bluuebunny/crossref_metadata_2025 huggingface dataset:
Education Modifies the Effect of Alcohol on Memory Impairment: The Third National Health and Nutrition Examination Survey
Authors: Zhang Yuqing , Heeren Timothy , Curtis Ellison R.
Published: September 2004

We examined whether the relation of alcohol consumption to prevalence of verbal memory impairment was modified by education among 4,804 elderly subjects in the Third National Health and Nutrition Examination Survey. Verbal memory was assessed using delayed recall, with impairment defined as a combined score <4. Alcohol consumption over the previous month prior to the interview was assessed using a food frequency questionnaire. Prevalence of verbal memory impairment decreased from 11.3 to 7.2, 5.7, 5.1 and 4.4% in increasing categories of alcohol consumption (none, 1–4, 5–14, 15–30 and >30 drinks per month) in men, and from 7.2 to 3.5 and 2.8% (for none, 1–14, and >14 per month) in women, respectively. Adjusting for age, race, and other factors, prevalence ratios of verbal memory impairment decreased with each increasing alcohol category, but the effect was attenuated when further adjusted for education. There was a much stronger protection from alcohol among subjects with more education: prevalence ratios were reduced from 1.0 to 0.2 to 0.1 for non-drinkers, 1–14, and >14 drinks/month, respectively (p for trend = 0.007). Our results suggest that alcohol intake is associated with a greater decrease in the prevalence of verbal memory impairment among more educated subjects than among those with less education, possibly related to differences in drinking patterns.
Prevalence and Incidence of Multiple Sclerosis in Las Palmas, Canary Islands, Spain
Authors: Aladro Y. , Alemany M.J. , Pérez-Vieitez M.C. , Amela R. , Conde M. , Reyes M.P. , Álamo F. , Angel-Moreno A.
Published: September 2004

Objectives: To determine the prevalence and incidence of multiple sclerosis (MS) in the city of Las Palmas (Canary Islands, Spain), geographically belonging to north-western Africa, but with European ancestry. Methods: This population-based survey was conducted for a period of 5 years (1998–2002) in a Sanitary District of Las Palmas city (28° 20’ N), with a population of 82,623 inhabitants. Multiple sources were periodically investigated for case ascertainment. Patients with definite and probable MS were included. Results: Sixty-four patients with MS were identified on prevalence day, December 31, 2002. According to Poser’s criteria the crude prevalence rate was 77.5 per 100,000 (95% CI: 59.7–98.9). This rate decreased to 73.8 (95% CI: 56.5–94.8) according to McDonald’s criteria. Age-adjusted rates for the world and European standard populations were 61.6 (95% CI: 47.1–78.9) and 70.6 (95% CI: 55–89), respectively. Prevalence was higher for women aged 25–44 years. In 17 patients onset of MS occurred within the study period. Average annual incidence was 4.1 per 100,000 (95% CI: 2.4–6.6). Conclusions: The prevalence and incidence rates in Las Palmas city are close to those reported from Continental Spain and other countries of southern Europe with similar social and ethnic background. These results highlight the role of racial-ethnic factors in the genesis of MS.
Brain Abscess: A Need to Screen for Pulmonary Arteriovenous Malformations
Authors: Gallitelli Mauro , Lepore Vito , Pasculli Giovanna , Di Gennaro Leonardo , Logroscino Giancarlo , Carella Aristide , White Robert Ingersoll , Sabbà Carlo
Published: September 2004

Background: Pulmonary arteriovenous malformations (PAVMs) are direct connections between an artery and a vein in the pulmonary circulation associated with hereditary hemorrhagic telangiectasia in up to 88% of cases. Patients with PAVMs are at increased risk of brain abscess (BA). This study aimed to provide preliminary data on the prevalence of PAVMs among BA patients. Methods: Administrative hospital discharge forms were used to identify patients with BA; possible PAVM patients were screened. Results: 126 patients with BA were identified. Two patients had undiagnosed PAVMs at the time of admission for BA. The age-adjusted incidence of BA was 6.3 cases/1 million/year, with a male:female ratio of 2.0. Conclusion: Although PAVMs are rare conditions, they play a role in the development of BA. PAVMs are usually not recognized at the time of BA, thus exposing patients to life-threatening risks.
E-Selectin Blockade Decreases Adventitial Inflammation and Attenuates Intimal Hyperplasia in Rat Carotid Arteries After Balloon Injury
Authors: Gotoh Ryo , Suzuki Jun-ichi , Kosuge Hisanori , Kakuta Tsunekazu , Sakamoto Shinji , Yoshida Masayuki , Isobe Mitsuaki
Published: September 2004

Objective—

Inflammation is one of the initial repair processes after vascular injury. E-selectin facilitates adherence of leukocytes to vascular endothelium at the site of inflammation. Because the role of E-selectin in this process is not fully understood, we studied the role of E-selectin in vascular injury with a flow chamber model and a rat model of carotid artery injury.

Methods and Results—

We established a rat aortic endothelial cell (RAEC) culture system from the aortas of adult male rats. When rat myelomonocytes were suspended in a flow chamber, rolling and adhesion to lipopolysaccharide (LPS)-stimulated RAECs were observed. Cell rolling and adhesion were greatly reduced by addition of anti–E-selectin monoclonal antibody (mAb). We then induced balloon injury in the left carotid arteries of rats. E-selectin expression was enhanced in endothelial cells at adventitial small vessels 7 days after injury. Rats with balloon injury were injected intraperitoneally with anti–E-selectin mAb for 8 days. Inflammatory cell infiltration was reduced by anti–E-selectin mAb treatment at the adventitia at 7 days after injury. This reduction was associated with attenuation of intimal hyperplasia in the rats treated with the mAb.

