bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral butyrate for mildly to moderately active Crohn's disease
Authors: SABATINO A. DI , MORERA R. , CICCOCIOPPO R. , CAZZOLA P. , GOTTI S. , TINOZZI F. P. , TINOZZI S. , CORAZZA G. R.
Published: October 2005

Background : Butyrate exerts anti‐inflammatory effects in experimental colitis and on Crohn's disease lamina propria mononuclear cells in vitro.

Aim : To explore the efficacy and safety of oral butyrate in Crohn's disease.

Methods : Thirteen patients with mild–moderate ileocolonic Crohn's disease received 4 g/day butyrate as enteric‐coated tablets for 8 weeks. Full colonoscopy and ileoscopy were performed before and after treatment. Endoscopical and histological score, laboratory data, Crohn's disease activity index and mucosal interleukin (IL)‐1β, IL‐6, IL‐12, interferon‐γ, tumour necrosis factor‐α and nuclear factor‐kappa B (NF‐κB) were assessed before and after treatment.

Results : One patient withdrew from the study, and three patients did not experience clinical improvement. Among the nine patients (69%) who responded to treatment, seven (53%) achieved remission and two had a partial response. Endoscopical and histological score significantly improved after treatment at ileocaecal level (P < 0.05). Leucocyte blood count, erythrocyte sedimentation rate and mucosal levels of NF‐κB and IL‐1β significantly decreased after treatment (P < 0.05).

Conclusions : Oral butyrate is safe and well tolerated, and may be effective in inducing clinical improvement/remission in Crohn's disease. These data indicate the need for a large investigation to extend the present findings, and suggest that butyrate may exert its action through downregulation of NF‐κB and IL‐1β.
The impact of ursodeoxycholic acid on cancer, dysplasia and mortality in ulcerative colitis patients with primary sclerosing cholangitis
Authors: WOLF J. M. , RYBICKI L. A. , LASHNER B. A.
Published: October 2005

Background : Colorectal cancer in primary sclerosing cholangitis patients with ulcerative colitis is mostly right‐sided where concentrations of carcinogenic secondary bile acids are highest.

Aim : To investigate whether ursodeoxycholic acid could be chemopreventive for colorectal cancer.

Methods : A historical cohort study was performed on primary sclerosing cholangitis patients with ulcerative colitis where the 28 patients (cases) who were treated with ursodeoxycholic acid for at least 6 months (mean 3.4 ± 2.7 years) were compared with the 92 patients (controls) who were not treated with ursodeoxycholic acid. The primary outcomes were colorectal cancer and dysplasia. The secondary outcome was overall mortality.

Results : The cumulative incidence of dysplasia or cancer was not significantly different between cases and controls (P = 0.17 by log‐rank test). The adjusted relative risk for cases of developing dysplasia or cancer was 0.59 (95% CI 0.26–1.36). The cumulative mortality was significantly different between groups (P = 0.02 by log‐rank test). The adjusted relative risk for cases of death was 0.44 (95% CI 0.22–0.90).

Conclusion : In ulcerative colitis patients with primary sclerosing cholangitis, ursodeoxycholic acid did not reduce the risk of developing cancer or dysplasia. However, ursodeoxycholic acid may reduce mortality.
Aerophagia in adults: a comparison with functional dyspepsia
Authors: CHITKARA D. K. , BREDENOORD A. J. , RUCKER M. J. , TALLEY N. J.
Published: October 2005

Background : Aerophagia is a functional upper gastrointestinal disorder that has not previously been well described in a large patient group.

Aims : To describe the initial evaluation of patients who presented with symptoms of aerophagia at a tertiary medical centre.

Methods : A computerized search was used to identify all patients who were diagnosed with aerophagia at the Mayo Clinic, Rochester between 1996 and 2003 (n = 79). Individual medical charts were abstracted for information on the demographics, clinical features, co‐morbid diagnoses, diagnostic workup and treatment. Information on presenting symptoms was also collected for a group of patients who were classified as having functional dyspepsia for comparison (n = 121).

Results : The median duration of symptoms in patients with aerophagia was 24 months. The most common symptoms were belching (56%), abdominal pain (19%), bloating (27%) and abdominal distension (19%). Patients with functional dyspepsia had a higher prevalence of reporting nausea, vomiting, early satiety, weight loss and abdominal pain (all P < 0.01, adjusting for age, gender and body mass index). Significantly more patients with aerophagia had anxiety (19%) than those with functional dyspepsia (6%, P < 0.01).

Conclusions : Individuals with aerophagia experience prolonged upper gastrointestinal symptoms. Initial presenting symptoms appear to be distinctly different from those who have functional dyspepsia.
Review article: the management of heartburn in pregnancy
Authors: RICHTER J. E.
Published: October 2005

Heartburn is a normal consequence of pregnancy. The predominant aetiology is a decrease in lower oesophageal sphincter pressure caused by female sex hormones, especially progesterone. Serious reflux complications during pregnancy are rare; hence upper endoscopy and other diagnostic tests are infrequently needed. Gastro‐oesophageal reflux disease during pregnancy should be managed with a step‐up algorithm beginning with lifestyle modifications and dietary changes. Antacids or sucralfate are considered the first‐line drug therapy. If symptoms persist, any of the histamine2‐receptor antagonists can be used. Proton pump inhibitors are reserved for women with intractable symptoms or complicated reflux disease. All but omeprazole are FDA category B drugs during pregnancy. Most drugs are excreted in breast milk. Of systemic agents, only the histamine2‐receptor antagonists, with the exception of nizatidine, are safe to use during lactation.
Helicobacter pylori eradication in childhood after failure of initial treatment: advantage of quadruple therapy with nifuratel to furazolidone
Authors: NIJEVITCH A. A. , SHCHERBAKOV P. L. , SATAEV V. U. , KHASANOV R. SH. , AL KHASHASH R. , TUYGUNOV M. M.
Published: October 2005

Background : Failures of Helicobacter pylori eradication in children are common.

