bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiences of problems in individuals with hypersensitivity to odours and chemicals
Authors: Larsson Christel , Mårtensson Lena
Published: August 2010

Aim.  The purpose of the study was to describe how individuals with hypersensitivity to odours and chemicals handle their problems.

Background.  One group of patients we often encounter consists of those with upper and lower respiratory problems who also have a pronounced sensitivity to odours and chemicals. Earlier studies have shown that these symptoms can be related to sensory hyperreactivity (SHR). This hyperreactivity is characterised by respiratory tract symptoms triggered by odours and chemicals, along with high sensitivity to inhaled capsaicin and a positive score on the chemical sensitivity scale for SHR. However, there is still a lack of studies in which SHR sufferers describe their situations in their own words.

Design.  The study was conducted using a qualitative approach.

Methods.  Eight individuals with confirmed SHR were selected from a population‐based epidemiological study and interviewed. A qualitative content analysis was performed on the data.

Results.  Four themes emerged from the data analysis: Limitations in one’s life situation, Lack of understanding from others, Concern that the symptoms will develop into a serious disease and Disparagement of one’s own personal experience. The results show how individuals manage their daily lives with the help of various strategies, how they relate to other people, how they cope with their concerns and the fact that they sometimes choose to disparage their own experience of their problems.

Conclusion.  The results indicate that people with SHR experience limitations in their life situations. These limitations consist of the adjustments they make to avoid triggering factors.

Relevance to clinical practice.  To improve care, nurses need to know how people experience SHR and how they cope with their hypersensitivity to odours and chemicals.
Correlation between serum lipoprotein (a) and angiographic coronary artery disease in non‐insulin‐dependent diabetes mellitus
Authors: CÖMLEKÇI̊ A. , BI̊BEROG̈LU S. , KOZAN O. , BAHÇECI̊ O. , ERGENE O. , NAZLI C. , KINAY O. , GÜNER G.
Published: August 2010

Abstract.Comlekqi A, Biberoglu S, Kozan 0, Bahqeci 0, Ergene 0, Nazli C, Kinay 0, Guner G (Dokuz Eylul University, Medical School, Inciralti, Izmir, Turkey). Correlation between serum lipoprotein(a) and angio‐graphic coronary artery disease in non‐insulin‐dependent diabetes mellitus. J Intern Med 1997; 242:449‐54.

Objectives:To examine the impact of diabetic state on the concentrations of lipoprotein(a) [Lp(a)] in patients with non‐insulin‐dependent diabetes mellitus (NIDDM) and the correlation between angiographic coronary artery disease (CAD) and serum Lp(a) concentrations in NIDDM.

Design:In this cross‐sectional study of 26 patients with NIDDM and 19 nondiabetic sex‐ and agematched patients who underwent coronary angiography, CAD was assessed visually using coronary artery score (CAS), and plasma Lp(a) was measured by an enzyme‐linked immunosorbent assay.

Setting:The study was performed in an internal medicine clinic at a university hospital.

Subjects:Twenty‐six age‐ and sex‐matched patients with NIDDM and 19 control patients without diabetes.

Results:There was no significant difference between the Lp(a) concentrations of patientswith NIDDM and nondiabetic subjects (P > 0.05). When patients with NIDDM were stratified by absence or presence of CAD, patients with CAD had higher levels of Lp(a) (P < 0.05). However, there was no significant correlation between the concentrations of Lp(a) and CAS (P > 0.05).

Conclusions:Diabetic state does not have any impact on Lp(a) concentrations. Lp(a) excess seems to be atherogenic in patients with NIDDM as shown in nondiabetic patients in previous studies. Although diabetic patients with CAD have higher Lp(a) concentrations than the diabetic patients without CAD, Lp(a) levels were not correlated with CAS.
Major haemorrhagic complications during oral anticoagulant therapy in a Danish Population‐based cohort
Authors: STEFFENSEN F. H. , KRISTENSEN K. , EJLERSEN E. , DAHLERUP J. F. , SØRENSEN H. T.
Published: August 2010

Abstract. Steffensen FH, Kristensen K, Ejlersen E, Dahlerup JF, S~rensen HT (University of Aarhus and Aarhus University Hospital, Arhus, and Aalborg Hospital, Aalborg, Denmark). Major haemorrhagic complications during oral anticoagulant therapy in a Danish population‐based cohort. 1 Intern Med 199 7; 242: 497‐503.

Objectives: To estimate the incidence of bleeding leading to death or hospital admission in out‐patients treated with oral anticoagulants.

Design: Population‐based historical cohort study 1 January 1992 to 31 September 1994.

Setting: The County of North Jutland, Denmark (488 000 inhabitants).

Subjects: Six hundred and eighty‐two consecutive patients commencing oral anticoagulant therapy.

Main outcome measures: Fatal bleeding or bleeding demanding hospital admission.

Results: In 756 treatment‐years of follow‐up, there were 45 major haemorrhagic events (6.0 per 100 treatment‐years) in 42 patients, of which seven (0.9 per 100 treatment‐years) were fatal. The risk of a first major haemorrhagic episode was highest during the first 90 days of treatment compared with duration above one year (incidence rate ratio, IRR, 1.9; 95% CI, 0.8‐4.1). The rate was highest above the age of 60 years, 6.8 per 100 treatment‐years, compared with 2.9 per 100 treatment‐years below 60 years (IRR 2.3; 95% CI, 1.0–5.6). The rate for a bleeding event was slightly higher in females than in males (IRR 1.3; 95% CI, 0.7‐2.3), but did not vary according to type of anticoagulant drug.

