bluuebunny/crossref_metadata_2025 huggingface dataset:
Binding properties of antagonists to Cannabinoid receptors in intact cells
Authors: Wennerberg Marie , Cheng Leifeng , Hjorth Stephan , Clapham John C. , Balendran Anudharan , Vauquelin Georges
Published: June 2010

The implication of the cannabinoid receptor 1 (CB1receptor) in several pathophysiological states has sparked the development of selective antagonists. Here we compare binding of the antagonists [3H]‐AZ12491187, [3H]‐taranabant and [3H]‐rimonabant to intact human embryonic kidney cells stably expressing recombinant human CB1receptors (CB1r cells). Unlabelled ligands decreased the total binding of the three radioligands with closely the same order of potency: i.e. AZ12288553 ∼ AZ12491187 ∼ taranabant > rimonabant. Nondisplaceable (i.e. nonspecific) binding to the CB1r cells was the same as total binding to the wells containing untransfected cells and it was more pronounced for [3H]‐AZ12491187 and [3H]‐rimonabant than for [3H]‐taranabant. [3H]‐Rimonabant and (to a lesser extent) [3H]‐AZ12491187 were also prone to bind nonspecifically to the walls of the wells. Compared to the other radioligands, [3H]‐rimonabant displayed lower potency for the CB1receptors in saturation binding studies and faster association and dissociation in kinetic experiments. When dissociated, the three radioligands also showed prominent rebinding to the cells in medium only. This could be relieved by the presence of excess of unlabelled ligand and of bovine serum albumin (BSA) but a combination thereof was most efficient. The long ‘residence time’ of AZ12491187 at the CB1receptor (because of slow dissociation and prominent rebinding) and its pronounced incorporation into the membranes of the cells could contribute to long‐lasting in vivo CB1receptor blockade.
Gender and the renin–angiotensin–aldosterone system
Authors: Komukai Kimiaki , Mochizuki Seibu , Yoshimura Michihiro
Published: June 2010

Premenopausal women are protected to some extent from cardiovascular and kidney diseases. Because this protection weakens after menopause, sex hormones are believed to play an important role in the pathogenesis of cardiovascular and kidney diseases. The cardiovascular system and the kidneys are regulated by the renin–angiotensin–aldosterone system (RAAS), which in turn, appears to be regulated by sex hormones. In general, oestrogen increases angiotensinogen levels and decreases renin levels, angiotensin‐converting enzyme (ACE) activity, AT1 receptor density, and aldosterone production. Oestrogen also activates counterparts of the RAAS such as natriuretic peptides, AT2 receptor density, and angiotensinogen (1‐7). Progesterone competes with aldosterone for mineralocorticoid receptor. Less is known about androgens, but testosterone seems to increase renin levels and ACE activity. These effects of sex hormones on the RAAS can explain at least some of the gender differences in cardiovascular and kidney diseases.
L'Asie est‐elle sur la voie de la flexicurité?
Authors: VANDENBERG Paul
Published: June 2010

Face à la concurrence mondiale, de nombreux pays optent pour la flexicurité, ce qui permet aux employeurs d'embaucher et de licencier avec plus de flexibilité tout en aidant les travailleurs à passer d'un emploi à l'autre. L'étude de six pays d'Asie montre que la Chine et la République de Corée ont mis en œuvre cette flexicurité; Singapour et la Malaisie y adhèrent à certains égards, mais sans l'assurance chǒmage; l'Inde et le Sri Lanka ont introduit peu de réformes et opèrent toujours sur la base d'un système traditionnel de sécurité d'emploi à la charge de l'employeur. Pour aider les travailleurs du secteur informel, les gouvernements de la Chine, de l'Inde et du Sri Lanka ont recours à des programmes de travaux publics, d'emploi indépendant et de formation professionnelle.
L'insécurité de l'emploi et ses conséquences pour les salariés: l'effet modérateur de la dépendance envers l'emploi
Authors: SORA Beatriz , CABALLER Amparo , PEIRÓ José María
Published: June 2010

La mondialisation et l'intensification de la concurrence internationale ont provoqué l'apparition de formes d'emploi flexibles et une précarisation de l'emploi. Le sentiment d'insécurité chez les salariés produit des effets sur leurs attitudes et leurs intentions que les auteurs se proposent d'examiner. Après un tour d'horizon des travaux de recherche sur la théorie du stress et la relation existant entre insécurité de l'emploi et ses conséquences, ils testent, sur un échantillon de 942 salariés d'Espagne, deux hypothèses. La première est que l'insécurité de l'emploi présente, d'une part, une corrélation négative avec la satisfaction au travail et l'engagement envers l'organisation et, d'autre part, une corrélation positive avec l'intention de quitter l'organisation; et la seconde, qu'il existe une interaction entre l'insécurité de l'emploi, le besoin économique et l'employabilité qui influe sur la prédiction de ces résultats.
Coǔt de la réglementation du travail et lacunes de l'indicateur «Doing Business»: l'exemple de l'Afrique du Sud
Authors: BENJAMIN Paul , BHORAT Haroon , CHEADLE Halton
Published: June 2010

L'indicateur «Embauche des travailleurs» de la base de donnée de la Banque mondiale «Doing Business», enquěte de 2006, a présenté des résultats mitigés sur le contenu et la portée de la réglementation du travail en Afrique du Sud. Les auteurs indiquent que ces mesures – avec leur vision étroite de la législation – ne fournissent qu'une image incomplète de la réglementation du travail. Ils proposent et étudient trois extensions possibles à la structure de «Doing Business», notamment: la «microlégislation», les institutions du marché du travail et l'interprétation jurisprudentielle. Ils concluent par un plaidoyer pour leur prise en compte dans l'évaluation du cadre réglementaire du travail.
Les pactes de non‐concurrence après l'emploi aux Etats‐Unis: cadre juridique et comportements sur le marché
Authors: Hannah Richard L.
Published: June 2010