Conclusions—

These data suggest that E-selectin regulates adventitial inflammation through leukocyte adhesion and contributes to the process of intimal hyperplasia after balloon injury.
Severe Periodontitis Enhances Macrophage Activation via Increased Serum Lipopolysaccharide
Authors: Pussinen Pirkko J. , Vilkuna-Rautiainen Tiina , Alfthan Georg , Palosuo Timo , Jauhiainen Matti , Sundvall Jouko , Vesanen Marja , Mattila Kimmo , Asikainen Sirkka
Published: September 2004

Objective—

In periodontitis, overgrowth of Gram-negative bacteria and access of lipopolysaccharide (LPS) to circulation may activate macrophages leading to foam cell formation. We investigated whether periodontal treatment affects proatherogenic properties of low-density lipoprotein (LDL) and, thus, macrophage activation.

Methods and Results—

LDL was isolated and characterized before and after treatment from 30 systemically healthy patients with periodontitis. Production of cytokines and LDL cholesteryl ester (LDL-CE) uptake by macrophages (RAW 264.7) was determined. Baseline periodontal variables correlated positively with serum LPS and C-reactive protein concentrations, as well as macrophage cytokine production and LDL-CE uptake. LPS concentration correlated positively with serum concentration of oxidized LDL and cytokine production. Higher cytokine production and LDL-CE uptake were induced by LDL isolated from patients with elevated number of affected teeth before treatment. Patients with serum LPS concentrations above the median (0.87 ng/mL) at baseline had higher serum high-density lipoprotein (HDL) cholesterol (baseline versus after treatment, 1.30±0.19 versus 1.48±0.28 mmol/L;
P
=0.002) and HDL/LDL ratio (0.31±0.01 versus 0.34±0.10;
P
=0.048), but lower serum LPS concentration (1.70±0.49 versus 0.98±0.50 ng/mL;
P
=0.004) and autoantibodies to β
2
-glycoprotein I (0.11±0.06 versus 0.09±0.04 ELISA units;
P
=0.022) after treatment.

Conclusions—

Our results suggest that in systemically healthy patients, the infected/inflamed area in periodontitis is associated with macrophage activation via increased serum LPS concentration.
Aspirin and Clopidogrel
Authors: Cattaneo Marco
Published: September 2004

Aspirin and the thienopyridines ticlopidine and clopidogrel are antiplatelet agents that display good antithrombotic activity. In the past few years, the concept of aspirin resistance has been largely emphasized in the medical literature, although its definition is still uncertain. I suggest that “aspirin-resistant” should be considered as a description for those individuals in whom aspirin fails to inhibit thromboxane A
2
production, irrespective of the results of unspecific tests of platelet function, such as the bleeding time, platelet aggregation, or the PFA-100 system. Less well known than aspirin resistance, but certainly better characterized, is the issue of “clopidogrel resistance,” which is probably mostly caused by inefficient metabolism of the prodrug clopidogrel to its active metabolite. At present, aspirin and clopidogrel resistance should not be looked for in the clinical setting, because there is no definite demonstration of an association with clinical events conditioning cost-effective changes in patient management.
High-Density Lipoprotein Subpopulation Profile and Coronary Heart Disease Prevalence in Male Participants of the Framingham Offspring Study
Authors: Asztalos Bela F. , Cupples L. Adrienne , Demissie Serkalem , Horvath Katalin V. , Cox Caitlin E. , Batista Marcelo C. , Schaefer Ernst J.
Published: September 2004

Objective—

High-density lipoprotein (HDL) is a heterogeneous lipoprotein class and there is no consensus on the value of HDL subspecies in coronary heart disease (CHD) risk assessment. We tested the hypothesis whether specific HDL subpopulations are significantly associated with CHD-prevalence.

Methods and Results—

ApoA-I concentrations (mg/dL) in HDL subpopulations were quantitatively determined by native 2d gel electrophoresis, immunoblotting, and image analysis in male participants in the Framingham Offspring Study (FOS). CHD cases (n=169) had higher preβ-1 and α-3 particle and lower α-1, preα-3, and preα-1 particle levels than either all (n=1277) or HDL cholesterol-matched (n=358) controls. α-1 and preα-3 levels had an inverse association, whereas α-3 and preα-1 particle levels had a positive association with CHD prevalence after adjusting the data for established CHD risk factors. Standardized logit coefficients indicated that α-1 HDL was most significantly associated with CHD prevalence. Moreover, each mg/dL increase in α-1 particle level decreased odds of CHD by 26% (
P
<0.0001), whereas each mg/dL increase in HDL cholesterol decreased odds of CHD by 2% in a model including all established CHD risk factors.

