bluuebunny/crossref_metadata_2025 huggingface dataset:
A bathymetric overview of the Mariana forearc
Authors: STERN ROBERTJ. , SMOOT N. CHRISTIAN
Published: September 2004

Bathymetric data at a 200‐m contour interval for the entire Mariana forearc, from south of 13°N to 25°N, permits the first comprehensive overview of this feature. The Mariana forearc represents a sediment‐starved end‐member. The forearc in its southern and central sections is divisible into a structurally complex eastern province and a less‐deformed western province. Despite the absence of an accretionary complex the Mariana forearc has a well‐defined outer‐arc high; this probably results from a greater concentration of low‐density serpentinized mantle lithosphere beneath the outer forearc relative to the inner forearc. This serpentinization gradient is coupled with differing deformational styles of thinner and more brittle lithosphere beneath the outer forearc compared to thicker and more ductile lithosphere beneath the inner forearc. The bathymetric data also support models calling for extension along‐strike of the forearc, reflecting an increase in arc length accompanying the crescent‐shaped opening of the Mariana Trough back‐arc basin. Both northeast and northwest ridges and grabens can be identified, with the latter restricted to the southern part of the forearc and the former widely distributed in the central and northern forearc. Northeast‐oriented extensional structures are supplanted northward by long, linear northwest‐trending structures that are interpreted as left‐lateral strike–slip faults. These variations in deformation along‐strike of the forearc manifest a transition from nearly orthogonal convergence in the south to highly oblique convergence in the north.
Peridotites from the southern Mariana forearc: Heterogeneous fluid supply in mantle wedge
Authors: OHARA YASUHIKO , ISHII TERUAKI
Published: September 2004

Detailed petrological work was carried out on serpentinized peridotite dredged and sampled by submersible from the southern part of the Mariana Trench to reveal the nature of the mantle wedge in the southern Mariana forearc. The southern part of the Mariana Trench is important in that we should expect to find a transect of a typical island arc structure; that is, from east to west, the Mariana forearc, the Mariana arc proper, the Mariana Trough (active back‐arc spreading center), and the West Mariana Ridge (remnant arc). The most striking feature of peridotites from the southern part of the trench is that primary hornblende is a major constituent mineral in many specimens. Thus, the peridotite samples are divided into anhydrous (A‐type), hydrous (H‐type) and intermediate (I‐type) groups. Petrological data suggest that each type of peridotite is a residue of extensive partial melting in the upper mantle. It is argued here that the I‐ and H‐type peridotites were modified from `proto‐A‐type peridotite' by fluid infiltration. The fluid was enriched in Al, Ti, Fe, and alkalis, and may have caused changes in mineral and bulk chemical compositions of the peridotites. A‐type peridotite derives from the `proto‐A‐type peridotite' directly, without any fluid contamination. After the formation of the `proto‐A‐, I‐, and H‐type peridotites', lower‐temperature fluids, probably of seawater origin, produced retrograde metamorphism and alteration including serpentinization. The mantle wedge in the southern Mariana forearc was heterogeneous in fluid supply.
C‐reactive protein may be a marker of bacterial translocation in experimental intestinal obstruction
Authors: Çevikel Mehmet Hakan , Özgün Hedef , Boylu Sükrü , Demirkiran Ahmet Ender , Aydin Neriman , Sari Cavide , Erkus Muhan
Published: September 2004

Background:  C‐reactive protein (CRP) is used as a marker of intestinal ischaemia. This study evaluated whether CRP levels can be used to detect ischaemia‐induced (strangulated) intestinal obstruction and subsequent bacterial translocation.

Methods:  Forty‐eight rats, divided into four groups underwent the following procedures: anaesthesia alone (native controls), laparotomy (sham‐operated controls), or surgical induction of simple or strangulated intestinal obstruction (simple and strangulated obstruction groups, respectively). Blood samples were collected for culture and serum CRP analysis. In addition, liver and mesenteric lymph node (MLN) specimens were collected for culture, to determine the presence of bacterial translocation; and ileal segments, for histopathological investigation.

Results:  CRP levels and rates of bacterial translocation, expressed as colony forming units (cfu) per gram wet tissue, were higher in both intestinal obstruction groups than in the native and sham‐operated control groups (P < 0.001 for both). The increases in CRP levels paralleled increases in the number of cfu in the MLN and liver cultures (P < 0.01). Compared to controls, animals in the obstruction groups also had a higher incidence of positive blood cultures (P < 0.005) and greater histopathologic evidence of inflammatory infiltration of the lamina propria (P < 0.01). However, no significant difference between the simple and strangulated obstruction groups was observed.

Conclusion:  CRP levels increase with the severity of bacterial translocation in acute intestinal obstruction but do not permit discrimination between simple and strangulated intestinal obstruction.
Comparison of pulmonary hydatid cysts in children and adults
Authors: Kanat Fikret , Turk Emel , Aribas Olgun Kadir
Published: September 2004

Background:  The purpose of the present study was to compare the clinical features and the surgical approaches of the pulmonary hydatid cysts in children and adults.

Methods:  One hundred and thirty‐four patients, operated on for pulmonary hydatid cysts over the last 10 years were retrospectively evaluated in two groups: 39 children who were younger than 18 years old (29%) and 95 adults (71%). The patients in each group were analysed according to their clinical, radiological and surgical findings.