Aim : To evaluate the efficacy of amoxicillin, bismuth subcitrate and omeprazole and nifuratel or furazolidone for H. pylori eradication in children who failed initial treatment with a standard triple therapy.

Methods : Seventy‐six consecutive H. pylori‐positive paediatric out‐patients (aged 12–16 years; mean age 13.7 ± 1.4) with chronic abdominal complaints who had failed one attempt of eradication of H. pylori using metronidazole‐containing triple therapy were enrolled. It was an open prospective study. Patients were randomized to receive a 2‐week course of bismuth subcitrate (8 mg/kg/day, q.d.s.), amoxicillin (50 mg/kg/day, q.d.s.), with either nifuratel (15 mg/kg/day, q.d.s.) or furazolidone (10 mg/kg/day, q.d.s.), plus omeprazole (0.5 mg/kg, once daily).

Results : There were 37 patients in the nifuratel group and 39 in the furazolidone group. Helicobacter pylori was eradicated in 33 of 37 (89%; 95% CI: 74.5–96.9; intention‐to‐treat) in nifuratel group and in 34 of 39 (87%; 95% CI: 72.5–95.7) in furazolidone group, respectively. Frequency of severe side‐effects was greater with furazolidone (21%) than with nifuratel (3%; P = 0.0289).

Conclusions : Nitrofuran‐containing therapies consisting of a proton‐pump inhibitor, amoxicillin and bismuth citrate plus either nifuratel or furazolidone produced good cure rates even among those who had failed prior therapy. Nifuratel is preferred because of the lower frequency of side‐effects.
Increased carotid intima–media thickness in patients with inflammatory bowel disease
Authors: PAPA A. , SANTOLIQUIDO A. , DANESE S. , COVINO M. , CAMPLI C. Di , URGESI R. , GRILLO A. , GUGLIELMO S. , TONDI P. , GUIDI L. , VITIS I. DE , FEDELI G. , GASBARRINI G. , GASBARRINI A.
Published: October 2005

Background : Patients with inflammatory bowel disease have an increased risk of thrombotic complications; moreover, mesenteric microvascular thrombosis has been hypothesized as a contributing factor in the pathogenesis of inflammatory bowel disease.

Aim : To assess the extent of subclinical atherosclerosis in inflammatory bowel disease by measuring the intima–media thickness of the common carotid artery.

Methods : Fifty‐two patients were enrolled in the study. Patients aged >45 years, with a history of cardiovascular disease and known risk factors for atherosclerosis were excluded from the study. Twenty healthy subjects were studied as controls. Carotid ultrasonography was performed in all patients and controls. intima–media thickness was measured proximal to the carotid bifurcation over both right and left common carotid arteries. The clinical characteristics and the laboratory parameters relevant to disease activity were recorded for all inflammatory bowel disease patients. In particular, plasma homocysteine, a well‐known risk factor for thrombosis, was assessed.

Results : Common carotid artery intima–media thickness was significantly higher in inflammatory bowel disease patients (0.63 ± 0.15 mm) compared with controls (0.53 ± 0.08 mm). Multiple regression analysis revealed a significant association of carotid intima–media thickness with homocysteine levels and age.

Conclusions : Inflammatory bowel disease patients have an increased risk of early atherosclerosis than healthy controls as showed by greater values of carotid intima–media thickness. Homocysteine levels and age resulted independently associated with the increased arterial wall thickness.
Influence of ghrelin on gastric emptying and meal‐related symptoms in idiopathic gastroparesis
Authors: TACK J. , DEPOORTERE I. , BISSCHOPS R. , VERBEKE K. , JANSSENS J. , PEETERS T.
Published: October 2005

Background : Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor, is released from the stomach. Animal studies suggest that ghrelin stimulates gastrointestinal motor activity.

Aim : To investigate the influence of ghrelin on gastric emptying rate and meal‐related symptoms in idiopathic gastroparesis.

Methods : In six patients with idiopathic gastroparesis, a breath test was used to measure gastric emptying rates (t1/2) for solids and liquids after administration of saline or ghrelin 40 μg/30 min in a double‐blind, randomized fashion. At each breath sampling, the patient was asked to grade the intensity of six different symptoms (epigastric pain, bloating, postprandial fullness, nausea, belching and epigastric burning) and these were added to obtain meal‐related symptom severity score.

Results : Ghrelin significantly enhanced liquid emptying (t1/2: 86 ± 7 vs. 53 ± 6 min, P = 0.02) and tended to enhance solid emptying (144 ± 45 vs. 98 ± 15 min, P = 0.06). Ghrelin pre‐treatment significantly decreased cumulative meal‐related symptom score (196 ± 30 vs. 136 ± 23, P = 0.04) and individual scores for fullness (55 ± 8 vs. 39 ± 8, P = 0.02), and for pain (40 ± 8 vs. 16 ± 5, P < 0.05).

Conclusions : In idiopathic gastroparesis, administration of ghrelin enhances gastric emptying and improves meal‐related symptoms. These observations suggest a potential for ghrelin receptor agonists in the treatment of gastroparesis.
Comparison of the effects of intravenously and orally administered esomeprazole on acid output in patients with symptoms of gastro‐oesophageal reflux disease
Authors: METZ D. C. , MINER P. B. , HEUMAN D. M. , CHEN Y. , SOSTEK M.
Published: October 2005

Background : Intravenous esomeprazole may be beneficial for patients who cannot take oral medications.