Conclusions—

Specific HDL subpopulations were positively correlated, whereas others were inversely correlated with CHD prevalence in male subject in the FOS, indicating that the various HDL particles might have different roles in the cause of CHD.
Human Apolipoprotein A-II Enrichment Displaces Paraoxonase From HDL and Impairs Its Antioxidant Properties
Authors: Ribas Vicent , Sánchez-Quesada José Luis , Antón Rosa , Camacho Mercedes , Julve Josep , Escolà-Gil Joan Carles , Vila Luís , Ordóñez-Llanos Jordi , Blanco-Vaca Francisco
Published: September 2004

Apolipoprotein A-II (apoA-II), the second major high-density lipoprotein (HDL) apolipoprotein, has been linked to familial combined hyperlipidemia. Human apoA-II transgenic mice constitute an animal model for this proatherogenic disease. We studied the ability of human apoA-II transgenic mice HDL to protect against oxidative modification of apoB-containing lipoproteins. When challenged with an atherogenic diet, antigens related to low-density lipoprotein (LDL) oxidation were markedly increased in the aorta of 11.1 transgenic mice (high human apoA-II expressor). HDL from control mice and 11.1 transgenic mice were coincubated with autologous very LDL (VLDL) or LDL, or with human LDL under oxidative conditions. The degree of oxidative modification of apoB lipoproteins was then evaluated by measuring relative electrophoretic mobility, dichlorofluorescein fluorescence, 9- and 13-hydroxyoctadecadienoic acid content, and conjugated diene kinetics. In all these different approaches, and in contrast to control mice, HDL from 11.1 transgenic mice failed to protect LDL from oxidative modification. A decreased content of apoA-I, paraoxonase (PON1), and platelet-activated factor acetyl-hydrolase activities was found in HDL of 11.1 transgenic mice. Liver gene expression of these HDL-associated proteins did not differ from that of control mice. In contrast, incubation of isolated human apoA-II with control mouse plasma at 37°C decreased PON1 activity and displaced the enzyme from HDL. Thus, overexpression of human apoA-II in mice impairs the ability of HDL to protect apoB-containing lipoproteins from oxidation. Further, the displacement of PON1 by apoA-II could explain in part why PON1 is mostly found in HDL particles with apoA-I and without apoA-II, as well as the poor antiatherogenic properties of apoA-II–rich HDL.
The Indian Maritime Merchant, 1500-1800
Authors: Prakash Om
Published: September 2004

The paper analyses the composition, social organization and wide range of activities of the Indian maritime merchant of the early modern period. Regional contrasts between Gujarat, the Coromandel coast and Bengal are discussed. The last section of the paper discusses the interaction between the Indian maritime merchants and the Europeans, both the corporate enterprises as well as private traders. It is argued that the Indian merchants displayed a remarkable degree of adaptiveness and resilience and refused to be overwhelmed by the competition provided by the Europeans. Cet article analyse la composition, l'organisation sociale, et les activités diverses qu'exploitent les marchands maritimes indiens du début de la période moderne. Les contrastes régionaux entre le Gujarat, la côte du Coromandel et le Bengal passeront la revue. La dernière section de l'article est consacrée à l'interaction entre les marchands maritimes indiens et les Européens, tant les grandes sociétés de négoce que la marine de commerce privée. Il est avancé que les marchands indiens se montrèrent très adaptifs et dynamiques et qu'ils refusèrent d'être subjugués par la concurrence survenue par l'arrivée des Européens.
A new species of Cnemidophorus (Squamata: Teiidae) from western Argentina
Authors: Cabrera Mario
Published: September 2004

A new species of whiptail lizard of the genus Cnemidophorus (Teiidae) is described from La Rioja province, western Argentina. The species is characterized by a broad light brown-grayish middorsal pattern, the lack of vertebral and paravertebral stripes, alternating white and brown stripes from dorsolateral to flanks, pointed snout, postnasal scale usually longer than loreal scale, and 10 longitudinal rows of ventral scales. The previous and current states of knowledge on southern South American Cnemidophorus species are discussed.
Dentitional specialisations for durophagy in the Common Wolf snake, Lycodon aulicus capucinus
Authors: Jackson Kate , Fritts Thomas
Published: September 2004

The Common Wolf snake, Lycodon aulicus capucinus, is a species known to feed on durophagous prey such as skinks. Here we examine in detail the dentitional morphology of L. aulicus capucinus to see whether it possesses morphological specialisations for durophagy comparable to those found in other squamates. We find that L. aulicus capucinus has greatly enlarged anterior maxillary teeth, followed by a large diastema. At the diastema, the maxilla is significantly arched. The diastema is followed by a row of small, closely-packed teeth. Finally, after a short second diastema are enlarged, but ungrooved posterior maxillary fangs, with the posterior surfaces modified into blades. We propose that this dentition helps L. aulicus capucinus to ingest hard-bodied skinks in several ways: The enlarged anterior teeth and arched maxilla encircle the prey during biting, preventing it from being squeezed out of the mouth anteriorly, the short, spatulate teeth may catch under the scales of the prey, preventing escape during swallowing, and the bladelike posterior fang may slice through the hard, cycloid scales of the prey.
Intra-cultural Variation and Job Autonomy in 42 Countries
Authors: Au Kevin , Cheung Mike W. L.
Published: September 2004

Intra-cultural variation (ICV)—dispersion of individuals within a culture—is not often the focus of international management compared to the cultural mean. However, researchers in international management and multi-level modeling have acknowledged the theoretical uniqueness of ICV, and have pled for its use in theory building and empirical testing. Responding to such a call, this paper explains at the societal level the theoretical importance of ICV of job autonomy. It also demonstrates, using secondary data from 42 countries, that the ICV of job autonomy influences organizational and social outcomes beyond the cultural mean of job autonomy. Specifically, the cultural mean and ICV of job autonomy exert different effects on job satisfaction and life satisfaction. The effect of the cultural mean is positive and that of the ICV is negative. Moreover, the effect of the ICV is independent of and similar in magnitude to that of the cultural mean. Research implications for international management and multi-level research are discussed.
Effect of Fiber Content and Fiber Treatment on Flexural Properties of Sisal Fiber/Glass Fiber Hybrid Composites
Authors: John K. , Naidu S. Venkata
Published: September 2004

