bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening of blood donors for hepatitis C virus RNA with the MagNA Pure‐COBAS AmpliScreen method
Authors: Palomäki Pekka , Wessberg Susanna , Tuomi Katri , Laitinen Harri
Published: August 2006

BACKGROUND: This report describes the validation results and the performance characteristics of a new, semiautomated minipool nucleic acid amplification method for testing of blood products to reduce the transmission of hepatitis C virus (HCV) by transfusions.

STUDY DESIGN AND METHODS: Minipools of 96 donations were prepared with the Tecan Genesis pipettors. Nucleic acids were isolated from plasma samples with the MagNA Pure LC instrument (Roche Diagnostics GmbH) and amplified and detected with the COBAS AmpliScreen second‐generation HCV assay (Roche Molecular Systems, Inc.). Sensitivity of the method was determined with the WHO International Standard for HCV RNA (NIBSC 96/790) as a reference. The risk of cross‐contamination during the nucleic acid extraction and postelution steps was studied with a highly viremic sample.

RESULTS: Detection limit of the assay (95% hit rate) was calculated to be 11.7 IU per mL. Altogether 2,423 minipools (232,600 donations) were screened with the following performance characteristics: initially false‐reactive results (0%), failure of run control detection (0.45%), and failure of internal control detection (0.90%). Two cross‐contamination cases caused by a highly viremic sample were found during the validation phase but not in the routine screening period, although nine HCV RNA–positive minipool samples were observed.

CONCLUSION: This combination of HCV RNA screening methods showed the detection limit that is well below the sensitivity requirements of the regulatory bodies. Robustness of the validated HCV RNA screening method has proved to be acceptable for routine screening of blood donors on a large scale.
Noninvasive determination of fetalRHDstatus by examination of cell‐free DNA in maternal plasma
Authors: Brojer E. , Żupanska B. , Guz K. , Orziñska A. , Kaliñska A.
Published: August 2006

BACKGROUND:Cell‐free fetal DNA in maternal plasma opens the way for routine risk‐free diagnosis of fetal D status of D– mothers. The focus was on accuracy ofRHDtyping and confirmation of fetal DNA in maternal plasma whileRHDwas not detected.

STUDY DESIGN AND METHODS:Plasma DNA was extracted (by manual and/or automatic method) from 255 D– pregnant women and amplified in exons 7 and 10 and intron 4 ofRHDgene with real‐time polymerase chain reaction. The presence of fetal DNA was confirmed by testingSRYand, when negative, by one of 11 different polymorphisms found in the father but not in the mother. The results were compared with the D status of the newborns.

RESULTS:After exclusion of 25 cases (10%) because of material shortage, in 230 cases (90%) available for complete study, the predictive value of the procedure of fetalRHDtesting (RHDgenotyping plus confirmation of fetal DNA) was 99.6 percent.SRYdetection confirmed fetal DNA presence in maternal plasma in all boys, whereas the detection of various polymorphisms in all girls but one.

CONCLUSIONS:FetalRHDgenotyping from maternal plasma may be used with confidence, although additional polymorphisms for confirmation of fetal DNA should be included for 100 percent predictive value (instead of 99.6%).
Maternal alloimmunization against the rare platelet‐specific antigen HPA‐9b (Maxa) is an important cause of neonatal alloimmune thrombocytopenia
Authors: Peterson Julie A. , Balthazor Stephanie M. , Curtis Brian R. , McFarland Janice G. , Aster Richard H.
Published: August 2006

BACKGROUND: Neonatal alloimmune thrombocyto‐penia (NATP) is an important cause of morbidity and mortality in the newborn. Optimal management of subsequent pregnancies requires knowledge of the alloantigen that caused maternal immunization, but this is possible only in a minority of cases. This study investigated whether this can be explained in part by maternal immunization against the “rare” alloantigen HPA‐9b (Maxa), implicated previously only in a single NATP case.

STUDY DESIGN AND METHODS: Archived paternal DNA from unresolved cases of NATP and normal individuals was typed for platelet (PLT)‐specific antigens with real‐time polymerase chain reaction and direct sequencing. PLT‐specific alloantibodies were character‐ized by flow cytometry and solid‐phase enzyme‐linked immunosorbent assay. Recombinant GPIIb/IIIa was expressed in stably transfected Chinese hamster ovary cells. Clinical information was obtained directly from attending physicians.

RESULTS: Six of 217 fathers were positive for the presence of HPA‐9b (Maxa), an incidence about seven times that in the general population. In each of five cases studied, maternal serum samples reacted with intact paternal PLTs and paternal GPIIb/IIIa. Only one of three serum samples tested recognized recombinant GPIIb/IIIa carrying the HPA‐9b (Maxa) mutation. These seemingly discrepant reactions may reflect different requirements for oligosaccharides linked to residues close to the mutation in GPIIb that determines HPA‐9b (Maxa). NATP in the affected children was severe and was associated with intracranial hemorrhage in three of six infants on whom information was obtained.

CONCLUSIONS: Maternal immunization against HPA‐9b (Maxa) is an important cause of NATP and should be considered in cases of apparent NATP not resolved on the basis of maternal‐fetal incompatibility for “common” PLT antigens.
Soluble glycoprotein V as a quality marker of platelet concentrates stressed by transportation
Authors: Javela Kaija , Eronen Juha , Sarna Seppo , Kekomäki Riitta
Published: August 2006

BACKGROUND: Despite ongoing improvements in storage conditions for platelet concentrates (PCs) for clinical use, leukoreduced platelets (PLTs) undergo subtle changes that are partly due to PLT activation. As PLTs are activated, the expression of P‐selectin (CD62P) increases, and soluble glycoprotein V (sGPV) is released. GPV, part of the GPIbIXV complex, has been suggested as a marker of PLT activation.