Aim : To compare intravenous esomeprazole with oral esomeprazole for effects on maximal acid output during pentagastrin stimulation in patients with gastro‐oesophageal reflux disease symptoms.

Methods : In four separate open‐label, randomized, two‐way crossover studies, adult patients were administered esomeprazole 20 or 40 mg once daily either orally or intravenously (by 15‐min infusion or 3‐min injection) for 10 days and switched to the other formulation with no washout period. Basal acid output and maximal acid output were measured on days 11, 13 and 21.

Results : In the four studies (total of 183 patients), least‐squares mean maximal acid output ranged from 3.0 to 4.1 mmol/h after intravenous esomeprazole 40 or 20 mg and from 2.2 to 3.3 mmol/h after oral esomeprazole 20 or 40 mg. Differences between formulations were small and not statistically significant but did not meet the prospectively defined criterion for non‐inferiority of the intravenous formulation. Median basal acid output values ranged from 0.04 to 0.27 mmol/h after intravenous administration and from 0.05 to 0.25 mmol/h after oral esomeprazole.

Conclusions : Intravenous esomeprazole is an acceptable alternative to the oral formulation for treatment of up to 10 days of duration.
The effects of an acute serotonergic challenge on brain–gut responses in irritable bowel syndrome patients and controls
Authors: KILKENS T. O. C. , HONIG A. , FEKKES D. , BRUMMER R.‐J. M.
Published: October 2005

Background : Serotonin, a key denominator of the brain–gut axis is involved in the regulation of gastrointestinal function as well as cognition, mood and hypothalamic‐pituitary‐adrenal axis‐mediated neuroendocrine responses.

Aim : To assess the effects of an acutely increased serotonergic activity, using a 20 mg intravenous citalopram challenge test on visceral perception, affective memory performance, mood and neuroendocrine responses, respectively, in diarrhoea‐predominant irritable bowel syndrome patients and controls.

Methods : In a randomized, double‐blind crossover design, 14 diarrhoea‐predominant irritable bowel syndrome patients and 14 matched controls were studied under citalopram and placebo conditions, respectively. Visceral perception was scored in response to rectal distensions. Affective memory performance, mood, levels of adrenocorticotropic hormone, cortisol, prolactin and biochemical parameters of serotonergic metabolism were simultaneously assessed.

Results : Visceral perception did not significantly differ between the citalopram and placebo condition. Citalopram administration enhanced affective memory performance because of a bias towards positive material but no significant changes in mood. Citalopram significantly increased plasma serotonin, adrenocorticotropic hormone and cortisol levels compared with placebo. Citalopram did not differentially affect the patient or control group.

Conclusions : We have provided evidence that acutely increased serotonergic activity influences neuroendocrine responses and cognition in diarrhoea‐predominant irritable bowel syndrome and controls without a significant effect on visceral perception.
Systematic review: the chemoprevention of oesophageal adenocarcinoma
Authors: MEHTA S. , JOHNSON I. T. , RHODES M.
Published: October 2005

The incidence of oesophageal adenocarcinoma is increasing in the UK faster than any other malignancy. Despite its relatively poor prognosis and the limited success of existing treatments, there is enthusiasm that chemopreventive agents might be able to stem the transition from normal squamous epithelium to adenocarcinoma.

We discuss gastro‐oesophageal reflux as the main risk factor for the development of Barrett's metaplasia, the only known precursor of oesophageal adenocarcinoma. Treatment options for reflux disease are considered with regard to their effects on cancer risk. Recent advances in the molecular and cell biology of Barrett's are outlined, and potential targets for chemoprevention examined.

Available treatments for reflux disease have not convincingly altered the likelihood of cancer development. Epidemiological and animal studies support the use of non‐steroidal anti‐inflammatory drugs as potential chemopreventive agents. Dietary agents, however, have a more favourable side‐effect profile and may prove to be an attractive alternative, although more work is needed to fully explore this prospect.
Windy weather and low humidity are associated with an increased number of hospital admissions for acute pain and sickle cell disease in an urban environment with a maritime temperate climate
Authors: Jones Simon , Duncan Edward R. , Thomas Nikki , Walters Joan , Dick Moira C. , Height Susan E. , Stephens Adrian D. , Thein Swee Lay , Rees David C.
Published: October 2005

Sickle cell disease (SCD) is characterised by intermittent episodes of acute severe pain, related to vaso‐occlusion. Environmental factors are thought to play an important role, and studies in tropical countries have suggested that cold and rainy seasons are associated with increased episodes of acute pain. We have studied retrospectively the number of admissions with acute pain and SCD to King's College Hospital, London, together with daily meteorological records collected locally. Data from 1400 d and 1047 separate admissions were analysed. Increased admissions were significantly associated with increased wind speed and low humidity, but showed no relationship to temperature, rainfall or barometric pressure. The strongest effect was for (maximum wind speed)/humidity, with 464 admissions on days in the lowest two quartiles of this parameter and 582 in the highest quartiles. The effect of high wind and low humidity is likely to be related to skin cooling.
Evaluation of cytomegalovirus‐specific T‐cell reconstitution in patients after various allogeneic haematopoietic stem cell transplantation using interferon‐γ‐enzyme‐linked immunospot and human leucocyte antigen tetramer assays with an immunodominant T‐cell epitope
Authors: Ohnishi Mutsuko , Sakurai Toshiharu , Heike Yuji , Yamazaki Rie , Kanda Yoshinobu , Takaue Yoichi , Mizoguchi Hideaki , Kawakami Yutaka
Published: October 2005