The variations of flexural strength and flexural modulus of unsaturated polyester-based sisal/glass hybrid composites with fiber content have been studied. The hybrid composites showed an increase in flexural properties with glass fiber loading. The effects of alkali treatment and silane treatment of fibers on the flexural properties of these sisal/glass hybrid composites have also been studied. No significant effect on the flexural properties has been observed by silane treatment but a small increase in these properties has been observed by alkali treatment.
New Hydraulic System Modelling
Authors: Pfeiffer Friedrich , Borchsenius Fredrik
Published: September 2004

The efficient design of hydraulic systems requires fast simulation methods. In most simulation programs, the hydraulic components are coupled by compressible joints. Since the compressibility of oil is very small, this leads to stiff differential equations. To avoid these difficulties stiff elastic couplings can be replaced by algebraic and, in some cases, unilateral constraints. Examples for hydraulic components with unilateral behavior are check valves, cylinders with stop limits and fluid volumes, in which cavitation can occur. The resulting complementarity equations can be solved with a standard Lemke algorithm. Compared to conventional methods, this leads to a significant reduction of computational effort.
Use of Advanced Thermal Spray Processes for Corrosion Protection in Marine Environments
Authors: Shrestha S. , Sturgeon A.J.
Published: September 2004

The microstructure and aqueous electrochemical corrosion characteristics of stainless steel 316L (UNS S31603) and nickel alloy 625 (UNS N06625) coatings deposited onto a carbon steel substrate using commercial high velocity oxyfuel (HVOF) spraying systems and a new high velocity wire flame spraying system were assessed. The electrochemical corrosion behaviour of the as prepared coatings was compared with their respective materials in wrought form. A HVOF sprayed coating of nickel alloy 625 was found to be more corrosion resistant in an aqueous saline environment than a coating of stainless steel 316L. However, the nickel alloy coating did not match the corrosion resistance of the same nickel alloy in wrought form, but may have the ability to offer corrosion resistance in saline aqueous environments approaching that of a wrought stainless steel. A porosity level of < 2.5% may not have a significant effect on the electrochemical activities of the HVOF sprayed coatings near the free corrosion (rest) potential. However, the level of oxidation depending upon the spraying system was shown to have an effect on the corrosion resistance of the sprayed coatings. The stainless steel and nickel alloy coatings produced using the high velocity wire flame spray system displayed much higher oxides compared with those produced using HVOF processes and. consequently, poorer corrosion resistance.
Sealing of Thermally Sprayed Coatings
Authors: Oksa M. , Turunen E. , Varis T.
Published: September 2004

The use of coatings in fluidised bed boilers is increasing owing to the harsh conditions that modern boilers meet. High temperatures, combined with inhomogeneous, high chlorine and alkali containing fuels such as biomass, cause severe material wastage to metallic parts in boilers. Thermally sprayed coatings have been reported to provide protection to boiler tubes. However, thermally sprayed coatings have encountered serious problems, such as corrosion on the substrate material owing to voids and oxides in lamella boundaries. Sealing of the coatings can solve these problems. This paper investigates the sealing of coatings. Thermally sprayed metallic coatings were sealed with different commercial sealing agents and laser treatment. The coatings were tested after sealing by simulating fluidised bed boiler superheater conditions. Specimens were examined by optical microscopy and SEM and analysed by energy dispersive X-ray analysis. Some of the tested sealants protected the coatings adequately in a short term alkali chloride– alkali sulphate exposure test. The best sealant contained aluminium oxide and aluminium phosphate. Laser treated coatings had good corrosion resistance in a short term test.
Electrochemical Aspects of Laser Clad Nickel Base Coatings
Authors: Roman I.
Published: September 2004

A comparative assessment is presented, by cyclic voltammetry, of the electrochemical performances of experimental samples of nickel base superalloy layer samples L1, with a maximum thickness of 0.5 mm, and L2 and L3 successively thinned, produced by laser cladding on a support of carbon steel OLC45 as compared with the reference materials, commercial nickel base superalloys with a similar chemical composition, as well as an analysis of the variation of these properties in the bulk of the layer. The electrolyte used was 1N sulphuric acid; the polarisation rate, between -400 and 1200 mV(SCE), was 200 mV s-1 at 18°C. The superalloy samples present complete electrochemical passivation in two stages during the first polarisation cycle, with passivation currents ( ip) of order only 20–60 m A cm-2. The spontaneous passivation tendency shown by all the analysed superalloy samples is not seen on the L1, L2 and L3 samples; they suffer net electrochemical passivation processes during all 10 polarisation cycles, and the passivation current does not fall below 800 m A cm-2; the passivation critical potentials ( icp) are also situated in another, more noble field. The existence of two passivation critical potentials is specific for nickel and hardening γ and γ phases. The nickel behaves characteristically only for the L1 sample, the two current maxima ( icp1 and icp2) being attributed to it. The other L samples, with the successively thinned layers, are electrochemically passivated in a single stage, marked by high current consumption. Nevertheless, the laser clad layers have typical passivation properties in reducing acids, such as the sulphuric acid in the present study. The electrochemical performance of these layers decreases as the investigation depth increases, approaching the steel base which has an active behaviour, lacking passivation properties. It can be supposed that iron diffusion from the steel base took place, as higher as the section is approaching the steel/layer interface.
Effect of Annealing on Structural, Surface and Optical Properties of PVD-EBE α-MoO3 Thin Films For Electrochromic Devices
Authors: Sivakumar R. , Jayachandran M. , Sanjeeviraja C.
Published: September 2004