STUDY DESIGN AND METHODS: An array of assays, used for quality control of PCs, was performed and the results were compared. The tests included PLT count, swirling, mean PLT volume, extent of shape change (ESC), hypotonic shock response (HSR), CD62P, lysosomal membrane protein (CD63), sGPV, and the metabolic tests (pH, pO2, pCO2, lactate, glucose). The performance of the assays was evaluated during the storage period by comparing buffy coat–derived PCs (24 PCs of 4 units) stored on flatbed agitator or stressed twice by overnight transportation.

RESULTS: The repeatability of all tests was good. ESC and HSR correlated with each other (r = 0.559). Importantly, there were also associations between sGPV and ESC (r = −0.564) and HSR (r = −0.389). The correlations of sGPV with lactate and glucose concen‐trations and with expression of CD62P and CD63 were also good. No significant changes were induced by two overnight transportations.

CONCLUSION: sGPV might be applicable for statistical process control of the quality of PCs, in addition to metabolic tests. It may also be helpful in analyzing potential improvements in blood component processing. Repeat transportation of PCs may cause minimal changes on PLT in vitro properties, if any.
Evaluation of BacT/ALERT plastic culture bottles for use in testing pooled whole blood–derived leukoreduced platelet‐rich plasma platelets with a single contaminated unit
Authors: Brecher M.E. , Hay S.N. , Rose A.D. , Rothenberg S.J.
Published: August 2006

BACKGROUND: In certain countries, whole blood–derived platelet (PLT)‐rich plasma PLTs can only be pooled within 4 hours of transfusion. One prerequisite for prestorage pooling is the ability to detect low levels of bacteria from a single unit (approx. 10 colony‐forming units [CFUs]/mL) once pooled (10/6 approx. 2 CFUs/mL). This study evaluated the BacT/ALERT (bioMérieux) for detection of bacteria in 1 unit of a 6‐unit pool.

STUDY DESIGN AND METHODS: Bacillus cereus, Clostridium perfringens, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Streptococcus viridans, and Propionibacterium acnes were inoculated into single PLT units (target, 10 and 100 CFUs/mL; mean recovered, 5 and 92 CFUs/mL) and then pooled with 5 sterile units. Four milliliters was inoculated into both plastic aerobic and anaerobic bottles, and 0.5 mL was plated (10 sets).

RESULTS: All cases were detected when the single unit had at least 6 CFUs per mL. With B. cereus (≤2 CFUs/mL), all bottles were reactive. With K. pneumoniae and S. viridans (≤3 CFUs/mL), all samples were detected with a two‐bottle set, but not all bottles were reactive. With S. marcescens (<2 CFUs/mL), only 7 of the 10 sets were reactive. With C. perfringens (0.2 CFUs/mL), only 3 of 10 samples were detected in the anaerobic bottles.

CONCLUSIONS: This study evaluates the use of the BacT/ALERT system for detection of bacteria in PLT pools. Overall, the BacT/ALERT detected all contami‐nated pooled PLTs when the single inoculated unit had a calculated or recovered concentration at least 3 CFUs per mL with 10 different species of bacteria. Low recovered concentrations (≤2 CFUs/mL) were, in some cases, only detected with a two‐bottle set.
The application of a new quantitative assay for the monitoring of integrin‐associated protein CD47 on red blood cells during storage and comparison with the expression of CD47 and phosphatidylserine with flow cytometry
Authors: Stewart Andrew , Urbaniak Stan , Turner Marc , Bessos Hagop
Published: August 2006

BACKGROUND:After the introduction of universal leukoreduction, the role of factors other than white blood cells in red cell (RBC) storage lesion is attracting increasing attention. These include changes in the levels of CD47 and phosphatidylserine (PS) markers on RBCs during storage. The aim of this study was to monitor these changes with both flow cytometry (FACS) and a newly developed quantitative enzyme‐linked immunosorbent assay (ELISA).

STUDY DESIGN AND METHODS:A new quantitative ELISA (monoclonal antibody immobilization of RBC antigens [MAIRA]) was developed. The assay yielded consistent linear curves that enabled the measurement of CD47 expression on RBCs. In addition, FACS was used to measure both CD47 expression and PS on RBCs (n = 3 units) during storage (Days 4, 10, 24, and 31).

RESULTS:A significant reduction in CD47 expression was observed both by MAIRA assay and by FACS by Days 24 and 31 (p < 0.01), and the correlation between the two assays was significant (p < 0.01). In addition, a significant increase in PS was observed by the same storage days with FACS (p < 0.01).

CONCLUSION:The MAIRA assay appears to be suitable for the quantitative measurement of RBC markers during storage. Significant changes in CD47 and PS levels were observed during storage, which may have detrimental immunomodulatory and hemostatic effects on the transfused RBCs.
Effects of Right, Left, and Biventricular Pacing on Myocardial Perfusion in Ischemic Conditions
Authors: LAFITTE STEPHANE , REANT PATRICIA , LABROUSSE LOUIS , BORDACHAR PIERRE , TARIOSSE LILIANE , BEAUVOIT BERTRAND , SERRI KARIM , BONORON‐ADÈLE SIMONE , ROUDAUT RAYMOND , SANTOS PIERRE DOS
Published: August 2006

Objectives: In normal hearts, the distribution of regional myocardial perfusion is altered by ventricular pacing. Little is known about the impact of ventricular pacing on regional myocardial perfusion in ischemic conditions. In this acute echocardiographic study, we compared the respective effects of right ventricular pacing (RVP), left ventricular pacing (LVP), and biventricular pacing (BVP) on regional perfusion in a swine model of graded ischemia.

