bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunization of
Saimiri sciureus
Monkeys with a Recombinant Hybrid Protein Derived from the
Plasmodium falciparum
Antigen Glutamate-Rich Protein and Merozoite Surface Protein 3 Can Induce Partial Protection with Freund and Montanide ISA720 Adjuvants
Authors: Carvalho Leonardo J. M. , Alves Francisco A. , Bianco Cesare , Oliveira Salma G. , Zanini Graziela M. , Soe Soe , Druilhe Pierre , Theisen Michael , Muniz José A. P. C. , Daniel-Ribeiro Cláudio T.
Published: February 2005

The immunogenicity and efficacy of a hybrid recombinant protein derived from the N-terminal end of the glutamate-rich protein (GLURP) and the C-terminal portion of the merozoite surface protein 3 (MSP3) of
Plasmodium falciparum
was evaluated in
Saimiri sciureus
monkeys. The GLURP/MSP3 hybrid protein, expressed in
Lactococcus lactis
, was administered in association with alum, Montanide ISA720, or complete or incomplete Freund adjuvant (CFA/IFA) in groups of five animals each. The three formulations were shown to be immunogenic, but the one with alum was shown to be weak compared to the other two, particularly CFA/IFA, which provided very high antibody titers (enzyme-linked immunosorbent assay titers of >3,000,000 and immunofluorescence antibody test titers of 6,400). After a challenge infection with
P. falciparum
FUP strain, all five monkeys from the GLURP/MSP3-alum group showed a rapid increase in parasitemia, reaching 10% and were treated early. The two monkeys with the highest antibody titers in group GLURP/MSP3-Montanide ISA720 had a delay in the course of parasitemia and were treated late due to a low hematocrit. In the GLURP/MSP3-CFA/IFA group, parasitemia remained below this threshold in four of the five animals and, after it reached a peak, parasitemia started to decrease and monkeys were treated late. When all animals were grouped according to the outcome, a statistically significant association between high antibody titers and partial protection was observed. The challenge infection boosted the antibody titers, and the importance of this event for vaccine efficacy in areas where this parasite is endemic is discussed. In conclusion, these data suggest that GLURP and MSP3 can induce protection against malaria infection if antibodies are induced at properly high titers.
Approach to Validating an Opsonophagocytic Assay for
Streptococcus pneumoniae
Authors: Hu Branda T. , Yu Xinhong , Jones Thomas R. , Kirch Carol , Harris Sarah , Hildreth Stephen W. , Madore Dace V. , Quataert Sally A.
Published: February 2005

Streptococcus pneumoniae
(pneumococcus) polysaccharide serotype-specific antibodies that have opsonophagocytic activity are considered a primary mechanism of host defense against pneumococcal disease. In vitro opsonophagocytic assays (OPAs) with antibody and complement to mediate opsonophagocytic killing of bacteria have been designed and developed as an adjunct to the standardized serum immunoglobulin G antipneumococcal capsular polysaccharide enzyme immunoassay to assess the effectiveness of pneumococcal vaccines. OPA presents challenges for assay standardization and assay precision due to the multiple biologically active and labile components involved in the assay, including human polymorphonuclear leukocytes or cultured effector cells, bacteria, and complement. Control of these biologically labile components is critical for consistent assay performance. An approach to validating the performance of the assay in accordance with International Conference for Harmonization guidelines, including its specificity, intermediate precision, accuracy, linearity, and robustness, is presented. Furthermore, we established parameters for universal reagents and standardization of the use of these reagents to ensure the interlaboratory reproducibility and validation of new methodologies.
Evaluation of Western Blot CagA Seropositivity in
Helicobacter pylori
-Seropositive and -Seronegative Subjects
Authors: Simán J. Henrik , Engstrand Lars , Berglund Göran , Florén Claes-Henrik , Forsgren Arne
Published: February 2005

CagA seropositivity is an important risk factor for gastric adenocarcinoma and duodenal ulcer. However, CagA seropositivity is also found in
Helicobacter pylori
-seronegative subjects. Is CagA seropositivity in these subjects a sign of a past
H. pylori
infection, or does it represent a false-positive reaction? This study investigates the intensity of the CagA immune reaction and the variation in CagA seroprevalence with year of birth for 650 subjects belonging to the Malmö Preventive Medicine cohort. CagA and
H. pylori
seroprevalences were determined by Western blot analysis (Helicoblot 2.1) and enzyme-linked immunosorbent assay. The peak intensity of the CagA band was significantly lower in
H. pylori
-seronegative subjects than in those with concomitant
H. pylori
seropositivity. In
H. pylori
-seropositive subjects, peak CagA intensity had a bimodal distribution. The prevalence of CagA-seropositive but
H. pylori
-seronegative subjects increased successively and significantly with year of birth, in contrast to the prevalence of CagA-seropositive and
H. pylori
-seropositive subjects, which decreased significantly. However, within
H. pylori
-seropositive and -seronegative subgroups, CagA seroprevalences were constant for different birth cohorts. If CagA seropositivity in
H. pylori
-seronegative subjects represents a past
H. pylori
infection, there must have been some mechanisms of eradication that were more common in younger subjects and that were of more importance than the presence of gastric atrophy and the longer duration and higher prevalence of
H. pylori
infection found in older subjects. Antibiotic treatment of
H. pylori
was not common practice at the time of enrollment. On the other hand, a false-positive reaction would be constant and independent of birth cohorts, as with the
H. pylori
-seronegative subgroup of our study. Peak CagA intensity in
H. pylori
-seronegative subjects corresponded to the lower part of the bimodal distribution of peak CagA intensity in
H. pylori
-seropositive subjects. We conclude that a major proportion of CagA seropositivity in
H. pylori
-seronegative subjects represents a false-positive reaction. Peak CagA intensity has a bimodal distribution in
H. pylori
-seropositive subjects. Low-intensity CagA seropositivity in
H. pylori
-seropositive subjects is indeterminate, representing both false-positive and true-positive reactions.
Novel Immunofluorescence Assay Using Recombinant Nucleocapsid-Spike Fusion Protein as Antigen To Detect Antibodies against Severe Acute Respiratory Syndrome Coronavirus
Authors: He Qigai , Manopo Ivanus , Lu Liqun , Leung Bernard P. , Chng Hiok Hee , Ling Ai Ee , Chee Li Lian , Chan Shzu-Wei , Ooi Eng Eong , Sin Yeo Lee , Ang Brenda , Kwang Jimmy
Published: February 2005