Conclusions: The reported rates of major bleeding in this routine community setting implied a higher bleeding risk than was found in randomized trials or when patients are monitored in specialist anticoagulation clinics.
Cardiovascular autonomic neuropathy in insulin‐dependent diabetes mellitus: prevalence and estimated risk of coronary heart disease in the general population
Authors: May O. , Arildsen H. , Damsgaard E. M. , Mickley H.
Published: August 2010

Abstract.May O, Arildsen H, Damsgaard EM, Mickley H (Odense University Hospital, Odense, and Horsens Hospital, Horsens, Denmark). Cardiovascular autonomic neuropathy in insulin‐dependent diabetes mellitus: prevalence and estimated risk of coronary heart disease in the general population.J Intern Med2000;248:483–491.

Objectives.The aim of the study was to estimate the prevalence of cardiovascular autonomic neuropathy (CAN) in Type 1 diabetes mellitus in the general population and to assess the relationship between CAN and risk of future coronary heart disease (CHD).

Methods.The Type 1 diabetes mellitus population in the municipality of Horsens, Denmark, was delineated by the prescription method and a random sample of 120 diabetics aged 40–75 years was recruited. Type 1 diabetes mellitus was registered if fasting C‐peptide was below 0.30 nmol L−1. The E/I ratio was calculated as the mean of the longestR–Rinterval in expiration divided by the shortest in inspiration during deep breathing at 6 breaths min−1and taken to express the degree of CAN. A maximal symptom‐limited exercise test was carried out and the VA Prognostic Score, indicating risk of cardiovascular death or non‐fatal myocardial infarction, was computed. Additionally, the 10‐year risk of CHD was calculated using the Framingham model.

Results.A total of 84 people responded, of whom 71 had Type 1 diabetes mellitus. The E/I ratio was measured in 69 people. The prevalence of CAN expressed as an E/I ratio below the normal 5th percentile was 38%. The E/I ratio was significantly reduced in old age, long duration of diabetes, female gender, high fasting blood glucose, triglyceride, systolic blood pressure and urinary albumin excretion. A high risk of future CHD calculated using the Framingham model was associated with a low E/I ratio (r = − 0.39,P = 0.001). Exercise capacity, rise in systolic blood pressure and heart rate were positively correlated with the E/I ratio. A high VA Prognostic Score was correlated with a low E/I ratio (r = − 0.58,P < 0.0005). The risks estimated by the two models were significantly correlated (r = 0.60,P < 0.0005).

Conclusion.The prevalence of CAN in the 40–75‐year‐old Type 1 diabetes mellitus population is estimated to be 38%. CAN is associated with exercise test parameters and a coronary risk factor profile indicating a high risk of future CHD.
Twenty‐four hour ambulatory blood pressure in a population of elderly men
Authors: Björklund K. , Lind L. , Lithell H.
Published: August 2010

Abstract. Björklund K, Lind L, Lithell H (University of Uppsala, Uppsala, Sweden). Twenty‐four hour ambulatory blood pressure in a population of elderly men. J Intern Med 2000; 248: 503–512.

Objectives. The principal aim was to study ambulatory and office blood pressure in a population of elderly men. We also wanted to describe the prevalence of hypertension and investigate the blood pressure control in treated elderly hypertensives.

Design. A cross‐sectional study of a population of elderly men, conducted between 1991 and 1995.

Subjects. Seventy‐year‐old men (n = 1060), participants of a cohort study that began in 1970.

Main outcome measures. Office and 24 h ambulatory blood pressure.

Results. Average 24 h blood pressure in the population was 133 ± 16/75 ± 8 mmHg, and daytime blood pressure 140 ± 16/80 ± 9 mmHg. Corresponding values in untreated subjects (n = 685) were 131 ± 16/74 ± 7 and 139 ± 16/79 ± 8, respectively. An office recording of 140/90 mmHg corresponded to an ambulatory pressure of 130/78 (24 h) and 137/83 mmHg (daytime) in untreated subjects. In subjects identified as normotensives according to office blood pressure (n = 270), the 95th percentiles of average 24 h and daytime blood pressures were 142/80 and 153/85 mmHg, respectively. The prevalence of hypertension, defined as office blood pressure ≥ 140/90 mmHg, was 66%. Despite treatment, treated hypertensives (n = 285) showed higher office (157/89 vs. 127/76 mmHg) and 24 h ambulatory (138/78 vs. 122/71 mmHg) pressures than normotensives (P < 0.05). Fourteen per cent of the treated hypertensives had an office blood pressure < 140/90 mmHg.

Conclusions. Our results provide a basis for 24 h ambulatory blood pressure reference values in elderly men. The study confirms previous findings of a high prevalence of hypertension at older age. It also indicates that blood pressure is inadequately controlled in elderly treated hypertensives.
Growth hormone overproduction in a patient with multiple endocrine neoplasia type I
Authors: Hermans M. M. H. , Lips C. J. M. , Bravenboer B.
Published: August 2010

Abstract.  Hermans MMH, Lips CJM, Bravenboer B (Catharina Hospital Eindhoven, Eindhoven, and University Hospital Utrecht, Utrecht, the Netherlands). Growth hormone overproduction in a patient with multiple endocrine neoplasia type I (Case Report). J Intern Med 2000; 248: 527–532.