Methods and Results: Ventricular pacing leads were placed at the apex of the right ventricle and on the lateral wall of the left ventricle in nine open‐chest pigs. Myocardial contrast echocardiography was successively performed during spontaneous rhythm (SR), RVP, LVP, and BVP in random order at baseline and during three stages of incremental ischemia (left anterior descending + circumflex). At baseline, RVP decreased myocardial perfusion of the septal and inferior walls compared to SR (P < 0.05), whereas LVP decreased perfusion of the lateral wall (P < 0.05). No significant differences were observed in regional perfusion during BVP compared to SR. In ischemic conditions, RVP worsened myocardial perfusion in the ischemic anterior wall as well as in the septal and inferior walls (P < 0.05), whereas both LVP and BVP did not alter perfusion in the ischemic area compared to SR.

Conclusion: Compared to baseline, in ischemic conditions, RVP has a more pronounced detrimental impact on perfusion abnormalities. In contrast, BVP induced a significant improvement in local myocardial perfusion. Therefore, BVP could be preferred to RVP in patients with ischemic cardiomyopathy.
Post‐Operative Atrial Fibrillation Is Influenced by Beta‐Blocker Therapy But Not by Pre‐Operative Atrial Cellular Electrophysiology
Authors: WORKMAN ANTONY J. , PAU DAVIDE , REDPATH CALUM J. , MARSHALL GILLIAN E. , RUSSELL JULIE A. , KANE KATHLEEN A. , NORRIE JOHN , RANKIN ANDREW C.
Published: August 2006

Introduction: We investigated whether post‐cardiac surgery (CS) new‐onset atrial fibrillation (AF) is predicted by pre‐CS atrial cellular electrophysiology, and whether the antiarrhythmic effect of beta‐blocker therapy may involve pre‐CS pharmacological remodeling.

Methods and Results: Atrial myocytes were obtained from consenting patients in sinus rhythm, just prior to CS. Action potentials and ion currents were recorded using whole‐cell patch‐clamp technique. Post‐CS AF occurred in 53 of 212 patients (25%). Those with post‐CS AF were older than those without (67 ± 2 vs 62 ± 1 years, P = 0.005). In cells from patients with post‐CS AF, the action potential duration at 50% and 90% repolarization, maximum upstroke velocity, and effective refractory period (ERP) were 13 ± 4 ms, 217 ± 16 ms, 185 ± 10 V/s, and 216 ± 14 ms, respectively (n = 30 cells, 11 patients). Peak L‐type Ca2+ current, transient outward and inward rectifier K+ currents, and the sustained outward current were −5.0 ± 0.5, 12.9 ± 2.4, −4.1 ± 0.4, and 9.7 ± 1.0 pA/pF, respectively (13–62 cells, 7–19 patients). None of these values were significantly different in cells from patients without post‐CS AF (P > 0.05 for each, 60–279 cells, 29–86 patients), confirmed by multiple and logistic regression. In patients treated >7 days with a beta‐blocker pre‐CS, the incidence of post‐CS AF was lower than in non‐beta‐blocked patients (13% vs 27%, P = 0.038). Pre‐CS beta‐blockade was associated with a prolonged pre‐CS atrial cellular ERP (P = 0.001), by a similar degree (∼20%) in those with and without post‐CS AF.

Conclusion: Pre‐CS human atrial cellular electrophysiology does not predict post‐CS AF. Chronic beta‐blocker therapy is associated with a reduced incidence of post‐CS AF, unrelated to a pre‐CS ERP‐prolonging effect of this treatment.
Lifetime Cumulative Incidence of Syncope in the General Population: A Study of 549 Dutch Subjects Aged 35–60 Years
Authors: GANZEBOOM KARIN S. , MAIRUHU GIDEON , REITSMA JOHANNES B. , LINZER MARK , WIELING WOUTER , VAN DIJK NYNKE
Published: August 2006

Introduction:There are limited and conflicting data on the lifetime cumulative incidence of syncope in the general population. The aim of our study was to determine the lifetime cumulative incidence and triggers of syncope in the general population.

Methods:Questions about syncope were added to a cross‐sectional survey on cardiovascular risk factors carried out between 2001 and 2003 in 549 native Dutch respondents, aged 35–60 years.

Results:The lifetime cumulative incidence of syncope in our study population was 35% (95% confidence interval 31–39%). Syncope occurred more often in women than in men (41% vs 28%; P = 0.003). A peak in the incidence of syncope occurred around the age of 15 years in both men and women. The median number of episodes in persons with syncope was 2 (Inter Quartile Range 1–5). The top five most frequently mentioned triggers of syncope included warm environment, pain, insufficient food intake, seeing blood/venipuncture, and emotion.

Conclusion:In conclusion, our study shows that the lifetime cumulative incidence of syncope in the general population is high. Females experience syncope more often than males. The majority of the syncope triggers were related to conditions that affect orthostatic blood pressure regulation and vasomotor responses.
TiO2‐Doped Zirconia: Crystal Structure, Monoclinic‐Tetragonal Phase Transition, and the New Tetragonal Compound Zr3TiO8
Authors: Troitzsch Ulrike
Published: August 2006

Zirconia samples with up to 27 mol% TiO2were synthesized at low and elevated pressures, significantly extending the range of ZrO2–TiO2solid solution compared with previous crystal structure studies of monoclinic and tetragonal zirconia (<17.5 mol%). Crystal structure data collected by powder X‐ray diffraction (XRD) at ambient conditions reveal that the solid solution of TiO2in monoclinic zirconia (baddeleyite structure,P21/c) is limited to about 25 mol%, where the tetragonal compound Zr3TiO8forms. Changes in the monoclinic crystal structure with increasing TiO2can be understood in the light of the nearing monoclinic–tetragonal phase change. Unit‐cell dimensionsaandbbecome near identical, cell angle β starts to drop toward 90°, and atom positions start to change toward those of the tetragonal cell. The cation coordination polyhedron in the monoclinic structure becomes increasingly distorted, and bond–valence sums worsen. The transition from the monoclinic to the tetragonal lattice with increasing TiO2is not smooth however, but shows a significant jump in many of the parameters, in line with the first‐order character of this transition.