Severe acute respiratory syndrome (SARS) is caused by a novel and highly infectious virus named SARS coronavirus (SARS-CoV). Among the serological tests currently available for the detection of SARS-CoV, a whole-virus-based immunofluorescence assay (IFA) was considered one of the most sensitive assays and served as a “gold standard” during the SARS epidemic in Singapore in 2003. However, the need to manipulate live SARS-CoV in the traditional IFA limits its wide application due to the requirement for a biosafety level 3 laboratory and the risk of laboratory infection. Previously, we have identified two immunodominant epitopes, named N195 and Sc, in the two major structural proteins, the N and S proteins, of SARS-CoV (Q. He, K. H. Chong, H. H. Chng, B. Leung, A. E. Ling, T. Wei, S. W. Chan, E. E. Ooi, and J. Kwang, Clin. Diagn. Lab. Immunol., 11:417-422, 2004; L. Lu, I. Manopo, B. P. Leung, H. H. Chng, A. E. Ling, L. L. Chee, E. E. Ooi, S. W. Chan, and J. Kwang, J. Clin. Microbiol. 42:1570-1576, 2004). In the present study, the N195-Sc fusion protein was highly expressed in insect (Sf9) cells infected with a recombinant baculovirus bearing the hybrid gene under the control of a polyhedrin promoter. An IFA based on Sf9 cells producing the fusion protein was standardized with 23 serum samples from patients with SARS, 20 serum samples from patients with autoimmune diseases, and 43 serum samples from healthy blood donors. The detection rates were comparable to those obtained with a commercial SARS-CoV IFA kit (EUROIMMUN, Gross Groenau, Germany) and a conventional IFA performed at the Singapore General Hospital. Our data showed that the newly developed IFA could detect SARS-CoV in 22 of the 23 SARS-CoV-positive serum samples and gave no false-positive results when the sera from patients with autoimmune diseases and healthy individuals were tested. The detection rate was identical to those of the two whole-virus-based IFAs. Thus, the novel N-S fusion antigen-based IFA could be an attractive alternative to present whole-virus-based IFAs for the diagnosis of SARS-CoV infection.
LcrV Capture Enzyme-Linked Immunosorbent Assay for Detection of
Yersinia pestis
from Human Samples
Authors: Gomes-Solecki Maria J. C. , Savitt Anne G. , Rowehl Rebecca , Glass John D. , Bliska James B. , Dattwyler Raymond J.
Published: February 2005

In the United States, there is currently a major gap in the diagnostic capabilities with regard to plague. To address this, we developed an antigen capture assay using an essential virulence factor secreted by
Yersinia
spp., LcrV, as the target antigen. We generated anti-LcrV monoclonal antibodies (MAbs) and screened them for the ability to bind bacterially secreted native
Yersinia pestis
LcrV. Anti-LcrV MAb 19.31 was used as a capture antibody, and biotinylated MAb 40.1 was used for detection. The detection limit of this highly sensitive
Yersinia
LcrV capture enzyme-linked immunosorbent assay is 0.1 ng/ml. The assay detected LcrV from human sputum and blood samples treated with concentrations as low as 0.5 ng/ml of bacterially secreted native
Y. pestis
LcrV. This assay could be used as a tool to help confirm the diagnosis of plague in patients presenting with pneumonia.
Antigens of
Mycobacterium tuberculosis
Recognized by Antibodies during Incipient, Subclinical Tuberculosis
Authors: Singh Krishna K. , Dong Yuxin , Belisle John T. , Harder Jeffrey , Arora Vijay K. , Laal Suman
Published: February 2005

Serum samples obtained from human immunodeficiency virus (HIV)-infected tuberculosis (TB) patients months prior to clinical TB were used to delineate the profile of
Mycobacterium tuberculosis
culture filtrate proteins recognized during subclinical TB. A subset of ∼12 antigens was recognized by antibodies in these serum samples. Antibodies to two of these antigens (81 [88]-kDa malate synthase [GlcB] and MPT51) were present in serum samples obtained during incipient subclinical TB in 19 (∼90%) of the 21 HIV-infected TB patients tested. These antigens will be useful for devising diagnostic tests that can identify HIV-positive individuals who are at a high risk for developing clinical TB.
Performance of Two Commercial Enzyme-Linked Immunosorbent Assay Kits Using Recombinant Glycoprotein G2 Antigen for Detection of Herpes Simplex Virus Type 2 Specific Antibodies
Authors: Reddy Sharmila M. , Balakrishnan P. , Uma S. , Thyagarajan S. P. , Solomon Suniti
Published: February 2005