Cytomegalovirus (CMV) infection is a major complication for patients who received allogeneic haematopoietic stem cell transplantation (HSCT). Accurate monitoring of CMV‐specific T‐cell reconstitution is required for appropriate decision on treatment, such as anti‐viral drugs, which have adverse effects. Although human leucocyte antigen (HLA) tetramer and interferon‐γ‐enzyme‐linked immunospot (IFN‐γ‐ELISPOT) assays have been used to measure CMV‐specific T cells, detailed comparison of these assays and kinetics of anti‐CMV T‐cell reconstitution between reduced‐intensity transplantation (RIST) and conventional HSCT has not yet been performed. In this study, we performed prospective comparative monitoring of CMV‐specific T cells using HLA tetramer and IFN‐γ‐ELISPOT assays with a single immunodominant CMV495 peptide in 28 HLA‐A*0201 and 9 HLA‐A*0206 patients after various allogeneic HSCTs. The IFN‐γ‐ELISPOT assay was more sensitive for evaluation of functional T cells than the HLA tetramer assay, and CMV‐specific T cells were reconstituted earlier in patients who received RIST without anti‐thymocyte globulin (ATG) than those receiving RIST with ATG or conventional HSCT. The threshold level for protection from CMV reactivation was estimated as over 1 × 106 cells/l peripheral blood with the IFN‐γ‐ELISPOT assay. These results demonstrate that the IFN‐γ‐ELISPOT assay with CMV495 provides more accurate evaluation on CMV immunity in HLA‐A*0201 and ‐A*0206 patients, and may be useful for determining timing of various treatments.
Milk–alkali syndrome is a major cause of hypercalcaemia among non‐end‐stage renal disease (non‐ESRD) inpatients
Authors: Picolos Michalis K. , Lavis Victor R. , Orlander Philip R.
Published: October 2005

Objective  Milk–alkali syndrome, once a common cause of hypercalcaemia, is now considered rare. Our aim was to estimate the prevalence of milk–alkali syndrome among hypercalcaemic, non‐end‐stage renal disease (non‐ESRD) inpatients of a University Hospital and identify patients’ and syndrome characteristics.

Design and patients  In this retrospective chart review study, we identified patients hospitalized with possible hypercalcaemia between November 1998 and October 2003 by a computer search of admission, discharge and consultation diagnoses. Patients with renal transplantation, stage 5 chronic kidney disease (CKD‐5) and those admitted for parathyroidectomy were excluded. The remaining patients’ charts were reviewed for confirmation of hypercalcaemia and identification of the cause. In patients with milk–alkali syndrome, additional historical, clinical, laboratory and imaging data were collected.

Results  We identified 125 patients with hypercalcaemia, 11 (8·8%) of whom had milk–alkali syndrome, 42 (33·6%) had malignancy and 37 (29·6%) hyperparathyroidism. Thirty‐five patients had severe hypercalcaemia, defined as corrected serum calcium  3·5 mmol/l. Malignancy accounted for 13 of those patients (37·1%) and milk–alkali for nine (25·7%). Conditions prevalent among the milk–alkali inpatients were female gender, hypertension, chronic kidney disease, osteoporosis, upper gastrointestinal diseases, diuretic treatment and vitamin D derivative supplementation. Five of the patients with milk–alkali syndrome were treated with bisphosphonates and all five developed hypocalcaemia, compared to one of the five who received conventional treatment (P = 0·047).

Conclusion  Milk–alkali was the third leading cause of hypercalcaemia of any degree and the second cause of severe hypercalcaemia among inpatients without ESRD. In milk–alkali syndrome, treatment with bisphosphonates contributes to post‐treatment hypocalcaemia.
An unusual distribution of supplemental teeth in the primary dentition
Authors: ROBERTS A. , BARLOW S. T. , COLLARD M. M. , HUNTER M. L.
Published: October 2005

Supernumerary teeth are more common in the permanent than the primary dentition [1]. In the latter, the majority occur in the maxillary lateral incisor region or as a mesiodens. Indeed, in one study conducted in the USA, all 26 cases of primary supernumerary teeth examined were found to be lateral incisors [2]. This report describes a case presenting with three erupted supernumerary (supplemental) teeth in the primary dentition, including, somewhat unusually, bilateral duplication of maxillary canines.
Cyclosporin‐induced gingival overgrowth in children
Authors: WRIGHT G. , WELBURY R. R. , HOSEY M. T.
Published: October 2005

Cyclosporin is a potent immunosuppressant drug commonly used to prevent organ transplant rejection. In recent years, there has been a widening of its therapeutic use and an increase in the number of patients undergoing transplantation. Gingival overgrowth is one of several oral side‐effects of cyclosporin, with a quoted prevalence of between 8% and 100%. There is continued debate over the factors which modify the degree of overgrowth, including individual sensitivity, age, dose of drug, duration of drug therapy and the presence of dental plaque. The exact mechanism of gingival overgrowth is still being debated, but appears to be caused by a combination of the proliferation of fibroblasts within the gingival tissue, an increase in the deposition of collagen and extracellular matrix, and a decrease in phagocytosis with a net gain in gingival tissue mass. A number of treatment options are utilized in the treatment of gingival overgrowth, including CO2 laser surgery, improved oral hygiene, the use of antibiotics such as metronidazole and azithromycin, and surgical intervention. In the clinical application of cyclosporin, there is little correlation between cyclosporin dose, serum trough levels and total exposure to the drug, making it difficult to achieve the desired therapeutic response. These problems were previously further complicated by the variability of absorption of the drug via the gastrointestinal tract. The original cyclosporin formulation, Sandimmune®, was replaced by a new formulation, Neoral®, which has a more reliable absorption, and gives a closer correlation between trough concentration levels and individual bioavailability. There is a conflict of opinion over whether or not the side‐effect profile of Neoral varies from its precursor Sandimmune. It has yet to be seen whether the increased bioavailability of Neoral will result in an increased severity and prevalence of gingival overgrowth. An alternative immunosuppressant drug, tacrolimus, which is a macrolide antibiotic with a different side‐effect profile, has emerged as a substitute for cyclosporin in organ transplantation. However, there have been conflicting reports of its side‐effects and its capacity to cause gingival overgrowth.
The VirE1VirE2 complex of Agrobacterium tumefaciens interacts with single‐stranded DNA and forms channels
Authors: Duckely Myriam , Oomen Clasien , Axthelm Fabian , Van Gelder Patrick , Waksman Gabriel , Engel Andreas
Published: October 2005