The previously unknown inorganic compound Zr3TiO8has a structure related to that of tetragonal zirconia (P42/nmc), whereby weak superstructure reflections indicate that the structure is ordered and has a doubledc‐dimension. Zr3TiO8has the unit‐cell dimensionsa=5.0317(4) Å andc=10.4273(7) Å, space group (I‐42m), and is isostructural with the compound Zr3GeO8, with Ti4+in tetrahedral coordination and Zr4+in eightfold coordination. The stabilization of tetragonal Zr3TiO8at ambient conditions depends strongly on the cooling rate, which has to be slow enough (e.g., 1°C/min) to allow for ordering to occur. Rapid quenching (e.g., ∼140°C/s) of the same composition results in monoclinic zirconia. The lowering of the tetragonal–monoclinic phase transition to ambient conditions near 25 mol% TiO2is in good agreement with extrapolations from previous studies. The relatively coarse grain size (<20 μm) of the Zr3TiO8crystals suggest that the tetragonal structure was not retained because of grain‐size effects, but was stabilized predominantly by crystal structure adjustments based on cation size. Broadening and shortening of selected XRD peaks especially upon grinding suggests that tetragonal Zr3TiO8, depending on cooling rate and degree of ordering, may be retained metastably at room temperature, and is thus a potential candidate for TZP ceramics.
Formation of Strontium‐Stabilized β‐Tricalcium Phosphate from Calcium‐Deficient Apatite
Authors: Kannan S. , Pina S. , Ferreira J. M. F.
Published: August 2006

A series of strontium‐stabilized β‐tricalcium phosphate (β‐TCP) was prepared via the aqueous precipitation method, and characterized by X‐ray diffraction and infrared fourier spectrometer techniques. The general principle of preparing calcium‐deficient apatite and thereby heat‐treating the resultant apatite above 700°C to form single‐phase β‐TCP was attempted to create strontium‐substituted β‐TCP. The results have proved that single phase β‐TCP could be formed with the substituted strontium with only an influence on the increase in lattice constants with an increase in the concentration of strontium. Further, it is also stated from the present findings that strontium has a specific role in the crystallinity of the resultant β‐TCP.
Fabrication of Low‐Density Ferrous Metallic Foams by Reduction of Chemically Bonded Ceramic Foams
Authors: Verdooren A. , Chan H. M. , Grenestedt J. L. , Harmer M. P. , Caram H. S.
Published: August 2006

Closed cell ferrous foams were fabricated using a chemically bonded oxide ceramic foam precursor. The major constituent of the ceramic foam precursor was iron oxide (Fe2O3), which was mixed with various foaming/setting additives. The density of the foam was modified by varying the ambient pressure under which foaming was carried out. Further, a magnesium–ammonium phosphate‐based cement system was utilized to promote more rapid setting times and hence minimize foam collapse. The oxide foam was then reduced by heating at 1240°C in a non‐flammable hydrogen/inert gas mixture to obtain metallic foams. The relative density of samples foamed under a reduced pressure (∼380 Torr) was 0.13±0.006, which is the lowest value reported to date for a closed cell ferrous foam. A relative density of 0.21±0.01 was achieved for samples foamed under atmospheric pressure. With regard to the foam morphology, the average cell diameter was 1.41±0.6 mm for the low‐density (LD) foams, and 0.96±0.2 mm for the high‐density (HD) foams. The iron foams were tested in compression and yielded an average compressive strength of 11±1 and 19±4 MPa for the LD and HD foams, respectively. A comparison based on a bending strength performance index showed that the properties of the ceramic–precursor‐derived foams compared favorably with those of steel foams fabricated by other techniques.
A New Scheme of Finding the Master Sintering Curve
Authors: Kiani S. , Pan J. , Yeomans J. A.
Published: August 2006

The master sintering curve approach represents densification data in terms of a master variable that combines sintering time and temperature. Recently, a finite‐element scheme to predict sintering deformation that requires only the master sintering curve instead of a full constitutive law as the input data has been developed. Here, a modification to the original master sintering curve approach, so that it is more suitable for finite‐element analysis, is presented. Finite‐element shape functions are used to represent the densification data as well as the master sintering curve. This approach confers extra flexibility to the master sintering curve approach, even when it is not used with finite‐element analysis. For example, by using shape functions, a varying activation energy can be used to obtain a master sintering curve for a set of densification data that cannot be fitted using a constant activation energy.
The criterion validity of the Geriatric Depression Scale: a systematic review
Authors: Wancata J. , Alexandrowicz R. , Marquart B. , Weiss M. , Friedrich F.
Published: August 2006

Objective:  The objective was to provide a systematic review of the screening accuracy of both versions of the Geriatric Depressions Scale (GDS‐30, GDS‐15).

Method:  An electronic search was performed by using Medline, Embase, Cinahl, Psyndex and the Cochrane library. The selection and examination of papers were performed by two reviewers independently.

Results:  Among the 42 papers included, important methodological aspects such as sampling methods or blinding of research workers often were not reported. For both GDS versions, similar validity indices were found (GDS‐30: sensitivity 0.753, specificity 0.770; GDS‐15: sensitivity 0.805, specificity 0.750). Using comparative studies based on the identical samples, both GDS versions showed significantly better validity indices than the ‘Yale‐1‐question’ screen, but were similar to the ‘Center for Epidemiological Studies Depression scale’ (CES‐D).

