bluuebunny/crossref_metadata_2025 huggingface dataset:
Postgenomic Approach To Identify Novel
Mycobacterium leprae
Antigens with Potential To Improve Immunodiagnosis of Infection
Authors: Geluk Annemieke , Klein Michèl R. , Franken Kees L. M. C. , van Meijgaarden Krista E. , Wieles Brigitte , Pereira Kelly Cristina , Bührer-Sékula Samira , Klatser Paul R. , Brennan Patrick J. , Spencer John S. , Williams Diana L. , Pessolani Maria C. V. , Sampaio Elizabeth P. , Ottenhoff Tom H. M.
Published: August 2005

Early detection of
Mycobacterium leprae
infection is considered an important component of strategies aiming at reducing transmission of infection, but currently available diagnostic tools often lack sufficient sensitivity and specificity to reach this goal. Recent comparative genomics have revealed the presence of 165
M. leprae
genes with no homologue in
M. tuberculosis
. We selected 17 of these genes for further study. All 17 genes were found to be expressed at the mRNA level in
M. leprae
from infected mice and from a multibacillary leprosy patient. Additional comparative genomic analyses of all currently available mycobacterial genome databases confirmed 12 candidate genes to be unique to
M. leprae
, whereas 5 genes had homologues in mycobacteria other than
M. tuberculosis
. Evaluation of the immunogenicity of all 17 recombinant proteins in PBMC from 127 Brazilians showed that five antigens (ML0576, ML1989, ML1990, ML2283, and ML2567) induced significant gamma interferon levels in paucibacillary leprosy patients, reactional leprosy patients, and exposed healthy controls but not in most multibacillary leprosy patients, tuberculosis patients, or endemic controls. Importantly, among exposed healthy controls 71% had no detectable immunoglobulin M antibodies to the
M. leprae
-specific PGL-I but responded to one or more
M. leprae
antigen(s). Collectively, the
M. leprae
proteins identified are expressed at the transcriptome level and can efficiently activate T cells of
M. leprae
-exposed individuals. These proteins may provide new tools to develop tests for specific diagnosis of
M. leprae
infection and may enhance our understanding of leprosy and its transmission.
Early Cytokine Production Is Associated with Protection from Murine Cerebral Malaria
Authors: Mitchell Andrew J. , Hansen Anna M. , Hee Leia , Ball Helen J. , Potter Sarah M. , Walker John C. , Hunt Nicholas H.
Published: August 2005

Cerebral malaria (CM) is an infrequent but serious complication ofPlasmodium falciparuminfection in humans. Animal and human studies suggest that the pathogenesis of CM is immune mediated, but the precise mechanisms leading to cerebral pathology are unclear. In mice, infection withPlasmodium bergheiANKA results in CM on day 6 postinoculation (p.i.), while infection with the closely related strainP. bergheiK173 does not result in CM. Infection withP. bergheiK173 was associated with increased plasma gamma interferon (IFN-γ) at 24 h p.i. and with increased splenic and hepatic mRNAs for a range of cytokines (IFN-γ, interleukin-10 [IL-10], and IL-12) as well as the immunoregulatory enzyme indoleamine 2,3-dioxygenase. In contrast,P. bergheiANKA infection was associated with an absence of cytokine production at 24 h p.i. but a surge of IFN-γ production at 3 to 4 days p.i. When mice were coinfected with both ANKA and K173, they produced an early cytokine response, including a burst of IFN-γ at 24 h p.i., in a manner similar to animals infected withP. bergheiK173 alone. These coinfected mice failed to develop CM. In addition, in a low-doseP. bergheiK173 infection model, protection from CM was associated with early production of IFN-γ. Early IFN-γ production was present in NK-cell-depleted, γδ-cell-depleted, and Jα281−/−(NKT-cell-deficient) mice but absent from β2-microglobulin mice that had been infected withP. bergheiK173. Taken together, the results suggest that the absence of a regulatory pathway involving IFN-γ and CD8+T cells inP. bergheiANKA infection allows the development of cerebral immunopathology.
vpaH
, a Gene Encoding a Novel Histone-Like Nucleoid Structure-Like Protein That Was Possibly Horizontally Acquired, Regulates the Biogenesis of Lateral Flagella in
trh
-Positive
Vibrio parahaemolyticus
TH3996
Authors: Park Kwon-Sam , Arita Michiko , Iida Tetsuya , Honda Takeshi
Published: August 2005

A histone-like nucleoid structure (H-NS) is a major component of the bacterial nucleoid and plays a crucial role in the global gene regulation of enteric bacteria. Here, we cloned and characterized the gene for the H-NS-like protein VpaH in
Vibrio parahaemolyticus. vpaH
encodes a protein of 134 amino acids that shows approximately 55%, 54%, and 41% identities with VicH in
Vibrio cholerae
, H-NS in
V. parahaemolyticus
, and H-NS in
Escherichia coli
, respectively. The
vpaH
gene was found in only
trh
-positive
V. parahaemolyticus
strains and not in Kanagawa-positive or in
trh
-negative environmental strains. Moreover, the G+C content of the
vpaH
gene was 38.6%, which is lower than the average G+C content of the whole genome of this bacterium (45.4%). These data suggest that
vpaH
was transmitted to
trh
-possessing
V. parahaemolyticus
strains by lateral transfer. The
vpaH
gene was located about 2.6 kb downstream of the
trh
gene, in the convergent direction of the
trh
transcription. An in-frame deletion mutant of
vpaH
lacked motility on semisolid motility assay plates. Western blot analysis and electron microscopy observations revealed that the mutant was deficient in lateral flagella biogenesis, whereas there was no defect in the expression of polar flagella. Additionally, the
vpaH
mutant showed a decreased adherence to HeLa cells and a decrease in biofilm formation compared with the wild-type strain. Introduction of the
vpaH
gene in the
vpaH
-negative strain increased the expression of lateral flagella compared with the wild-type strain. In conclusion, our findings suggest that VpaH affects lateral flagellum biogenesis in
trh
-positive
V. parahaemolyticus
strain TH3996.
Cationic Liposomes Containing Mycobacterial Lipids: a New Powerful Th1 Adjuvant System
Authors: Rosenkrands Ida , Agger Else Marie , Olsen Anja W. , Korsholm Karen S. , Andersen Claire Swetman , Jensen Klaus T. , Andersen Peter
Published: August 2005

