied by diagnostic syndrome [intellectual disability (ID) only, cerebral palsy, Down syndrome, autism], as well as by cultural group.Methods  Behaviour disorders in young adults with moderate to severe ID were assessed from information provided by 282 caregivers during in‐home interviews. The sample consisted of 150 Anglo participants, and 132 Latino, primarily Spanish‐speaking, participants drawn from Southern California.Results  Behaviour disorders and maternal well‐being showed the same pattern across disability syndromes. Autism was associated with the highest scores in multiple behaviour problem areas as well as maternal reports of lower well‐being. Down syndrome was associated with the lowest behaviour problem scores and the highest maternal well‐being. When behaviour problems were controlled for, diagnostic groups accounted for no additional variance in maternal stress or depression. The pattern of behaviour problems and well‐being did not differ by sample (Anglo vs. Latino), although level on well‐being measures did. Latina mothers reported significantly higher depression symptoms and lower morale, but also higher positive impact from their child than did Anglo mothers.Conclusions  Caregivers of young adults with autism report more maladaptive behaviour problems and lower personal well‐being, or stress, relative to other diagnostic groups, regardless of cultural group. However, cultural differences exist in caregiver reports of depression, morale, and positive perceptions. Implications for service provision aimed at families of children with challenging behaviour problems are discussed in the context of culture.
Comparative phylogeography across two trophic levels: the oak gall wasp Andricus kollari and its chalcid parasitoid Megastigmus stigmatizans
Authors: HAYWARD ALEXANDER , STONE GRAHAM N. 
Published: December 2005

AbstractInsect parasitoids are important components of many terrestrial ecosystems. However, relatively little is known about the mechanisms responsible for structuring their populations. Here we investigate the ability of Megastigmus stigmatizans, an oak gall wasp parasitoid, to track its host Andricus kollari over two different timescales, and examine its current population structure across a divide in host population structure. The divide represents a transition in gall wasp host‐plant species and offers the opportunity to examine whether the split, which divides gall wasp populations, manifests itself in the next trophic level. Analysis of mitochondrial haplotype data for parasitoid and host reveals: (i) A similar phylogeographic population structure for both, with Iberian populations more derived with respect to more eastern populations. (ii) It is likely that the host colonized the Iberian refuge earlier than the parasitoid, probably by at least one glacial cycle. (iii) Recent range expansion of central European host populations northwards has resulted in pursuit by parasitoids from the same geographic origin. (iv) In addition, Iberian parasitoid populations have crossed a major divide in host population structure to invade northern Europe. Such human‐facilitated escape from natural refugial distributions may have important implications for the composition and structure of northern European gall wasp communities.