Thin films of molybdenum oxide (MoO3) were deposited by a physical vapour deposition method, i.e.the electron beam evaporation technique, using Corning 7059 microscopic glass and SnO2:F as substrates. The effects of annealing temperature on the structural, surface morphological and optical properties of the films were studied and the results are discussed in detail.
Microbial Corrosion of Protective Coatings
Authors: Kopteva ZH.P. , Zanina V.V. , Kozlova I.A.
Published: September 2004

Research studies have shown that protective coatings of diverse chemical composition represent a powerful factor stimulating the bacterial activity of corrosion inducers. On the film and mastic coatings investigated in the present paper, bacterial communities are formed, which consist of bacteria of various ecological trophic groups. Bacteria in a biofilm are characterised by high metabolic activity and the ability to destroy traditional coatings. As a result of microbial destruction, the physical mechanical and chemical properties of a material undergo significant changes. The characteristics of strength, elasticity and adhesion deteriorate, thus degrading the main function of the coatings, i.e.protection of metal against corrosion. An efficient method of protection against biodeterioration is the addition of corrosion inhibitors with biocide action into their composition. It was established that the population of bacteria on oil bitumen coatings modified by antimicrobial bonds is 1–4 orders lower than on materials with no such additives. Protection of underground structures against corrosion should be performed comprehensively with consideration of the biocorrosivity of soils and bioresistance of coatings.
Introduction to Vapour Phase Corrosion Inhibitors in Metal Packaging
Authors: Vuorinen E. , Kálmán E. , Focke W.
Published: September 2004

For a compound to be classified as a volatile corrosion inhibitor (VCI), it must possess two basic properties: volatility and ability of the vapour to retard the corrosion rate. VCIs can be used in cases where other protection methods are not feasible or when protection could be very expensive. Usually, most organic compounds giving inhibitive action against corrosion of metals have one or more electronegative atoms (e. g. oxygen, nitrogen, sulphur) in the form of functional groups and/or have an unsaturated bond. Inhibitors for atmospheric corrosion can be used economically only in enclosed spaces. When metal items are in transit, the following protection methods should be considered: protective oils, water or oil based formulations and/or protective packaging. In the manufacture and use of corrosion inhibitors and their products (e.g.VCI paper), workers are occupationally exposed to various chemicals, noise and elevated air temperatures. The concentrations of chemicals in workplace air are dependent on the manufacturing process and equipment used. It is recommended that any plant processing VCIs should have good processing equipment and ventilation. Workers should wear protective clothing, safety glasses and gloves when handling VCI products.
Surface Modification of Various Fe–si and Fe–mn Alloys by Oxidation/Reduction Treatments
Authors: Parezanović I. , Spiegel M.
Published: September 2004

Oxidation of segregated elements (Si, Mn, Al, Cr) during annealing of steel sheets in a 5%H2 –N2 atmosphere at 820°C and dew point -30°C makes the steel surface unsuitable for subsequent galvanising, as the oxides formed are poorly wetted by the Zn. One way to modify these surfaces is by selective oxidation achieved by changing the partial pressure of O2 in the annealing atmosphere, and another way is by preoxidation of the sheets before annealing. During preoxidation, the formation of Fe oxides is primarily expected. These oxides can be reduced in the annealing cycle, leaving metallic Fe on the surface, which is well wetted in a Zn bath. Various Fe–Si (Fe with 1%, 1.5%, 3% and 5% Si) and Fe–Mn (Fe with 0.3%, 1%, 3% and 5%Mn) model alloys were chosen and investigated after preoxidation in air at 700°C and subsequent annealing. X-ray photoelectron spectroscopy and field emission scanning electron microscopy measurements were used to characterise the surfaces.
Functional gene expression analysis of clonal plasma cells identifies a unique molecular profile for light chain amyloidosis
Authors: Abraham Roshini S. , Ballman Karla V. , Dispenzieri Angela , Grill Diane E. , Manske Michelle K. , Price-Troska Tammy L. , Paz Natalia Gonzalez , Gertz Morie A. , Fonseca Rafael
Published: September 2004

Immunoglobulin light chain amyloidosis (AL) is characterized by a clonal expansion of plasma cells within the bone marrow. Gene expression analysis was used to identify a unique molecular profile for AL using enriched plasma cells (CD138+) from the bone marrow of 24 patients with AL and 28 patients with multiple myeloma (MM) and 6 healthy controls. Class prediction analysis (PAM) revealed a subset of 12 genes, which included TNFRSF7 (CD27), SDF-1, and PSMA2, that distinguished between these 2 groups with an estimated and observed accuracy of classification of 92%. This model was validated with an independent dataset of 11 patients with AL and 12 patients with MM with 87% accuracy. Differential expression for the most discriminant genes in the 12-gene subset was validated using quantitative real-time polymerase chain reaction and protein expression analysis, which upheld the observations from the micro-array expression data. Functional analyses using a novel network mapping software revealed a number of potentially significant pathways that were dysregulated in patients with AL, with those regulating proliferation, apoptosis, cell signaling, chemotaxis, and migration being substantially represented. This study provides new insight into the molecular profile of clonal plasma cells and its functional relevance in the pathogenesis of light chain amyloidosis.
Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas
Authors: Krishnan Amrita , Molina Arturo , Zaia John , Smith David , Vasquez Debbie , Kogut Neil , Falk Peter M. , Rosenthal Joseph , Alvarnas Joseph , Forman Stephen J.
Published: September 2004