The immunostimulation provided by the mycobacterial cell wall has been exploited for many decades, e.g., in Freund's complete adjuvant. Recently, the underlying mechanism behind this adjuvant activity, including Toll receptor signaling, has begun to be unraveled, confirming the potential of mycobacterial constituents to act as adjuvants. In this study, the immunostimulatory properties of a
Mycobacterium bovis
BCG lipid extract were tested for their adjuvant activity. Administration of the lipids in dimethyl dioctadecyl ammonium bromide-based cationic liposomes induced a powerful Th1 response characterized by markedly elevated antigen-specific immunoglobulin G2a (IgG2a) isotype antibodies and substantial production of gamma interferon. The adjuvant formulation (designated mycosomes) elicited high levels of gamma interferon both in C57BL/6 as well as in Th2-prone BALB/c mice. Furthermore, the mycosomes induced immune responses to protein antigens from several sources including
Mycobacterium tuberculosis
,
Chlamydia muridarum
, and tetanus toxoid. In a tuberculosis challenge model, the mycosomes combined with the Ag85B-ESAT-6 fusion protein were demonstrated to have a unique ability to maintain sustained immunological memory at a level superior to live BCG.
Novel Role of the Lipopolysaccharide O1 Side Chain in Ferric Siderophore Transport and Virulence of
Vibrio anguillarum
Authors: Welch Timothy J. , Crosa Jorge H.
Published: August 2005

From a library of approximately 20,000 transposon mutants, we have identified mutants affected in chromosomal genes involved in synthesis of the siderophore anguibactin, as well as in ferric anguibactin utilization. Genetic and sequence analyses of one such transport-defective mutant revealed that the transposon insertion occurred in an open reading frame (ORF) with homology to
rmlC
, a dTDP-rhamnose biosynthetic gene. This ORF resides within a cluster of four ORFs, all of which are predicted to function in the biosynthesis of this O side chain precursor. The same phenotype was seen in a mutant obtained by allelic exchange in
rmlD
, another ORF in this dTDP-rhamnose biosynthetic cluster. This mutation could be complemented with the wild-type
rmlD
gene, restoring both production of the O1 antigen side chain and ferric anguibactin transport. Presence of the O1 side chain was crucial for the resistance of
Vibrio anguillarum
to the bactericidal action of nonimmune serum from the fish host. Surprisingly, further analysis demonstrated that these mutations were pleiotropic, leading to a dramatic decrease in the levels of FatA, the outer membrane protein receptor for ferric anguibactin transport, and a concomitant reduction in iron transport. Thus, our results in this work demonstrate that the lipopolysaccharide O1 side chain is required for the operation of two critical virulence factors in
V. anguillarum
: serum resistance and anguibactin-mediated iron transport. These factors allow
V. anguillarum
to survive in serum and multiply in the iron-limiting milieu of the host vertebrate.
Cyclic Diguanylate Regulates
Vibrio cholerae
Virulence Gene Expression
Authors: Tischler Anna D. , Camilli Andrew
Published: August 2005

The cyclic dinucleotide second messenger cyclic diguanylate (c-diGMP) has been implicated in regulation of cell surface properties in several bacterial species, including
Vibrio cholerae
. Expression of genes required for
V. cholerae
biofilm formation is activated by an increased intracellular c-diGMP concentration. The response regulator VieA, which contains a domain responsible for degradation of c-diGMP, is required to maintain a low concentration of c-diGMP and repress biofilm formation. The VieSAB three-component signal transduction system was, however, originally identified as a regulator of
ctxAB
, the genes encoding cholera toxin (CT). Here we show that the c-diGMP phosphodiesterase activity of VieA is required to enhance CT production. This regulation occurred at the transcriptional level, and ectopically altering the c-diGMP concentration by expression of diguanylate cyclase or phosphodiesterase enzymes also affected
ctxAB
transcription. The c-diGMP phosphodiesterase activity of VieA was also required for maximal transcription
toxT
but did not influence the activity of ToxR or expression of TcpP. Finally, a single amino acid substitution in VieA that increases the intracellular c-diGMP concentration led to attenuation in the infant mouse model of cholera. Since virulence genes including
toxT
and
ctxA
are repressed by a high concentration of c-diGMP, while biofilm genes are activated, we suggest that c-diGMP signaling is important for the transition of
V. cholerae
from the environment to the host.
Highly Immunogenic and Protective Recombinant Vaccine Candidate Expressed in Transgenic Plants
Authors: Chargelegue Daniel , Drake Pascal M. W. , Obregon Patricia , Prada Alessandra , Fairweather Neil , Ma Julian K-C.
Published: August 2005