Results:  The frequency of pulmonary hydatid cysts in children was significantly higher in boys (74%) than in girls (26%). However, there was no sex tendency in adults (52% in male vs 48% in women). The sex difference in hydatid cyst frequencies between adults and children was significant (P < 0.05). Among preoperative pleural complications, pneumothorax (15.5%) in children and empyema (11%) in adults were more frequent. The frequency of concomitant hepatic cysts was less in children than in adults (33%vs 79%). Huge pulmonary cysts (=10 cm) were more common in children (31%) than in adults (22%). Cystotomy with capitonnage was the most frequently preferred method in both groups. Postoperative complications developed in six children (16%) and 19 adults (19%), and were more frequent in patients with huge cysts (27%vs 16%). No recurrence was observed in both groups.

Conclusions:  Isolated pulmonary cysts are more common in children than adults. The cysts also tend to be bigger in children than adults. The frequency of concomitant hepatic cysts is less in children. Because of higher lung expansion ability and improvement capacity in children, resection should be avoided and lung saving surgical procedures should be performed. In spite of differences observed in the clinical features it does not change the treatment of pulmonary hydatid cysts in children.
Role of Gastrografin in assigning patients to a non‐operative course in adhesive small bowel obstruction
Authors: Roadley Graeme , Cranshaw Isaac , Young Michael , Hill Andrew G.
Published: September 2004

Background:  Adhesive small bowel obstruction (SBO) is a common surgical emergency. Water soluble contrast agents have been used to identify patients who might be treated non‐operatively rather than operatively. The present study was designed to audit the introduction of such use of Gastrografin contrast into clinical practice.

Method:  Patients presenting acutely to hospital with clinically suspected and radiologically proven SBO were entered in the study. As soon as practicable, 100 mL of undiluted Gastrografin was given either orally or by the nasogastric tube (which was then spigotted). After 4 h, a plain supine abdominal X‐ray (AXR) was taken. If the contrast was seen in the large bowel, and there had been no deterioration in the patient's condition, then non‐operative treatment was continued. If the contrast remained in the small bowel, a clinical judgement was made as to whether to proceed with operative intervention.

A group of historical controls were obtained by a retrospective review of the hospital medical records through data obtained from the Department of General Surgery Audit System.

Results:  Twenty‐five patients were entered into the study. In 20 of these patients the contrast was seen to arrive in the large bowel at 4 h. All of these patients completed a non‐operative course to full recovery. In another two patients a successful decision was made to pursue a non‐operative management strategy. These 22 patients had a mean hospital stay of 3.9 days. Eighty historical controls had successfully completed a non‐operative course for SBO. They had a mean hospital stay of 5.6 days. This was significantly longer than that of the Gastrografin group (P < 0.016, t‐test).

Conclusion:  This paper has demonstrated that undiluted Gastrografin may be safely used to assign patients to a non‐operative management plan and this results in a decreased hospital stay.
Cat bites of the hand
Authors: Mitnovetski Sergei , Kimble Frank
Published: September 2004

Background:  Cat bites are the second most common mammalian bites. Cat bites of the hand in particular represent a potentially devastating problem in terms of wound infection and long‐term disability if not treated appropriately. The purpose of the present study is to give an overview of demographics, management and follow up of the patients with cat bite injuries of the hand treated at the Royal Hobart Hospital.

Methods:  Retrospective and prospective data of all patients with cat bites of the hand seen at the Royal Hobart Hospital for a period of 3 years (January 2000 to April 2003) were collected. Demographics, anatomical site, presentation, assessment, investigations, management and follow up of the patients with this type of injury were analysed. The accuracy of the obtained data was checked by analysing questionnaires returned by our patients.

Results:  Forty‐one patients were treated for cat bites of the hand. Twenty‐six were managed in the department of emergency medicine and 15 were admitted and managed by the department of plastic and reconstructive surgery. Five of 15 admitted patients required surgery. Compliance was not a major problem in our study as very few patients were lost to follow up. Almost all patients had close follow up and extensive hand physiotherapy achieving overall good long‐term results. Out of 39 patients who were sent questionnaires only one indicated long‐term problems with the hand (response rate 46%).

Conclusion:  Appropriate early treatment of cat bites of the hand is the key to success. Treatment with antibiotics, surgical drainage, debridement and copious irrigation, and use of corticosteroids in some cases, proved to be effective. Hand elevation and intensive physiotherapy after a short period of immobilization is critical. We believe that prophylactic antibiotics should be given even in case of a minor infection following cat bites of the hand. Clear guidelines for clinical recognition of infection, hospital admission and management are provided in our study.
Endoscopic totally extraperitoneal inguinal hernioplasty for recurrence after open repair
Authors: Lau Hung
Published: September 2004

Background:  Whether endoscopic totally extraperitoneal inguinal hernioplasty (TEP) for recurrent inguinal hernia is as safe and efficacious as that for primary inguinal hernia has rarely been examined. The objective of the present study was to compare the early and late outcomes of TEP for primary and recurrent inguinal hernia. The clinical pattern of recurrence after previous open repair of inguinal hernia was also examined.

Methods:  Between August 1999 and November 2003, 100 consecutive patients who underwent TEP for recurrent inguinal hernia were recruited. The outcomes of these patients were compared to a randomly selected control group (n = 100) who had TEP for primary inguinal hernia during the same period. All data had been prospectively collected and analysed.

Results:  Demographic features were comparable between the two groups. The recurrent group had a significantly higher incidence of direct inguinal hernia than the control group (P < 0.001). Comparison of operative duration, postoperative morbidity, pain score, length of hospital stay and time taken to resume normal activities showed no significant differences between the two groups. However, the incidence of peritoneal tear in the recurrent group (46%) was significantly higher than that of the control group (28%) (P < 0.05). With a mean follow‐up of 1 year, the incidences of recurrence and chronic groin pain were similar for both groups.