For 93 stored serum samples tested by HerpeSelect2 and the Euroimmun enzyme-linked immunosorbent assay for detection of herpes simplex virus type 2-specific immunoglobulin G antibodies, the concordance of positive and negative results was 100%. Moreover, all the results that were equivocal by HerpeSelect2 (negative by Euroimmun) were confirmed as being negative by a Western blot assay.
Antibody Responses to Asian and American Genotypes of Dengue 2 Virus in Immunized Mice
Authors: Bernardo Lidice , Yndart Adriana , Vázquez Susana , Morier Luis , Guzmán María G.
Published: February 2005

The possibility of a correlation between dengue virus genotype groups and disease severity is currently under discussion. The objective of this investigation was to identify any immunogenic difference between the American and Asian dengue 2 virus genotypes through the study of antibody development (virus-binding immunoglobulin G and neutralizing antibodies) in mice. Differences in the neutralization pattern between the strains studied were observed, suggesting the presence of slight antigenic variations among them. The lack of recognition of one of the Asian genotype strains was remarkable.
NEW LATTICE KINETIC SCHEMES FOR INCOMPRESSIBLE VISCOUS FLOWS
Authors: PENG Y. , SHU C. , CHEW Y. T. , ZHENG H. W.
Published: February 2005

A new two-dimensional lattice kinetic scheme on the uniform mesh was recently proposed by Inamuro, based on the standard lattice Boltzmann method (LBM). Compared with the standard LBM, this scheme can easily implement the boundary condition and save computer memory. In order to remove the shortcoming of a relatively large viscosity at a high Reynolds number, a first-order derivative term is introduced in the equilibrium density distribution function. However, the parameter associated with the derivative term is very sensitive and was chosen in a narrow range for a high Reynolds number case. To avoid the use of the derivative term while removing the shortcoming of a relatively large viscosity, new lattice kinetic schemes are proposed in this work following the original lattice kinetic scheme. In these new lattice kinetic schemes, the derivative term is dropped out and the difficulty of the relatively large viscosity is eased by controlling the time step δt or sonic speed cs. To validate these new lattice kinetic schemes, the numerical simulations of the two-dimensional square driven cavity flow at Reynolds numbers from 100 to 1000 are carried out. The results using the new lattice kinetic schemes are compared with the benchmark data.
CRITICAL BEHAVIOR OF AN EPIDEMIC MODEL OF DRUG RESISTANT DISEASES
Authors: DA SILVA C. R. , FULCO U. L. , LYRA M. L. , VISWANATHAN G. M.
Published: February 2005

In this work, we study the critical behavior of an epidemic propagation model that considers individuals that can develop drug resistance. In our lattice model, each site can be found in one of the four states: empty, healthy, normally infected (not drug resistant) and strain infected (drug resistant) states. The most relevant parameters in our model are related to the mortality, cure and mutation rates. This model presents two distinct stationary active phases: a phase with co-existing normal and drug resistant infected individuals, and an intermediate active phase with only drug resistant individuals. We employed a finite-size scaling analysis to compute the critical points and the critical exponents, β/ν and 1/ν, governing the phase transitions between these active states and the absorbing inactive state. Our results are consistent with the hypothesis that these transitions belong to the directed percolation universality class.
APPLYING SYMMETRY PROPERTIES OF FINITE SYSTEM TO ITS FIELD THEORY DESCRIPTION
Authors: SEREDYUK B. A. , TOVSTYUK K. D. , TOVSTYUK N. K.
Published: February 2005

The self-energy is received using the theory group and field techniques, based on the wave functions of the classes of point symmetry group and accounting for the two-particle system. It contains components responsible not only for relaxation processes but also for the oscillating ones, caused by a different degree of occupation of the class of point symmetry group by particles of the structure. Analyzing the character of energy oscillations depending on the degree of the class occupation, the mechanisms of diffusion, catalysis, chemical reactions and Le-Shatelje principle are described.
LASER TECHNOLOGY IN PEACE AND WAR
Authors: BLOEMBERGEN N.
Published: February 2005

Lasers emit light with a very high degree of monochromaticity, directionality and intensity. They can produce much higher intensities than incoherent light sources, such as incandescent lamps, fluorescent tubes and arcs. The first operating laser was realized in 1960, and much early research was funded by military agencies, but at the present time the commercial laser market is four times as large as the military market. Most applications of lasers are for peaceful purposes. Among the most important of these are fiber-optic communications and laser surgery. Other applications include laser printing, laser machining, construction alignment, and data storage on CD disks. Some military uses of lasers are also reviewed.
ASSESSING THE EFFECT OF COULOMB REPULSION ASYMMETRY ON ELECTRON PAIRING
Authors: RAISSI FARSHID
Published: February 2005

Coulomb repulsion between two moving electrons loses its spherical symmetry due to relativistic effects. In presence of a uniform positive ion background, this asymmetry uncovers an angular dependent attraction potential in the direction of motion. The quantum mechanical response to such an attraction potential is obtained through perturbation. It is shown that the transition amplitude between states with the symmetry of the attraction potential becomes negative and if the density of states is anisotropic, occurrence of a superconducting state becomes possible.
MAGNETIC PROPERTIES OF U1-xYxMnAl SYSTEM
Authors: LUPSA ILEANA
Published: February 2005

The magnetic measurements on U 1-x Y x MnAl system were performed in the 4–600 K temperature range and fields up to 70 kOe. YMnAl presents spin fluctuation characteristics due to manganese atoms with a Curie–Weiss type behavior over the T* temperature. The gradual substitution of uranium for yttrium leads to similar behavior evidencing higher molar Curie constants and supporting a contribution due to uranium atom. The effective magnetic moment on uranium positions is that of U 3+ ion (3.1μB) and is composition-independent. The spin fluctuating state of manganese is characterized by the effective magnetic moment of 3μB/ Mn atom. The intrinsic Mn moment order is discussed in the critical Mn – Mn separation term.
NATURAL CONVECTION DURING CZOCHRALSKI SINGLE CRYSTAL GROWTH OF SUPERCONDUCTING MATERIALS
Authors: LI Y. R. , WU S. Y. , LAN P. , FENG C. H.
Published: February 2005