Vaccine development has been hampered by difficulties in developing new and safe adjuvants, so alternative technologies that offer new avenues forward are urgently needed. The goal of this study was to express a monoclonal recombinant immune complex in a transgenic plant. A recombinant protein consisting of a tetanus toxin C fragment-specific monoclonal antibody fused with the tetanus toxin C fragment was designed and expressed. Immune complex formation occurred between individual fusion proteins to form immune complex-like aggregates that bound C1q and FcγRIIa receptor and could be targeted to antigen-presenting cells. Unlike antigen alone, the recombinant immune fusion complexes were highly immunogenic in mice and did not require coadministration of an adjuvant (when injected subcutaneously). Indeed, these complexes elicited antibody titers that were more than 10,000 times higher than those observed in animals immunized with the antigen alone. Furthermore, animals immunized with only 1 μg of recombinant immune complex without adjuvant were fully protected against lethal challenge. This the first report on the use of a genetic fusion between antigen and antibody to ensure an optimal expression ratio between the two moieties and to obtain fully functional recombinant immune complexes as a new vaccine model.
Merozoite Surface Protein 1 of
Plasmodium vivax
Induces a Protective Response against
Plasmodium cynomolgi
Challenge in Rhesus Monkeys
Authors: Dutta Sheetij , Kaushal Deep C. , Ware Lisa A. , Puri Sunil K. , Kaushal Nuzhat A. , Narula Atul , Upadhyaya D. S. , Lanar David E.
Published: August 2005

The 42-kDa fragment of the merozoite surface protein 1 (MSP-1
42
) is a leading candidate for the development of a vaccine to control malaria. We previously reported a method for the production of
Plasmodium vivax
MSP-1
42
(PvMSP-1
42
) as a soluble protein (S. Dutta, L. W. Ware, A. Barbosa, C. F. Ockenhouse, and D. E. Lanar, Infect. Immun.
69:
5464-5470, 2001). We report here a process to manufacture the same PvMSP-1
42
protein but as an insoluble inclusion body-derived protein which was then refolded in vitro. We compared the immunogenicity and protective efficacy of the soluble and refolded forms of PvMSP-1
42
protein by using a heterologous but closely related
P. cynomolgi
-rhesus monkey challenge model. As comparative controls we also expressed, purified, and immunized rhesus with the soluble and refolded forms of the
P. cynomolgi
MSP-1
42
(PcMSP-1
42
) proteins. All proteins induced equally high-titer, cross-reacting antibodies. Upon challenge with
P. cynomolgi
, none of the MSP-1
42
-vaccinated groups demonstrated sterile protection or a delay in the prepatent period. However, following an initial rise in parasitemia, all MSP-1-vaccinated animals had significantly lower parasite burdens as indicated by lower cumulative parasitemia, lower peak parasitemia, lower secondary peak parasitemia, and lower average daily parasitemia compared to the adjuvant control group (
P
< 0.05). Except the soluble PcMSP-1
42
group, monkeys in all other groups had fewer numbers of days with parasitemia of >10,000 parasites mm
−3
. Interestingly, there was no significant difference in the level of partial protection observed in the homologous and heterologous groups in this challenge model. The soluble and refolded forms of PcMSP-1
42
and PvMSP-1
42
proteins also appeared to have a similar partially protective effect.
Interaction of Enteropathogenic and Shiga Toxin-Producing
Escherichia coli
and Porcine Intestinal Mucosa: Role of Intimin and Tir in Adherence
Authors: Girard Francis , Batisson Isabelle , Frankel Gad M. , Harel Josée , Fairbrother John M.
Published: August 2005

The ileal in vitro organ culture (IVOC) model using tissues originating from colostrum-deprived newborn piglets has proven to be an effective way to study the attaching and effacing (A/E) phenotype of porcine enteropathogenic
Escherichia coli
(EPEC) ex vivo. The aim of this study was to investigate the role of intimin subtype and Tir in the adherence of EPEC and Shiga-toxin-producing
E. coli
(STEC), isolated from different animal species, to porcine intestinal IVOC. Moreover, the role of intimin in Tir-independent adherence of the human EPEC strain E2348/69 was investigated using intimin and Tir-deficient derivatives. Our results demonstrated that A/E
E. coli
strains (AEEC) from various animal species and humans induce the A/E phenotype in porcine ileal IVOC and that intimin subtype influences intestinal adherence and tropism of AEEC strains. We also showed that a
tir
mutant of EPEC strain E2348/69 demonstrates close adherence to the epithelial cells of porcine ileal IVOC segments, with microvillous effacement but with no evidence of actin polymerization or pedestal formation, and that intimin seems to be involved in this phenotype. Overall, this study provides further evidence for the existence of one or more host-cell-encoded intimin receptor(s) in the pig gut.
Hydrophilic Domain II of
Escherichia coli
Dr Fimbriae Facilitates Cell Invasion
Authors: Das Margaret , Hart-Van Tassell Audrey , Urvil Petri T. , Lea Susan , Pettigrew David , Anderson K. L. , Samet Alfred , Kur Jozef , Matthews Steve , Nowicki Stella , Popov Vsevolod , Goluszko Pawel , Nowicki Bogdan J.
Published: August 2005