In a 69‐year‐old woman with a complicated history of multiple endocrine neoplasia type I (MEN 1), growth hormone overproduction was found without clinical features of acromegaly. Zollinger‐Ellison syndrome was diagnosed at the age of 36 years. Total gastrectomy and partial pancreatectomy were performed. Two years later hypercalcaemia occurred, hyperparathyroidism was suspected and three hyperplastic parathyroid glands were removed. In 1994 the plasma gastrin level was elevated and a computertomography of the abdomen revealed a 1.5‐cm large pancreatic tumour. Screening of the pituitary functions was unremarkable and a magnetic resonance scan of the pituitary gland showed no abnormalities. In 1995 type II diabetes mellitus was diagnosed. In 1997 basal plasma growth hormone levels were raised and plasma IGF‐I levels were alternately high and normal. The patient had no clinical signs of acromegaly, but glucose tolerance testing resulted in a paradoxical rise in growth hormone concentration compatible with the diagnosis of growth hormone overproduction. Magnetic resonance imaging of the pituitary gland revealed a microadenoma.
Evidence of a dynamic aldosterone‐independent distal tubular control of renal sodium excretion in compensated liver cirrhosis*
Authors: SANSOÈ G. , SILVANO S. , ROSINA F. , SMEDILE A. , RIZZETTO M.
Published: August 2010

Background and aim.  In preascitic cirrhosis increased sodium retention occurs in kidney distal tubule in spite of normal aldosterone plasma levels. No clearance technique can dissect the respective contribution to sodium retention exerted by Henle's loop, distal convoluted tubule and collecting duct, so we evaluated proximal and distal tubular sodium handling in preascites during two manoeuvres that temporarily increase aldosterone secretion.

Methods.  Ten patients with compensated cirrhosis and nine controls were studied in recumbency, during standing and after dopamine receptor blockade with metoclopramide through: 4 h renal clearances of sodium, potassium, lithium and creatinine; plasma levels of active renin and aldosterone.

Results.  Whilst comparable in recumbency, aldosterone levels significantly rose during standing and after metoclopramide in both groups. In patients, dopaminergic blockade caused a fall of distal sodium delivery (P < 0.01) but urinary sodium excretion was unchanged because the reabsorbed fraction of distal sodium delivery also fell (P < 0.03). Cirrhotic patients showed the same findings in the passage from recumbency to standing.

Conclusions.  In preascitic cirrhosis, the distal tubular segments of the nephron are able to cope with decreases in tubular flow by reducing reabsorption at an aldosterone‐independent site (possibly the loop of Henle).
Effects of 17β‐oestradiol plus different doses of drospirenone on adipose tissue, adiponectin and atherogenic metabolites in postmenopausal women
Authors: TANKÓ L. B. , CHRISTIANSEN C.
Published: August 2010

Objective.  To investigate how variation in the dose of the progestogen influence the impact of 17β‐oestradiol plus drospirenone (DRSP) treatment on adipose tissue and its secretor function with direct implications for atherogenic metabolites.

Design.  Randomized, double‐blind, placebo‐controlled trial.

Setting.  Primary care, single study site.

Subjects.  A total of 240 healthy postmenopausal women 53–65 years old, 178 completer.

Intervention.  Daily treatment with 1 mg 17β‐oestradiol plus 1, 2, or 3 mg DRSP, or placebo for 2 years.

Main outcome measures.  Absolute changes in central (CFM) and peripheral fat mass (PFM; dual‐energy X‐ray absorptiometry, DEXA), adipokines [interleukin (IL)‐6 and adiponectin], atherogenic metabolites [triglycerides, high‐density lipoprotein cholesterol (HDL‐C), glucose] and blood pressure.

Results.  Oestradiol plus 1 mg DRSP evoked significant decreases in CFM and the CFM/PFM ratio from baseline. These benefits virtually decreased with increasing dose of DRSP confounded by dose‐dependent increases in CFM and PFM in smokers (P‐value for trends <0.001), in whom the increases in bioavailable oestradiol were half of that in nonsmokers (P < 0.001). Treatment with 3 mg DRSP induced decreases in serum adiponectin by month 6 (P < 0.05), which persisted in nonsmokers only and led to significant increases in glucose and triglycerides and decreases in HDL‐C (P < 0.05). Adiponectin in smokers normalized by the end of the study parallel with the increases in body fat mass.

Conclusions.  Interactions of the sex steroids with adipose tissue and its secretor function are important determinants of the overall impact of hormone therapy on cardiovascular risk. A DRSP dose up to 2 mg does not seem to exert adverse effects when combined with 1 mg 17β‐oestradiol.
What will whole genome searches for susceptibility genes for common complex disease offer to clinical practice?
Authors: Lango H. , Weedon M. N.
Published: August 2010

In the developed world the majority of disease results from common, but complex disorders such as diabetes, obesity and cancer. Genetic variation explains a large proportion of an individual’s risk of developing these diseases; however, success in identifying the particular gene variants involved has been limited. Recent advances in high‐throughput genotyping technology, and a better understanding of the genetic architecture of complex disease has led to the development of genome‐wide association studies (GWA), which are providing novel and important insights into disease processes. The results from these studies could be of substantial clinical importance in the relatively near future. In this review, we present some recent, exciting findings from studies that have used the GWA approach, and discuss the clinical application of identifying disease susceptibility genes and variants.
Mitochondrial dysfunction as a cause of ageing
Authors: Trifunovic A. , Larsson N.‐G.
Published: August 2010