En réponse aux changements fondamentaux du marché qui donnent au travail un rǒle beaucoup plus central sur le marché concurrentiel des produits, les employeurs cherchent souvent à prolonger leur contrǒle sur le capital humain au‐delà de la fin de la relation d'emploi. Bien que les études empiriques sur le sujet soient rares, le recours aux pactes de non‐concurrence après l'emploi semble répandu. Mais jusqu'où les employeurs peuvent‐ils légalement restreindre la liberté de leurs anciens salariés? L'auteur examine les arguments que les tribunaux ont considérés aux Etats‐Unis pour équilibrer les intérěts économiques légitimes des employeurs, l'efficacité du marché du travail, et la liberté et la mobilité des travailleurs après leur emploi.
La légalisation de l'emploi occasionnel en Hongrie
Authors: Tésits Róbert , Szenoradszki Endre
Published: June 2010

En Hongrie, à l'origine, la loi sur l'emploi occasionnel de 1997 visait à légaliser, en appliquant une procédure simplifiée, les relations d'emploi des particuliers en tant qu'employeurs. Après maintes utilisations abusives, cette forme d'emploi très souple est toutefois étendue à tous les employeurs, avec notamment une augmentation du nombre de jours de travail autorisés, une réduction drastique des cotisations de sécurité sociale et d'importants avantages fiscaux. Les objectifs étaient ainsi de réduire le chǒmage et l'incidence du travail illicite en repoussant les limites de l'emploi formel, mais aucun n'a été atteint. Au contraire, selon les auteurs, la tentative de flexicurité a considérablement augmenté la vulnérabilité des travailleurs.
Type I receptor binding of bone morphogenetic protein 6 is dependent on N‐glycosylation of the ligand
Authors: Saremba Stefan , Nickel Joachim , Seher Axel , Kotzsch Alexander , Sebald Walter , Mueller Thomas D.
Published: June 2010

Bone morphogenetic proteins (BMPs), together with transforming growth factor (TGF)‐β and activins/inhibins, constitute the TGF‐β superfamily of ligands. This superfamily is formed by more than 30 structurally related secreted proteins. The crystal structure of human BMP‐6 was determined to a resolution of 2.1 Å; the overall structure is similar to that of other TGF‐β superfamily ligands, e.g. BMP‐7. The asymmetric unit contains the full dimeric BMP‐6, indicating possible asymmetry between the two monomeric subunits. Indeed, the conformation of several loops differs between both monomers. In particular, the prehelix loop, which plays a crucial role in the type I receptor interactions of BMP‐2, adopts two rather different conformations in BMP‐6, indicating possible dynamic flexibility of the prehelix loop in its unbound conformation. Flexibility of this loop segment has been discussed as an important feature required for promiscuous binding of different type I receptors to BMPs. Further studies investigating the interaction of BMP‐6 with different ectodomains of type I receptors revealed that N‐glycosylation at Asn73 of BMP‐6 in the wrist epitope is crucial for recognition by the activin receptor type I. In the absence of the carbohydrate moiety, activin receptor type I‐mediated signaling of BMP‐6 is totally diminished. Thus, flexibility within the binding epitope of BMP‐6 and an unusual recognition motif, i.e. an N‐glycosylation motif, possibly play an important role in type I receptor specificity of BMP‐6.
Influence of nanostructure on charge transport in RuO2 thin films
Authors: Steeves M. M. , Lad R. J.
Published: June 2010

Polycrystalline thin films of RuO2 were grown on fused-quartz substrates and a parametric study was carried out to probe the influence of film nanostructure on the four-point Van der Pauw resistivity and Hall coefficient. The films were grown via reactive rf magnetron sputtering of a Ru target in an Ar∕O2 plasma using deposition rates from 0.27to3.5Å∕s and substrate temperatures from 16to500°C. Room-temperature resistivities of the RuO2 films ranged from 58to360μΩcm. Upon first heating following deposition, some films showed decreasing resistivity with increasing temperature, but the resistivities also decreased upon subsequent cooling suggesting that the annealing treatment reduces the film defect density. The temperature coefficient of resistance was found to be small (<0.001K−1) in agreement with previous investigations. Hall coefficient measurements of the polycrystalline thin films demonstrated that either n-type or p-type majority carriers can be present depending on deposition conditions and the resulting nanostructure, in contrast to single-crystal RuO2, which is an n-type metal. Grain size and homogeneous strain within the films were measured by x-ray diffraction and are correlated to the majority carrier type.
Photoluminescence properties of SrAl2O4:Eu2+,Dy3+ thin phosphor films grown by pulsed laser deposition
Authors: Ntwaeaborwa O. M. , Nsimama P. D. , Pitale Shreyas , Nagpure I. M. , Kumar Vinay , Coetsee E. , Terblans J. J. , Swart H. C. , Sechogela P. T.
Published: June 2010