Conclusion:  Early and late outcomes of TEP for recurrent inguinal hernia were equivalent to those for primary inguinal hernia but a higher incidence of peritoneal tear was encountered during TEP for recurrent inguinal hernia. A predominance of direct hernia was observed in the recurrent group.
Imaging of an enterovaginal fistula with flexible colposcopy, an endoscopic retrograde cholangiopancreatography cannula and radiographic screening
Authors: Nguyen M. H. , Zakon Joseph , Wagner Tim , Lloyd David
Published: September 2004

The diagnosis of a rectovaginal or enterovaginal fistula is mostly made by a careful historical of a faecal vaginal discharge. When a rectovaginal fistula is low, an examination will demonstrate it with ease. However, when there is a high and small fistula into the vault or the fornix of the vagina, traditional methods of small bowel enema and barium enema may not demonstrate the fistula. Ultrasound and magnetic resonance imaging may demonstrate a fistula but not the nature of the bowel involved. Vaginography has been the most successful imaging method to date.

Demonstrating an enterovaginal fistula and substantiating whether or not the rectum, the small bowel alone or both are implicated are important for operation planning; a fistulogram through the vagina by endoscopic method is a simple and useful adjunct to the available methods of imaging enterovaginal fistulas.

We report a case and discuss a technique of endoscopic fistulography through a small fistulous opening high in the vagina. We believe that this technique is accurate, simple and complementary to vaginography in demonstrating an enterovaginal fistula.
Towards a hybrid philosophy of surgical education
Authors: Hall John C. , Crebbin Wendy , Ellison Anne
Published: September 2004

Background:  Surgical training involves a complex amalgam of skills. This publication seeks to incorporate concepts about higher education into a philosophy of surgical education.

Methods:  The core of the present review is derived from a literature search of a computer database (Medline). The notion of competence is used to illustrate the concept of a philosophy of surgical education.

Conclusion:  A predefined philosophy of surgical education may serve as a useful reference point when choices arise during the development of surgical training.
Biogeochemistry of a gypsum‐encrusted microbial ecosystem
Authors: CANFIELD D. E. , SØRENSEN K. B. , OREN A.
Published: September 2004

Gypsum crusts containing multicolored stratified microbial populations grow in the evaporation ponds of a commercial saltern in Eilat, Israel. These crusts contain two prominent cyanobacterial layers, a bright purple layer of anoxygenic phototrophs, and a lower black layer with active sulphate reduction. We explored the diel dynamics of oxygen and sulphide within the crust using specially constructed microelectrodes, and further explored the crust biogeochemistry by measuring rates of sulphate reduction, stable sulphur isotope composition, and oxygen exchange rates across the crust–brine interface. We explored crusts from ponds with two different salinities, and found that the crust in the highest salinity was the less active. Overall, these crusts exhibited much lower rates of oxygen production than typical organic‐rich microbial mats. However, this was mainly due to much lower cell densities within the crusts. Surprisingly, on a per cell‐volume basis, rates of photosynthesis were similar to organic‐rich microbial mats. Due to relatively low rates of oxygen production and deep photic zones extending from 1.5 to 3 cm depth, a large percentage of the oxygen produced during the day accumulated into the crusts. Indeed, only between 16% to 34% of the O2 produced in the crust escaped, and the remainder was internally recycled, used mainly in O2 respiration. We view these crusts as potential homologs to ancient salt‐encrusted microbial ecosystems, and we compared them to the 3.45 billion‐year‐old quartz barite deposits from North Pole, Australia, which originally precipitated gypsum.
A laboratory model of abiotic peloid formation
Authors: BOSAK T. , SOUZA‐EGIPSY V. , NEWMAN D. K.
Published: September 2004

Peloids are rounded grains of micritic calcite whose origin has been attributed to various biological and abiotic mechanisms. To constrain abiotic parameters that favour the formation of peloids, we precipitated calcite crusts in the absence of microorganisms. Clotted opaque fabrics that formed during the initial stages of the experiment consisted of ∼10 µm peloids, while compact clear sparitic crusts precipitated in subsequent stages. The increasing supersaturation of the solution in time is responsible for this morphological succession. Initially, peloids form by the radial growth of spar crystals around a small number of nuclei. As the supersaturation increases, more spar crystals nucleate and aggregate nonradially into compact crusts. Rounded clotted precipitates are a consequence of the growth in suspension and geopetal settling, and isopachous crusts grow in the absence of these processes. Although peloids are commonly assumed to have a microbial origin, our results show that very similar morphologies can be created by purely abiotic mechanisms. Thus, the biological origin of rounded micritic calcite grains in the rock record must be verified against the abiotic null‐hypothesis in each specific case.
Linking geochemical processes with microbial community analysis: successional dynamics in an arsenic‐rich, acid‐sulphate‐chloride geothermal spring
Authors: MACUR R. E. , LANGNER H. W. , KOCAR B. D. , INSKEEP W. P.
Published: September 2004