The treatment of HIV-associated lymphoma has changed since the widespread use of highly active antiretroviral therapy. HIV-infected individuals can tolerate more intensive chemotherapy, as they have better hematologic reserves and fewer infections. This has led to higher response rates in patients with HIV-associated Hodgkin disease (HD) or non-Hodgkin lymphoma (NHL) treated with chemotherapy in conjunction with antiretroviral therapy. However, for patients with refractory or relapsed disease, salvage chemotherapy still offers little chance of long-term survival. In the non-HIV setting, patients with relapsed Hodgkin disease (HD) or non-Hodgkin lymphoma (NHL) have a better chance of long-term remission with high-dose chemotherapy with autologous stem cell rescue (ASCT) compared with conventional salvage chemotherapy. In a prior report we demonstrated that this approach is well tolerated in patients with underlying immunodeficiency from HIV infection. Furthermore, similar engraftment to the non-HIV setting and low infectious risks have been observed. Herein, we expand upon this early experience with the largest single institution series of 20 patients. With long-term follow-up we demonstrate that ASCT can lead to an 85% progression-free survival, which suggests that this approach may be potentially curative in select patients with relapsed HIV-associated HD or NHL.
Effect of fondaparinux on platelet activation in the presence of heparin-dependent antibodies: a blinded comparative multicenter study with unfractionated heparin
Authors: Savi Pierre , Chong Beng H. , Greinacher Andreas , Gruel Yves , Kelton John G. , Warkentin Theodore E. , Eichler Petra , Meuleman Dick , Petitou Maurice , Herault Jean-Pascal , Cariou Roger , Herbert Jean-Marc
Published: September 2004

Heparin-induced thrombocytopenia (HIT) is a complication of heparin therapy caused by antibodies against a complex of platelet factor 4 and heparin. Fondaparinux (Arixtra) is a new synthetic selective factor Xa inhibitor. We performed a serologic study to determine the cross-reactivity of HIT sera with fondaparinux. Using a prospective, blinded study design, 39 clinically and serologically confirmed sera from patients with HIT and 15 control sera were sent to 3 different laboratories, each of which specialized in a particular HIT assay. These include the serotonin release assay, heparin-induced platelet agglutination assay, and platelet aggregation assay. Two of 82 assays (2.4%) performed in the presence of control sera were positive, both with unfractionated heparin. In the presence of HIT sera, 75 of 94 (79.8%) evaluable assays were positive with unfractionated heparin; fondaparinux was significantly (P < .001) less reactive than unfractionated heparin, only 3 of 91 evaluable assays (3.3%) being positive. Using flow cytometry, unlike unfractionated heparin, fondaparinux did not induce the binding of PAC1 and anti-CD62 monoclonal antibodies or of annexin V to platelets with HIT sera. Together, these results suggest that fondaparinux is nonreactive to HIT sera and raise the possibility that the drug may be used for prophylaxis and treatment of thrombosis in patients with a history of HIT.
PATTERNFINDER: combined analysis of DNA regulatory sequences and double-helix stability
Authors: Huang Yanlin , Kowalski David
Published: September 2004

Background

Regulatory regions that function in DNA replication and gene transcription contain specific sequences that bind proteins as well as less-specific sequences in which the double helix is often easy to unwind. Progress towards predicting and characterizing regulatory regions could be accelerated by computer programs that perform a combined analysis of specific sequences and DNA unwinding properties.

Results

Here we present PATTERNFINDER, a web server that searches DNA sequences for matches to specific or flexible patterns, and analyzes DNA helical stability. A batch mode of the program generates a tabular map of matches to multiple, different patterns. Regions flanking pattern matches can be targeted for helical stability analysis to identify sequences with a minimum free energy for DNA unwinding. As an example application, we analyzed a regulatory region of the human c-myc proto-oncogene consisting of a single-strand-specific protein binding site within a DNA region that unwindsin vivo. The predicted region of minimal helical stability overlapped both the protein binding site and the unwound DNA region identified experimentally.

Conclusions

The PATTERNFINDER web server permits localization of known functional elements or landmarks in DNA sequences as well as prediction of potential new elements. Batch analysis of multiple patterns facilitates the annotation of DNA regulatory regions. Identifying specific pattern matches linked to DNA with low helical stability is useful in characterizing regulatory regions for transcription, replication and other processes and may predict functional DNA unwinding elements.

PATTERNFINDER can be accessed freely at: http://wings.buffalo.edu/gsa/dna/dk/PFP/
HIV-1 Vif and APOBEC3G: Multiple roads to one goal
Authors: Goncalves Joao , Santa-Marta Mariana
Published: September 2004

The viral infectivity factor, Vif, of human immunodeficiency virus type 1, HIV-1, has long been shown to promote viral replication in vivo and to serve a critical function for productive infection of non-permissive cells, like peripheral blood mononuclear cells (PBMC). Vif functions to counteract an anti-retroviral cellular factor in non-permissive cells named APOBEC3G. The current mechanism proposed for protection of the virus by HIV-1 Vif is to induce APOBEC3G degradation through a ubiquitination-dependent proteasomal pathway. However, a new study published in Retrovirology by Strebel and colleagues suggests that Vif-induced APOBEC3G destruction may not be required for Vif's virus-protective effect. Strebel and co-workers show that Vif and APOBEC3G can stably co-exist, and yet viruses produced under such conditions are fully infectious. This new result highlights the notion that depletion of APOBEC3G is not the sole protective mechanism of Vif and that additional mechanisms exerted by this protein can be envisioned which counteract APOBEC3G and enhance HIV infectivity.
Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis
Authors: Appel Heiner , Kuon Wolfgang , Kuhne Maren , Wu Peihua , Kuhlmann Stefanie , Kollnberger Simon , Thiel Andreas , Bowness Paul , Sieper Joachim
Published: September 2004