Thin films of SrAl2O4:Eu2+,Dy3+ phosphor were deposited on silicon [Si (100)] substrates using a 248 nm KrF pulsed laser. Deposition parameters, such as substrate temperature, pulse repetition rate, number of laser pulses, and base pressure, were varied during the film deposition process. Based on the x-ray diffraction data, all the films were amorphous but were emitting visible light when excited by a monochromatic xenon lamp. The chemical composition and the stoichiometry of the films determined by the Rutherford backscattering spectroscopy were consistent with the commercial SrAl2O4:Eu2+,Dy3+ powder used to prepare the films. Photoluminescence (PL) emission spectra of the films were characterized by major green emission with a maximum at ∼520 nm and minor red emission with a maximum at 630 nm. The green and red photoluminescence at 520 and 630 nm are associated with the 4f65d→4f7(S87/2) and D50-F72 transitions of Eu2+ and residual Eu3+ ions, respectively. Brighter films were shown to have relatively higher values of the root mean square surface roughness, which were determined from the atomic force microscopy data. The effects of processing parameters on the PL intensity are discussed.
Vacuum system of the 3 GeV Taiwan photon source
Authors: Chen J. R. , Hsiung G. Y. , Chang C. C. , Chen C. L. , Chan C. K. , Cheng C. M. , Yang C. Y. , Wu L. H. , Hsueh H. P.
Published: June 2010

The design and a prototype of the vacuum system of a low-emittance 3 GeV synchrotron light source, the Taiwan photon source (TPS) (with circumference of 518.4 m), are described. The TPS vacuum system has low-outgassing aluminum beam ducts, a low-impedance structure, an oil-less pumping system, and oil-less fabrication. Little dust, a stable mechanical structure, and highly reliable components are achieved for this vacuum system. A prototype (length 14 m) of the TPS vacuum system was fabricated. Two bending-magnet chambers, 4 m long, were made with computer-numerical control machining and lubricated with ethanol to protect the aluminum surface from oil contamination. Cleaning with ozonized water was applied to decrease the rate of photostimulated desorption from the chamber surfaces. Then an automatic welding system is used to implement the side welding seams of bending chambers. The design considerations, the critical factors in fabrication, and the test results of the vacuum system prototype are presented.
Synergistic Ag (111) and Cu (111) texture evolution in phase-segregated Cu1−xAgx magnetron sputtered composite thin films
Authors: Filoti D. I. , Bedell A. R. , Harper J. M. E.
Published: June 2010

The authors investigated the texture and microstructure evolution of Cu1−xAgx composite thin films through x-ray diffraction pole figures as a function of composition for x≤0.5. As codeposited at room temperature by magnetron sputtering, the fcc nanocomposite Cu1−xAgx forms a phase-segregated thin film, when the Ag volume fraction represents more than 15 at. % up to 50 at. %, and a single phase thin film when the Ag volume fraction represents less than 15 at. %. Comparison between texture evolutions of Cu (111) and Ag (111) in phase-segregated Cu–Ag thin films and Cu (111) and Ag (111) in the same thickness pure copper or silver thin films shows that texture selection in each phase evolves in two different modes during microstructure evolution. First, a stronger perpendicular (111) fiber texture is obtained in the phase-segregated films than in the pure Cu or Ag films. Second, biaxial crystallographic alignment is observed for the Ag component that develops an in-plane alignment of Ag (200) related to the deposition direction. By the use of transmission electron microscopy we found that development of Cu (111) and Ag (111) textures does not correlate to the in-plane grain size differences observed for the different compositions of Cu1−xAgx thin films.
Study on Ohmic contact improvement of organic Schottky diode utilizing self-assembled monolayer and PEDOT:PSS layers
Authors: Kwon Jungmin , Seol Y. G. , Lee Nae-Eung , Chung IlSub
Published: June 2010

The authors fabricated organic Schottky diode using ink-jet print, where 6,13-bis(triisopropyl-silylethynyl) pentacene (TIPS-pentacene) was used as an active layer. As for a reference diode, they also fabricated pentacene Schottky diodes on the polyethersulfone substrate by evaporating pentacene as an active layer. Alternatively, the Ohmic contact variations due to the presence of either self-assembled monolayer or Poly(3,4–ethylenedioxythiophene):polystyrenesulfonate acid (PEDOT:PSS) layer was also investigated using the evaporated pentacene Schottky diode. They found that pentacene Schottky diode with PEDOT:PSS layer yielded the best rectifying behavior in terms of the contact voltage, forward bias current, and rectifying ratio. In this study, Au was used to form Ohmic contact, while Al was used to form Schottky contact with either pentacene or TIPS-pentacene.
Hydrogen-dominated plasma, due to silane depletion, for microcrystalline silicon deposition
Authors: Howling A. A. , Sobbia R. , Hollenstein Ch.
Published: June 2010

Plasma conditions for microcrystalline silicon deposition generally require a high flux of atomic hydrogen, relative to SiHα=0→3 radicals, on the growing film. The necessary dominant partial pressure of hydrogen in the plasma is conventionally obtained by hydrogen dilution of silane in the inlet flow. However, a hydrogen-dominated plasma environment can also be obtained due to plasma depletion of the silane in the gas mixture, even up to the limit of pure silane inlet flow, provided that the silane depletion is strong enough. At first sight, it may seem surprising that the composition of a strongly depleted pure silane plasma consists principally of molecular hydrogen, without significant contribution from the partial pressure of silane radicals. The aim here is to bring some physical insight by means of a zero-dimensional, analytical plasma chemistry model. The model is appropriate for uniform large-area showerhead reactors, as shown by comparison with a three-dimensional numerical simulations. The SiHα densities remain very low because of their rapid diffusion and surface reactivity, contributing to film growth which is the desired scenario for efficient silane utilization. Significant SiHα densities due to poor design of reactor and gas flow, on the other hand, would result in powder formation wasting silane. Conversely, hydrogen atoms are not deposited, but recombine on the film surface and reappear as molecular hydrogen in the plasma. Therefore, in the limit of extremely high silane depletion fraction (>99.9%), the silane density falls below the low SiHα densities, but only the H radical can eventually reach significant concentrations in the hydrogen-dominated plasma.
Fabrication of vertically aligned Si nanowires on Si (100) substrates utilizing metal-assisted etching
Authors: Hong Junki , Kim Kyohyeok , Kwon Namyong , Lee Jaehyun , Whang Dongmok , Chung Ilsub
Published: June 2010