The source waters of acid‐sulphate‐chloride (ASC) geothermal springs located in Norris Geyser Basin, Yellowstone National Park contain several reduced chemical species, including H2, H2S, As(III), and Fe(II), which may serve as electron donors driving chemolithotrophic metabolism. Microorganisms thriving in these environments must also cope with high temperatures, low pH (∼3), and high concentrations of sulphide, As(III), and boron. The goal of the current study was to correlate the temporal and spatial distribution of bacterial and archaeal populations with changes in temperature and geochemical energy gradients occurring throughout a newly formed (redirected) outflow channel of an ASC spring. A suite of complimentary analyses including aqueous geochemistry, microscopy, solid phase identification, and 16S rDNA sequence distribution were used to correlate the appearance of specific microbial populations with biogeochemical processes mediating S, Fe, and As cycling and subsequent biomineralization of As(V)‐rich hydrous ferric oxide (HFO) mats. Rapid As(III) oxidation (maximum first order rate constants ranged from 4 to 5 min−1, t1/2 = 0.17 − 0.14 min) was correlated with the appearance of Hydrogenobaculum and Thiomonas–like populations, whereas the biogenesis of As(V)‐rich HFO microbial mats (mole ratios of As:Fe ∼0.7) was correlated with the appearance of Metallosphaera, Acidimicrobium, and Thiomonas–like populations. Several 16S sequences detected near the source were closely related to sequences of chemolithotrophic hyperthermophilic populations including Stygiolobus and Hydrogenobaculum organisms that are known H2 oxidizers. The use of H2, reduced S(–II,0), Fe(II) and perhaps As(III) by different organisms represented throughout the outflow channel was supported by thermodynamic calculations, confirming highly exergonic redox couples with these electron donors. Results from this work demonstrated that chemical energy gradients play an important role in establishing distinct community structure as a function of distance from geothermal spring discharge.
The societal costs and quality of life of patients suffering from bipolar disorder in the Netherlands
Authors: Hakkaart‐van Roijen L. , Hoeijenbos M. B. , Regeer E. J. , Ten Have M. , Nolen W. A. , Veraart C. P. W. M. , Rutten F. F. H.
Published: September 2004

Objective:  To assess the societal costs and quality of life of patients suffering from bipolar disorder in the Netherlands.

Method:  Forty persons with a lifetime diagnosis of bipolar disorder (SCID/DSM‐IV) and representative for the Dutch general population were interviewed to collect data on direct (use of medical resources) and indirect (productivity losses because of absence from work and reduced efficiency at work) costs of illness. Respondents’ quality of life was also assessed. Prevalence (5.2%) of bipolar disorder was used to estimate total costs.

Results:  Total costs of bipolar disorder were estimated at $US1.83 billion (total direct costs = $US454 million; total indirect costs = $US1.37 billion). Participants’ quality‐of‐life scores were lower than those of the general population.

Conclusion:  The societal costs form patients suffering of bipolar disorder in the Netherlands were high, especially the indirect costs because of absence from work. The quality of life of bipolar patients was lower than the general population.
A real‐time PCR‐based method to independently sample single simian immunodeficiency virus genomes from macaques with a range of viral loads
Authors: Williams Dawnnica , Overbaugh Julie
Published: September 2004

Abstract:  The generation of a diverse population of viral variants is a hallmark of simian immunodeficiency virus (SIV) infection. In order to address what role this diversity plays in disease progression, accurate sampling of the viral population is necessary. However, traditional PCR‐based methods often rely on amplification of multiple genomes in one reaction, leading to resampling of viral genomes and potential errors in the estimations of viral diversity, especially when sequences from only one or a small number of PCRs are examined and/or viral copy number is low. Here we describe a method to amplify one viral envelope gene per PCR, thereby avoiding resampling. For this purpose we developed a highly accurate real‐time PCR method to quantify SIV copy number, then used a single SIV template in a sensitive, high‐fidelity full‐length envelope PCR. Using this method, we have estimated the intra‐animal viral diversity for a cohort of five pig‐tailed macaques (Macaca nemestrina) infected with SIVMne variants, which displayed a broad range of viral loads at setpoint.
SIV‐induced activation of the blood‐brain barrier requires cell‐associated virus and is not restricted to endothelial cell activation
Authors: MacLean Andrew G. , Rasmussen Terri A. , Bieniemy Dana N. , Alvarez Xavier , Lackner Andrew A.
Published: September 2004

Abstract:  It has never been determined if activation of the blood‐brain barrier (BBB) during simian immunodeficiency virus/human immunodeficiency virus (SIV/HIV) infection is a function of high levels of circulating virus or if the virus has to be within a cell capable of crossing the BBB to activate it. In vitro models of the BBB are becoming recognized as an acceptable method for determining the cellular events associated with HIV neuroinvasion. Cell free virus (when added in the physiologically relevant lumen) although capable of activating the endothelial cells of our in vitro BBB did not activate astrocytes beneath. SIVmac251‐infected CEMx174 cells, however, were capable of activating both components of the BBB model. Here we demonstrate that an in vitro model of the BBB can be activated in a physiologically relevant manner, that SIV requires to be cell‐associated and that endothelial cells of the BBB are not the only components that are activated during SIV neuroinvasion.
Insoluble zinc, cupric and tin pyrophosphates inhibit the formation of volatile sulphur compounds
Authors: Jonski G. , Young A. , Wåler S. M. , Rölla G.
Published: September 2004