Mitochondrial dysfunction is heavily implicated in the ageing process. Increasing age in mammals correlates with accumulation of somatic mitochondrial DNA (mtDNA) mutations and decline in respiratory chain function. The age‐associated respiratory chain deficiency is typically unevenly distributed and affects only a subset of cells in various human tissues, such as heart, skeletal muscle, colonic crypts and neurons. Studies of mtDNA mutator mice has shown that increased levels of somatic mtDNA mutations directly can cause a variety of ageing phenotypes, such as osteoporosis, hair loss, greying of the hair, weight reduction and decreased fertility. Respiratory‐chain‐deficient cells are apoptosis prone and increased cell loss is therefore likely an important consequence of age‐associated mitochondrial dysfunction. There is a tendency to automatically link mitochondrial dysfunction to increased generation of reactive oxygen species (ROS), however, the experimental support for this concept is rather weak. In fact, respiratory‐chain‐deficient mice with tissue‐specific mtDNA depletion or massive increase of point mutations in mtDNA typically have minor or no increase of oxidative stress. Mitochondrial dysfunction is clearly involved in the human ageing process, but its relative importance for mammalian ageing remains to be established.
Quantitative determination of FtsA at different growth rates in Escherichia coli using monoclonal antibodies
Authors: Wang Haichao , Gayda Randall C.
Published: August 2010

FtsA is an essential cell division protein in Escherichia coli. Its synthesis in low amounts makes the investigation of its functions difficult. Partially purified FtsA protein was obtained by solubilizing cellular inclusion bodies after overexpression of the ftsA gene for the purpose of raising monoclonal antibodies. Mice were immunized with this FtsA protein fraction and their spleen cells were fused to Sp2/0‐AG14 mouse myeloma cells. Hybrid cells were screened and two clones were positively identified as FtsA monoclonal antibody producers by enzyme‐linked immunosorbent assay and Western blotting. A quantitative assay using these monoclonal antibodies indicated that the average number of FtsA molecules per cell to be between 50 and 200. However, the concentration of FtsA protein normalized to total cell protein was constant over a wide range of growth rates. This finding is in agreement with the hypothesized role of FtsA protein as a stoichiometric component of the septum.
RsaL provides quorum sensing homeostasis and functions as a global regulator of gene expression in Pseudomonas aeruginosa
Authors: Rampioni Giordano , Schuster Martin , Greenberg Everett Peter , Bertani Iris , Grasso Marco , Venturi Vittorio , Zennaro Elisabetta , Leoni Livia
Published: August 2010

The quorum sensing (QS) signalling system of Pseudomonas aeruginosa controls many important functions, including virulence. Although the production of the QS signal molecule N‐3‐oxo‐dodecanoyl‐homoserine lactone (3OC12‐HSL) is positively autoregulated, its concentration reaches a steady level long before stationary phase. The RsaL protein represses transcription of the lasI signal synthase gene, and thus reduces QS signal production. We show that RsaL binds simultaneously with LasR to the rsaL‐lasI bidirectional promoter thereby preventing the LasR‐dependent activation of both genes. In an rsaL mutant, 3OC12‐HSL production continues to increase throughout growth. Thus RsaL provides homeostasis by functioning in opposition to LasR and limiting 3OC12‐HSL production to a physiological concentration. Furthermore, transcription profiling revealed that RsaL regulates 130 genes independent of its effect on QS signal molecule production, including genes involved in virulence. We show that RsaL can repress pyocyanin and hydrogen cyanide virulence genes in two ways: directly, by binding to their promoters, and indirectly, by decreasing levels of the signals for their QS signal‐dependent transcription. These investigations highlight the importance of RsaL as a global regulator of P. aeruginosa physiology that provides a counterbalance to 3OC12‐HSL‐dependent gene activation via multiple mechanisms.
Experimental analysis of Helicobacter pylori transcriptional terminators suggests this microbe uses both intrinsic and factor‐dependent termination
Authors: Castillo Andrea R. , Arevalo Sonia S. , Woodruff Andrew J. , Ottemann Karen M.
Published: August 2010

In this study, we report experimental analysis of transcriptional terminators in the human pathogen Helicobacter pylori. Previous bioinformatics approaches came to differing conclusions regarding transcriptional termination in this bacterium. We used a reporter construct, the tnpR‐encoded resolvase, to assess terminators. In our first experiments, we found that a subset of previously predicted intrinsic terminators for H. pylori are functional. In our second experiments, we used an unbiased screen to identify putative terminators and then characterized 18 of these. We found that these putative terminators overlap genomic regions that are either intergenic or intragenic. Using reverse transcription PCR, we showed that an intergenic terminator and an intragenic antisense terminator function at their endogenous loci. Additionally, we found that putative terminators contain features of both intrinsic and Rho‐dependent termination, but that intrinsic terminators define the majority. We were unable to delete rho, however, in H. pylori, suggesting that it is essential and likely important. Finally, we carried out a mutational analysis of one of our randomly identified terminators that has both intrinsic and Rho‐dependent features, and found that they are both functional. In conclusion, we found that H. pylori possesses numerous Rho‐dependent and intrinsic terminators including some found in intragenic regions.
Multiple Ku orthologues mediate DNA non‐homologous end‐joining in the free‐living form and during chronic infection of Sinorhizobium meliloti
Authors: Kobayashi Hajime , Simmons Lyle A. , Yuan Daniel S. , Broughton William J. , Walker Graham C.
Published: August 2010