Reports of the use of HLA-B27/peptide tetrameric complexes to study peptide-specific CD8+ T cells in HLA-B27+-related diseases are rare. To establish HLA-B27 tetramers we first compared the function of HLA-B27 tetramers with HLA-A2 tetramers by using viral epitopes. HLA-B27 and HLA-A2 tetramers loaded with immunodominant peptides from Epstein–Barr virus were generated with comparable yields and both molecules detected antigen-specific CD8+ T cells. The application of HLA-B27 tetramers in HLA-B27-related diseases was performed with nine recently described Chlamydia-derived peptides in synovial fluid and peripheral blood, to examine the CD8+ T cell response against Chlamydia trachomatis antigens in nine patients with Chlamydia-triggered reactive arthritis (Ct-ReA). Four of six HLA-B27+ Ct-ReA patients had specific synovial T cell binding to at least one HLA-B27/Chlamydia peptide tetramer. The HLA-B27/Chlamydia peptide 195 tetramer bound to synovial T cells from three of six patients and HLA-B27/Chlamydia peptide 133 tetramer to synovial T cells from two patients. However, the frequency of these cells was low (0.02–0.09%). Moreover, we demonstrate two methods to generate HLA-B27-restricted T cell lines. First, HLA-B27 tetramers and magnetic beads were used to sort antigen-specific CD8+ T cells. Second, Chlamydia-infected dendritic cells were used to stimulate CD8+ T cells ex vivo. Highly pure CD8 T cell lines could be generated ex vivo by magnetic sorting by using HLA-B27 tetramers loaded with an EBV peptide. The frequency of Chlamydia-specific, HLA-B27 tetramer-binding CD8+ T cells could be increased by stimulating CD8+ T cells ex vivo with Chlamydia-infected dendritic cells. We conclude that HLA-B27 tetramers are a useful tool for the detection and expansion of HLA-B27-restricted CD8+ T cells. T cells specific for one or more of three Chlamydia-derived peptides were found at low frequency in synovial fluid from HLA-B27+ patients with Ct-ReA. These cells can be expanded ex vivo, suggesting that they are immunologically functional.
Infliximab therapy in rheumatoid arthritis and ankylosing spondylitis-induced specific antinuclear and antiphospholipid autoantibodies without autoimmune clinical manifestations: a two-year prospective study
Authors: Ferraro-Peyret Carole , Coury Fabienne , Tebib Jacques G , Bienvenu Jacques , Fabien Nicole
Published: September 2004

Treatment of rheumatoid arthritis (RA) with infliximab (Remicade®) has been associated with the induction of antinuclear autoantibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) autoantibodies. In the present study we investigated the humoral immune response induced by infliximab against organ-specific or non-organ-specific antigens not only in RA patients but also in patients with ankylosing spondylitis (AS) during a two-year followup. The association between the presence of autoantibodies and clinical manifestations was then examined. The occurrence of the various autoantibodies was analyzed in 24 RA and 15 AS patients all treated with infliximab and in 30 RA patients receiving methotrexate but not infliximab, using the appropriate methods of detection. Infliximab led to a significant induction of ANA and anti-dsDNA autoantibodies in 86.7% and 57% of RA patients and in 85% and 31% of AS patients, respectively. The incidence of antiphospholipid (aPL) autoantibodies was significantly higher in both RA patients (21%) and AS patients (27%) than in the control group. Most anti-dsDNA and aPL autoantibodies were of IgM isotype and were not associated with infusion side effects, lupus-like manifestations or infectious disease. No other autoantibodies were shown to be induced by the treatment. Our results confirmed the occurrence of ANA and anti-dsDNA autoantibodies and demonstrated that the induction of ANA, anti-dsDNA and aPL autoantibodies is related to infliximab treatment in both RA and AS, with no significant relationship to clinical manifestations.
Frequency of CHEK2 mutations in a population based, case–control study of breast cancer in young women
Authors: Friedrichsen Danielle M , Malone Kathleen E , Doody David R , Daling Janet R , Ostrander Elaine A
Published: September 2004

Introduction

The cell-cycle checkpoint kinase (CHEK)2 protein truncating mutation 1100delC has been associated with increased risk for breast or prostate cancer. Multiple studies have found an elevated frequency of the 1100delC variant in specific stratifications of breast cancer patients with a family history of the disease, including BRCA1/BRCA2 negative families and families with a history of bilateral disease or male breast cancer. However, the 1100delC mutation has only been investigated in a few population-based studies and none from North America.

Methods

We report here on the frequency of three CHEK2 variants that alter protein function – 1100delC, R145W, and I175T – in 506 cases and 459 controls from a population based, case–control study of breast cancer conducted in young women from western Washington.

Results

There was a suggestive enrichment in the 1100delC variant in the cases (1.2%) as compared with the controls (0.4%), but this was based on small numbers of carriers and the differences were not statistically significant. The 1100delC variant was more frequent in cases with a first-degree family history of breast cancer (4.3%; P = 0.02) and slightly enriched in cases with a family history of ovarian cancer (4.4%; P = 0.09).