To understand the characteristics of the flow, heat and mass transfer in the Ba - Cu - O melt for superconducting material YBa 2 Cu 3 O 2-x ( Y 123) single crystal growth by Czochralski method, this paper presents the numerical simulations of the two-dimension unsteady flow, thermal and Y concentration fields in the Ba - Cu - O melt for Y123 single crystal growth. The results show that the flow is steady at a small temperature difference. As the temperature difference in the radial direction increases, the simulation can predict oscillatory flow.
DYNAMICAL CONDUCTIVITY IN DISORDERED TWO-DIMENSIONAL SQUARE LATTICES AROUND HALF FILLING
Authors: ZHANG Q. , YANG Y. H.
Published: February 2005

Quantum interference (QI) correction to dynamical conductivity is calculated with the diagrammatic technique in a weakly-disordered two-dimensional (2D) square lattice around half filling, in which the pointlike nonmagnetic impurities are assumed to be substituted randomly for the host atoms. It is found that the conductivity correction is inversely proportional to the frequency for the case of perfectly-nested Fermi surface, resulting from the contribution of diffusive π modes to the QI effect. Such an antilocalization effect is strikingly different from the logarithmic weak-localization correction predicted for 2D free electron systems.
Paradigm Shift of the Plasma Membrane Concept from the Two-Dimensional Continuum Fluid to the Partitioned Fluid: High-Speed Single-Molecule Tracking of Membrane Molecules
Authors: Kusumi Akihiro , Nakada Chieko , Ritchie Ken , Murase Kotono , Suzuki Kenichi , Murakoshi Hideji , Kasai Rinshi S. , Kondo Junko , Fujiwara Takahiro
Published: February 2005

▪ Abstract  Recent advancements in single-molecule tracking methods with nanometer-level precision now allow researchers to observe the movement, recruitment, and activation of single molecules in the plasma membrane in living cells. In particular, on the basis of the observations by high-speed single-particle tracking at a frame rate of 40,000 frames s−1, the partitioning of the fluid plasma membrane into submicron compartments throughout the cell membrane and the hop diffusion of virtually all the molecules have been proposed. This could explain why the diffusion coefficients in the plasma membrane are considerably smaller than those in artificial membranes, and why the diffusion coefficient is reduced upon molecular complex formation (oligomerization-induced trapping). In this review, we first describe the high-speed single-molecule tracking methods, and then we critically review a new model of a partitioned fluid plasma membrane and the involvement of the actin-based membrane-skeleton “fences” and anchored-transmembrane protein “pickets” in the formation of compartment boundaries.
ATMOSPHERIC MOIST CONVECTION
Authors: Stevens Bjorn
Published: February 2005

▪ Abstract  Various forms of atmospheric moist convection are reviewed through a consideration of three prevalent regimes: stratocumulus; trade-wind; and deep, precipitating, maritime convection. These regimes are chosen because they are structural components of the general circulation of the atmosphere and because they highlight distinguishing features of this polymorphous phenomenon. In particular, the ways in which varied forms of moist convection communicate with remote parts of the flow through mechanisms other than the rearrangement of fluid parcels are emphasized. These include radiative, gravity wave, and/or microphysical (precipitation) processes. For each regime, basic aspects of its phenomenology are presented along with theoretical frameworks that have arisen to help rationalize the phenomenology. Recent developments suggest that the increased capacity for numerical simulation and increasingly refined remote sensing capabilities bodes well for major advances in the coming years.
Combination unilateral amygdaloid and ventromedial hypothalamic lesions: evidence for a feeding pathway
Authors: Grundmann Scott J. , Pankey Edward A. , Cook Misty M. , Wood Aimee L. , Rollins Bethany L. , King Bruce M.
Published: February 2005

Previous studies have reported hyperphagia and obesity in female rats with bilateral lesions of the most posterodorsal part of the amygdala. In rats with unilateral posterodorsal amygdaloid lesions, a dense pattern of anterograde degeneration appears in the ipsilateral ventromedial hypothalamus, but not the contralateral nucleus. In the present study, female rats with unilateral ventromedial hypothalamic lesions or sham lesions were given either sham lesions or unilateral lesions of the posterodorsal amygdala (PDA) 20 days later. Unilateral lesions of the ventromedial hypothalamus resulted in hyperphagia and excessive weight gain. Subsequent amygdaloid lesions that were contralateral to the initial hypothalamic lesions resulted in hyperphagia and additional excessive weight gains, but amygdaloid lesions ipsilateral to the initial hypothalamic lesions did not. It is concluded that the effects of the two lesions on body weight are not additive and that the PDA and ventromedial hypothalamus are part of the same ipsilateral pathway regulating feeding behavior and body weight regulation.
Methodological Considerations in the Study of Genetic Discrimination
Authors: Treloar Susan , Taylor Sandra , Otlowski Margaret , Barlow-Stewart Kristine , Stranger Mark , Chenoweth Kellie
Published: February 2005