Oral malodour is mainly a result of the production of volatile sulphur compounds (VSC). The present study was concerned with investigating the anti‐VSC effect of insoluble pyrophosphates (PP) of zinc, copper(II) and tin(II). The hypothesis to be tested was that the sulphide anions produced when VSC are solubilized in water have a higher affinity for the respective metal ions than the PP anion. The anti‐VSC effects of insoluble PP were compared with the corresponding soluble metal salts using three in vitro methods: saliva putrefaction; dialysis of a suspension of PP and saliva against water; and analysis of water containing hydrogen sulphide and methyl mercaptan gases, and gases in the headspace. The levels of VSC were analysed by gas chromatography in the first and third methods, and released metal ions were analysed by atomic absorption spectroscopy in the second. The results showed that: the insoluble metal PP inhibited VSC formation in saliva by 99–100%; under dialysis, only minute amounts of metal ions are released from the combination of PP and saliva; and the PP lost their metal cations in water containing dissolved gases and inhibited VSC formation. Hence, the results support the experimental hypothesis. Sulphide ions are obviously very strong ligands for these metal ions.
Protective effect of salivary nitrate and microbial nitrate reductase activity against caries
Authors: Doel J. J. , Hector M. P. , Amirtham C. V. , Al‐Anzan L. A. , Benjamin N. , Allaker R. P.
Published: September 2004

To test the hypothesis that a combination of high salivary nitrate and high nitrate‐reducing capacity are protective against dental caries, 209 children attending the Dental Institute, Barts and The London NHS Trust were examined. Salivary nitrate and nitrite levels, counts of Streptococcus mutans and Lactobacillus spp., and caries experience were recorded. Compared with control subjects, a significant reduction in caries experience was found in patients with high salivary nitrate and high nitrate‐reducing ability. Production of nitrite from salivary nitrate by commensal nitrate‐reducing bacteria may limit the growth of cariogenic bacteria as a result of the production of antimicrobial oxides of nitrogen, including nitric oxide.
Human jaw muscle strength and size in relation to limb muscle strength and size
Authors: Raadsheer M. C. , Van Eijden T. M. G. J. , Van Ginkel F. C. , Prahl‐Andersen B.
Published: September 2004

The aim of the present study was to investigate to what extent general factors (e.g. genotype, hormones) and factors at the craniofacial level (e.g. craniofacial size, jaw muscle architecture) contribute to the size and strength of the jaw muscles. A strong relationship of jaw muscle size and strength with that of other muscles would argue for general influences, whereas a weak relationship would argue for craniofacial influences. In 121 adult individuals, moments of maximal bite force, arm flexion force and leg extension force were measured. In addition, thicknesses of jaw muscles, arm flexor muscles and leg extensor muscles were measured using ultrasound. Relationships were assessed by using a principal component analysis. In females, one component was found in which all force moments were represented. Bite force moment, however, loaded very low. In males, two components were found. One component loaded for arm flexion and leg extension moments, the other loaded for bite force moments. In both females and males, only one component was found for the muscle thicknesses in which all muscle groups loaded similarly. It was concluded that the size of the jaw muscles was significantly related to the size of the limb muscles, suggesting that they were both subject to the same general influences. Maximal voluntary bite force moments were not significantly related to the moments of the arm flexion and leg extension forces, suggesting that besides the general influence on the muscle size, variation in bite force moment was also influenced by local variables, such as craniofacial morphology.
Crack closure on rehydration of glass‐ionomer materials
Authors: Sidhu Sharanbir K. , Pilecki Peter , Sherriff Martyn , Watson Timothy F.
Published: September 2004

Moisture‐sensitivity of immature glass‐ionomer cements suggests that hydration‐induced volumetric expansion might close and potentially heal established cracks. Crack closure in glass‐ionomer cements (GICs) was observed following rehydration. Circular cavities were prepared in 15 teeth: 10 were restored with resin‐modified GICs (5 with Fuji II LC and 5 with Photac‐Fil) and 5 were restored with a conventional GIC (Fuji IX); all were dehydrated for 1 min with air and imaged immediately by confocal microscopy. Crack formation in each was located, after which water was placed on the surface and observed for 15 min via a CCD camera. Dehydration caused cracks with measurable gaps, while rehydration resulted in varying degrees of closure: closure was limited in the conventional GIC, and complete or near complete along part/s of the crack in the resin‐modified GICs. In all, closure movement became imperceptible after the first 10 min. Statistical analysis indicated no significant difference between the closure behavior of all materials. However, the resin‐modified GICs appeared to show a greater potential for closure of established cracks than the conventional GIC upon rehydration.
Regulation of secretion of osteoprotegerin in rat dental follicle cells
Authors: Wise G. E. , Ding D. , Yao S.
Published: September 2004

Tooth eruption requires alveolar bone resorption and formation, both of which appear to be regulated by the dental follicle. Osteoclastogenesis needed for this bone resorption appears to occur as a result of a reduction in the expression of the osteoprotegerin (OPG) gene in the dental follicle at a specific time. This reduction in expression is mediatedin vitroin the follicle cells by colony‐stimulating factor‐1 (CSF‐1) and parathyroid hormone‐related protein (PTHrP). Using enzyme‐linked immunosorbent assays and immunoblotting, this study shows that the reduction in expression ofOPGafter incubation of the dental follicle cells in either CSF‐1 or PTHrP also results in a reduction in its secretion. We also show, by laser capture microdissection, that PTHrP is expressedin vivoin the stellate reticulum such that it could inhibitOPGexpression via a paracrine effect on the follicle. Bone formation is enhanced by OPG secretion, and incubation of the follicle cells with bone morphogenetic protein‐2 (BMP‐2) enhances OPG secretion. Thus, a reduction in secretion of the OPG protein at defined times may promote the osteoclastogenesis and alveolar bone resorption needed for eruption, and enhancement of OPG secretion at other times may promote alveolar bone formation.
Deletion of gtfC of Streptococcus mutans has no influence on the composition of a mixed‐species in vitro biofilm model of supragingival plaque
Authors: Van Der Ploeg Jan R. , Guggenheim Bernhard
Published: September 2004

