bluuebunny/crossref_metadata_2025_split huggingface dataset:
The structural basis of interlamellar cohesion in the intervertebral disc wall
Authors: Pezowicz Celina A. , Robertson Peter A. , Broom Neil D. 
Published: March 2006

AbstractThe purpose of this study was to investigate the structural mechanisms that create cohesion between the concentric lamellae comprising the disc annulus. Sections, 50–60 µm thick, were obtained using a carefully chosen cutting plane that incorporated the fibrous component in alternating lamellae as in‐plane and cross‐sectioned arrays. These sections were then subjected to microtensile stretching both across (radial) and along (tangential) the in‐plane fibre direction, in their fully hydrated state. Structural responses were studied by simultaneously viewing the sections using high‐resolution Nomarski interference contrast light microscopy. Additional bulk samples of annulus were fixed while held in a constant, radially stretched state in order to investigate the potential for interlamellar separation to occur in a state more representative of the intact disc wall. The study has provided a detailed picture of the structural architecture creating disc wall cohesion, revealing a complex hierarchy of interconnecting relationships within the disc wall, not previously described. Importantly, because our experimental approach offers a high‐resolution view of the response of the interlamellar junction to deformation in its fully hydrated condition, it is a potentially useful method for investigating subtle changes in junction cohesion resulting from both early degeneration and whole‐disc trauma.
Expression of Concern: Antioxidant compounds have potent anti‐fibrillogenic and fibril‐destabilizing effects for α‐synuclein fibrils in vitro
Authors: Ono Kenjiro , Yamada Masahito 
Published: March 2006

AbstractThe aggregation of α‐synuclein (αS) in the brain has been implicated as a critical step in the development of Lewy body diseases (LBD) and multiple system atrophy (MSA). Various antioxidants not only inhibit the formation of β‐amyloid fibrils (fAβ), but also destabilize preformed fAb in vitro. Using fluorescence spectroscopy with thioflavin S and electron microscopy, here we examined the effects of the antioxidants nordihydroguaiaretic acid, curcumin, rosmarinic acid, ferulic acid, wine‐related polyphenols [tannic acid, myricetin, kaempferol (+)‐catechin and (–)‐epicatechin], docosahexaenoic acid, eicosapentaenoic acid, rifampicin and tetracycline on the formation of αS fibrils (fαS) and on preformed fαS. All molecules, except for docosahexaenoic acid and eicosapentaenoic acid, dose‐dependently inhibited the formation of fαS. Moreover, these molecules dose‐dependently destabilized preformed fαS. The overall activity of the molecules examined was in the order of: tannic acid = nordihydroguaiaretic acid = curcumin = rosmarinic acid = myricetin > kaempferol = ferulic acid > (+)‐catechin = (–)‐epicatechin > rifampicin = tetracycline. These compounds with anti‐fibrillogenic as well as antioxidant activities could be key molecules for the development of preventives and therapeutics for LBD and MSA as well as Alzheimer's disease.
Dopamine transporter is essential for the maintenance of spontaneous activity of auditory nerve neurones and their responsiveness to sound stimulation
Authors: Ruel Jérôme , Wang Jing , Demêmes Danielle , Gobaille Serge , Puel Jean‐Luc , Rebillard Guy 
Published: March 2006

AbstractDopamine, a neurotransmitter released by the lateral olivocochlear efferents, has been shown tonically to inhibit the spontaneous and sound‐evoked activity of auditory nerve fibres. This permanent inhibition probably requires the presence of an efficient transporter to remove dopamine from the synaptic cleft. Here, we report that the dopamine transporter is located in the lateral efferent fibres both below the inner hair cells and in the inner spiral bundle. Perilymphatic perfusion of the dopamine transporter inhibitors nomifensine and N‐[1‐(2‐benzo[b]thiophenyl)cyclohexyl]piperidine into the cochlea reduced the spontaneous neural noise and the sound‐evoked compound action potential of the auditory nerve in a dose‐dependent manner, leading to both neural responses being completely abolished. We observed no significant change in cochlear responses generated by sensory hair cells (cochlear microphonic, summating potential, distortion products otoacoustic emissions) or in the endocochlear potential reflecting the functional state of the stria vascularis. This is consistent with a selective action of dopamine transporter inhibitors on auditory nerve activity. Capillary electrophoresis with laser‐induced fluorescence (EC‐LIF) measurements showed that nomifensine‐induced inhibition of auditory nerve responses was due to increased extracellular dopamine levels in the cochlea. Altogether, these results show that the dopamine transporter is essential for maintaining the spontaneous activity of auditory nerve neurones and their responsiveness to sound stimulation.
Amino acid sequence motifs and mechanistic features of the membrane translocation of α‐synuclein
Authors: Ahn Keun Jae , Paik Seung R. , Chung Kwang Chul , Kim Jongsun 
Published: March 2006