The potential significance and dimensions of genetic discrimination have been described extensively in published literature, but epidemiological and verified case data are limited. Obtaining unbiased data from individuals about discrimination which has been based on erroneous or unjustifiable assumptions about their genetic predispositions poses unique challenges. Through review and discussion of research literature, we identify methodological considerations for collecting valid epidemiological data on genetic discrimination from individuals in the community; in particular, we consider issues which relate to sampling, selection and response. We identify issues to promote sound study design, with particular attention to verification of genetic discrimination, and highlight the importance of clinical and genetic knowledge of complex genotype-phenotype relationships.
Short-Term Psychological Impact of Predictive Testing for Machado-Joseph Disease: Depression and Anxiety Levels in Individuals at Risk from the Azores (Portugal)
Authors: Gonzalez Carlos , Lima Manuela , Kay Teresa , Silva Catarina , Santos Cristina , Santos Jorge
Published: February 2005

Objective: The short-term impact of the pre-symptomatic genetic test (PT) for Machado-Joseph disease (MJD) in the Azores (Portuguese Islands) was assessed in 46 individuals at risk who completed the PT Program. Methods: Scores for depression and anxiety were used as indicators of the subjects’ emotional status immediately before the PT and 1 year after disclosure of the results. Results: Global levels of participation in the Azorean PT Program for MJD were high (20.7%), particularly in Flores Island (35.8%). For the total sample, mean scores of depression and anxiety before and after the PT presented without clinical significance. No differences were found for depression and anxiety scores before and after the PT. Furthermore, when grouped by test results (carriers/non-carriers), there were no differences between pre- and post-test levels. Conclusions: Results indicate that the test result did not cause a decrease in the psychological well-being of the individuals tested. The high number of participants performing the PT in the small and isolated community of Flores Island, where MJD represents a source of stigma, was interpreted as an indication that in this particular population the PT offers the individuals at risk the possibility of liberating from a stigma, and, hence, from exclusion.
A Community Profile of Alpha Thalassaemia in Western Australia
Authors: Prior J.F. , Bittles A.H. , Erber W.N.
Published: February 2005

Objective: To investigate the current prevalence of α-thalassaemia in the population of Western Australia, which has received substantial immigration from South-East Asia during the last 30 years. Method: Over a 1-year period commencing July 2002, α-thalassaemia DNA testing was performed on 920 blood samples received from the Migrant Health Service, referring doctors or pathology laboratories in Western Australia. Molecular testing for α-thalassaemia was performed on extracted DNA for single and double α-globin gene deletions and mutations by PCR. Results: An α-globin gene abnormality was detected in 35.4% (326/920) of samples. There were 177 cases (50.6%) with a single gene deletion α+-thalassaemia, most commonly –3.7 kb, and 102 cases (31.2%) with double α-gene deletions (α⁰-thalassaemia), including 7 cases of HbH disease. Conclusion: Overall, the findings amount to 1.7 new cases of α-thalassaemia per 10,000 population in the 12-month period and demonstrate that α-thalassaemia is an increasingly common disorder in the Western Australian population. This has important implications for community outreach programmes, genetic counselling and the screening of at-risk populations.
Marfan Syndrome in Europe
Authors: De Bie Sylvia , De Paepe Anne , Delvaux Isabelle , Davies Sally , Hennekam Raoul C.M.
Published: February 2005

Objectives: Marfan syndrome (MFS) is a relatively frequent systemic connective tissue disorder with an important physical morbidity and mortality. The influences of MFS on physical problems, perception of severity, and impact on the quality of life and psychosocial well-being have been studied only limitedly. The aim of this study was to assess the association between the severity derived from the reported symptoms and subjectively experienced severity of MFS (expressed as a global judgment), with special emphasis regarding impact on relationships and pregnancies, psychosocial adjustment, and differences between the seven European countries. Methods: A questionnaire designed specifically for this study and translated in each of the native languages was sent to 2,080 members of one of the patient support groups in Belgium, Denmark, France, Germany, The Netherlands, Switzerland, and the United Kingdom. 857 MFS patients of 13 years and older completed the questionnaire and were included in the data analysis. Results: Physical impairments were scored by perception of severity of physical symptoms by the patients (physical severity perception score) and by their perception of the influence of MFS on their life (subjective severity score). Main discrepancy between physical severity perception and subjective severity score was the higher percentage of patients scoring in physical severity perception as severe (53.5%) compared to subjectively severe (26.5%). 61% of those who scored on the physical severity score as severely affected were designated as being mildly-moderately affected on subjective scoring. Both severity scores increased significantly with age. Two hundred-twenty women have carried 430 pregnancies (1.95 pregnancies/woman), with cardiovascular complications in 1.6%. Prenatal studies for MFS were rejected by 7.6% of MFS patients of 25 years and older, 33.6% were undecided, and 48.5% favored prenatal diagnosis for MFS if available. A positive general self-image was reported by 91.5% of patients. However, more than 90% stated that MFS had a negative influence on their sexual relationships, which they ascribed to negative perception of their body image. Conclusions: MFS has significant impact on daily life activities, but the majority of patients come to terms with their condition. Acceptance is mainly determined by subjective severity, and less by physical symptoms as reported by the patients themselves. It is important to stimulate a positive attitude towards MFS.
Prenatal Diagnosis of an Extremely Rare Type of Conjoined Twins: Cranio-Rachi-Pygopagus Twins
Authors: Durin Luc , Hors Yann , Jeanne-Pasquier Corinne , Barjot Philippe , Herlicoviez Michel , Dreyfus Michel
Published: February 2005

Prenatal diagnosis of conjoined twins is rare. An accurate diagnosis is important to provide the parents the best information about the prognosis of the twins. We report a first-trimester diagnosis of an extremely rare type of conjoined twins using two-dimensional transvaginal ultrasound.
Local Anesthetic Procaine Protects Rat Pheochromocytoma PC12 Cells against β-Amyloid-Induced Neurotoxicity
Authors: Lecanu Laurent , Wenguo Yao , Xu Jing , Greeson Janet , Papadopoulos Vassilios
Published: February 2005