Glucosyltransferases from Streptococcus mutans are thought to play an important role in bacterial adherence to the tooth surface. The goal of the present study was to determine the effect of the deletion of the gtfC gene, which encodes a glucosyltransferase that catalyses primarily the formation of insoluble glucan (mutan), on colonization of S. mutans in a mixed‐species biofilm model of supragingival plaque. A gtfC deletion mutant of S. mutans UA159 grew poorly in biofilms on a polystyrene surface in Todd–Hewitt medium containing sucrose, but biofilm formation in the semi‐defined fluid universal medium (FUM) was not affected. The S. mutans gtfC mutant colonized with the same efficiency as the wild‐type strain when grown together with five other species in a mixed‐species biofilm on hydroxyapatite in a mixture of FUM and saliva with pulses of sucrose and showed the same ability to demineralize enamel in vitro. Colonization of mutant and wild‐type strains was also equal in an association experiment in specific‐pathogen‐free rats. However, the gtfC mutant gave rise to more dentinal fissure lesions and smooth surface caries than the wild‐type strain; this could be caused by a change in diffusion properties as a result of to the lack of mutan.
Effects of additional and extended acid etching on bonding to caries‐affected dentine
Authors: Arrais César Augusto Galvão , Giannini Marcelo , Nakajima Masatoshi , Tagami Junji
Published: September 2004

This study evaluated the effects of additional and extended acid etching on microtensile bond strength (µTBS) of two adhesive systems to sound (SD) and caries‐affected dentine (CAD). Flat surfaces of CAD surrounded by SD of 36 extracted carious third molars were assigned to four treatments (i): self‐etching adhesive system (Clearfil SE Bond) applied to dentine surfaces following manufacturer's instructions (MI); (ii) after additional etching for 15 s (35% phosphoric acid, PA); (iii) total‐etch one‐bottle adhesive (Single Bond) applied to dentine surfaces following MI; or (iv), after etching for 45 s with PA. Composite ‘blocks’ were built on bonded surfaces and restored teeth were vertically sectioned to obtain bonded slices of 0.7 mm thick. Slices were trimmed to create hourglass‐shaped specimens (cross‐sectional area of 1 mm2), which were tested under tension in a universal testing machine. Additional CAD and SD samples were prepared for scanning electron microscopy observations. Additional and extended etching significantly increased µTBS to CAD; however, µTBS of both adhesives to CAD were significantly lower than to SD. Additional and extended etching can improve bonding to CAD; however, adhesives applied on SD showed the best results for bonding.
Comparison of cellular and medium insulin and GABA content as markers for living β-cells
Authors: Wang Chen , Ling Zhidong , Pipeleers Daniel
Published: September 2004

Experimental and therapeutic use of islet cell preparations could benefit from assays that measure variations in the mass of living β-cells. Because processes of cell death can be followed by depletion and/or discharge of cell-specific substances, we examined whether in vitro conditions of β-cell death resulted in changes in tissue and medium content of insulin and of γ-aminobutyric acid (GABA), two β-cell-specific compounds with different cellular localization and turnover. Exposure of rat purified β-cells to streptozotocin (5 mM, 120 min) or to the nitric oxide donor GEA-3162 (GEA; 50 μM, 120 min) caused 80% necrosis within 24 h; at the end of this period, cellular insulin content was not significantly decreased, but cellular GABA content was reduced by 70%; when cultured at basal glucose (6 mM), the toxin-exposed cells did not discharge less insulin but released 80% less GABA in the period 8–24 h. As in rat β-cell purification, GABA comigrated with insulin during human islet cell isolation. Twenty-four hours after GEA (500 μM, 120 min), human islet cell preparations exhibited 90% dead cells and a 45 and 90% reduction, respectively, in tissue insulin and GABA content; in the period 9–24 h, insulin discharge in the medium was not reduced, but GABA release was decreased by 90%. When rat β-cells were cultured for 24 h with nontoxic interleukin (IL)-1β concentrations that suppressed glucose-induced insulin release, cellular GABA content was not decreased and GABA release increased by 90% in the period 8–24 h. These data indicate that a reduction in cellular and medium GABA levels is more sensitive than insulin as a marker for the presence of dead β-cells in isolated preparations. Pancreatic GABA content also rapidly decreased after streptozotocin injection and remained unaffected by 12 h of hyperglycemia. At further variance with insulin, GABA release from living β-cells depends little on its cellular content but increases with IL-1β-induced alterations in β-cell phenotype.
Human organic anion transporter MRP4 (ABCC4) is an efflux pump for the purine end metabolite urate with multiple allosteric substrate binding sites
Authors: Van Aubel Rémon A. M. H. , Smeets Pascal H. E. , van den Heuvel Jeroen J. M. W. , Russel Frans G. M.
Published: September 2004