The bacterial non‐homologous end‐joining (NHEJ) apparatus is a two‐component system that uses Ku and LigD to repair DNA double‐strand breaks. Although the reaction mechanism has been extensively studied, much less is known about the physiological role of bacterial NHEJ. Recent studies suggest that NHEJ acts under conditions where DNA replication is reduced or absent (such as in a spore or stationary phase). Interestingly, genes encoding Ku and LigD have been identified in a wide range of bacteria that can chronically infect eukaryotic hosts. Strikingly, Sinohizobium meliloti, an intracellular symbiont of legume plants, carries four genes encoding Ku homologues (sku1 to sku4). Deletion analysis of the sku genes indicated that all Ku homologues are functional. One of these genes, sku2, is strongly expressed in free‐living cells, as well as in bacteroid cells residing inside of the host plant. To visualize the NHEJ apparatus in vivo, SKu2 protein was fused to yellow fluorescent protein (YFP). Ionizing radiation (IR) induced focus formation of SKu2‐YFP in free‐living cells in a dosage‐dependent manner. Moreover, SKu2‐YFP foci formed in response to IR in non‐dividing bacteroids, indicating that NHEJ system is functional even during the chronic infection phase of symbiosis.
Gac/Rsm signal transduction pathway of γ‐proteobacteria: from RNA recognition to regulation of social behaviour
Authors: Lapouge Karine , Schubert Mario , Allain Frédéric H.‐T. , Haas Dieter
Published: August 2010

In many γ‐proteobacteria, the conserved GacS/GacA (BarA/UvrY) two‐component system positively controls the expression of one to five genes specifying small RNAs (sRNAs) that are characterized by repeated unpaired GGA motifs but otherwise appear to belong to several independent families. The GGA motifs are essential for binding small, dimeric RNA‐binding proteins of a single conserved family designated RsmA (CsrA). These proteins, which also occur in bacterial species outside the γ‐proteobacteria, act as translational repressors of certain mRNAs when these contain an RsmA/CsrA binding site at or near the Shine‐Dalgarno sequence plus additional binding sites located in the 5′ untranslated leader mRNA. Recent structural data have established that the RsmA‐like protein RsmE of Pseudomonas fluorescens makes specific contacts with an RNA consensus sequence 5′‐A/UCANGGANGU/A‐3′ (where N is any nucleotide). Interaction with an RsmA/CsrA protein promotes the formation of a short stem supporting an ANGGAN loop. This conformation hinders access of 30S ribosomal subunits and hence translation initiation. The output of the Gac/Rsm cascade varies widely in different bacterial species and typically involves management of carbon storage and expression of virulence or biocontrol factors. Unidentified signal molecules co‐ordinate the activity of the Gac/Rsm cascade in a cell population density‐dependent manner.
Characterization of the metalloactivation domain of an arsenite/antimonite resistance pump
Authors: Ruan Xiang , Bhattacharjee Hiranmoy , Rosen Barry P.
Published: August 2010

The ArsAB extrusion pump encoded by the ars operon of Escherichia coli plasmid R773 confers resistance to the toxic trivalent metalloids arsenite [As(III)] and antimonite [Sb(III)]. The ArsA ATPase, the catalytic subunit of the pump, has two homologous halves, A1 and A2. At the interface of these two halves are two nucleotide‐binding domains and a metalloid‐binding domain. Cys‐113 and Cys‐422 have been shown to form a high‐affinity metalloid binding site. The crystal structure of ArsA shows two other bound metalloid atoms, one liganded to Cys‐172 and His‐453, and the other liganded to His‐148 and Ser‐420. The contribution of those putative metalloid sites was examined. There was little effect of mutagenesis of residues His‐148 and Ser‐420 on metalloid binding. However, a C172A ArsA mutant and C172A/H453A double mutant exhibited significantly decreased affinity for Sb(III). These results suggest first that there is only a single high‐affinity metalloid binding site in ArsA, and second that Cys‐172 controls the affinity of this site for metalloid and hence the efficiency of metalloactivation of the ArsAB efflux pump.
A mitochondrial topoisomerase IA essential for late theta structure resolution in African trypanosomes
Authors: Scocca Jane R. , Shapiro Theresa A.
Published: August 2010

Trypanosomes and Leishmania, protozoans that cause major human diseases, have a topologically intricate mitochondrial DNA (kinetoplast or kDNA) in the form of a network of thousands of interlocked circles. This unusual system provides a useful reporter for studying topoisomerase functions in vivo. We now find that these organisms have three type IA topoisomerases, one of which is phylogenetically distinctive and which we designate topoisomerase IAmt. In Trypanosoma brucei topoisomerase IAmt immunolocalizes within the mitochondrion close to the kDNA disk in patterns that vary with the cell cycle. When expression of TOPIAmt is silenced by RNAi there is a striking accumulation of kDNA late theta structure replication intermediates, with subsequent loss of kDNA networks and halt in cell growth. This essential enzyme provides clear molecular evidence for the obligatory role of a type IA enzyme in the resolution of late theta structures in vivo. With no close orthologue in humans it also offers a target for the rational development of selectively toxic new antiprotozoal therapies.
UV‐inducible cellular aggregation of the hyperthermophilic archaeon Sulfolobus solfataricus is mediated by pili formation
Authors: Fröls Sabrina , Ajon Malgorzata , Wagner Michaela , Teichmann Daniela , Zolghadr Behnam , Folea Mihaela , Boekema Egbert J. , Driessen Arnold J. M. , Schleper Christa , Albers Sonja‐Verena
Published: August 2010