Alzheimer’s disease (AD) is the most common dementia occurring in elderly. We report herein the neuroprotective properties of procaine and other anesthetic agents against β-amyloid-induced neurotoxicity. Procaine displayed strong neuroprotective properties against the amyloid peptide Aβ1–42 and preserved Aβ1–42-induced ATP depletion on rat pheochromocytoma PC12 cells. Procaine also inhibited the neurotoxic effect that glutamate displayed on PC12 cells, suggesting that the reduction of glutamate-induced neurotoxicity may be the mechanism by which these compounds exert their ‘antiamyloid’ effects. In search of a mechanism of action we observed that procaine is a ligand for the σ1 receptor, a protein which ligands have been shown to protect mitochondrial function and to exert antidepressant properties. Procaine binds also to muscarinic receptors but the true meaning of this feature needs to be clarified. In conclusion, these data suggest that procaine exerts neuroprotective properties and may serve either as a treatment for AD or as a starting point for the development of novel therapies for AD.
No Evidence for Production of Intrathecal Immunoglobulin G against Acinetobacter or Pseudomonas in Multiple Sclerosis
Authors: Chapman Miles D. , Hughes Lucy E. , Wilson Clyde D. , Namnyak Simon , Thompson Edward J. , Giovannoni Gavin
Published: February 2005

The production of oligoclonal, polyspecific immunoglobulin G is characteristic of multiple sclerosis (MS), yet no pathogen has been identified as an infectious agent. Recent studies have proposed Acinetobactercalcoaceticus and Pseudomonas aeruginosa as candidate organisms, on the basis of a sequence homology between a bacterial enzyme and bovine myelin basic protein. To investigate this, we looked for specific, high-affinity immunoglobulin G against these pathogensin paired serum and cerebrospinal fluid from MS patients compared to other neurological diseases. We found no greater incidence of high-affinity antibodies against the organisms studied in MS vs. other neurological diseases, and so conclude that A. calcoaceticus and P. aeruginosa are unlikely to be implicated in the pathogenesis of MS.
Protective Effect of Intra-Rectal Administration of Rebamipide on Dextran Sulfate Sodium-Induced Rat Colitis
Authors: Okayama Mitsuaki , Tsubouchi Ryoichi , Nishio Hikaru , Kato Shinichi , Takeuchi Koji
Published: February 2005

Background/Aim: Rebamipide, an anti-ulcer drug, has various actions including radical scavenging and mucus-stimulating as well as anti-inflammatory effects, and exhibits both mucosal protective and healing promoting actions in the stomach. In the present study, we examined the effect of rebamipide on an animal model of colitis induced by dextran sulfate sodium (DSS). Methods: Experimental colitis was induced in rats by daily treatment with 3% DSS in drinking water for 7 days. Rebamipide (3–30 mg/kg), 5-aminosalicylic acid (5-ASA: 150 mg/kg) or metronidazole (10 and 30 mg/kg) was administered intra-rectally once daily for 6 days. The ulceration area, colon length, and mucosal myeloperoxidase (MPO) activity as well as thiobarbituric acid-reactive substance (TBARS) were measured on the 7th day after the onset of DSS treatment. The effects of rebamipide on the secretion of mucus in the colon was also examined. Results: DSS treatment caused severe lesions in the colon, accompanied by an increase in MPO activity and TBARS as well as a decrease in body weight gain and colon length. Repeated administration of rebamipide dose-dependently suppressed the colon lesions and improved the pathological changes induced by DSS treatment. Rebamipide significantly increased the mucus contents in the colon. Both 5-ASA and metronidazole also reduced the severity of DSS-induced lesions. Conclusion: These results suggest that intra-rectal administration of rebamipide is effective against DSS-induced colitis. The protective effect of rebamipide may be attributable to both the radical scavenging action and the increase in the production of mucus in the colon, the latter presumably suppressing the process of intestinal bacterial infiltration.
Esomeprazole 40 mg Administered Intravenously Has Similar Safety and Efficacy Profiles to the Oral Formulation in Patients with Erosive Esophagitis
Authors: Schneider Herbert , van Rensburg Christoffel , Schmidt Stephen , Aboo Nazimuddin , Mäkelä Heli , Nauclér Emma , Hallerbäck Bengt , Svedberg Lars-Erik
Published: February 2005

Background/Aims: An intravenous formulation of esomeprazole has been developed for use in patients where oral administration is not appropriate. This study evaluated safety after 1 and 4 weeks, and efficacy after 4 weeks’ esomeprazole 40 mg once daily treatment, administered via an intravenous injection, intravenous infusion or orally, in patients with erosive esophagitis. Methods: In this double-blind, multi-centre study, patients with endoscopically confirmed erosive esophagitis (Los Angeles grade A–D) were randomized to receive 1 week’s treatment of esomeprazole 40 mg once daily, via a 3-min injection, a 30-min infusion or orally, followed by 3 weeks of open treatment with oral esomeprazole 40 mg once daily. Safety variables were evaluated following 1 and 4 weeks’ esomeprazole treatment. Healing rates at 4 weeks were estimated. Results: Intravenous and oral esomeprazole were equally well tolerated during the first week, and after 4 weeks’ treatment. The 3 treatment groups showed similar levels of healing following 4 weeks’ treatment with esomeprazole (injection + oral: 79.7%; infusion + oral: 80.2%; oral alone: 82.6%). Conclusions: Esomeprazole 40 mg administered via an intravenous injection, intravenous infusion or orally administered for 1 week, followed by 3 weeks of oral dosing, is well tolerated and provides effective healing of erosive esophagitis.
A Clinico-Pathological Study of Heart and Brain Lesions in Vascular Dementia
Authors: Andin Ulla , Gustafson Lars , Passant Ulla , Brun Arne
Published: February 2005