AbstractMany lines of evidence suggest that α‐synuclein can be secreted from cells and can penetrate into them, although the detailed mechanism is not known. In this study, we investigated the amino acid sequence motifs required for the membrane translocation of α‐synuclein, and the mechanistic features of the phenomenon. We first showed that not only α‐synuclein but also β‐ and γ‐synucleins penetrated into live cells, indicating that the conserved N‐terminal region might be responsible for the membrane translocation. Using a series of deletion mutants, we demonstrated that the 11‐amino acid imperfect repeats found in synuclein family members play a critical role in the membrane translocation of these proteins. We further demonstrated that fusion peptides containing the 11‐amino acid imperfect repeats of α‐synuclein can transverse the plasma membrane, and that the membrane translocation efficiency is optimal when the peptide contains two repeat motifs. α‐Synuclein appeared to be imported rapidly and efficiently into cells, with detectable protein in the cytoplasm within 5 min after exogenous treatment. Interestingly, the import of α‐synuclein at 4°C was comparable with the import observed at 37°C. Furthermore, membrane translocation of α‐synuclein was not significantly affected by treatment with inhibitors of endocytosis. These results suggest that the internalization of α‐synuclein is temperature‐insensitive and occurs very rapidly via a mechanism distinct from normal endocytosis.
Increased glutathione biosynthesis by Nrf2 activation in astrocytes prevents p75NTR‐dependent motor neuron apoptosis
Authors: Vargas Marcelo R. , Pehar Mariana , Cassina Patricia , Beckman Joseph S. , Barbeito Luis 
Published: March 2006

AbstractAstrocytes may modulate the survival of motor neurons in amyotrophic lateral sclerosis (ALS). We have previously shown that fibroblast growth factor‐1 (FGF‐1) activates astrocytes to increase secretion of nerve growth factor (NGF). NGF in turn induces apoptosis in co‐cultured motor neurons expressing the p75 neurotrophin receptor (p75NTR) by a mechanism involving nitric oxide (NO) and peroxynitrite formation. We show here that FGF‐1 increased the expression of inducible nitric oxide synthase and NO production in astrocytes, making adjacent motor neurons vulnerable to NGF‐induced apoptosis. Spinal cord astrocytes isolated from transgenic SOD1G93Arats displayed increased NO production and spontaneously induced apoptosis of co‐cultured motor neurons. FGF‐1 also activates the redox‐sensitive transcription factor nuclear factor erythroid 2‐related factor 2 (Nrf2) in astrocytes. Because Nrf2 increases glutathione (GSH) biosynthesis, we investigated the role of GSH production by astrocytes on p75NTR‐dependent motor neuron apoptosis. The combined treatment of astrocytes with FGF‐1 andt‐butylhydroquinone (tBHQ) increased GSH production and secretion, preventing motor neuron apoptosis. Moreover, Nrf2 activation in SOD1G93Aastrocytes abolished their apoptotic activity. The protection exerted by increased Nrf2 activity was overcome by adding the NO donor DETA‐NONOate to the co‐cultures or by inhibiting GSH synthesis and release from astrocytes. These results suggest that activation of Nrf2 in astrocytes can reduce NO‐dependent toxicity to motor neurons by increasing GSH biosynthesis.
Prevalence of Helicobacter pylori in Georgian Patients with Dyspepsia
Authors: Olivares Asalia , Buadze Merab , Kutubidze Tina , Lobjanidze Manana , Labauri Levani , Kutubidze Ramaz , Chikviladze Daredjan , Zhvania Manana , Kharzeishvili Omar , Lomidze Nodar , Perez‐Perez Guillermo I. 
Published: March 2006