The hyperthermophilic archaeon Sulfolobus solfataricus has been shown to exhibit a complex transcriptional response to UV irradiation involving 55 genes. Among the strongest UV‐induced genes was a putative pili biogenesis operon encoding a potential secretion ATPase, two pre‐pilins, a putative transmembrane protein and a protein of unknown function. Electron microscopy and image reconstruction of UV‐treated cells showed straight pili with 10 nm in diameter, variable in length, not bundled or polarized and composed of three evenly spaced helices, thereby clearly being distinguishable from archaeal flagella. A deletion mutant of SSO0120, the central type II/IV secretion ATPase, did not produce pili. It could be complemented by reintroducing the gene on a plasmid vector. We have named the operon ups operon for UV‐inducible pili operon of Sulfolobus. Overexpression of the pre‐pilins, Ups‐A/B (SSO0117/0118) in Sulfolobus resulted in production of extremely long filaments. Pronounced cellular aggregation was observed and quantified upon UV treatment. This aggregation was a UV‐dose‐dependent, dynamic process, not inducible by other physical stressors (such as pH or temperature shift) but stimulated by chemically induced double‐strand breaks in DNA. We hypothesize that pili formation and subsequent cellular aggregation enhance DNA transfer among Sulfolobus cells to provide increased repair of damaged DNA via homologous recombination.
Thyrotropin‐Releasing Hormone Potently Modulates Peristaltic Motor Activity of the Guinea Pig Small Intestine
Authors: Holzer P. , Pertl Ch. , Wolf G.
Published: August 2010

Thyrotropin‐releasing hormone (TRH) is present in enteric neurons of the guinea pig intestine, which indicates it may have a role in the control of gut motility. Isolated segments of the guinea pig duodenum‐jejunum and ileum were used to examine the effect of TRH on intestinal peristalsis. The peristaltic waves in the proximal small intestine were triggered at a higher intraluminal pressure and exhibited a higher frequency and a lower amplitude than those in the ileum. TRH (0.3–300 nM) induced a concentration‐related increase in the pressure threshold at which peristaltic waves were elicited and a moderate decrease in the amplitude of the peristaltic waves in both regions. However, while the frequency of the peristaltic waves was increased by the peptide in the ileum, it was diminished by TRH (0.3 and 3 nM) in the duodenum‐jejunum. Since the contractile effect of carbachol on the circular muscle of the duodenum‐jejunum remained unaffected by TRH, it appears that the peptide does not act on the muscle directly but influences peristalsis by acting on enteric neurons. The data further suggest that TRH released from enteric neurons may play a physiologic role in the regulation of propulsive motor activity of the gut.
[3H]Nitrendipine Binding to Rabbit Colonic Smooth Muscle
Authors: Hyman Paul E. , Hsu Chung T. , Jing Jennie , Tomomasa Takeshi , Kao Henry W. , Snape William J.
Published: August 2010

We used [3H] nitrendipine binding to isolated smooth muscle cells and isometric tension studies of muscle strips to characterize the calcium channels from rabbit proximal and distal colon. At 25°C [3H] nitrendipine binding was rapid, saturable, reversible, specific, and linearly proportional to cell number. The affinity of the ligand for its receptor was similar in proximal and distal colon (KD129 ± 21 pM and 124 ± 17 pM, respectively). In the proximal colon there were 68,000 receptors per cell, compared to 58,000 receptors per cell in the distal colon (p > .1). The Hill coefficient for nitrendipine was close to unity, suggesting binding to a single receptor. Although nitrendipine and nifedipine competitively inhibited [3H]nitrendipine binding, verapamil did not alter [3H] nitrendipine binding, suggesting the presence of at least two discrete, noninteracting sites for the binding of drugs that block calcium channels. In studies with muscle strips nitrendipine competitively inhibited isometric tension stimulated by both bethanechol and high extracellular potassium concentration. There were no significant differences in response from proximal and distal colon. These results suggest that calcium antagonist binding characteristics to calcium channels are similar in proximal and distal colon, and do not explain previously observed differences in the function of muscle in these tissues.
Central and Peripheral Actions of Adenosine and Its Analogues on Intestinal Myoelectric Activity and Propulsion in Rats
Authors: Fargeas M. J. , Fioramonti J. , Bueno L.
Published: August 2010

The effects of centrally and peripherally administered adenosine and its analogues on intestinal myoelectric activity were examined in conscious fasted and fed rats fitted with electrodes implanted in the duodenojejunal wall and a cannula in a lateral ventricle of the brain. The effects on small intestinal transit were evaluated in rats equipped with a duodenal catheter and killed 30 minutes after duodenal administration of a marker (Na51CrO4). In fasted rats intraperitoneal administration of adenosine and its analogues induced either a disrupted migrating myoelectric complex (MMC) pattern, which was replaced by irregular spike activity, or an inhibition of the MMC pattern, depending on the compound and dose. The change from a cyclic MMC pattern to continuous spike activity was correlated with an increase of intestinal propulsion, while inhibition of myoelectrical activity was characterized by a marked decrease in propulsion. Peripheral administration of adenosine and its analogues after a meal induced a short inhibition of intestinal myoelectric activity. In contrast, central administration, induced the reappearance of the MMC pattern, with an associated decrease in intestinal propulsion. It is concluded that adenosine and its analogues are able to modulate fed and fasted intestinal motor profiles at both peripheral and central levels and, as a result, the propulsion of intestinal contents.
Anticholinesterase Activity of Histamine H2‐Receptor Antagonists in the Dog: Their Possible Role in Gastric Motor Activity
Authors: Mizumoto Akiyoshi , Fujimura Masaki , Iwanaga Yuji , Miyashita Naoshi , Yoshida Naoyuki , Kondo Yoichi , Itoh Zen
Published: August 2010