The VirE2 protein is crucial for the transfer of single‐stranded DNA (ssDNA) from Agrobacterium tumefaciens to the nucleus of the plant host cell because of its ssDNA binding activity, assistance in nuclear import and putative ssDNA channel activity. The native form of VirE2 in Agrobacterium's cytoplasm is in complex with its specific chaperone, VirE1. Here, we describe the ability of the VirE1VirE2 complex to both bind ssDNA and form channels. The affinity of the VirE1VirE2 complex for ssDNA is slightly reduced compared with VirE2, but the kinetics of binding to ssDNA are unaffected by the presence of VirE1. Upon binding of VirE1VirE2 to ssDNA, similar helical structures to those reported for the VirE2–ssDNA complex were observed by electron microscopy. The VirE1VirE2 complex can release VirE1 once the VirE2–ssDNA complexes assembled. VirE2 exhibits a low affinity for small unilamellar vesicles composed of bacterial lipids and a high affinity for lipid vesicles containing sterols and sphingolipids, typical components of animal and plant membranes. In contrast, the VirE1VirE2 complex associated similarly with all kind of lipids. Finally, black lipid membrane experiments revealed the ability of the VirE1VirE2 complex to form channels. However, the majority of the channels displayed a conductance that was a third of the conductance of VirE2 channels. Our results demonstrate that the binding of VirE1 to VirE2 does not inhibit VirE2 functions and that the effector–chaperone complex is multifunctional.
The flagellar hierarchy of Rhodobacter sphaeroides is controlled by the concerted action of two enhancer‐binding proteins
Authors: Poggio Sebastian , Osorio Aurora , Dreyfus Georges , Camarena Laura
Published: October 2005

The expression of the bacterial flagellar genes follows a hierarchical pattern. In Rhodobacter sphaeroides the flagellar genes encoding the hook and basal body proteins are expressed from σ54‐dependent promoters. This type of promoters is always regulated by transcriptional activators that belong to the family of the enhancer‐binding proteins (EBPs). We searched for possible EBPs in the genome of R. sphaeroides and mutagenized two open reading frames (ORFs) (fleQ and fleT), which are in the vicinity of flagellar genes. The resulting mutants were non‐motile and could only be complemented by the wild‐type copy of the mutagenized gene. Transcriptional fusions showed that all the flagellar σ54‐dependent promoters with exception of fleTp, required both transcriptional activators for their expression. Interestingly, transcription of the fleT operon is only dependent on FleQ, and FleT has a negative effect. Both activators were capable of hydrolysing ATP, and were capable of promoting transcription from the flagellar promoters at some extent. Electrophoretic mobility shift assays suggest that only FleQ interacts with DNA whereas FleT improves binding of FleQ to DNA. A four‐tiered flagellar transcriptional hierarchy and a regulatory mechanism based on the intracellular concentration of both activators and differential enhancer affinities are proposed.
BapA, a large secreted protein required for biofilm formation and host colonization of Salmonella enterica serovar Enteritidis
Authors: Latasa Cristina , Roux Agnès , Toledo‐Arana Alejandro , Ghigo Jean‐Marc , Gamazo Carlos , Penadés José R. , Lasa Iñigo
Published: October 2005

In environmental settings, biofilms represent the common way of life of microorganisms. Salmonella enterica serovar Enteritidis, the most frequent cause of gastroenteritis in developed countries, produces a biofilm whose matrix is mainly composed of curli fimbriae and cellulose. In contrast to other bacterial biofilms, no proteinaceous compound has been reported to participate in the formation of this matrix. Here, we report the discovery of BapA, a large cell‐surface protein required for biofilm formation by S. Enteritidis. Deletion of bapA caused the loss of the capacity to form a biofilm whereas the overexpression of a chromosomal copy of bapA increased the biofilm biomass formation. We provide evidence that overproduction of curli fimbriae and not cellulose can compensate for the biofilm deficiency of a bapA mutant strain. BapA is secreted through a type I protein secretion system (BapBCD) situated downstream of the bapA gene and was found to be loosely associated with the cell surface. Experiments with mixed bacterial populations positive or negative for BapA showed that BapA minus cells are not recruited into the biofilm matrix. The expression of bapA is coordinated with that of genes encoding curli fimbriae and cellulose, through the action of csgD. Studies on the contribution of BapA to S. Enteritidis pathogenesis revealed that orally inoculated animals with a bapA‐deficient strain survived longer than those inoculated with the wild‐type strain. Also, a bapA mutant strain showed a significantly lower colonization rate at the intestinal cell barrier and consequently a decreased efficiency for organ invasion compared with the wild‐type strain. Taken together, these data demonstrate that BapA contributes both to biofilm formation and invasion through the regular Salmonella infection route.
Brain activation responses to subliminal or supraliminal rectal stimuli and to auditory stimuli in irritable bowel syndrome
Authors: Andresen V. , Bach D. R. , Poellinger A. , Tsrouya C. , Stroh A. , Foerschler A. , Georgiewa P. , Zimmer C. , Mönnikes H.
Published: October 2005