Vertically aligned Si nanowires were fabricated utilizing a metal-assisted chemical etching scheme using a thin anodic aluminum oxide (AAO) template formed on (100) Si substrate. The diameter and length of the obtained Si nanowires were about 55 and 340 nm, respectively, when the thickness of the AAO template was about 600 nm. The diameters and shapes of the Si nanowires were determined by the hole size and shape of the Ag mesh on the AAO template. In addition, the lengths of the vertical Si nanowires depended on both the AAO thickness and the Ag film thickness.
Electron microscopy characterization of hexagonal molybdenum trioxide (MoO3) nanorods
Authors: Ramana C. V. , Troitskaia I. B. , Atuchin V. V. , Ramos M. , Ferrer D.
Published: June 2010

A simple low-temperature chemical method to produce metastable hexagonal phase molybdenum oxide (h-MoO3) nanorods and their excellent structural characteristics has been demonstrated. In this approach, h-MoO3 samples were prepared by precipitating molybdenum oxide from an ammonium paramolybdate solution by the adding nitric acid. The structure of h-MoO3 nanorods was examined in detail using high-resolution scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HR-TEM). The SEM data reveal that the nanorod h-MoO3 crystals have the shape of straight hexagonal rods with an aspect ratio ∼60. The HR-TEM results confirm the hexagonal structure of the MoO3 nanocrystals. Computations of the observed TEM data along with x-ray diffraction pattern further confirm the stability of the nanostructure of h-MoO3 rods.
Study of silicon strain in shallow trench isolation
Authors: Belyansky M. , Klymko N. , Conti R. , Chidambarrao D. , Liu F.
Published: June 2010

Raman spectroscopy has been used as a primary tool to measure silicon strain on shallow trench isolation (STI) test structures. Different STI dielectric gap fill materials have been evaluated as well as the effect of tensile and compressive STI liners on silicon strain. It has been shown that both intrinsic stress of thin film dielectric material and STI structure type affect strain in silicon. Ways of generating high stress in silicon are discussed including the effect of the STI chemical vapor deposition liner material on Si strain. Strain simulation data are found to be in reasonably good agreement with the active area silicon. Advantages and limitations of Raman based strain metrology in the semiconductor industry are delineated. The findings have been confirmed electrically on metal-oxide-semiconductor field effect transistor devices with tensile and compressive strains in the STI region. An improvement in p-type field-effect transistor performance has been demonstrated for silicon on insulator devices with tensile dielectric in STI.
Infinitely high etch selectivity during CH2F2/H2 dual-frequency capacitively coupled plasma etching of silicon nitride to chemical vapor-deposited a-C
Authors: Kim J. S. , Kwon B. S. , Heo W. , Jung C. R. , Park J. S. , Shon J. W. , Lee N.-E.
Published: June 2010

For fabrication of a multilevel resist (MLR) structure with silicon nitride (Si3N4) and amorphous carbon (a-C) layers, highly selective etching of the Si3N4 layer using a chemical vapor-deposited (CVD) a-C etch mask was investigated by varying the following process parameters in CH2F2/H2/Ar plasmas: etch gas flow ratio, high-frequency source power (PHF), and low-frequency source power (PLF) in a dual-frequency superimposed capacitively coupled plasma etcher. The results of etching the ArF photoresist/bottom antireflective coating/SiOx/CVD a-C/Si3N4 MLR structure showed the possibility of obtaining an infinitely high selective etch process for the Si3N4 layer using a thin CVD a-C etch mask for high aspect-ratio pattern formation. The CH2F2/H2 gas flow ratio was found to play a critical role in determining the process window for infinite Si3N4/CVD a-C etch selectivity, due to the change in the degree of polymerization on Si3N4 and CVD a-C surfaces.
Resistivity characteristics of transparent conducting impurity-doped ZnO films for use in oxidizing environments at high temperatures
Authors: Nomoto Jun-ichi , Konagai Manabu , Miyata Toshihiro , Minami Tadatsugu
Published: June 2010

The behavior of resistivity in transparent conducting Al-doped ZnO (AZO) and Ga-doped ZnO (GZO) thin films, prepared with the same thickness under the same deposition conditions by dc magnetron sputtering, was investigated for use in oxidizing environments at high temperatures. These thin films with thicknesses in the range from 100 to 3000 nm were prepared on glass substrates at a temperature of 200 °C. The increase in resistivity of GZO thin films over long-term testing at 85% relative humidity and 85 °C was lower than that of AZO thin films, while, in contrast, that of AZO thin films over long-term testing at 90% relative humidity and 60 °C was lower than that exhibited by GZO. The moist-resistant tests showed that both AZO and GZO thin films prepared with a thickness above 500 nm were suitable for transparent electrode applications used in thin-film solar cells. The resistivity increase of GZO thin films after heat treatment for 30 min in air at a temperature up to 400 °C was lower than that of AZO thin films. The resistivity of both GZO and AZO thin films prepared with a thickness above 200 nm was stable for heat tests at 300 °C. The heat-resistant tests demonstrated that both GZO and AZO thin films were suitable for use as a transparent electrode for thin-film solar cells. The resistivity increase after testing was found to exhibit two different mechanisms: a decrease of both carrier concentration and Hall mobility mainly attributable to grain boundary scattering as well as a decrease of carrier concentration mainly attributable to ionized impurity scattering. This difference in resistivity behavior is mainly attributed to the grain size associated with the crystallinity of deposited films.
Serotonergic Neurons Mediate Dyskinesia Side Effects in Parkinson’s Patients with Neural Transplants
Authors: Politis Marios , Wu Kit , Loane Clare , Quinn Niall P. , Brooks David J. , Rehncrona Stig , Bjorklund Anders , Lindvall Olle , Piccini Paola
Published: June 2010