Conclusion:  The GDS does not show a better criterion validity than the CES‐D, but methodological limitations of primary studies hamper the generalizability of pooled analyses.
Antidepressants and sexual dysfunction
Authors: Werneke U. , Northey S. , Bhugra D.
Published: August 2006

Objective: Many patients with depression suffer from sexual dysfunction and sexual dysfunction is a recognized side‐effect of antidepressants. The aim of this review was to examine the prevalence of psychosexual dysfunction associated with antidepressants, and to review treatment options which are specific to the affected component of sexual functioning and antidepressants.

Method: Comprehensive literature review using Medline and Cochrane databases.

Results: Up to 70% of patients with depression may have sexual dysfunction. Tricyclic antidepressants, selective‐serotonin reuptake inhibitors and venlafaxine are most and the non‐serotonergic antidepressants and duloxetine least likely to produce sexual dysfunction. Pharmacological treatment options include antidepressants less likely associated or ‘antidotes’ to reverse sexual dysfunction.

Conclusion: Sexual dysfunction may be a preventable or treatable side‐effect of antidepressants. Patients need routinely to be asked about sexual function to identify problems early. If sexual dysfunction is ignored it may maintain the depression, compromise treatment outcome and lead to non‐compliance.
Expression pattern of somatostatin receptor subtypes 1–5 in human skin: an immunohistochemical study of healthy subjects and patients with psoriasis or atopic dermatitis
Authors: Hagströmer Lena , Emtestam Lennart , Stridsberg Mats , Talme Toomas
Published: August 2006

Abstract:  In psoriasis and atopic dermatitis, the inflammatory events have neurogenic components and the neuropeptides modify the functions of immuno‐active cells in the skin. Somatostatin is a neuropeptide with several neuroendocrine and immunomodulating properties and mediates its actions by five distinct subtypes of G‐protein‐coupled receptors (SSTR1‐5). This study describes the distribution of SSTR1–5, analysed with immunohistochemistry, in psoriasis, atopic dermatitis and controls. Normal human skin and lesional skin from patients with psoriasis or atopic dermatitis showed many similarities, but also some differences, as regards SSTR expression. SSTR1–3 were strongly expressed in the epidermis of healthy skin, and in the skin of patients with psoriasis or atopic dermatitis. It is noteworthy that SSTR4 and 5 were strongly expressed in the epidermis of psoriasis patients, but weakly expressed in the epidermis of those with atopic dermatitis and normal skin. The intensity of the staining also varied considerably between the different layers of the epidermis, especially in psoriasis patients. In all cases, the dendritic cells, found mostly in the papillary and upper reticular dermis, showed a strong expression of SSTR1–4, but a weak expression of SSTR5. SSTR1–5 were strongly expressed in the sweat glands in all skin biopsies. Hair follicles and sebaceous glands expressed all five subtypes. Striated muscle fibres showed an intense positive expression of SSTR1–4, but a weak or negative expression of SSTR5. The wide distribution and expression pattern of all five SSTRs in human skin suggest that somatostatin is involved in the interactions between the nervous system and the skin.
Oestrogen receptor‐β expression in melanocytic lesions
Authors: Schmidt Adriana N. , Nanney Lillian B. , Boyd Alan S. , King Lloyd E. , Ellis Darrel L.
Published: August 2006

Abstract:  Melanomas rarely occur before puberty, have a higher death rate for males, and tend to be more invasive during pregnancy. Prior to the discovery of a second oestrogen receptor (ERβ), studies with the initial oestrogen receptor, ERα, showed no obvious role for oestrogen in the pathophysiology of benign or malignant melanocytic lesions. To investigate the specific immunostaining patterns of ERα and ERβ, benign nevocytic nevi, dysplastic nevi with mild, moderate and severe cytological atypia, lentigo malignas and melanomas of varying depth (Clark) and thickness (Breslow) were studied. ERβ but not ERα was the predominant oestrogen receptor we found in all types of benign and malignant melanocytic lesions. The most intense ERβ immunostaining was seen in melanocytes in dysplastic nevi with severe cytological atypia and in lentigo malignas. ERβ expression levels also correlated with the malignant tumor microenvironment; i.e., melanocytes in proximity with keratinocytes>deeper dermal melanocytes in contact with stroma>minimally invasive melanomas>Clark Level III/IV or thick melanomas (Breslow). Discovery that ERβ expression varies in relation to the tumor microenvironment and increasing depth of invasion suggests its possible usefulness as a surrogate marker for neoplasia and prognosis in malignant melanoma.
Cross-correlation of Wilkinson Microwave Anisotropy Probe third-year data and the Sloan Digital Sky Survey DR4 galaxy survey: new evidence for dark energy
Authors: Cabré A. , Gaztañaga E. , Manera M. , Fosalba P. , Castander F.
Published: August 2006

We cross-correlate the third-year Wilkinson Microwave Anisotropy Probe (WMAP) data with galaxy samples extracted from the SDSS DR4 (SDSS4) covering 13 per cent of the sky, increasing the volume sampled in previous analysis by a factor of 3.7. The new measurements confirm a positive cross-correlation with higher significance (total signal-to-noise ratio of about 4.7). The correlation as a function of angular scale is well fitted by the integrated Sachs–Wolfe (ISW) effect for Λ cold dark matter (ΛCDM) flat Friedmann–Robertson–Walker models with a cosmological constant. The combined analysis of different samples gives ΩΛ = 0.80–0.85 (68 per cent confidence level, CL) or 0.77–0.86 (95 per cent CL). We find similar best-fitting values for ΩΛ for different galaxy samples with median redshifts of z≃ 0.3 and z≃ 0.5, indicating that the data scale with redshift as predicted by the LCDM cosmology (with equation of state parameter w =−1). This agreement is not trivial, but cannot yet be used to break the degeneracy constraints in the w versus ΩΛ plane using only the ISW data.
The remedy in conversion: confusing property and obligation
Authors: Curwen Nick
Published: August 2006