Abstract  Visceral hypersensitivity in irritable bowel syndrome (IBS) has been associated with altered cerebral activations in response to visceral stimuli. It is unclear whether these processing alterations are specific for visceral sensation. In this study we aimed to determine by functional magnetic resonance imaging (fMRI) whether cerebral processing of supraliminal and subliminal rectal stimuli and of auditory stimuli is altered in IBS. In eight IBS patients and eight healthy controls, fMRI activations were recorded during auditory and rectal stimulation. Intensities of rectal balloon distension were adapted to the individual threshold of first perception (IPT): subliminal (IPT −10 mmHg), liminal (IPT), or supraliminal (IPT +10 mmHg). IBS patients relative to controls responded with lower activations of the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) to both subliminal and supraliminal stimulation and with higher activation of the hippocampus (HC) to supraliminal stimulation. In IBS patients, not in controls, ACC and HC were also activated by auditory stimulation. In IBS patients, decreased ACC and PFC activation with subliminal and supraliminal rectal stimuli and increased HC activation with supraliminal stimuli suggest disturbances of the associative and emotional processing of visceral sensation. Hyperreactivity to auditory stimuli suggests that altered sensory processing in IBS may not be restricted to visceral sensation.
Activation of peripheral 5‐HT4receptors attenuates colonic sensitivity to intraluminal distension
Authors: Greenwood‐van Meerveld B. , Venkova K. , Hicks G. , Dennis E. , Crowell M. D.
Published: October 2005

Abstract Tegaserod is a 5‐HT4receptor partial agonist approved for the treatment of irritable bowel syndrome in women with constipation and in both men and women with chronic constipation. The efficacy of tegaserod is based on the importance of 5‐HT4receptors regulating intestinal peristalsis and secretion, and possibly visceral sensory pathways. Our aim was to investigate the effect of tegaserod on colorectal sensitivity using models of normal and exaggerated responsiveness to colorectal distension (CRD). The visceromotor responses (VMR) to CRD at graded pressures (0–60 mmHg) were measured by the number of reflex abdominal contractions. Acute colorectal hypersensitivity was induced by intracolonic infusion of dilute acetic acid. Chronic hypersensitivity was observed in rats following spontaneous resolution of trinitrobenzenesulfonic acid‐induced colitis. Rats with normosensitive colons served as controls. Tegaserod (0.1–10 mg kg−1) caused dose‐dependent reduction of the VMR to CRD in control rats and in those with colonic hypersensitivity. 5‐HT4antagonists reversed the effects of tegaserod in rats with normosensitive colons, and partially inhibited effects in rats with colonic hypersensitivity. Central administration of tegaserod had no inhibitory effect. These results support the assumption that colonic hypersensitivity could be normalized by tegaserod acting, at least in part, through peripheral 5‐HT4receptors.
Efficacy of the R2 resistance gene as a component for the durable management of potato late blight in France
Authors: Pilet F. , Pellé R. , Ellissèche D. , Andrivon D.
Published: October 2005

Many race‐specific resistance genes to potato late blight are overcome in France, but the disease appears later on genotypes carrying the R2 gene. This study examined whether R2 could contribute to durable late‐blight control in France, and analysed the conditions of its performance. Plants grown from tubers of different physiological ages showed no difference in R2 expression in field and climate‐chamber experiments, demonstrating that the delay in epidemic onset provided by R2 was not the result of gene inactivation in old plants. Among isolates collected at one site, those virulent on R2 were classified into three AFLP profiles. AFLP‐VII comprised exclusively isolates virulent to R2, whereas AFLP‐IV and AFLP‐V included both virulent and avirulent isolates. No significant aggressiveness differences were observed between virulent and avirulent isolates from AFLP‐V; however, isolates from AFLP‐VII were significantly less aggressive than virulent isolates from AFLP‐V. These results indicate that: (i) the delayed onset of epidemics on R2 cultivars is the result of the breakdown of R2 by virulent isolates; (ii) aggressiveness of isolates virulent to R2 depends primarily on the genetic background of the pathogen where the mutation to virulence occurs; and (iii) this mutation does not lead per se to lower pathogenic fitness. It is suggested that R2 is unlikely to make a lasting contribution to late‐blight control in France, and that diversification strategies such as cultivar mixtures might not considerably increase its durability.
Identification of a defective molecule derived from DNA‐A of the bipartite begomovirus of East African cassava mosaic virus
Authors: Ndunguru J. , Legg J. P. , Fofana I. B. F. , Aveling T. A. S. , Thompson G. , Fauquet C. M.
Published: October 2005

Geminivirus defective interfering DNAs arise spontaneously in mechanically inoculated test plants, and have previously been found with DNA‐B of the bipartite cassava mosaic geminiviruses, but not DNA‐A. Reported here for the first time is the cloning and characterization of a naturally occurring truncated form of cassava mosaic geminivirus DNA‐A, which at 1525 nt is around half the expected full size. Sequence analysis has shown it to be a defective (df) form of East African cassava mosaic virus (EACMV) DNA‐A that has retained its cis elements essential for replication by the helper virus, and it has been termed df DNA‐A 15. Phylogenetic comparisons placed the df DNA‐A 15 molecule close to mild and severe isolates of EACMV‐UG2. Biolistic inoculation of Nicotiana benthamiana with infectious df DNA‐A 15 clone and East African cassava mosaic Cameroon virus (EACMCV) resulted in symptom amelioration as compared with EACMCV singly inoculated plants, and there was an accumulation of df DNA‐A 15 in systemically infected leaves. In addition, the level of EACMV DNA‐B accumulation was reduced in the coinoculated plants compared with those inoculated with EACMCV alone. PCR and sequence analysis confirmed the helper virus as EACMV.
Possible phytoplasma transovarial transmission in the psyllids Cacopsylla melanoneura and Cacopsylla pruni
Authors: Tedeschi R. , Ferrato V. , Rossi J. , Alma A.
Published: October 2005