Two patients with Parkinson’s disease, successfully treated with fetal tissue transplants more than a decade ago, developed troublesome involuntary movements, which could be treated with a serotonin receptor agonist.
Diffuse oesophageal spasm: diagnosis by ambulatory 24 hour manometry
Authors: Barham C P , Gotley D C , Fowler A , Mills A , Alderson D
Published: June 2010

Background—Diffuse oesophageal spasm (DOS) is a potential cause of intermittent chest pain and/or dysphagia. In the past, the diagnosis of DOS has relied on criteria obtained from standard oesophageal manometry (more than one simultaneous contraction in a series of 10 wet swallows with the rest being peristaltic). As symptoms are intermittent, however, 24 hour manometry may well be more suited to its investigation.

Aims—To determine the ability of 24 hour manometry to detect the symptomatic contractions of DOS and to compare standard, laboratory based manometry with 24 hour manometry in its diagnosis.

Patients—Three hundred and ninety consecutive patients referred with suspected oesophageal disorders.

Methods—Standard laboratory based manometry and 24 hour outpatient manometry.

Results—Sixteen patients were classified by 24 hour manometry as having DOS on the basis of painful contractions (spasms) of excessive duration and increased amplitude. Laboratory based manometry failed to detect the majority of these patients with DOS (14/16), and 53/55 were incorrectly labelled as having DOS on the basis of asymptomatic manometric findings.

Conclusion—The detection of symptomatic DOS requires 24 hour manometry.
Rectal cell proliferation and colon cancer risk in patients with hypergastrinaemia
Authors: Renga M , Brandi G , Paganelli G M , Calabrese C , Papa S , Tosti A , Tomassetti P , Miglioli M , Biasco G
Published: June 2010

Background—The influence of gastrin on the colonic mucosa is still uncertain. Some authors have suggested a stimulating effect on the growth of normal and malignant colonic epithelium, while others have shown no association between gastrin and neoplastic development.

Aims—To evaluate the effect of gastrin on colorectal cell proliferation, patients with chronic endogenous hypergastrinaemia underwent proctoscopy. Biopsy specimens were taken in order to study rectal cell kinetics.

Patients and controls—Ten patients with chronic autoimmune gastritis (CAG), six patients with Zollinger-Ellison syndrome (ZES), and 16 hospital controls took part in this study. Patients with CAG and ZES had basal serum gastrin concentrations significantly higher than controls (p<0.001).

Methods—Immunohistochemistry was performed on 3 μm sections of rectal biopsy specimens incubated with 5′-bromodeoxyuridine.

Results—The percentage of proliferating cells in the entire crypts (overall labelling index) was similar in all the groups. However, the labelling frequency in the upper two fifths of the glands (φh value) was significantly higher in patients with CAG or ZES compared with controls (p<0.01 in both patient groups versus controls).

Conclusions—Endogenous hypergastrinaemia is associated with rectal cell proliferation defects, similar to those observed in conditions at high risk for colon cancer. The effect of the increased serum concentrations of gastrin on the colorectal mucosa after treatment with drugs inhibiting gastric acid secretion should be investigated.
Gastrointestinal transit and prolonged ambulatory colonic motility in health and faecal incontinence
Authors: Herbst F , Kamm M A , Morris G P , Britton K , Woloszko J , Nicholls R J
Published: June 2010

Background—Colonic motor function has not been studied in the ambulatory setting over a prolonged period in the unprepared state. Furthermore, the disturbance of this function in patients with faecal incontinence is unknown.

Aim—To study colonic function over two to three days in the ambulatory, unprepared state in health and in patients with idiopathic faecal incontinence.

Methods—Six healthy women and six women with faecal incontinence and a structurally intact anal sphincter ingested a dual radioisotope meal, and had a six sensor, solid state manometric probe colonoscopically inserted into the left colon. Scanning was performed until radioisotope left the gut and pressure was recorded for a median of 44 hours.

Results—Three of six patients showed abnormal gastric emptying. Patients showed no disturbance of colonic radioisotope transit. Controls had a median of 12, whereas patients had a median of 16, high amplitude propagated waves per 24 hours. In three patients urge incontinence was associated with high amplitude (up to 500 cm water) propagated waves which often reached the rectum. These high pressure waves were identical to those occuring in healthy subjects, the only difference being the lack of adequate sphincter response. Passive incontinence was not associated with colonic motor activity. Defaecation in all subjects was associated with identical propagated waves, and distal movement of 13% (median) of right colonic content and excretion of 32% from the left colon and rectum. The urge to defaecate was associated with either propagated waves (45%) or non-propagated contractions (55%). Rectal motor complexes were recorded in both groups of subjects, but similar rhythmic activity was also recorded in the sigmoid and descending colon.