Uropathogenic and diarrheal
Escherichia coli
strains expressing adhesins of the Dr family bind to decay-accelerating factor, invade epithelial cells, preferentially infect children and pregnant women, and may be associated with chronic or recurrent infections. Thus far, no fimbrial domain(s) that facilitates cell invasion has been identified. We used alanine scanning mutagenesis to replace selected amino acids in hydrophilic domain II of the structural fimbrial subunit DraE and evaluated recombinant mutant DraE for attachment, invasion, and intracellular compartmentalization. The mutation of amino acids V28, T31, G33, Q34, T36, and P40 of DraE reduced or abolished HeLa cell invasion but did not affect attachment. Electron micrographs showed a stepwise entry and fusion of vacuoles containing
Escherichia coli
mutants T36A and Q34A or corresponding beads with lysosomes, whereas vacuoles with wild-type Dr adhesin showed no fusion. Mutants T31A and Q34A, which were deficient in invasion, appeared to display a reduced capacity for clustering decay-accelerating factor. Our findings suggest that hydrophilic domain II may be involved in cell entry. These data are consistent with the interpretation that in HeLa cells the binding and invasion phenotypes of Dr fimbriae may be separated.
Paneth Cells and Antibacterial Host Defense in Neonatal Small Intestine
Authors: Sherman Michael P. , Bennett Stephen H. , Hwang Freda F. Y. , Sherman Jan , Bevins Charles L.
Published: August 2005

Paneth cells are specialized epithelia in the small bowel that secrete antimicrobial proteins. Paneth cells are vital to the innate immunity of the small bowel in adult mammals, but their role during neonatal infection of the small bowel is not well established. Dithizone selectively damages Paneth cells, and when dithizone-treated newborn rats are infected enterally with
Escherichia coli
, the numbers of
E. coli
cells in their jejunal and ileal lavage fluid are significantly increased compared to controls. The data support that Paneth cells are necessary for neonatal antibacterial defense.
Mannheimia
(
Pasteurella
)
haemolytica
Leukotoxin Binding Domain Lies within Amino Acids 1 to 291 of Bovine CD18
Authors: Gopinath R. S. , Ambagala T. C. , Deshpande M. S. , Donis R. O. , Srikumaran S.
Published: August 2005

Previously, we identified bovine CD18 as the receptor for leukotoxin secreted by
Mannheimia
(
Pasteurella
)
haemolytica
. In this study, we constructed bovine-murine CD18 chimeras to locate the leukotoxin binding domain on CD18. Leukotoxin specifically lysed transfectants expressing bovine CD18 fragment encompassing amino acids 1 to 291, indicating that leukotoxin binding domain lies within amino acids 1 to 291 of bovine CD18.
Effects on sleep of microdialysis of adenosine A1and A2areceptor analogs into the lateral preoptic area of rats
Authors: Methippara Melvi M. , Kumar Sunil , Alam Md. Noor , Szymusiak Ronald , McGinty Dennis
Published: August 2005

Evidence suggests that adenosine (AD) is an endogenous sleep factor. The hypnogenic action of AD is mediated through its inhibitory A1and excitatory A2Areceptors. Although AD is thought to be predominantly active in the wake-active region of the basal forebrain (BF), a hypnogenic action of AD has been demonstrated in several other brain areas, including the preoptic area. We hypothesized that in lateral preoptic area (LPOA), a region with an abundance of sleep-active neurons, AD acting via A1receptors would induce waking by inhibition of sleep-active neurons and that AD acting via A2Areceptors would promote sleep by stimulating the sleep-active neurons. To this end, we studied the effects on sleep of an AD transport inhibitor, nitrobenzyl-thio-inosine (NBTI) and A1and A2Areceptor agonists/antagonists by microdialyzing them into the LPOA. The results showed that, in the sleep-promoting area of LPOA: 1) A1receptor stimulation or inhibition of AD transport by NBTI induced waking and 2) A2Areceptor stimulation induced sleep. We also confirmed that NBTI administration in the wake promoting area of the BF increased sleep. The effects of AD could be mediated either directly or indirectly via interaction with other neurotransmitter systems. These observations support a hypothesis that AD mediated effects on sleep-wake cycles are site and receptor dependent.
The Association of Pulmonary Lymphangioleiomyomatosis with Renal and Hepatic Angiomyolipomas in a Prepubertal Girl: A Previously Unreported Entity
Authors: Ciftci Arbay O. , Sanlıalp Ibrahim , Tanyel F. Cahit , Büyükpamukçu Nebil
Published: August 2005

Pulmonary lymphangioleiomyomatosis (PLAM) is a rare, diffuse progressive interstitial lung disease that affects females of childbearing age and is characterized by diffuse proliferation of abnormal smooth muscle fibers predominantly developing in the lung and leading to cystic destruction. A prepubertal 13-year-old girl with PLAM associated with renal and hepatic angiomyolipomas who was treated by nephroureterectomy and thoracoscopic pleurodesis is presented. To the best of our knowledge, this is the first reported case of PLAM associated with renal and hepatic angiomyolipomas at the prepubertal age. After evaluating the clinicopathologic features of this rare entity, the authors conclude that PLAM should be considered in the differential diagnosis of cystic pulmonary pathologies in children, particularly teenagers. The most important clinical aid is to bear this rare entity in mind when a child presents with renal and/or hepatic angiomyolipomas. Thoracoscopic pleurodesis is the most effective treatment modality for recurrent pneumothoraces.
Automatic Computerized Diagnosis of Fetal Sinusoidal Heart Rate
Authors: Maeda Kazuo , Nagasawa Takashi
Published: August 2005