The possible transovarial transmission of two phytoplasmas, ‘Candidatus Phytoplasma mali’ and ‘Candidatus Phytoplasma prunorum’, through their respective psyllid vectors Cacopsylla melanoneura and Cacopsylla pruni, was investigated. Different life stages of the progeny of infected female psyllids were analysed by PCR detection of phytoplasma DNA. While ‘Ca. Phytoplasma mali’ could not be detected in any of the C. melanoneura life stages tested, ‘Ca. Phytoplasma prunorum’ could be detected in eggs, nymphs and newly emerged adults of C. pruni. Infectivity tests using both nymphs and newly emerged adults of C. pruni showed that ‘Ca. Phytoplasma prunorum’ inherited from infected females can be transmitted to healthy plum plants. Although further validations are required, these findings open up new perspectives on the study of the epidemiology of diseases associated with European stone fruit yellows.
Hormonally controlled expression of the Arabidopsis MAX4 shoot branching regulatory gene
Authors: Bainbridge Katherine , Sorefan Karim , Ward Sally , Leyser Ottoline
Published: October 2005

The Arabidopsis MORE AXILLARY BRANCHING 4 (MAX4) gene is required for the production of a long‐range, graft‐transmissible signal that inhibits shoot branching. Buds of max4 mutant plants are resistant to the inhibitory effects of apically applied auxin, indicating that MAX4 is required for auxin‐mediated bud inhibition. The RAMOSUS 1 (RMS1) and DECREASED APICAL DOMINANCE 1 (DAD1) genes of pea and petunia, respectively, are orthologous to MAX4 and function in a similar way. Here we show that, despite the similarities between these three genes, there are significant differences in the regulation of their expression. RMS1 is known to be upregulated by auxin in the shoot, suggesting a straightforward link between the RMS1‐dependent branch‐inhibiting signal and auxin, whereas we find that MAX4 is only upregulated by auxin in the root and hypocotyl, and this is not required for the inhibition of shoot branching. Furthermore, both RMS1 and DAD1 are subject to feedback regulation, for which there is no evidence for MAX4. Instead, overexpression studies and reciprocal grafting experiments demonstrate that the most functionally significant point of interaction between auxin and MAX4 is post‐transcriptional and indeed post‐synthesis of the MAX4‐dependent graft‐transmissible signal.
The association between HLA class II haplotype with Graves' disease in Thai population
Authors: Wongsurawat T. , Nakkuntod J. , Charoenwongse P. , Snabboon T. , Sridama V. , Hirankarn N.
Published: October 2005

The distribution of HLA‐DRB1, ‐DQA1 and ‐DQB1 alleles were analysed in 124 Graves' disease (GD) patients compared to 124 normal controls in order to identify the alleles/haplotypes associated with GD in Thai population. The DRB1*1602‐DQA1*0102‐DQB1*0502 haplotype was significantly increased in GD patients (P = 0.0209, OR = 2.55). DRB1*07‐DQA1*0201‐DQB1*0201 haplotype (P = 0.039, OR = 0.32) and HLA‐DRB1*12‐DQA1*0601‐DQB1*0301 haplotype (P = 0.0025, OR = 0.28) were significantly decreased in GD patients. Interestingly, a protective DRB1*07 allele in Thai population lacks an arginine at position 74 similar to DRB1*0311 (a protective allele in Caucasians). A significant association of DRB1*1602‐DQA1*0102‐DQB1*0502 and HLA‐DRB1*12‐DQA1*0601‐DQB1*0301 alleles and haplotypes with GD was recently reported in Korean but not in any Caucasian studies. Thus, DRB1*1602 allele and closely linked haplotype, DRB1*1602‐DQA1*0102‐DQB1*0502, might serve as a marker for genetic susceptibility to GD in Asian population.
Generation of the B*41 group of alleles as indicated by intron sequences†
Authors: Martínez‐Laso J. , Moscoso J. , Zamora J. , Gómez‐Casado E. , Arnaiz‐Villena A.
Published: October 2005

The generation of the B*41 alleles has been analysed using exon 1, intron 1, exon 2, intron 2 and exon 3 sequences. Results showed that B*4102 may have been generated as the first B*41 allele by a recombination mechanism between B*400102 and B*0801 or B*4201 involving intron 2. B*4101, B*4104 and B*4107 alleles could have been generated from B*4102 by a gene conversion event taking three different fragments from sequences belonging to intron 2/exon 3 of B*45, B*50 or B*49 alleles. B*4105 and B*4106 could be generated from B*4101 allele by point mutations, and B*4103 generation is unclear due to the lack of intron 2. The importance of introns in HLA‐B allele polymorphism generation is stressed.
Mechanisms of inhibition by fluoride of urease activities of cell suspensions and biofilms of Staphylococcus epidermidis, Streptococcus salivarius, Actinomyces naeslundii and of dental plaque
Authors: Barboza‐Silva E. , Castro A. C. D. , Marquis R. E.
Published: October 2005

Background/aims:  Fluoride is known to be a potent inhibitor of bacterial ureases and can also act in the form of hydrofluoric acid as a transmembrane proton conductor to acidify the cytoplasm of intact cells with possible indirect, acid inhibition of urease. Our research objectives were to assess the inhibitory potencies of fluoride for three urease‐positive bacteria commonly found in the mouth and to determine the relative importance of direct and indirect inhibition of ureases for overall inhibition of intact cells or biofilms.