Where a defendant wrongfully detains the claimant’s goods the standard remedy in conversion permits the defendant to pay the value of the goods to the claimant instead of returning the goods. This amounts to legally sanctioned compulsory purchase. It will be argued that such a remedy is both muddled and unfair. It is muddled because it confuses a proprietary claim with a claim in tort. The action exists in a state of arrested development, never having advanced in step with the action of ejectment, which long ago ensured that wrongfully detained land could be recovered. It is unfair because it sanctions the purchase of the claimant’s goods against their will without any overriding public interest justification. The remedy in conversion needs to be unravelled to produce two distinct actions. One would be a true proprietary action that guarantees the recovery of wrongfully detained goods; the other would be a claim in tort providing personal remedies for wrongful interferences with title to goods. This can be achieved by reviving detinue but confining its ambit to the recovery of goods, leaving conversion to act as a tort.
To foster or to temper? Regulating the political activities of the voluntary and community sector
Authors: Dunn Alison
Published: August 2006

A recent consultation by the European Commission on a draft code of conduct for the voluntary and community sector to combat illegal political activities highlights the regulation of the sector. This paper considers the European Commission’s code in light of the current regulation for charities and the wider voluntary and community sector, questioning whether sector-specific regulation of political activities is achievable and how such regulation could be best achieved.
Law reform and human rights – Scarman’s great legacy
Authors: Kirby Michael
Published: August 2006

Leslie Scarman was one of the most influential common law judges of the twentieth century. As a judge, he was relatively conventional and sometimes unadventurous. His technique can be contrasted with that of his contemporary, Lord Denning. However, his role in establishing the Law Commission of England and Wales afforded a model that has been copied throughout the world. His early support for a law of human rights encouraged the adoption of the Human Rights Act 1998. This paper explains the essential unity of Scarman’s legal philosophy and the importance of his contribution at a time when basic assumptions about governance in Westminster democracies are being re-examined and sometimes found wanting.
Causation in personal injury: legal or epidemiological common sense?
Authors: Miller Chris
Published: August 2006

The approach adopted by epidemiologists when attributing a causal mechanism to an observed statistical association is contrasted with the common law of causation in personal injury cases. By recognising the need to distinguish between probabilistic measures of (1) the strength of an association and (2) the fact-finder’s ‘degree of belief’ in the claimant’s causal hypothesis, the verdicts in a number of epidemiology-based cases, mostly in British courts, are shown to be questionable. The argument is then made for a wider application of proportionate liability, extending beyond defective drug cases (where epidemiological evidence is most often found) to medical negligence, occupational injury and tobacco-related litigation. An increased coherence in the common law of personal injury can be achieved without compromising the fundamental aims of tort and, it is argued, by reaffirming the importance of just one ‘policy’ precedent on liability for increasing risk.
Actinobacillus actinomycetemcomitansOuter Membrane Protein 100 Triggers Innate Immunity and Production of β-Defensin and the 18-Kilodalton Cationic Antimicrobial Protein through the Fibronectin-Integrin Pathway in Human Gingival Epithelial Cells
Authors: Ouhara Kazuhisa , Komatsuzawa Hitoshi , Shiba Hideki , Uchida Yushi , Kawai Toshihisa , Sayama Koji , Hashimoto Koji , Taubman Martin A. , Kurihara Hidemi , Sugai Motoyuki
Published: August 2006

Antimicrobial peptides, human β-defensin (hBD), and the 18-kDa cationic antimicrobial protein (CAP18) are components of innate immunity. These peptides have antimicrobial activity against bacteria, fungi, and viruses.Actinobacillus actinomycetemcomitansis a gram-negative facultative anaerobe implicated in the initiation of periodontitis. The innate immunity peptides have antibacterial activity againstA. actinomycetemcomitans. We investigated the molecular mechanism of human gingival epithelial cells (HGEC) responding to exposure toA. actinomycetemcomitans. HGEC constitutively express hBD1 and inducibly express hBD2, hBD3, and CAP18 on exposure toA. actinomycetemcomitans. The level of expression varies among clinical isolates. In the signaling pathway for hBD2 induction by the bacterial contact, we demonstrate that the mitogen-activated protein (MAP) kinase and not the NF-κB transcription factor pathway is used. We found the outer membrane protein 100 (Omp100; identified by molecular mass) is the component inducing the hBD2 response. Omp100 binds to fibronectin, an extracellular matrix inducing hBD2 via the MAP kinase pathway. Anti-integrin α5β1, antifibronectin, genistein, and PP2 suppress the Omp100-induced expression of hBD2, suggesting that Src kinase is involved through integrin α5β1. The inflammatory cytokines, tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-8, produced by HGEC on contact withA. actinomycetemcomitansalso stimulate expression of hBD2. Further, neutralizing antibody against TNF-α or IL-8 partially inhibits the induction of hBD2 on bacterial contact. Therefore, we found that the induction of the antimicrobial peptides is mediated by a direct response principally through an Omp100-fibronectin interaction, and using secondary stimulation by inflammatory cytokines induced by the bacterial exposure.
Porphyromonas gingivalis
Vesicles Enhance Attachment, and the Leucine-Rich Repeat BspA Protein Is Required for Invasion of Epithelial Cells by “
Tannerella forsythia
”
Authors: Inagaki Satoru , Onishi Shinsuke , Kuramitsu Howard K. , Sharma Ashu
Published: August 2006