The end product of human purine metabolism is urate, which is produced primarily in the liver and excreted by the kidney through a well-defined basolateral blood-to-cell uptake step. However, the apical cell-to-urine efflux mechanism is as yet unidentified. Here, we show that the renal apical organic anion efflux transporter human multidrug resistance protein 4 (MRP4), but not apical MRP2, mediates ATP-dependent urate transport via a positive cooperative mechanism ( Kmof 1.5 ± 0.3 mM, Vmaxof 47 ± 7 pmol·mg−1·min−1, and Hill coefficient of 1.7 ± 0.2). In HEK293 cells overexpressing MRP4, intracellular urate levels were lower than in control cells. Urate inhibited methotrexate transport (IC50of 235 ± 8 μM) by MRP4, did not affect cAMP transport, whereas cGMP transport was stimulated. Urate shifted cGMP transport by MRP4 from positive cooperativity ( Kmand Vmaxvalue of 180 ± 20 μM and 58 ± 4 pmol·mg−1·min−1, respectively, Hill coefficient of 1.4 ± 0.1) to single binding site kinetics ( Kmand Vmaxvalue of 2.2 ± 0.9 mM and 280 ± 50 pmol·mg−1·min−1, respectively). Finally, MRP4 could transport urate simultaneously with cAMP or cGMP. We conclude that human MRP4 is a unidirectional efflux pump for urate with multiple allosteric substrate binding sites. We propose MRP4 as a candidate transporter for urinary urate excretion and suggest that MRP4 may also mediate hepatic export of urate into the circulation, because of its basolateral expression in the liver.
17β-Estradiol replacement improves renal function and pathology associated with diabetic nephropathy
Authors: Mankhey Richard W. , Bhatti Faizah , Maric Christine
Published: September 2004

The protective factor of female gender appears to be lost in diabetes; the incidence of diabetes and its complications, including diabetic nephropathy, are equal in women and men. This study examined the effects of estrogen deficiency by ovariectomy (OVX) and replacement with 17β-estradiol (OVX+E2) on renal function and pathology in the nondiabetic (ND) and streptozotocin (STZ)-induced diabetic (D) rat kidneys for 12 wk. Diabetes was associated with an increase in urine albumin excretion (UAE; ND, 0.39 ± 0.03; D, 5.9 ± 0.8 mg/day; P < 0.001), decrease in creatinine clearance (CrCl; ND, 0.69 ± 0.03; D, 0.43 ± 0.09 mg·min−1·100 g body wt−1; P < 0.05), increase in the index of glomerulosclerosis [GSI; ND, 0.01 ± 0.01; D, 0.15 ± 0.04 arbitrary units (AU); P < 0.01], tubulointerstitial fibrosis (TIFI; ND, 0.04 ± 0.04; D, 0.68 ± 0.2 AU; P < 0.01), and transforming growth factor-β (TGF-β) protein expression (ND, 0.61 ± 0.02; D, 1.25 ± 0.07 AU; P < 0.01). In the D group, the severity of these changes was augmented with OVX (UAE, 8.1 ± 0.6 mg/day; CrCl, 0.40 ± 0.04 mg·min−1·100 g body wt−1; GSI, 0.29 ± 0.04 AU; TIFI, 0.90 ± 0.06 AU; TGF-β, 1.26 ± 0.10 AU), whereas E2 replacement attenuated these changes (UAE, 6.3 ± 0.8 mg/day; CrCl, 0.66 ± 0.03 mg·min−1·100 g body wt−1; GSI, 0.06 ± 0.02 AU; TIFI, 0.36 ± 0.08 AU; TGF-β, 0.57 ± 0.08 AU). We conclude that E2 deficiency increases the severity of renal disease in a diabetic animal model and that E2 replacement is renoprotective by attenuating the decline in renal function and pathology associated with diabetes.
Receptor tyrosine kinases mediate epithelial Na+channel inhibition by epidermal growth factor
Authors: Tong Qiusheng , Stockand James D.
Published: September 2004

Epidermal growth factor (EGF) decreases Na+reabsorption across distal nephron epithelia. Activity of the epithelial Na+channel (ENaC) is limiting for Na+transport in this portion of the nephron. Abnormal ENaC activity and EGF signaling are both associated with polycystic kidney disease localized to the distal nephron. We tested here whether EGF and other ligands for receptor tyrosine kinases (RTK) decrease ENaC activity. EGF markedly and quickly decreased ENaC activity. The RTK inhibitor erbstatin blocked EGF actions on ENaC and when added alone increased channel activity, uncovering basal suppression by endogenous RTK. The protein tyrosine phosphatase inhibitor vanadate, similar to EGF, decreased ENaC activity. Growth factors and vanadate decreased ENaC activity by decreasing open probability. ENaC was not phosphorylated in response to EGF, indicating that intermediary proteins transduce the inhibitory signal from the EGF receptor (EGFR) to ENaC. We find that neither MAPK 1/2 nor c-Src is signaling intermediaries between EGFR and ENaC. Inhibition of ENaC paralleled decreases in plasma membrane phosphatidylinositol 4,5- bisphosphate levels [PtdIns(4,5)P2] and was abolished by clamping PtdIns(4,5)P2. We conclude that EGF and other ligands for RTK decrease ENaC open probability by decreasing membrane PtdIns(4,5)P2levels.
Regulated interaction of the Fanconi anemia protein, FANCD2, with chromatin
Authors: Montes de Oca Rocio , Andreassen Paul R. , Margossian Steven P. , Gregory Richard C. , Taniguchi Toshiyasu , Wang XiaoZhe , Houghtaling Scott , Grompe Markus , D'Andrea Alan D.
Published: September 2004