Objectives: Computerized automatic detection of pathologic fetal sinusoidal heart rate (FSHR) and its differentiation from physiologic FSHR is the purpose of this study. The results will be applied in the objective evaluation of fetal heart rate (FHR) with artificial neural network computer. Methods: FHR tracings of pathologic FSHR of 9 cases of fetal-neonatal anemia, death, or severe asphyxia, those of 7 physiologic FSHR followed by normal outcome, and those of 5 normal FHR are processed with fast Fourier transform (FFT) analysis after digitization, and their power spectrums are obtained. The peak power spectrum frequency (PPSF), peak power spectrum density (PPSD), the area under the power spectrum of 0.03125–0.1Hz (La), the area under the whole power spectrum (Ta), and the ratio of La/Ta (%) of pathologic FSHR are compared to those of physiologic FSHR and normal FHR. Results: The La/Ta ratio and PPSD are significantly larger in the pathologic FSHR than those of physiologic FSHR and normal FHR. The true positive rate is 100%, false negative and false positive rates are 0%, respectively, when the pathologic FSHR is diagnosed by such combined criteria as 39% or more of La/Ta ratio and 300 or more of PPSD. Conclusion: Pathologic FSHR is clearly separated from physiologic FSHR and normal FHR by the La/Ta ratio and PPSD obtained by FFT frequency analysis of FHR. Consequently, it is capable to automatically diagnose pathologic FSHR, and to apply it to neural network computer evaluation of FHR.
Reassuring Fetal Middle Cerebral Artery Doppler Velocimetry in Alloimmunised Pregnancies: Neonatal Outcomes without Invasive Procedures
Authors: Abdel-Fattah Sherif A. , Shefras Julia , Kyle Phillipa M. , Cairns Pamela , Hunter Alyson , Soothill Peter W.
Published: August 2005

Objective: To assess the neonatal outcome in red blood cell alloimmunised pregnancies at increased risk of fetal anaemia where invasive testing was avoided based on reassuring middle cerebral artery (MCA) Doppler velocity results. Methods: We included 28 alloimmunised pregnant women at significant risk of fetal or neonatal anaemia who did not have invasive testing because of reassuring MCA Doppler velocimetry. Women requiring invasive testing or intrauterine transfusion were excluded. Outcome measures were admission to neonatal intensive care unit, cord haemoglobin and bilirubin levels and neonatal therapy. Results: Ten neonates (36%) were anaemic at birth while 18 (64%) had normal haemoglobin. Seven neonates (25%) did not require any form of neonatal therapy, 10 (36%) had phototherapy only, 7 (25%) required exchange transfusions and 4 (14%) top-up transfusions. There were no treatment-related complications. Mean cord haemoglobin was 13.9 g/dl (range 7–18.9) and mean bilirubin was 84.1 µmol/l (range 29–192). Conclusion: Avoiding invasive procedures in pregnancies at risk of fetal anaemia by relying on reassuring MCA Doppler velocimetry did not result in life-threatening fetal or neonatal morbidities. The extent of neonatal therapy was acceptable. The routine use of this test can lead to less unnecessary invasive procedures in at-risk fetuses.
Identification of Maternal Hematopoietic Cells in a 2nd-Trimester Fetus
Authors: Götherström Cecilia , Johnsson Anna Maria , Mattsson Jonas , Papadogiannakis Nikos , Westgren Magnus
Published: August 2005

Objective: To study the subset of maternal cells in fetal tissue in a 2nd-trimester fetus with malformations. Methods: By cell sorting and PCR amplification, we studied the presence of maternal CD3+ (T cells), CD19+ (B cells), CD34+ (hematopoietic progenitor cells), and CD45+ (leukocytes) in different tissues in a 2nd trimester fetus. Results: Maternal cells could be detected in fetal liver, lung, heart, thymus, spleen, adrenal gland, kidney, and placenta, but not in pancreas or gonadal tissue. In thymus, liver, and spleen, cell separation showed CD3+, CD19+, CD34+, and CD45+ positive cells of maternal origin. Conclusions: The present study indicates that maternal cells are widely distributed in a 2nd-trimester fetus. In addition, we found subpopulations of maternal cells belonging to lymphoid and myeloid lineages and hematopoietic progenitors with engraftment capacity in liver, spleen, and thymus. The study warrants further investigations on presence and possible biological function of maternal cells in normal and malformed fetuses.
Effects on the Maternofetal Unit of the Rabbit Model after Substitution of the Amniotic Fluid with Perfluorocarbons
Authors: Muensterer Oliver J. , Klis Verena J. , Till Holger , von Schweinitz Dietrich , Simbruner Georg
Published: August 2005

Objectives: Exchanging amniotic fluid (AF) with perfluorocarbon (PFC) may serve as a medium for fetoscopic surgery. This study evaluates the distribution and physiologic effects of intraamniotic PFC as a medium for fetoscopy. Methods: Fetuses of 17 pregnant rabbits underwent either exchange of the AF with PFC, electrolyte solution (ES), or control. The quality of vision during fetoscopy was assessed in AF and PFC. After 6 h, we determined the distribution of PFC in the maternofetal unit. Results: Quality of vision during fetoscopy was better in PFC than with AF. There was no difference in fetal survival between the study groups. PFC was demonstrated on X-ray in the pharynx of 4 fetuses, and the esophagus in 1. Conclusions: PFC provided an ideal medium for fetoscopy without fetal compromise.
Plasma Atrial Natriuretic Peptide in Fetuses with Cardiac Disease
Authors: Bartha Jose L. , Penney Michael D. , Soothill Peter W.
Published: August 2005