Conclusions—Normal colonic function consists of frequent high pressure propagated waves. Rhythmic activity occurs both proximal to and in the rectum. Defaecation is characterised by high pressure propagated waves associated with coordinated anal sphincter relaxation. Patients with faecal incontinence may have a widespread disturbance of gut function. Urge incontinence, an urge to defaecate, and defaecation can all be associated with identical high amplitude propagated pressure waves.
Association between genetic polymorphism of the pepsinogen C gene and gastric body ulcer: the genetic predisposition is not associated with Helicobacter pylori infection
Authors: Ohtaki Y , Azuma T , Konishi J , Ito S , Kuriyama M
Published: June 2010

Background and aims—The genetic trait plays a part in the pathogenesis of peptic ulcer disease. To identify a DNA marker for peptic ulcer disease, the association between the restriction fragment length polymorphism (RFLP) of the pepsinogen C (PGC) gene and peptic ulcer disease was investigated.

Patients and methods—One hundred and seventy seven unrelated controls, 75 patients with gastric ulcer, and 70 with duodenal ulcer were studied. PGC-RFLP was analysed by polymerase chain reaction (PCR), and the association between PGC-RFLP and peptic ulcer disease was examined. The relation between the genetic association of PGC polymorphism with peptic ulcer and Helicobacter pyloriinfection was also examined.

Results—Four alleles, 480 (allele 1), 450 (allele 2), 400 (allele 3), and 310 bp (allele 4), were detected by PCR. The frequency of allele 4 was significantly higher in patients with gastric body ulcer than in controls (χ2=9.92, p<0.005). Genotypes containing allele 4 were significantly more frequent in patients with gastric body ulcer than in controls and patients with gastric angular or antral ulcer. The relative risk of gastric body ulcer associated with the presence of allele 4, compared with its absence, was 4.63 and was statistically significant (χ2=14.84, p<0.005). There were no significant differences in the allelic frequencies between H pyloripositive and H pylori negative groups in controls, patients with gastric body ulcer, or patients with gastric angular or antral ulcer. Both in H pylori negative and H pylori positive cases, there was an increased frequency of allele 4 in patients with gastric body ulcer compared with controls.

Conclusions—These results suggest that there is a significant association between this genetic polymorphism at the PGC gene locus and gastric body ulcer. There are differences in the genetic aetiology between gastric body ulcer and gastric angular or antral ulcer. PGC-RFLP may be used as a genetic marker for a genetic predisposition to gastric body ulcer; this genetic predisposition is not associated with H pylori infection.
Severe upper gastrointestinal polyposis associated with sparse colonic polyposis in a familial adenomatous polyposis family with an APC mutation at codon 1520
Authors: Leggett B A , Young J P , Biden K , Buttenshaw R L , Knight N , Cowen A E
Published: June 2010

Background—Familial adenomatous polyposis usually results in colonic polyposis with hundreds to thousands of polyps, congenital hypertrophy of the retinal pigment epithelium (CHRPE), and variable extracolonic features. Recent reports indicate that patients with distal mutations between codons 1445 and 1578 do not express CHRPE and have a high incidence of desmoid tumours.

Patients—The family studied has an unusual phenotype of sparse colonic polyposis but profuse upper gastrointestinal polyposis. Affected subjects do not have CHRPE.

Methods—The protein truncation test followed by sequencing identified a 2 base pair deletion at codon 1520 in the APC gene. This results in a frameshift creating a stop codon 13 codons downstream.

Results—This family demonstrates that sparse colonic polyposis but severe upper tract polyposis may be associated with mutations between codons 1445 and 1578.

Conclusions—Study of duodenal and colonic polyps in further cases with mutations in this region is warranted. Such mutations may preferentially cause duodenal adenomas and desmoid tumours as somatic mutations in these tumours also occur in this region, unlike colorectal tumours where somatic mutations occur more proximally. This study emphasises the importance of screening the upper gastrointestinal tract even when the colonic disease is mild.
Are complications of endoscopic sphincterotomy age related?
Authors: Deans G T , Sedman P , Martin D F , Royston C M S , Leow C K , Thomas W E G , Brough W A
Published: June 2010

Background—Endoscopic retrograde cholangiopancreatography sphincterotomy is increasingly performed in younger patients undergoing laparoscopic cholecystectomy. However, the safety of endo- scopic sphincterotomy in this age group, relative to that in older patients, is unknown.

Aim—To determine whether the development of short term complications following endoscopic sphincterotomy is age related.

Patients and methods—A prospective multicentre audit of 958 patients (mean age 73, range 14–97, years) undergoing a total of 1000 endoscopic sphincterotomies.

Results—Two deaths occurred, both from postsphincterotomy acute pancreatitis. Postprocedural complications developed in 24 patients: pancreatitis in 10, ascending cholangitis in seven, bleeding in four, and retroperitoneal perforation in three. There were six complications (five cases of pancreatitis and one bleed; 2.2%) and no deaths in the 281 (29.3%) patients aged under 65 years. In comparison, 18 (2.6%) of the 677 patients aged over 65 years developed a complication (cholangitis in seven, pancreatitis in five, bleeding in three, and perforation in three). Patients under 35, 45, 55, and 65 years were not at significantly increased risk of complication than those over these ages (relative risk for those under compared with those over 65 years 0.83, 95% confidence intervals 0.41–1.67, p=0.74).

Conclusion—Short term complications following endoscopic sphincterotomy are not related to age. Younger patients undergoing laparoscopic cholecystectomy need not be denied endoscopic sphincterotomy for fear that the risks are greater than if they undergo surgical exploration of the common bile duct.
Liposome mediated gene transfer into the rat oesophagus
Authors: Schmid R M , Weidenbach H , Draenert G F , Liptay S , Lührs H , Adler G
Published: June 2010

Background—Cancer of the oesophagus has so far eluded every attempt at pharmacological treatment. The recent advent of somatic gene therapy offers a new therapeutic approach to malignant tumours.