DNA damage activates the monoubiquitination of the Fanconi anemia (FA) protein, FANCD2, resulting in the assembly of FANCD2 nuclear foci. In the current study, we characterize structural features of FANCD2 required for this intranuclear translocation. We have previously identified 2 normal mRNA splice variants of FANCD2, one containing exon 44 sequence at the 3′ end (FANCD2-44) and one containing exon 43 sequence (FANCD2-43). The 2 predicted FANCD2 proteins differ in their carboxy terminal 24 amino acids. In stably transfected FANCD2—/— fibroblasts, FANCD2-44 and FANCD2-43 proteins were monoubiquitinated on K561. Only FANCD2-44 corrected the mitomycin C (MMC) sensitivity of the transfected cells. We find that monoubiquitinated FANCD2-44 was translocated from the soluble nuclear compartment into chromatin. A mutant form of FANCD2-44 (FANCD2-K561R) was not monoubiquitinated and failed to bind chromatin. A truncated FANCD2 protein (Exon44-T), lacking the carboxy terminal 24 amino acids encoded by exon 44 but retaining K561, and another mutant FANCD2 protein, with a single amino acid substitution at a conserved residue within the C-terminal 24 amino acids (D1428A), were monoubiquitinated. Both mutants were targeted to chromatin but failed to correct MMC sensitivity. Taken together, our results indicate that monoubiquitination of FANCD2 regulates chromatin binding and that D1428 within the carboxy terminal acidic sequence encoded by exon 44 is independently required for functional complementation of FA-D2 cells. We hypothesize that the carboxy terminus of FANCD2-44 plays a critical role in sensing or repairing DNA damage.
IL-8 and its CXCR1 and CXCR2 receptors participate in the control of megakaryocytic proliferation, differentiation, and ploidy in myeloid metaplasia with myelofibrosis
Authors: Emadi Sharareh , Clay Denis , Desterke Christophe , Guerton Bernadette , Maquarre Eliane , Charpentier Agnès , Jasmin Claude , Le Bousse-Kerdilès Marie-Caroline ,   for the French INSERM Research Network on MMM
Published: September 2004

Myeloproliferation, myelofibrosis, and neoangiogenesis are the 3 major intrinsic pathophysiologic features of myeloid metaplasia with myelofibrosis (MMM). The myeloproliferation is characterized by an increased number of circulating CD34+ progenitors with the prominent amplification of dystrophic megakaryocytic (MK) cells and myeloid metaplasia in the spleen and liver. The various biologic activities of interleukin 8 (IL-8) in hematopoietic progenitor proliferation and mobilization as well as in neoangiogenesis prompted us to analyze its potential role in MMM. We showed that the level of IL-8 chemokine is significantly increased in the serum of patients and that various hematopoietic cells, including platelets, participate in its production. In vitro inhibition of autocrine IL-8 expressed by CD34+ cells with either a neutralizing or an antisense anti–IL-8 treatment increases the proliferation of MMM CD34+-derived cells and stimulates their MK differentiation. Moreover, addition of neutralizing anti–IL-8 receptor (CXC chemokine receptor 1 [CXCR1] or 2 [CXCR2]) antibodies to MMM CD34+ cells cultured under MK liquid culture conditions increases the proliferation and differentiation of MMM CD41+ MK cells and restores their polyploidization. Our results suggest that IL-8 and its receptors participate in the altered MK growth that features MMM and open new therapeutic prospects for this still incurable disease.
Mortality in sickle cell patients on hydroxyurea therapy
Authors: Bakanay Sule M. , Dainer Erin , Clair Betsy , Adekile Adekunle , Daitch Lisa , Wells Leigh , Holley Leslie , Smith David , Kutlar Abdullah
Published: September 2004

The efficacy of hydroxyurea (HU) and its role in the reduction in mortality in sickle cell patients has been established. Nevertheless, many patients still die of complications of this disease while on HU. Of the 226 patients treated with HU at our center, 38 died (34 of sickle cell–related causes). Acute chest syndrome (ACS) was the most common (35%) cause of death. Deceased and surviving patients did not differ significantly in average HU dose, baseline fetal hemoglobin (Hb F), or maximum Hb F response. However, the deceased patients were significantly older when HU was instituted, were more anemic, and more likely to have BAN or CAM haplotypes. They also had significantly higher serum blood-urea-nitrogen (BUN) and creatinine levels. Sickle cell patients who die while on HU therapy may represent a subgroup of older patients, possibly with more severe disease and more severe organ damage. Such patients need early identification and prompt HU institution.
SPI-CI and SPI-6 cooperate in the protection from effector cell–mediated cytotoxicity
Authors: Bots Michael , Kolfschoten Ingrid G. M. , Bres Sandra A. , Rademaker Mirjam T. G. A. , de Roo Guido M. , Krüse Margreet , Franken Kees L. M. C. , Hahne Michael , Froelich Christopher J. , Melief Cornelis J. M. , Offringa Rienk , Medema Jan Paul
Published: September 2004

Tumors have several mechanisms to escape from the immune system. One of these involves expression of intracellular anticytotoxic proteins that modulate the execution of cell death. Previously, we have shown that the serine protease inhibitor (serpin) SPI-6, which inactivates the cytotoxic protease granzyme B (GrB), is capable of preventing cytotoxic T lymphocyte (CTL)–mediated apoptosis. Despite its potent antiapoptotic activity, SPI-6 does not prevent membranolysis induced by cytotoxic lymphocytes. We now provide evidence that several colon carcinoma cell lines do resist membranolysis and that this protection is dependent on SPI-6 but also requires expression of a closely related serpin called SPI-CI (serine protease inhibitor involved in cytotoxicity inhibition). Expression of SPI-CI is absent from normal colon but observed in placenta, testis, early during embryogenesis, and in cytotoxic lymphocytes. SPI-CI encodes a chymotrypsin-specific inhibitor and irreversibly interacts with purified granzyme M. Moreover, SPI-CI can protect cells from purified perforin/GrM-induced lysis. Our data therefore indicate that SPI-CI is a novel immune escape molecule that acts in concert with SPI-6 to prevent cytotoxic lymphocyte-mediated killing of tumor cells.