Objective: To investigate atrial natriuretic peptide (ANP) levels in fetuses with cardiac defects and to evaluate the relationships between plasma ANP levels and the presence of polyhydramnios. Methods: Plasma ANP levels were measured by radioimmunoassay in 27 fetuses with cardiac abnormalities and in 14 normal healthy fetuses. Results: Fetal plasma ANP levels were similar in the two studied groups (p = 0.18) but they were significantly higher in a subset of cases with cardiac disease and polyhydramnios (n = 7) than in those with cardiac disease and normal amniotic fluid (n = 20; p = 0.036) and controls (p = 0.01). Conclusion: Polyhydramnios in fetuses with heart conditions might be explained by increased fetal diuresis secondary to increased ANP production.
Arnold-Chiari in a Fetal Rat Model of Dysraphism
Authors: Weber Guimarães Barreto Maria , Ferro Marcelo M. , Bittencourt Daniel , Violin Pereira Luis A. , Barini Ricardo , Sbragia Lourenço
Published: August 2005

Dysraphism is a defect in neural tube development, leading to dysplastic growth of the spinal cord and meninges. Myelomeningocele (MM) is just one of its forms. Hydrocephalus is among the most important alterations in MM and occurs as a consequence of Arnold-Chiari malformation (AC). Experimental models have been developed in sheep, rabbits and rats to study MM physiopathology, allowing a more detailed evaluation of clinical parameters involved in this anomaly. Objective: Using the experimental model of dysraphism in fetal rats, the aim of this study was to evaluate the relevance of AC malformations, clinical parameters and grade of histological lesions. Materials and Methods: Three groups with 16 fetuses in each were compared, MM, Control and Sham, after intrauterine surgical creation of MM on day 18.5 of gestation (term = 22 days). AC was evaluated by photographic comparison of sagittal cuts of fetal heads. Clinical and histological evaluations were also made. Results: 88% of AC (14/16) in MM fetuses were obtained, besides 100% of clinical alterations. Necrosis and erosion of the spinal cord exposed to amniotic fluid were verified in histology. Conclusion: The presence of AC in the dysraphism rat model was high. These results allowed the use of this model to study alterations and intrauterine evolution of MM in a fashion similar to those observed in humans.
Relationship between Oxidative Stress in Cord Blood and Route of Delivery
Authors: Inanc Fatma , Kilinc Metin , Kiran Gurkan , Guven Alanur , Kurutas Ergul Belge , Cikim I. Gurkan , Akyol Omer
Published: August 2005

Objective: To investigate the effect of route of delivery on the antioxidant system of newborns. Methods: We used the cord blood taken during labor of 56 vaginal deliveries and 50 elective cesarean sections. The specimens were analyzed for the plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glucose 6-phosphate dehydrogenase (G6PD) activity and leukocyte count. Results: SOD and CAT activities were significantly higher in the elective cesarean group than the vaginal delivery group (p < 0.01 and p < 0.005, respectively), but G6PD activity was similar between the groups. Plasma MDA level was lower in the cesarean group compared to the vaginal delivery group (p < 0.001). Leukocyte count was higher in the vaginal delivery group (p < 0.005). Conclusion: Our findings suggest that the route of delivery has an effect on oxidative stress in newborns exposed to oxidative stress during delivery. It can be suggested that the antioxidant system works more efficiently to overcome oxidative stress in newborns delivered via cesarean section.
Successful Management of Supraventricular Tachycardia in a Fetus Using Fetal Magnetocardiography
Authors: Abe Kanako , Hamada Hiromi , Chen Yang-Jen , Abe Azusa , Watanabe Hideki , Fujiki Yutaka , Yoshikawa Hiroyuki , Murakami Takashi , Horigome Hitoshi
Published: August 2005

We report a fetus at 33 weeks of gestation with supraventricular tachycardia, which was successfully managed by transplacental administration of an antiarrhythmic agent. Fetal magnetocardiography (fMCG) revealed supraventricular tachycardia of the long RP’ tachycardia type. Transplacental administration of sotalol, instead of digoxin, was selected as the first-line drug, and it successfully converted supraventricular tachycardia to sinus rhythm. The diagnosis of the type of supraventricular tachycardia was confirmed by electrocardiography after birth. Sotalol was also effective after birth to maintain sinus rhythm. This case demonstrates that fMCG is potentially useful for prenatal differentiation of the type of supraventricular tachycardia and for prenatal treatment of fetal tachyarrhythmias.
Pulmonary Arteriovenous Malformations, Hereditary Hemorrhagic Telangiectasia, and Brain Abscess
Authors: Gallitelli Mauro , Guastamacchia Edoardo , Resta Francesco , Guanti Ginevra , Sabbà Carlo
Published: August 2005