Aim—To investigate whether and how gene transfer into the oesophagus can be achieved.

Methods—A LacZ reporter gene was used as marker and transferred into the oesophagus of rats using cationic liposomes. Gene transfer was achieved by either luminal instillation into a closed segment using a double balloon catheter, or by intramural injection through a needle. Expression of β-galactosidase was monitored in the oesophagus and various control tissues by histochemistry, polymerase chain reaction (PCR), reverse transcriptase PCR, and Southern blotting.

Results—Up to 100 days after in vivo gene transfer β-galactosidase activity could be demonstrated in the oesophagus. Following luminal application, the transgene was expressed in epithelial cells whereas intramural injection induced preferential expression in fibroblasts.

Conclusion—In vivo gene transfer into the oesophagus is feasible and safe, and the route of administration largely determines cell type specificity. This novel approach will enable in vivo studies of growth, differentiation, and malignant transformation in the oesophagus, and may open new avenues to the confinement of oesophageal malignancies.
Oesophageal motor responses to gastro-oesophageal reflux in healthy controls and reflux patients
Authors: Anggiansah A , Taylor G , Marshall R E K , Bright N F , Owen W A , Owen W J
Published: June 2010

Aims—To compare oesophageal motor responses to gastro-oesophageal reflux (GOR) in 16 healthy controls (group 1) and 25 reflux patients, 15 without (group 2) and 10 with (group 3) oesophagitis.

Methods—All subjects underwent 24 hour ambulatory oesophageal pH measurements (5 cm above the lower oesophageal sphincter (LOS)) combined with pressure monitoring (5, 10, and 15 cm above the LOS for oesophageal body motility and 27 cm above the LOS for voluntary swallow detection). Contraction patterns (peristaltic, simultaneous, isolated, mixed type, and non-transmitted swallows) and peristaltic contraction wave characteristics (amplitude, duration, and velocity) during GOR were compared in the three groups.

Results—The average number of motor activities per minute was significantly higher in group 1 (p<0.05). In all groups, the most common motor contraction pattern was peristaltic. The percentage of peristaltic activity per subject was significantly higher in group 1 (p<0.05). There were no significant differences in other contraction patterns among the three groups (p>0.05). Of the peristaltic contraction wave characteristics there were no significant differences in any parameters (amplitude, duration, and velocity) among the three groups (p>0.05). The average pH increment in response to motor activities was significantly higher in group 1 (p<0.05).

Conclusions—Motor responses to GOR were found to be predominantly primary peristaltic in all groups. During GOR, reflux patients have less frequent activity, a smaller proportion of activity is peristaltic, and the average pH increment in response to motor activities is reduced compared with controls.
Endoscopic screening of relatives of patients with colorectal cancer
Authors: Hunt L M , Rooney P S , Hardcastle J D , Armitage N C
Published: June 2010

Background—The risk of colorectal cancer is higher among relatives of those affected. The neoplastic yield reported from screening such individuals varies enormously between studies and depends on the age and strength of the family history of those screened.

Aims—To ascertain the neoplastic yield of endoscopic screening of first degree relatives of patients with colorectal cancer by age and familial risk.

Subjects—A total of 330 individuals with a family history of colorectal cancer.

Method—Endoscopic screening conducted according to a protocol.

Results—Adenomas were found in 12%, and adenomas larger than 1 cm in 8%, of “high risk” individuals screened primarily by colonoscopy. Of those with neoplasia, 26% had lesions at or proximal to the splenic flexure. Neoplasia was found in 9.5% of individuals at lower familial risk, screened primarily by 60 cm flexible sigmoidoscopy, 4% of whom had neoplasia larger than 1 cm in size or cancer. Neoplastic yield was greatest in the fourth and fifth decades in those at highest risk, but increased with age in those at lower risk.

Conclusions—For individuals with two or more first degree relatives, or relatives who have developed colorectal cancer at a young age, colonoscopy appears to be the only satisfactory method of screening, but 60 cm flexible sigmoidoscopy may be useful in those at lower levels of risk.
Use of mesalazine slow release suppositories 1 g three times per week to maintain remission of ulcerative proctitis: a randomised double blind placebo controlled multicentre study
Authors: Marteau P , Crand J , Foucault M , Rambaud J-C
Published: June 2010

Background—Daily administration of rectal formulations of mesalazine is effective in preventing relapse of ulcerative proctitis. Maintenance of remission with lower doses would be an advantage.

Aim—The efficacy of mesalazine suppositories (Pentasa) 1 g three times a week v placebo to maintain remission in patients with cryptogenetic proctitis was studied.

Methods—Ninety five patients with cryptogenetic proctitis were randomised within two weeks of remission to receive for one year or until relapse three suppositories per week of either Pentasa (n=48) or placebo (n=47). In the case of a relapse, the patients received one suppository/day.

Results—It was found that 25 of 48 subjectsv 18 of 47 remained in remission in the mesalazine and placebo groups respectively. The relapse rate was lower in the mesalazine group for the following time intervals: 0–90 days (19%v 38%, p=0.035), 0–180 days (29% v 54%, p=0.017), 0–270 days (38% v 60%, p=0.031), and 0–365 days (48% v 62%, p=0.18). Treatment of relapse with one suppository/day induced remission in 11 of 18 and 2 of 26 patients in the mesalazine and placebo groups respectively (p=0.001). Overall, 61%v 28% patients remained in the protocol and were in remission at one year (p=0.001). Tolerance was good.