AbstractBackground:  Georgia has showed a high prevalence of peptic ulcer disease (PUD), but the prevalence of Helicobacter pylori in this country is practically unknown. The purpose of this study was to determine the prevalence of H. pylori and specific genotypes in different populations in Georgia.Materials and Methods:  We studied 62 patients from several hospitals in Tbilisi, Georgia. More than 55% of patients had PUD. We determined H. pylori presence as well as specific genotypes cagA and vacA by polymerase chain reaction. In addition, we studied serum samples from 94 healthy persons to determine H. pylori and CagA prevalence by ELISA.Results:  We found a high prevalence of H. pylori and CagA in the healthy population (70.2 and 57.4%, respectively) and a high prevalence of CagA among the H. pylori‐positive persons (71.2%). Prevalence increased with age as reported in other countries (p = .05). Among symptomatic persons, we found nearly the same high prevalence of H. pylori (64.5%) as in the asymptomatic population. Furthermore, in symptomatic H. pylori patients, we found 65.0 and 67.5% prevalence of cagA and vacA, respectively. For 33 patients with PUD, 24 patients (72.7%) were H. pylori positive and 66.7% of them were cagA positive. In contrast, among the patients with non‐ulcer dyspepsia (NUD), 16 (55.2%) were H. pylori positive and 62.5% of them were colonized with cagA‐positive strains. H. pylori and cagA prevalence were not significantly different between PUD and patients with NUD.Conclusions:  We confirmed that among individuals in Georgia, the prevalence of H. pylori is high and cagA‐positive strains were equally present among H. pylori‐positive patients with PUD and NUD and asymptomatic persons.
Helicobacter pylori Infection and Colorectal Cancer Risk: A Meta‐Analysis
Authors: Zumkeller Natalia , Brenner Hermann , Zwahlen Marcel , Rothenbacher Dietrich 
Published: March 2006

AbstractBackground:  Several studies suggested an association between Helicobacter pylori infection and colorectal carcinoma or adenoma risk. However, different authors reported quite varying estimates. We carried out a systematic review and meta‐analysis of published studies investigating this association and paid special attention to the possibility of publication bias and sources of heterogeneity between studies.Materials and Methods:  An extensive literature search and cross‐referencing were performed to identify all published studies. Summary estimates were obtained using random‐effects models. The presence of possible publication bias was assessed using different statistical approaches.Results:  In a meta‐analysis of the 11 identified human studies, published between 1991 and 2002, a summary odds ratio of 1.4 (95% CI, 1.1–1.8) was estimated for the association between H. pylori infection and colorectal cancer risk. The graphical funnel plot appeared asymmetrical, but the formal statistical evaluations did not provide strong evidence of publication bias. The proportion of variation of study results because of heterogeneity was small (36.5%).Conclusions:  The results of our meta‐analysis are consistent with a possible small increase in risk of colorectal cancer because of H. pylori infection. However, the possibility of some publication bias cannot be ruled out, although it could not be statistically confirmed. Larger, better designed and better controlled studies are needed to clarify the situation.
The Mechanism of Heat‐Shock Protein 70 Gene Expression Abolition in Gastric Epithelium Caused byHelicobacter pyloriInfection
Authors: Pierzchalski Piotr , Krawiec Agata , Ptak‐Belowska Agata , Barańska Aleksandra , Konturek Stanisław J. , Pawlik Wiesław W. 
Published: March 2006

AbstractBackground: The members of the family of heat shock factors coordinate the inducible transcription of heat shock genes in response to diverse stimuli. Any disturbances in signal transduction may lead to the attenuation of heat shock proteins synthesis and to cell death due to apoptosis. It has been shown by others that different nuclear factors, such as nuclear factor interleukine 6 or signal transducer and activator of transcription 3, co‐operate with heat shock factors, mostly enhancing their activator effect on heat shock proteins genes expression. Therefore, we sought to determine whether apoptosis induced in the gastric epithelium exposed to liveHelicobacter pylorimight occur due to the elimination of HSP70 expression and deregulation of the heat shock response of the cell.Materials and Methods: Experiments were performed on KATO III gastric epithelial cells exposed to live cagA, vacA expressingHpover different periods of time. Total cellular RNA, cytoplasmic and nuclear proteins were isolated for polimerase chain reaction, western‐blot, electrophoretic mobility shift assay, decoy and co‐immunoprecipitation studies.Results: We found that in human gastric epithelium exposed toHelicobacter pylori, heat shock factor 1 is bound and restrained in complexes by phosphorylated signal transducer and activator of transcription 3 protein. In consequence, heat shock factor 1 bound up with phosphorylated signal transducer and activator of transcription 3 protein is unable to activate HSP70 protein synthesis in KATO III cells under stress conditions.Helicobacter pylorialso causes changes in bax/bcl‐2 cellular equilibrium, leading to the induction of apoptosis.Conclusions: The observed phenomenon might be the mechanism whereby gastric epithelium adapts to the infection ofHelicobacter pylori, eliminating cells which are damaged or altered by bacterial cytotoxic products from the tissue.
The Effects of Genetic Polymorphisms of IL‐1 and TNF‐A on Helicobacter pylori–Induced Gastroduodenal Diseases in Korea
Authors: Kim Nayoung , Cho Sung‐Il , Yim Jeong‐Yoon , Kim Jung Mogg , Lee Dong Ho , Park Ji Hyun , Kim Joo Sung , Jung Hyun Chae , Song In Sung 
Published: March 2006