We studied the anticholinesterase activity of three H2‐receptor antagonists (cimetidine, ranitidine, and famotidine) in vitro and in conscious dogs with chronically implanted strain‐gauge force transducers. In vivo, acetylcholine (ACh) was infused intravenously at a dose of 0.05 mg/(kg · min) for 5 minutes with or without a background continuous intravenous infusion of H2‐receptor antagonists or neostigmine during the quiescent period of the interdigestive state. Cimetidine and ranitidine enhanced the ACh‐induced contractions in a dose‐dependent manner in the gastric antrum, whereas famotidine did not. In vitro, the median inhibitory concentration (IC50) of the acetyl‐cholinesterase activity of ranitidine was 3.5 × 10−6M, and that of cimetidine 2.5 × 10−4M, whereas famotidine had no effect on cholinesterase activity even at concentrations up to 10−3M. The effects of a bolus intravenous injection of the three H2‐receptor antagonists on gastric motor activity also were examined in the digestive state. Cimetidine at 10.0 mg/kg and ranitidine at 3.0 mg/kg significantly increased gastric motor activity. This dose of ranitidine, however, sometimes caused the dogs to collapse and significantly decreased blood pressure in the anesthetized dogs. In conclusion, the H2‐receptor antagonists cimetidine and ranitidine enhanced gastric motor activity through the mechanism of their anticholinesterase activity, but further studies on gastric emptying and the circulatory system are needed.
Quantification of Resistance to Flow at the Esophagogastric Junction in Man
Authors: Mearin Fermin , Zacchi Paola , Arias Antonio , Malagelada Juan‐R.
Published: August 2010

Changes in resistance to flow at the esophagogastric junction contribute to the regulation of esophageal emptying and gastroesophageal reflux. To quantify esophagogastric resistance in man we have adapted our pneumatic resistometer, previously validated in the dog. The system is based on the measurement of nitrogen flow through a 5‐cm‐long polyurethane cylinder placed within the gut lumen and maintained electronically at a constant pressure gradient. In vitro experiments showed that the amplitude, length, and diameter of the constricted segment each contribute to resistance as measured by our instrument. In vivo studies performed on eight healthy volunteers showed that the esophagogastric junction was the place of maximal resistance in the gastroesophageal region. Intragastric resistance was also comparatively high whereas esophageal body resistance was negligible. Esophagogastric junction resistance was similar for antegrade and retrograde flow. During swallowing, it decreased to 10% of resting values. In three patients with achalasia, it was markedly increased and did not vary significantly during swallowing. We conclude that pneumatic resistometry accurately quantitates segmental resistance to flow in the esophagogastric region. Under normal conditions esophagogastric junction resistance exceeds gastric resistance and, hence, provides a gradient against gastroesophageal reflux. However, this resistance gradient between the junction and the stomach is much narrower than previously thought on the basis of manometric measurements.
Studies of Small Intestinal Myoelectrical Activity and Intraluminal Pressure Changes in the Unrestrained Conscious Rat
Authors: Arouni M. A. , Lof J. , Jacobs D. L. , Rikkers L. F. , Quigley E.M.M.
Published: August 2010

Our aim was to develop and validate a methodology to permit chronic recordings of small intestinal intraluminal pressure changes in the conscious rat and thereby to study regional variations in motor activity. A low‐flow (0.014 cc/min) perfusion system permitted reliable intraluminal pressure recordings at four sites along the small intestine from unrestrained animals. Comparison of overall patterns of fasted and fed motor activity and the various parameters of the migrating motor complex (MMC) from these recordings with those obtained from another group of animals prepared with serosal electrodes provided similar results in the proximal small intestine (MMC frequency 3.4 ± 0.5 vs. 3.9 ± 0.3 cycles/h, phase II duration 3.8 ± 0.7 vs. 4.7 ± 0.4 min, and phase III duration 4.0 ± 0.2 vs. 3.5 ± 0.2 min for duodenal catheters vs. electrodes, all NS). However, the distal deal phase II was considerably shorter in catheter than electrode recordings (6.0 ± 0.8 vs. 15.7 ± 2.4 min, p < 0.0001). Both methodologies confirmed significant regional variations in small intestinal motor parameters: the incidence of interdigestive myoelectrical complex (IDMEC) cycles was lower and phase II of the IDMEC was considerably prolonged in the distal Hewn. In summary, a system to permit chronic recordings of small intestinal intraluminal pressure has been developed and validated by comparison to myoelectrical recordings. Motor specialization was evident in the rat distal ileum.
Adrenergic Control of Interdigestive and Digestive Motility via the Pyloric Region
Authors: Holle G. E. , Milenov K. , Forth W.
Published: August 2010

This study examines the influence of an α‐adrenergic blocking drug, phentolamine, on inter digestive and digestive motility when given intraarterially, close to the pylorus. In seven mongrel dogs four extraluminal bipolar platinum electrodes and four strain‐gauge force transducers were placed at the antrum and proximal duodenum and three mini strain gauges and one electrode at the pyloric ring. After two migrating motor complexes (MMCs) were registered the drug was applied through a catheter inserted via the arteria gastroomentalis dextra to the pylorus, during phase I, the middle and end of phase II of the MMC, and 15 to 25 minutes after a meat meal. Local α‐adrenergic blockade of the pylorus caused immediate conversion of phase I to phase II of the MMC, with significant prolongation of phase II, broadening of antral and pyloric contractions, and in some animals giant contractions with vomiting and retching. The pyloric motility index in phase III increased up to 22%. It prolonged phase II by 237%. Phentolamine after the meat meal caused an increase in motility index, mainly in the pylorus, while the increase in contraction frequency was less pronounced. The results indicate inhibitory adrenergic control of the interdigestive motor pattern and digestive motility in the pyloric region.
Rat Colonic Motor Responses to Inflammatory Mediators In Vitro: A Poor Model for the Human Colon
Authors: Percy W. H. , Burton M. B. , Fallick F. , Burakoff R.
Published: August 2010