Conclusion

The CHEK2 variants are rare in the western Washington population and, based on accumulated evidence across studies, are unlikely to be major breast cancer susceptibility genes. Thus, screening for the 1100delC variant may have limited usefulness in breast cancer prevention programs in the USA.
Measurement of the activated clotting time during cardiopulmonary bypass: differences between Hemotec® ACT and Hemochron® Jr apparatus
Authors: Svenmarker S , Appelblad M , Jansson E , Häggmark S
Published: September 2004

Background: Measurement of the activated clotting time (ACT) represents a standard method for coagulatory assessments. The test employs specific agents to trigger the coagulation process. The present study aimed to compare kaolin (Hemotec®) versus a combination of silica, kaolin and phospholipid (Hemochron® Jr) ACTs.

Methods: Hemotec® and Hemochron® Jr ACT monitors were compared by simultaneous measurement of paired arterial blood samples ( n-114) with respect to precision and bias during clinical conditions of cardio-pulmonary bypass (CPB). The influence of haemodilution on the ACT was tested in an ex-vivo model.

Results: The precision of Hemotec® and Hemochron®Jr ACT measurements attained 21±2.6 s versus 27.0±2.6 s( p= 0.126) during CPB and 2.5±2.2 s versus 9.4±6.9 s ( p= 0.000) after protamine administration, respectively. The Hemochron® Jr monitor was associated with a bias of −102±13.7 s compared to the Hemotec® ACT monitor ( p= 0.000) during CPB and −6.9±2.9 s after protamine ( p= 0.025). Linear regression analysis of ACT readings between monitors reached r- 0.526 ( p= 0.000). Hemochron® Jr ACT values correlated with the erythrocyte volume fraction r- 0.379 ( p= 0.000). Ex-vivo data indicated that the Hemotec® ACT monitor was associated with relatively higher ACT readings after haemodilution.

Conclusion: The ACT is not a standardized measure. Test results are strongly associated with the specific compounds used to initiate the coagulation process.
Activation of EndothelinA Receptors in Frog Adrenocortical Cells Stimulates Both Calcium Mobilization from Intracellular Stores and Calcium Influx through L-Type Calcium Channels
Authors: Delarue Catherine , Jouet Isabelle Remy , Gras Marjorie , Galas Ludovic , Fournier Alain , Vaudry Hubert
Published: September 2004

We have previously shown that endothelin (ET)-1 stimulates corticosterone and aldosterone secretion by the frog adrenal gland through activation of ETA receptors positively coupled to both the adenylyl cyclase and phospholipase C (PLC) pathways. The purpose of the present study was to investigate the involvement of calcium in ET-1-induced stimulation of corticosteroid secretion. Cytoautoradiographic labeling using [125I]ET-1 as a tracer revealed the presence of ET-1 binding sites on adrenocortical cells. Administration of graded concentrations of ET-1 in the vicinity of adrenocortical cells provoked a dose-dependent increase in cytosolic calcium concentrations ([Ca2+]i). ET-1 induced a biphasic response consisting of an immediate and transient peak of [Ca2+]i followed by a plateau phase. Preincubation of the cells with the calcium-ATPase inhibitor thapsigargin or the PLC inhibitor U-73122 reduced the amplitude of the transient phase. Administration of the calcium chelator EGTA or the protein kinase A inhibitor H-89 attenuated the plateau phase. The [Ca2+]i response to ET-1 was markedly reduced during concomitant administration of U-73122 and H-89. Preincubation of the cells with the L-type calcium channel blocker nifedipine attenuated the plateau phase. Corticosteroid secretion from perifused frog adrenal slices was almost completely suppressed by thapsigargin and reduced by nifedipine. Taken together, these data indicate that activation of ETA receptors in frog adrenocortical cells provokes immediate stimulation of PLC, which causes an early mobilization of calcium from intracellular stores, and activates adenylyl cyclase, which results in delayed calcium influx through L-type calcium channels. The resulting increase in [Ca2+]i plays a pivotal role in ET-1-induced corticosteroid secretion.
Tumor Necrosis Factor-α Mediates Osteopenia Caused by Depletion of Antioxidants
Authors: Jagger C. J. , Lean J. M. , Davies J. T. , Chambers T. J.
Published: September 2004

We recently found that estrogen deficiency leads to a lowering of thiol antioxidant defenses in rodent bone. Moreover, administration of agents that increase the concentration in bone of glutathione, the main intracellular antioxidant, prevented estrogen-deficiency bone loss, whereas depletion of glutathione by buthionine sulfoximine (BSO) administration provoked substantial bone loss. It has been shown that the estrogen-deficiency bone loss is dependent on TNFα signaling. Therefore, a model in which estrogen deficiency causes bone loss by lowering antioxidant defenses predicts that the osteopenia caused by lowering antioxidant defenses should similarly depend on TNFα signaling. We found that the loss of bone caused by either BSO administration or ovariectomy was inhibited by administration of soluble TNFα receptors and abrogated in mice deleted for TNFα gene expression. In both circumstances, lack of TNFα signaling prevented the increase in bone resorption and the deficit in bone formation that otherwise occurred. Thus, depletion of thiol antioxidants by BSO, like ovariectomy, causes bone loss through TNFα signaling. Furthermore, in ovariectomized mice treated with soluble TNFα receptors, thiol antioxidant defenses in bone remained low, despite inhibition of bone loss. This suggests that the low levels of antioxidants in bone seen after ovariectomy are the cause, rather than the effect, of the increased resorption. These experiments are consistent with a model for estrogen-deficiency bone loss in which estrogen deficiency lowers thiol antioxidant defenses in bone cells, thereby increasing reactive oxygen species levels, which in turn induce expression of TNFα, which causes loss of bone.