Hereditary hemorrhagic telangiectasia (HHT) is a systemic angiodysplasia inherited as an autosomal dominant disease. Patients with HHT and pulmonary arteriovenous malformations (PAVMs) are at increased risk for brain abscess (BA), a potentially preventable condition as effective treatment for PAVMs is available. In a center dedicated to HHT, a history of BA was found in 6 out of 128 patients with a definite diagnosis: herewith, their histories are reported focusing on mistakes in the diagnosis and management of the disease. Patients with PAVMs and BA had a higher mean hemoglobin concentration (15.1 g/dl vs. 12.2 g/dl, p < 0.006 by Student’s t test) compared to patients with PAVMs alone. Other clinical features (genetics, bacteriology, types of PAVMs, treatments, outcomes) are also discussed. Prompt diagnosis and screening for visceral involvement is pivotal for HHT patients and their relatives.
Deep Subcutaneous Application of Poly-L-Lactic Acid as a Filler for Facial Lipoatrophy in HIV-Infected Patients
Authors: Borelli C. , Kunte C. , Weisenseel P. , Thoma-Greber E. , Korting H.C. , Konz B.
Published: August 2005

Introduction: Facial lipoatrophy is a crucial problem of HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Poly-L-lactic acid (PLA), provided as New-Fill®/Sculptra™, is known as one possible treatment option. In 2004 PLA was approved by the FDA as Sculptra™ for the treatment of lipoatrophy of the face in HIV-infected patients. While the first trials demonstrated relevant efficacy, this was to some extent linked to unwanted effects. As the depth of injection was considered relevant in this context, the application modalities of the preparation were changed. The preparation was to be injected more deeply into subcutaneous tissue, after increased dilution. Material and Methods: To test this approach we performed a pilot study following the new recommendations in 14 patients. Results: While the efficacy turned out to be about the same, tolerability was markedly improved. The increase in facial dermal thickness was particularly obvious in those patients who had suffered from lipoatrophy for a comparatively small period of time. Conclusion: With the new recommendations to dilute PLA powder and to inject it into the deeper subcutaneous tissue nodule formation is a minor problem. However, good treatment results can only be achieved if lipoatrophy is not too intense; treatment intervals should be about 2–3 weeks.
Lactobezoar with Perforation in a Premature Infant
Authors: Hall N.J. , Ward H.C.
Published: August 2005

An unusual case of neonatal gastric perforation secondary to a large milk curd bezoar (lactobezoar) in a premature infant is reported. Following surgical treatment the infant made a full and uncomplicated recovery. Aetiological factors associated with the development of lactobezoars and their diagnosis and treatment are discussed.
Probiotics as a Treatment Strategy for Gastrointestinal Diseases?
Authors: Bergonzelli Gabriela E. , Blum Stephanie , Brüssow Harald , Corthésy-Theulaz Irène
Published: August 2005

Current interest in probiotics is motivated not only by the clinical data showing efficacy of some probiotic bacteria but also by the increasing antibiotic resistance of pathogenic bacteria (particularly in hospitals) and the rise of consumers’ demand for natural substitutes of drugs. Only few randomized, double-blind placebo-controlled human trials are available, and some involved only small numbers of patients. They are difficult to compare because of differences in probiotic strains employed, doses and formulation. Among probiotic applications, reduction of diarrhea is probably the best-documented effect confirmed by recent meta-analyses. Literature on Helicobacter pylori indicates that probiotics are unable to eradicate the infection but could be useful in decreasing infection levels and as adjuvants of therapy-associated side effects. Studies performed in inflammatory bowel disease suggest that high doses of probiotics and most likely a combination of different lactobacilli and bifidobacteria are more effective in decreasing inflammatory score and maintaining patients in remission than a single probiotic strain. Probiotic studies evaluating amelioration of symptoms in irritable bowel syndrome would require more sustained patient numbers. However, accumulated data is encouraging and suggests that efficacy is strain-dependent. Finally, too few probiotic intervention trials have been reported on colon cancer to allow any firm conclusion.
On-Demand Therapy with Pantoprazole 20 mg as Effective Long-Term Management of Reflux Disease in Patients with Mild GERD: The ORION Trial
Authors: Scholten T. , Dekkers C.P.M. , Schütze K. , Körner T. , Bohuschke M. , Gatz G.
Published: August 2005

Aims: To compare safety and efficacy of on-demand pantoprazole 20 mg/40 mg versus placebo in the long-term management of patients with mild gastroesophageal reflux disease (GERD) after heartburn relief. Methods: A total of 634 patients with endoscopically confirmed GERD grade 0/I and heartburn were included. During the acute phase, patients were treated with pantoprazole 20 mg once daily for 4 weeks. Those patients relieved from heartburn entered the long-term phase, and were randomly assigned to either treatment group pantoprazole 20 mg, 40 mg or placebo. Over 6 months, patients took study medication on demand (antacids as rescue medication) and discontinued the drug once symptoms abated. Results: After 4 weeks a total of 87.1%/90.0% of patients were free of heartburn (ITT/PP), and entered the subsequent long-term phase. The perceived average daily symptom load (placebo: 3.93, pantoprazole 20 mg: 2.91, pantoprazole 40 mg: 2.71, ITT) and the number of antacid tablets taken (average number, placebo: 0.68, pantoprazole 20 mg: 0.45, pantoprazole 40 mg: 0.33, ITT) were significantly higher in the placebo than in both pantoprazole groups (p < 0.0001), with no statistically significant difference between the two pantoprazole groups. The discontinuation rate due to insufficient control of heartburn was significantly lower in both pantoprazole groups compared to placebo (placebo: 10.9, pantoprazole 20 mg: 2.8, pantoprazole 40 mg: 0.9, ITT). Conclusions: Our findings favor on-demand treatment with pantoprazole 20 mg for the long-term management of heartburn in patients with uncomplicated GERD (grade 0/I) with superiority to placebo.
Uric Acid Causes Vascular Smooth Muscle Cell Proliferation by Entering Cells via a Functional Urate Transporter
Authors: Kang Duk-Hee , Han Lin , Ouyang Xiaosen , Kahn Andrew M. , Kanellis John , Li Ping , Feng Lili , Nakagawa Takahiko , Watanabe Susumu , Hosoyamada Makoto , Endou Hitoshi , Lipkowitz Michael , Abramson Ruth , Mu Wei , Johnson Richard J.
Published: August 2005