AbstractObjective:  To evaluate whether or not genetic polymorphism of IL‐1B, IL‐1RN, and TNF‐Α is an important factor in the different expression of gastroduodenal diseases after Helicobacter pylori infection.Methods:  This study consisted of 1360 subjects: control, gastric cancer (GC, intestinal type, and diffuse type), benign gastric ulcer (BGU), duodenal ulcer, and first‐degree gastric cancer relative (GCR). IL‐1Β‐511 and TNF‐A‐308 biallelic polymorphism were genotyped by 5′ nuclease polymerase chain reaction (PCR) assays, and PCR‐restriction fragment length polymorphism (PCR‐RFLP). IL‐1RN penta‐allelic variable number of tandem repeats was genotyped by PCR.Results: There was no difference in the genetic polymorphism of IL‐1Β‐511, IL‐1RN and TNF‐A in the patients with gastric cancer regardless of H. pylori positivity compared with control. However, the frequencies of IL‐1B‐511 C/T (OR: 0.5, 95% CI: 0.3–0.7) and T carrier (OR: 0.6, 95% CI: 0.4–0.8) were lower in the H. pylori‐positive BGU patients. The IL‐1RN 2/2 was higher (OR: 5.5, 95% CI: 1.1–28.5) in the H. pylori‐positive GCR. There was no significance in the polymorphism of TNF‐Α‐308 regardless of H. pylori‐induced gastroduodenal diseases.Conclusions:  The IL‐1Β‐511 T‐carrier polymorphism has a negative effect on the development of H. pylori‐positive BGU, and high frequency of IL‐1RN 2/2 was found in the H. pylori‐positive relatives of GC patients, which suggest that this genetic polymorphism could play some role in the H. pylori‐induced gastroduodenal diseases in Korea.
Mucosal Immunization with a Urease B DNA Vaccine Induces Innate and Cellular Immune Responses Against Helicobacter pylori
Authors: Hatzifoti Caterina , Roussel Yvonne , Harris Andrew G. , Wren Brendan W. , Morrow John W. , Bajaj‐Elliott Mona 
Published: March 2006

AbstractBackground:  Helicobacter pylori is recognized as a major risk factor for recurrent gastroduodenal inflammatory diseases and gastric adenocarcinoma. The high prevalence of H. pylori infection worldwide, the risks of side‐effects from antibiotic therapy, and increasing resistance to antibiotics are the main primers for the development of improved H. pylori vaccines. The antigenic potential of its urease enzyme, a critical virulence factor required for colonization of the gastric mucosa, has been demonstrated in animal and human studies. An important but controversial issue in H. pylori vaccine studies is the type of immune response required to control infection. A new approach in H. pylori vaccinology is the administration of DNA vaccines, which has included heat‐shock protein and catalase DNA vaccines.Materials and Methods:  The H. pylori urease subunit B construct or vector alone was administered to mice via the intranasal route. Spleens and stomachs were examined on day 0 and weeks 3, 6, and 12 after immunization. Proliferation of spleen cells was assessed using the carboxyfluorescein diacetate succinimidyl ester‐based flow cytometry assay and cytokine secretion from cultured spleen cells was detected by ELISA, after stimulation with the urease subunit B recombinant antigen. Total RNA was isolated from stomach and spleen tissue and the expression of β‐defensin and cytokine genes was monitored by reverse transcription followed by polymerase chain reaction (RT‐PCR). Immunized mice were challenged with H. pylori and bacterial DNA quantified by TaqMan PCR.Results:  The urease B subunit DNA vaccine increased INF‐γ secretion and splenocyte proliferation without inducing adverse effects in the spleen. Increase in gastric β‐defensin 1 and marked induction in local IL‐10 : IFN‐γ ratio up to 12 weeks post‐immunization suggest a potential role for local innate immune responses in protection at the site of infection. Although significant bacterial reduction in the stomachs of urease B subunit DNA‐immunized mice was observed, intermediate reduction was also noted in the vector group. Increased defensin expression and adjuvant effects of the cytosine preceding guanosine motifs may contribute to this phenomenon. Our data confirm that cytosine preceding guanosine motifs, even without coadministration with antigen, can reduce extracellular bacterial load.Conclusions:  In this study, a DNA construct encoding the urease B subunit was assessed for its immune profile and its ability to reduce bacterial colonization in the murine stomach. Our studies suggest that local innate immune responses may play a greater role than previously supposed in limiting H. pylori colonization in the gastric mucosa.
Effects of Estradiol and Progesterone on Gastric Mucosal Response to Early Helicobacter pylori Infection in Female Gerbils
Authors: Saqui‐Salces Milena , Rocha‐Gutiérrez Brenda L. , Barrios‐Payán Jorge A. , Ruiz‐Palacios Guillermo , Camacho‐Arroyo Ignacio , Gamboa‐Dominguez Armando 
Published: March 2006