The human oral cavity harbors more than 500 species of bacteria. Periodontitis, a bacterially induced inflammatory disease that leads to tooth loss, is believed to result from infection by a select group of gram-negative periodontopathogens that includes
Porphyromonas gingivalis
,
Treponema denticola
, and “
Tannerella forsythia
” (opinion on name change from
Tannerella forsythensis
pending; formerly
Bacteroides forsythus
). Epithelial cell invasion by periodontopathogens is considered to be an important virulence mechanism for evasion of the host defense responses. Further, the epithelial cells with invading bacteria also serve as reservoirs important in recurrent infections. The present study was therefore undertaken to address the epithelial cell adherence and invasion properties of
T. forsythia
and the role of the cell surface-associated protein BspA in these processes. Further, we were interested in determining if
P. gingivalis
, one of the pathogens frequently found associated in disease, or its outer membrane vesicles (OMVs) could modulate the epithelial cell adherence and invasion abilities of
T. forsythia
. Here we show that epithelial cell attachment and invasion by
T. forsythia
are dependent on the BspA protein. In addition,
P. gingivalis
or its OMVs enhance the attachment and invasion of
T. forsythia
to epithelial cells. Thus, interactions between these two bacteria may play important roles in virulence by promoting host cell attachment and invasion.
ChronicSalmonella entericaSerovar Typhimurium-Induced Colitis and Cholangitis in Streptomycin-PretreatedNramp1+/+Mice
Authors: Stecher Bärbel , Paesold Günther , Barthel Manja , Kremer Marcus , Jantsch Jonathan , Stallmach Thomas , Heikenwalder Mathias , Hardt Wolf-Dietrich
Published: August 2006

Salmonella entericasubspecies 1 serovar Typhimurium is an enteric bacterial pathogen infecting a broad range of hosts. In susceptibleNramp1−/−(Slc11α1−/−) mice, serovar Typhimurium cannot efficiently colonize the intestine but causes a systemic typhoid-like infection. However, after pretreatment with streptomycin, these susceptible (C57BL/6 and BALB/c) mice develop acute serovar Typhimurium-induced colitis (M. Barthel et al., Infect. Immun.71:2839-2858, 2003). It was not clear whether resistantNramp1+/+(Slc11α1+/+) mouse strains would similarly develop colitis. Here we compared serovar Typhimurium infection in streptomycin-pretreated susceptible (C57BL/6) and resistant (DBA/2 and 129Sv/Ev) mouse strains: We found that acute colitis (days 1 and 3 postinfection) is strikingly similar in susceptible and resistant mice. In 129Sv/Ev mice we followed the serovar Typhimurium infection for as long as 6 weeks. After the initial phase of acute colitis, these animals developed chronic crypt-destructive colitis, including ulceration, crypt abscesses, pronounced mucosal and submucosal infiltrates, overshooting regeneration of the epithelium, and crypt branching. Moreover, we observed inflammation of the gall duct epithelium (cholangitis) in the 129Sv/Ev mice between days 14 and 43 of infection. Cholangitis was not attributable to side effects of the streptomycin treatment. Furthermore, chronic infection of 129Sv/Ev mice in a typhoid fever model did not lead to cholangitis. We propose that streptomycin-pretreated 129Sv/Ev mice provide a robust murine model for chronic enteric salmonellosis including complications such as cholangitis.
Role of the α-Helical Linker of the C-Terminal Translocator in the Biogenesis of the Serine Protease Subfamily of Autotransporters
Authors: Kostakioti Maria , Stathopoulos Christos
Published: August 2006

Autotransporters are secreted virulence factors that comprise three domains: an N-terminal signal peptide, an internal passenger domain, and a C-terminal β-domain. The mechanism of passenger translocation across the outer membrane remains undefined, with four models having been proposed: the “hairpin,” the “threading,” the “multimeric,” and the “Omp85 (YaeT)” models. In an attempt to understand autotransporter biogenesis, we screened the sequences of the serine protease subfamily of autotransporters (SPATEs) for conserved features indicative of a common secretion mechanism. Our analyses revealed a strictly conserved 14-amino-acid motif within the predicted α-helical linker region, upstream of the β-domain of SPATEs. We investigated the function of this motif through a mutagenesis approach using Tsh as a model. Our studies demonstrate that mutations throughout the conserved motif do not block insertion of the β-domain into the outer membrane. However, nonconservative mutations of four hydrophobic (V1099, L1102, G1107, and L1109) and three polar (N1100, K1104, and R1105) residues of the motif severely decrease or even abolish Tsh biogenesis. Further studies showed that these mutations interfere with passenger transport across the outer membrane. Bioinformatical analyses suggest that the critical polar and hydrophobic amino acids localize on opposite sides of the helix that runs through the β-barrel pore. Our data indicate that the conserved motif is important for passenger secretion across the outer membrane and that mutations in certain residues severely affect the secretion process. We discuss how these results fit with the four proposed models for autotransporter secretion and potential applications in antimicrobial and vaccine development.
Identification ofNeisseria meningitidisNonlipopolysaccharide Ligands for Class A Macrophage Scavenger Receptor by Using a Novel Assay
Authors: Peiser Leanne , Makepeace Katherine , Plüddemann Annette , Savino Silvana , Wright J. Claire , Pizza Mariagrazia , Rappuoli Rino , Moxon E. Richard , Gordon Siamon
Published: August 2006