All vascular dementia (VaD) cases, neuropathologically verified in a longitudinal prospective dementia project, were classified according to the vascular brain lesion type and related to the dementia type and cardiovascular pathology. From 1976 to 1995, there were 175 VaD cases, 49 of which were pure, without Alzheimer pathology and only one type of cerebrovascular lesion. Furthermore, it was found that 6 cases suffered hypoxic hypoperfusive disease, while 7 were found to have large vessel disease and 36 small vessel disease. In addition to Alzheimer pathology, more than one type of vascular brain pathology was found in the remaining 126 cases. In these cases, diagnosed in accordance with the predominant type of VaD, hypoxic-hypoperfusive lesions were found in 55, large vessel lesions in 50 and small vessel lesions in 110 cases. It should be stressed that 87% of all cases with hypoxic hypoperfusive lesions also had Alzheimer pathology. Cardiovascular and aortic pathologies were more prevalent in small vessel dementia than in the other VaD groups. Clinically diagnosed arterial hypertension was significantly associated with small vessel dementia, but not with hypoxic-hypoperfusive dementia. Cardiovascular symptoms varied considerably in frequency between different dementia groups. VaD is a heterogeneous group regarding lesions caused by different pathophysiological mechanisms and with different combinations of brain pathologies. It is therefore necessary to identify the various types of vascular brain lesions for a correlation with clinical symptoms and for diagnostic purposes in the search for risk factors and therapeutic strategies.
Age-Dependent Associations Between Sleep-Disordered Breathing and Hypertension
Authors: Haas Donald C. , Foster Gregory L. , Nieto F. Javier , Redline Susan , Resnick Helaine E. , Robbins John A. , Young Terry , Pickering Thomas G.
Published: February 2005

Background—

Sleep-disordered breathing (SDB) is associated with hypertension in the middle-aged. The association is less clear in older persons. Most middle-aged hypertensives have systolic/diastolic hypertension, whereas isolated systolic hypertension (ISH) is common among persons over 60 years. Mechanistically, only systolic/diastolic hypertension is expected to be associated with SDB, but few studies of SDB and hypertension distinguish systolic/diastolic hypertension from ISH. Prior investigations may have underestimated an association between SDB and systolic/diastolic hypertension in the elderly by categorizing individuals with ISH as simply hypertensive.

Methods and Results—

We conducted cross-sectional analyses of 6120 participants in the Sleep Heart Health Study, stratified by age: 40 to 59 (n=2477) and ≥60 years. Outcome measures included apnea-hypopnea index (AHI; average number of apneas plus hypopneas per hour of sleep), systolic/diastolic hypertension (≥140 and ≥90 mm Hg), and ISH (≥140 and <90 mm Hg). With adjustment for covariates, ISH was not associated with SDB in either age category. In those aged<60 years, AHI was significantly associated with higher odds of systolic/diastolic hypertension (AHI 15 to 29.9, OR=2.38 [95% CI 1.30 to 4.38]; AHI ≥30, OR=2.24 [95% CI 1.10 to 4.54]). Among those aged ≥60 years, no adjusted association between AHI and systolic/diastolic hypertension was found.

Conclusions—

SDB is associated with systolic/diastolic hypertension in those aged <60 years. No association was found between SDB and systolic/diastolic hypertension in those aged ≥60 years or between SDB and ISH in either age category. These findings have implications for SDB screening and treatment. Distinguishing between hypertensive subtypes reveals a stronger association between SDB and hypertension for those aged <60 years than previously reported.
Investigation of Second Genetic Hits at the
BMPR2
Locus as a Modulator of Disease Progression in Familial Pulmonary Arterial Hypertension
Authors: Machado Rajiv D. , James Victoria , Southwood Mark , Harrison Rachel E. , Atkinson Carl , Stewart Susan , Morrell Nicholas W. , Trembath Richard C. , Aldred Micheala A.
Published: February 2005

Background—

Primary pulmonary arterial hypertension (PAH) is a potentially devastating condition resulting from occlusion of the pulmonary arterioles by the formation of vascular lesions. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type II (
BMPR2
) have been identified in both familial (FPAH) and idiopathic PAH. Mutant alleles are typically of low penetrance, indicating that other factors are required for the onset of PAH. Previous reports have suggested that the characteristic plexiform lesions in affected lungs are akin to neoplasia, showing monoclonal expansion and microsatellite instability. We hypothesized that in patients with germline mutations,
BMPR2
might behave as a classic tumor suppressor gene, with somatic loss of the wild-type allele contributing to disease progression.

Methods and Results—

To test this hypothesis, plexiform and concentric vascular lesions were serially microdissected from lung explant tissue derived from 7 FPAH cases. DNA was analyzed for loss of heterozygosity at
BMPR2
and for microsatellite instability (MSI) at 5 loci. MSI was detected in 1 of 37 lesions at a single locus, BAT-26, whereas heterozygosity at
BMPR2
was retained at all informative loci. We also describe a FPAH patient carrying biallelic constitutional missense mutations of
BMPR2
who manifested disease at a stage and manner similar to heterozygous patients.