There is evidence that the rat colon exposed to trinitrobenzenesulfonic acid (TNBS) develops a colitis‐like inflammation which may be a model for inflammatory bowel disease (IBD) in humans. The aim of this study was to determine if the pharmacologic responses of the normal rat distal colon to several IBD‐associated inflammatory mediators were sufficiently similar to those of the normal human colon for the rat with TNBS‐induced colitis to provide an appropriate model for their effects on human colonic motility in IBD. Longitudinal and circular muscle mechanical properties were also investigated. Longitudinal muscle responded with concentration‐dependent contractions to histamine, leukotriene D4, and prostaglandins E2and F‐2α, which were mediated by a direct action. In general, circular muscle responses to these mediators were smaller, and in the cases of leukotriene D4and prostaglandin F2α, these were modulated by the concurrent activation of intrinsic inhibitory neurons. The mechanical properties of rat distal colonic longitudinal and circular muscle differed significantly from the equivalent human muscles. In most aspects studied normal rat distal colonic smooth muscles were at variance with previously reported properties of the equivalent human muscles. Thus the rat colon would be inappropriate as a model to study potential inflammatory mediator‐induced alterations of colonic motility in IBD.
Colonic and Cardiovascular Actions of the Atypical β‐Adrenergic Agonist SR 58611A in Rats
Authors: Croci Tiziano , Giudice Antonina , Bianchetti Alberto , Manara Luciano
Published: August 2010

Inhibition of colonic myoelectric activity by the new atypical β‐adrenergic agonist SR 58611A and its cardiovascular effects were investigated in orally dosed unanesthetized rats. SR 58611A and the reference compound ritodrine caused dose‐related reduction of the long spike burst frequency of the proximal colon (respective ED50values of 0.47 and 3.1 mg/kg); this was prevented by alprenolol but not by the β1‐ or β2‐selective adrenergic antagonists CGP 20712A and ICI 118,551. The minimal effective doses of SR 58611A and ritodrine raising heart rate were about 20 and 3 times their respective ED50values for inhibition of colonie motility. Ritodrine, unlike SR 58611A, caused a dose‐dependent increase in heart rate. Blood pressure was not affected by either drug. There was partial tolerance to the intestinal effects of SR 58611A and ritodrine, which fell by about half after 4 days' treatment but no further after 8 days. In the animal model investigated, SR 58611A was less liable than ritodrine to induce cardiovascular side effects. It should thus be of prospective therapeutic interest for intestinal hypermotility disorders.
Introduction of conventional microbial flora to germfree rats increases the frequency of migrating myoelectric complexes
Authors: HUSEBYE E. , HELLSTRÖM P. M. , MIDTVEDT T.
Published: August 2010

The present study demonstrates a direct stimulating influence of the viable conventional microbial flora on fasting myoelectric activity of the small intestine. Ten germfree AGUS rats were operated upon within sterile stainless steel isolators. Three bipolar electrodes were implanted into the muscular wall of the proximal small intestine, and fasting myoelectric recordings were performed one week later. Subsequently, the rats were transferred to the external conventional environment, and caecel content from conventional AGUS rats was given perorally and rectally. One week later, when the intestinal tract was colonized, myoelectric recordings were repeated. The frequency of activity fronts in proximal jejunum increased after introduction of conventional intestinal microflora, reflected by a decrease of the interval between activity fronts from median 17.6 min (15.2–23.4 min) (10th and 90th percentiles) to 13.9 min (11.4–17.6 min) (P < 0.05). The duration of activity fronts in proximal jejunum decreased from 4.9 min (3.8–5.9 min) to 3.6 min (3.2–3.9 min), respectively (P < 0.05). The propagation velocity of activity fronts was not significantly different. Stimulation of the fasting motility in the small intestine by conventional microbial flora may reflect activation of a physiological defense response in the host, in order to restrict bacterial colonization and avoid bacterial overgrowth of the small intestine.
Cisapride does not modify equine gastrointestinal motility disrupted byE. coliendotoxin or prostaglandin E2
Authors: KING J. N. , GERRING E. L.
Published: August 2010

Cisapride, E.coli endotoxin and prostaglandin E2were administered intravenously to ponies in which strain gauges had been attached to the stomach and proximal jejunum in order to test if cisapride could modify motility patterns induced by endotoxin or PGE2‐ Endotoxin at a dose of 0.1 μg kg−1and PGE2at a dose of 10 μg kg−1produced decreases in gastric motility and jejunal phase‐II motility with short intervals between jejunal phase‐Ill‐activity fronts. Cisapride at a dose of 0.2 mg kg1increased gastric motility and jejunal phase‐II activity with increased intervals between jejunal phase‐III‐activity fronts when given alone, but did not modify the motor effects of endotoxin or PGE2. Cisapride may be ineffective in improving gastrointestinal motility in clinical cases of equine ileus caused by endotoxaemia.
Development and validation of microcomputer analysis of gastric and small‐bowel manometry
Authors: WALDRON B. , SMITH D. , STOREY B. E. , WHITE G. , CAMPBELL F. C.
Published: August 2010

A novel microcomputer method for analysis of gastric and small‐bowel motility was developed for recognition and measurement of inter‐digestive migrating motor complexes (MMC) and associated features as well as fed‐state contraction characteristics. Facilities for removal of signal artefacts were also provided. This microcomputer method was validated against observer findings in 24‐h ambulatory gastric and small‐bowel motility studies of six volunteers. No significant differences were found between microcomputer and observer motility analysis relating to MMC number, MMC migration velocity, fed‐state contraction characteristics or artefact recognition. This method provides an accurate automated method for measurement of gastric and small‐bowel motor physiology.