Methods:  The experimental design involved intact bacteria in suspensions, mono‐organism biofilms, cell extracts, and dental plaque. Standard enzymatic assays for ammonia production from urea were used.

Results:  We found that ureolysis by cells in suspensions or mono‐organism biofilms of Staphylococcus epidermidis, Streptococcus salivarius or Actinomyces naeslundii was inhibited by fluoride at plaque levels of 0.1–0.5 mm in a pH‐dependent manner. The results of experiments with the organic weak acids indomethacin and capric acid, which do not directly inhibit urease enzyme, indicated that weak‐acid effects leading to cytoplasmic acidification are also involved in fluoride inhibition. However, direct fluoride inhibition of urease appeared to be the major mechanism for reduction in ureolytic activity in acid environments. Results of experiments with freshly harvested supragingival dental plaque indicated responses to fluoride similar to those of S. salivarius with pH‐dependent fluoride inhibition and both direct and indirect inhibition of urease.

Conclusion:  Fluoride can act to diminish alkali production from urea by oral bacteria through direct and indirect mechanisms.
Quantification and detection of bacteria from postoperative maxillary cyst by polymerase chain reaction
Authors: Yamaura M. , Sato T. , Echigo S. , Takahashi N.
Published: October 2005

Background/aims:  Postoperative maxillary cyst (POMC) is known to occur as a delayed complication of radical maxillary sinus surgery, such as Caldwell‐Luc surgery. The cyst gradually expands with no symptoms over a period of years, and then occasionally causes swelling and pain in the buccal region and/or the mucogingival fold. It is probable that bacterial infection affects the progression of POMC symptoms. The aims of this study were to determine the bacterial density and to examine the presence of 20 oral bacteria in POMC fluids.

Methods:  POMC fluids (4 purulent, 2 mucous and 4 serous) were sampled from 10 subjects (aged 43–77 years). Bacterial quantification and detection were performed by real‐time polymerase chain reaction (PCR) and nested PCR based on bacterial 16S rRNA genes, respectively.

Results:  Bacterial DNA was detected in all samples and the average concentrations of bacterial DNA were 5.9 (purulent), 0.5 (mucous), and 0.7 (serous) ng/mg of sample. Twelve bacterial species, including anginosus streptococci, known to be associated with abscess formation, were detected in the purulent fluids, while two and five species were detected in the mucous and serous fluids, respectively.

Conclusion:  Purulent fluids contained numerous bacteria of various types, thus suggesting that oral bacteria may cause symptoms such as pain in POMC with purulent fluids. Mucous and serous fluids also contained bacteria, although their numbers were small, thus suggesting an association between bacteria and progression of POMC.
Effects of zinc and copper on adhesion and hemagglutination of Prevotella intermedia and Prevotella nigrescens
Authors: Tamura M. , Hirano Y. , Koruda K. , Kuwata F. , Hayashi K.
Published: October 2005

This study investigated the mechanism of protein attachment to the surface of the putative periodontal pathogens Prevotella intermedia and Prevotella nigrescens in artificial gingival crevicular fluid, and ways to increase protein attachment to the bacterial cells. The effects of cations on protein attachment, bacterial adhesion, and hemagglutination were examined, and cation‐binding components on both bacterial species were identified. The presence of cations, especially zinc, copper and cerium, increased attachment of human serum proteins to both bacterial species. In contrast, the presence of hydrophobic inhibitors or sugars had little effect. Protein attachment was reduced by heat treatment of the bacterial cells. Pretreatment of bacteria with human serum proteins inhibited adhesion of both species to buccal epithelial cells and hemagglutination. These effects were enhanced by the presence of zinc and copper during pretreatment. Using a chelating column, specific zinc‐ and copper‐binding proteins were identified on the surfaces of both bacterial species.
In vitro susceptibility of oral Candida to seven antifungal agents
Authors: Kuriyama T. , Williams D. W. , Bagg J. , Coulter W. A. , Ready D. , Lewis M. A. O.
Published: October 2005

The in vitro susceptibility of 618 Candida isolates to fluconazole, itraconazole, voriconazole, ketoconazole, miconazole, amphotericin B, and nystatin was determined. The isolates were obtained from 559 patients who had attended the UK dental hospital departments in Cardiff, Belfast, Glasgow or London. Antifungal susceptibility was assessed using a broth microdilution method following the National Committee for Clinical Laboratory Standards (NCCLS) M27‐A guidelines. The majority of the test strains were C. albicans (n = 521) with few of these being resistant to fluconazole (0.3%). A low incidence of fluconazole resistance (0–6.8%) was similarly evident with all non albicans species (Candida glabrata, 5 of 59 resistant; Candida krusei, 0 of 7 resistant; Candida tropicalis, 0 of 13 resistant; Candida parapsilosis, 0 of 12 resistant; other Candida species, 0 of 6 resistant). Voriconazole, ketoconazole, and miconazole also revealed high activity against both C. albicans and non albicans isolates, and 23.7% of C. glabrata isolates were found to be resistant to itraconazole. There was little difference in the antifungal susceptibilities of Candida isolated from patients who had a history of previous antifungal therapy compared with those who had not received antifungal treatment. In summary, this surveillance study of antifungal susceptibility of oral candidal isolates in the UK, through the collaboration of four dental hospitals, demonstrates that oral Candida species have a high level of susceptibilities to a range of antifungal agents.