Macrophages (Mφ) may play an important role in the pathogenesis of invasive meningococcal infection. Previously, we have shown that the class A Mφ scavenger receptor (SR-A) is a major nonopsonic receptor forNeisseria meningitidison Mφ. SR-A contributes to host defense by binding proinflammatory polyanionic ligands such as lipopolysaccharide (LPS) and by the uptake and killing of live organisms. SR-A-deficient mouse Mφ display a substantial reduction in the number of meningococci ingested compared to wild-type Mφ, and SR-A is required for meningococcal phagocytosis but not for the release of tumor necrosis factor alpha. Although soluble lipid A and lipidIVA are reported as ligands for SR-A, we demonstrated that LPS and LPS expression were not essential for the uptake of whole meningococci. In the present study, we set out to discover protein ligand(s) for SR-A inN. meningitidislysates and outer membrane vesicles. Using various microbial mutant strains, we determined that molecules comprising the membrane capsule and pili, as well as the abundant surface Opa proteins were not essential for SR-A recognition. We developed a binding assay to detect SR-A ligands and identified three candidate proteins expressed on intact organisms, namely, NMB1220, NMB0278, and NMB0667. Soluble forms of these ligands were shown to block the binding of meningococci to CHO cells stably transfected with SR-A. Furthermore, NMB1220 was endocytosed by SR-A on Mφ and prevented internalization of soluble acetylated low-density lipoprotein. Thus, we have identified novel, unmodified protein ligands for SR-A that are able to inhibit meningococcal interactions with macrophages in vitro.
Differential Regulation of Iron- and Manganese-Specific MtsABC and Heme-Specific HtsABC Transporters by the Metalloregulator MtsR of Group A
Streptococcus
Authors: Hanks Tracey S. , Liu Mengyao , McClure Michael J. , Fukumura Maki , Duffy Angela , Lei Benfang
Published: August 2006

The genome of the human pathogen group A
Streptococcus
(GAS) encodes the transporters MtsABC, FtsABCD, and HtsABC to take up ferric and manganese ions, ferric ferrichrome, and heme, respectively. The GAS genome also encodes two metalloregulators PerR and MtsR. To understand the regulation of the expression of these transporters, the
mtsR
and
perR
deletion mutants of a GAS serotype M1 strain were generated, and the effects of the deletions and Fe
3+
, Mn
2+
, and Zn
2+
on the expression of
mtsA
,
htsA
, and
ftsB
were examined. Mn
2+
dramatically depresses
mtsA
transcription and levels of the MtsA protein but does not downregulate the expression of
htsA
and
ftsB
. Fe
3+
decreases the expression of
mtsA
and
htsA
but has no effect on
ftsB
expression. Zn
2+
has no effect on the expression of all three genes. The deletion of
mtsR
abolishes the Mn
2+
- and Fe
3+
-induced depression of
mtsA
expression and the Fe
3+
-dependent decrease in
htsA
expression. The deletion of
mtsR
does not significantly alter GAS virulence in a mouse model of subcutaneous infection. The deletion of
perR
does not affect the expression of the genes in response to the metal ions. MtsR binds to the
mts
promoter region in the presence of Mn
2+
or Fe
2+
. The results indicate that MtsR differentially regulates the expression of
mtsABC
and
htsABC
.
Morphine Withdrawal Lowers Host Defense to Enteric Bacteria: Spontaneous Sepsis and Increased Sensitivity to OralSalmonella entericaSerovar Typhimurium Infection
Authors: Feng Pu , Truant Allan L. , Meissler Joseph J. , Gaughan John P. , Adler Martin W. , Eisenstein Toby K.
Published: August 2006

Understanding the consequences of drug withdrawal on immune function and host defense to infection is important. We, and others, previously demonstrated that morphine withdrawal results in immunosuppression and sensitizes to lipopolysaccharide-induced septic shock. In the present study, the effect of morphine withdrawal on spontaneous sepsis and on oral infection withSalmonella entericaserovar Typhimurium was examined. Mice were chronically exposed to morphine for 96 h by implantation of a slow-release morphine pellet. Abrupt withdrawal was induced by removal of the pellet. In the sepsis model, bacterial colonization was examined and bacterial species were identified by necropsy of various tissues. It was found that at 48 h postwithdrawal, morphine-treated mice had enteric bacteria that were detected in the Peyer's patches (4/5), mesenteric lymph nodes (4/5), spleens (4/10), livers (6/10), and peritoneal cavities (8/10). In placebo pellet-withdrawn mice, only 2/40 cultures were positive. The most frequently detected organisms in tissues of morphine-withdrawn mice wereEnterococcus faeciumfollowed byKlebsiella pneumoniae. Both organisms are part of the normal gastrointestinal flora. In the infection model, mice were orally inoculated withS. enterica24 h post-initiation of abrupt withdrawal from morphine. Withdrawal significantly decreased the mean survival time and significantly increased theSalmonellaburden in various tissues of infected mice compared to placebo-withdrawn animals. Elevated levels of the proinflammatory cytokines were observed in spleens of morphine-withdrawn mice, compared to placebo-withdrawn mice. These findings demonstrate that morphine withdrawal sensitizes to oral infection with a bacterial pathogen and predisposes mice to bacterial sepsis.
Comparison of the Host Responses to Wild-Type andcpsBMutantKlebsiella pneumoniaeInfections
Authors: Lawlor Matthew S. , Handley Scott A. , Miller Virginia L.
Published: August 2006

Previously, we established an intranasal mouse model ofKlebsiella pneumoniaeinfection and validated its utility using a highly virulent wild-type strain and an avirulent capsular polysaccharide mutant. In the present study we compare the host responses to both infections by examining cytokine production, cellular infiltration, pulmonary histology, and intranasal immunization.