Conclusion—Mesalazine suppositories 1 g three times a week are effective for preventing relapses of cryptogenetic proctitis. Increasing the dose to 1 g/day is effective in a high proportion of subjects who relapsed.
Increased immunoglobulin G production by short term cultured duodenal biopsy samples from HIV infected patients
Authors: Schneider T , Zippel T , Schmidt W , Pauli G , Wahnschaffe U , Chakravarti S , Heise W , Riecken E O , Zeitz M , Ullrich R
Published: June 2010

Background—Secretory immunity is a major defence mechanism against infections at mucosal surfaces which are common in HIV infected patients.

Aims—To analyse intestinal immunoglobulin production in HIV infection in comparison with that in saliva and serum.

Patients and methods—Immunoglobulin G (IgG), A (IgA), and M (IgM) concentrations were determined in supernatants of short term cultured duodenal biopsy samples, serum, and saliva from HIV infected patients (n = 28) and controls (n = 14) by radial immunodiffusion.

Results—IgG was increased in the supernatants of short term cultured biopsy samples and saliva from HIV infected patients compared with controls (p<0.01), but IgA and IgM levels were normal. In contrast, both IgG and IgA concentrations in serum were higher in HIV infected patients than in controls (p<0.002). No correlation was found between IgA produced by duodenal biopsy specimens and serum IgA.

Conclusion—Abnormalities in mucosal immunoglobulin production in HIV infection were suprisingly small, indicating that specific secretory immunity rather than quantitative immunoglobulin production may be impaired. However, increased production of IgG could contribute to mucosal inflammation by complement activation. Our findings of normal mucosal IgA production and the lack of correlation between serum and mucosal IgA argues against an intestinal origin for the increased serum IgA levels in HIV infected patients.
Leucocyte endothelial cell adhesion in indomethacin induced intestinal inflammation is correlated with faecal pH
Authors: Arndt H , Palitzsch K-D , Schölmerich J
Published: June 2010

Background—Recent studies indicate that faecal pH is acidified in patients with inflammatory bowel disease compared with healthy controls. In healthy volunteers, stool pH, faecal flora, and bile acid concentration could be affected by means of elemental diets.

Aims—To assess the role of variations of faecal pH on leucocyte endothelial cell adhesion in indomethacin induced long lasting ileitis in rats.

Methods—Indomethacin (7.5 mg/kg subcutaneously) was injected twice, 24 hours apart. Rats were either fed with the identical diet before and 10 days after the induction of inflammation until the experiment, or the diet was changed at the time of induction. Ten postcapillary mesenteric venules (30 μm diameter) per animal were observed using intravital microscopy. Macroscopic visible intestinal ulceration was scored and faecal pH of different sections of the small bowel was determined.

Results—Small intestinal faecal pH was 8.5 in controls and 8.0 in indomethacin treated animals. Indomethacin significantly changed microcirculatory parameters: there was a 2.3-fold increase in leucocyte adherence, a 3.2-fold increase in leucocyte emigration, and a 20% reduction in shear rate. Application of various diets or diet combinations resulted in variations in faecal pH ranging from 7.8 to 8.8 which were inversely correlated with macroscopic ulcerations (r=−0.67). Leucocyte adherence was attenuated with increased pH and augmented with decreased pH (r=−0.55). Venular wall shear rate was positively correlated with faecal pH (r=0.48) while leucocyte emigration showed no correlation. Leucocyte rolling velocity was not significantly altered. Normalisation of faecal pH by different alkalising drugs induced a significant decrease in leucocyte adherence in standard fed, indomethacin treated rats.

Conclusions—Faecal pH is lowered in the indomethacin model of long lasting ileitis in rats, which is similar to human inflammatory bowel disease. Alkalisation of faecal pH due to different diets or alkalising drugs reduces indomethacin induced leucocyte endothelial cell adhesion and macroscopic intestinal damage. These results may provide a rationale for the therapeutic effect of enteral diets in Crohn’s disease.
Treatment of hepatocellular carcinoma with octreotide: a randomised controlled study
Authors: Kouroumalis E , Skordilis P , Thermos K , Vasilaki A , Moschandrea J , Manousos O N
Published: June 2010

Background—Standard treatment of inoperable hepatocellular carcinoma has not been established. Somatostatin has been shown to possess antimitotic activity against a variety of non-endocrine tumours.

Aims—To assess the presence of somatostatin receptors in human liver and to treat advanced hepatocellular carcinoma with the somatostatin analogue, octreotide.

Methods—Somatostatin receptors were measured in liver tissue homogenates from patients with acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Fifty eight patients with advanced hepatocellular carcinoma were randomised to receive either subcutaneous octreotide 250 μg twice daily, or no treatment. Groups were comparable with respect to age, sex, Okuda classification, presence of cirrhosis, and liver biochemistry and virology.

Results—Various amounts of somatostatin receptors were identified in liver tissue of all patients including those with hepatocellular carcinoma. Treated patients had an increased median survival (13 months versus four months, p=0.002, log rank test) and an increased cumulative survival rate at six and 12 months (75% versus 37%, and 56% versus 13% respectively). Octreotide administration significantly reduced α fetoprotein levels at six months. When a multivariable Cox’s proportional hazards model was fitted, variables associated with increased survival were: treatment administration, absence of cirrhosis, increased serum albumin, and small tumours. Treated patients clearly had a lower hazard (0.383) in the multivariate analysis.

Conclusions—Octreotide administration significantly improves survival and is a valuable alternative in the treatment of inoperable hepatocellular carcinoma.