Conclusions—

Taken together, these data demonstrate that MSI is uncommon in FPAH and suggest that somatic loss of the remaining wild-type
BMPR2
allele in heterozygous mutation carriers likely does not play a significant role in modulating the onset or progression of FPAH.
Impact of Regular Physical Activity on the NAD(P)H Oxidase and Angiotensin Receptor System in Patients With Coronary Artery Disease
Authors: Adams Volker , Linke Axel , Kränkel Nicolle , Erbs Sandra , Gielen Stephan , Möbius-Winkler Sven , Gummert Jan F. , Mohr Friedrich Wilhelm , Schuler Gerhard , Hambrecht Rainer
Published: February 2005

Background—

In patients with stable coronary artery disease, physical exercise training (ET) improves endothelial dysfunction. A potential mechanism mediating the enhanced vasomotor function is a reduced breakdown of endothelium-derived nitric oxide by reactive oxygen species (ROS). The aim of the present study was to analyze the impact of ET on sources of ROS generation in the left internal mammary artery of patients with symptomatic coronary artery disease.

Methods and Results—

In left internal mammary artery rings sampled during bypass surgery from 45 patients randomized to either a training (n=22) or an inactive control (n=23) group, the mRNA expression of NAD(P)H oxidase subunits, NAD(P)H oxidase activity, and ROS production were assessed. In addition, endothelial function, expression of angiotensin II (Ang II) receptor type 1 and 2 (AT
1
-R and AT
2
-R), and Ang II-mediated vasoconstriction were determined. ET resulted in a significant lower expression of gp91
phox
(23.1±0.5 versus 69.1±18.1 arbitrary units, training versus control), p22
phox
(0.7±0.3 versus 2.0±0.5 arbitrary units), and Nox4 (2.7±1.2 versus 5.4±1.0 arbitrary units). Enzymatic activity (2.1±0.3 versus 4.9±0.4 mU/mg) and ROS generation (0.02±0.01 versus 0.06±0.02 arbitrary units) were significantly lower in the training compared with the control group. On a functional level, ET resulted in improved acetylcholine-mediated vasodilatation and a 49% reduction in Ang II–induced vasoconstriction, accompanied by lower AT
1
-R (3.7±0.8 versus 16.6±5.7 arbitrary units, training versus control) and higher AT
2
-R (7.8±2.5 versus 1.6±0.7 arbitrary units) mRNA expression.

Conclusions—

ET reduces vascular expression of NAD(P)H oxidase and AT
1
-R, resulting in decreased local ROS generation. These molecular effects converge in a reduced Ang II–mediated vasoconstriction.
Attenuation-Based Estimates of Rainfall Rates Aloft with Vertically Pointing Ka-Band Radars
Authors: Matrosov Sergey Y.
Published: February 2005

An approach is suggested to retrieve low-resolution rainfall rate profiles and layer-averaged rainfall rates, Ra, from radar reflectivity measurements made by vertically pointing Ka-band radars. This approach is based on the effects of attenuation of radar signals in rain and takes advantage of the nearly linear relation between specific attenuation and rainfall rate at Ka-band frequencies. The variability of this relation due to temperature, details of raindrop size distributions, and the nature of rain (convective versus stratiform) is rather small (∼10%) and contributes little to errors in rainfall rate retrievals. The main contribution to the retrieval errors comes from the uncertainty of the difference in the nonattenuated radar reflectivities in the beginning and the end of the range resolution interval. For 2- and 1-dB uncertainties in this difference, the retrieval errors due to this main contribution are less than 34% and 17%, correspondingly, for rains with Ra ≈ 10 mm h−1 at a 1-km resolution interval. The heavier rain rates are retrieved with a better accuracy since this retrieval error contribution is proportional to 1/Ra. The retrieval accuracy can also be improved but at the expense of more coarse vertical resolutions of retrievals since the main retrieval error contribution is also proportional to the reciprocal of the resolution interval. The Mie scattering effects at Ka band results in less variability in nonattenuated reflectivities (cf. lower radar frequencies), which aids the suggested approach. Given that radar receivers are not saturated, the rainfall rates can be retrieved using cloud radars that were originally designed for measuring only nonprecipitating and weakly precipitating clouds. An important advantage of the attenuation-based retrievals of rainfall is that absolute radar calibration is not required. The inclusion of rainfall information will improve the characterization of the atmospheric column obtained with such radars used for climate research. The applications of the suggested approach are illustrated using the vertically pointing Ka-band radar measurements made during a field experiment in southern Florida. The retrieval results are in good agreement with surface estimates of rainfall rates.
Detiding ADCP Data in a Highly Variable Shelf Sea: The Celtic Sea
Authors: Carrillo L. , Souza A. J. , Hill A. E. , Brown J. , Fernand L. , Candela J.
Published: February 2005

This paper presents a comparison of two conventional detiding techniques carried out for ship-mounted acoustic Doppler current profiler (ADCP) data collected in the European shelf area of the Celtic Sea during the summer of 1998. One technique consisted of extracting the vertically averaged tidal currents obtained from a barotropic three-dimensional numerical tidal model. The second technique consisted of fitting the spatiotemporal ADCP data using least squares and polynomial spatial functions. In the least squares technique, the incorporation of zero velocity normal to the coast appears to improve the estimation of the tidal currents near the coast. Quantitative comparisons of the results from both techniques with historical current meter observations are shown. However, both methods showed limitations in accurately representing the tidal currents in the study area. Consequently, an alternative detiding technique is proposed. This technique consists of blending the tidal currents derived from the numerical model with those fitted to the ADCP data from the least squares method. Improved results were obtained using the blending technique. ADCP-derived residual currents were comparable with contemporaneous flows measured using drifting buoys and also with estimates obtained by geostrophic calculations.