AbstractBackground:  Gender differences have been shown regarding the changes in the inflammatory response, gastrin secretion, and gastric acidity during Helicobacter pylori infection.Aim:  To investigate the role of estradiol and progesterone in the changes of the gastric mucosa induced by H. pylori during the early stage of infection in female gerbils.Materials and Methods: Thirty‐three adult ovariectomized female gerbils were infected with H. pylori (SS1); 7 days after infection they were treated with low and high doses of estradiol (50 and 250 µg/60 days pellet), progesterone (15 and 50 mg/60 days pellet) and vehicle. Non‐ovariectomized infected gerbils were used as control. Gerbils were euthanized after 6 weeks of infection. Histologic evaluation, immunohistochemical detection of proliferation cell nuclear antigen (PCNA), gastrin, and apoptosis by terminal deoxynucleotide nick end labeling (TUNEL) assay were performed. Positive cells for PCNA, TUNEL, and gastrin were counted in 10 oriented glands per animal. Two‐sided p = .05 was considered significant.Results:  Estradiol‐treated groups showed more intense and extended acute and follicular gastritis compared to the vehicle group, whereas progesterone‐treated groups presented less gastritis than the other groups. Proliferation and apoptosis indexes were significantly lower in the vehicle group when compared with those of the control; both indexes were increased in the high‐dose estradiol and progesterone groups as compared with those of the vehicle. Grade I nonmetaplastic atrophy was observed in the vehicle and progesterone groups. The high‐dose progesterone group showed a significant reduction in the number of gastrin cells.Conclusions:  Estradiol and progesterone participate in the gastric mucosal response to early H. pylori infection in gerbils.
Carbonation of Cl‐rich scapolite boudins in Skallen, East Antarctica: evidence for changing fluid condition in the continental crust
Authors: SATISH‐KUMAR M. , HERMANN J. , TSUNOGAE T. , OSANAI Y. 
Published: March 2006

AbstractSpectacular reaction textures in poikiloblastic scapolitite boudins, within marbles in the continental crust exposed in the Lützow–Holm Complex, East Antarctica, provide insights into the changing fluid composition and movement of fluid along grain boundaries and fractures. Petrographic and geochemical features indicate scapolite formation under contrasting fluid compositions. Core composition of scapolite poikiloblasts (ScpI) are marialitic (Cl = 0.7 apfu) whereas rims in contact with biotite or clinopyroxene are meionite rich. Fine‐grained recrystallized equigranular scapolite (ScpII) shows prominent chemical zoning, with a marialitic core and a meionitic rim (Cl = 0.36 apfu). Scapolite poikiloblasts are traversed by ScpIII reaction zones along fractures with compositional gradients. Pure CO2 fluid inclusions are observed in healed fractures in scapolite poikiloblasts. These negative crystal‐shaped fluid inclusions are moderately dense, and are believed to be coeval with ScpIII formation at temperatures >600 °C and a minimum pressure of c. 3.8 kbar. Grain‐scale LA‐ICPMS studies on trace and rare earth elements on different textural types of scaplolites and a traverse through scapolite reaction zone with compositional gradient suggest a multistage fluid evolution history. ScpI developed in the presence of an internally buffered, brine‐rich fluid derived probably from an evaporite source during prograde to peak metamorphism. Recrystallization and grain size reduction occurred in the presence of an externally sourced carbonate (CaCO3)‐bearing fluid, resulting in the leaching of Cl, K, Rb and Ba from ScpI along fractures and grain boundaries. Movement of fluids was enhanced by micro‐fracturing during the transformation of ScpI to ScpIII. Fractures in fluorapatite are altered to chlorapatite proving evidence for the pathways of escaping Cl‐bearing fluids released from ScpI. The present study thus provides evidence for the usefulness of scapolite in fingerprinting changing volatile composition and trace element contents of fluids that percolate within the continental crust.