Background: Soluble uric acid stimulates vascular smooth muscle cell (VSMC) proliferation by activating mitogen-activated protein kinases, and stimulating COX-2 and PDGF synthesis. The mechanism by which uric acid enters the VSMC is not known. We hypothesized that uric acid enters via transporters similar to that observed in the kidney. Methods: We studied the uptake of uric acid into rat VSMC under polarized and depolarized conditions and in the presence of organic anion transport (OAT) inhibitors (probenecid and benzbromarone) or p-aminohippurate (PAH). We also examined the ability of probenecid to inhibit uric acid-induced VSMC proliferation and monocyte chemoattractant protein-1 (MCP-1) synthesis. Results:14C-Urate uptake was shown in VSMC and was enhanced under depolarized conditions. 14C-Uric acid uptake was inhibited by probenecid and benzbromarone, as well as by unlabelled urate and PAH. Probenecid blocked VSMC proliferation and MCP-1 expression in response to uric acid. VSMC did not express rOAT1-3, rOAT-5 or URAT-1 mRNA by PCR, but did express the voltage-sensitive transporter (UAT) by both PCR and RNase protection assay. Conclusions: Urate enters VSMC by both voltage-sensitive and OAT pathways, and the uptake, cell proliferation and MCP-1 expression can be blocked by OAT inhibitors. The specific transporter(s) responsible for the urate uptake remains to be determined.
Complement Activation in Angiotensin II–Induced Organ Damage
Authors: Shagdarsuren Erdenechimeg , Wellner Maren , Braesen Jan-Hinrich , Park Joon-Keun , Fiebeler Anette , Henke Norbert , Dechend Ralf , Gratze Petra , Luft Friedrich C. , Muller Dominik N.
Published: August 2005

We tested whether or not complement activation participates in angiotensin (Ang) II–induced vasculopathy. We used double transgenic rats harboring human renin and angiotensinogen genes (dTGR) with or without losartan or the human renin inhibitor aliskiren. Sprague–Dawley (SD) rats were controls. DTGR had increased blood pressure at week 5 that increased further by week 7. Albuminuria was absent at week 5 but increased markedly in weeks 6 and 7. C-reactive protein (CRP) elevation, macrophages, T cells, tumor necrosis factor (TNF)-α, C1q, C3, C3c, and C5b-9 expression preceded albuminuria. C1q, C3, C3c, and C5b-9 were observed in the dTGR vessel media. C5b-9 colocalized with interleukin (IL)-6. Losartan and aliskiren reduced albuminuria and complement expression. We also studied vascular smooth muscle cells (VSMC) from dTGR compared VSMC from SD. C3 and IL-6 mRNA were analyzed after Ang II, TNF-α, and CRP stimulation. VSMC from dTGR showed increased proliferation and C3 expression compared with SD. Ang II did not induce C3 mRNA in either VSMC type. However, TNF-α and CRP induced C3 mRNA slightly in SD VSMC but markedly in dTGR VSMC, whereas IL-6 induction was similar in both. Thus, complement activation and cell infiltration occurred before the onset of albuminuria in Ang II–mediated renal damage. TNF-α and CRP played a major role in C3 activation. VSMC from dTGR are more sensitive for C3 activation. Our data show that, in this Ang II–induced model, complement activation is a major participant and suggest that TNF-α and CRP may play a role in its induction.
Displacement Measurement Errors from Moving Platforms
Authors: Mahrt L. , Vickers Dean , Drennan William M. , Graber Hans C. , Crawford Timothy L.
Published: August 2005

Errors in eddy correlation measurements from moving platforms (aircraft, ships, buoys, blimps, tethered balloons, and kites) include contamination of the measured fluctuations by superficial fluctuations associated with vertical movement of the platform in the presence of mean vertical gradients. Such errors occur even with perfect removal of the motion of the platform. These errors are investigated here from eddy correlation data collected from the LongEZ research aircraft and the air–sea interaction spar (ASIS) buoy during the Shoaling Waves Experiment (SHOWEX).
Virtual CSU-CHILL Radar: The VCHILL
Authors: Chandrasekar V. , Cho Yoong-Goog , Brunkow D. , Jayasumana A.
Published: August 2005

The Virtual CHILL (VCHILL) system makes it possible to transfer the educational and research experience of the Colorado State University dual polarization radar to remote locations over the Internet. The VCHILL operation includes remote control of radar and display of radar images, as well as the ability to locally process high-bandwidth radar data transferred over data networks. The low-bandwidth VCHILL operation allows the distant users to access the archived and real-time data estimated at the radar site and simultaneously display them on their local systems. A parallel receiver was developed exclusively for the high-bandwidth VCHILL. End-system architectures were designed to accommodate the demands of the high-bandwidth VCHILL operations in real time. A graphic user interface was also developed with the objective of easy installation and usage at various end-user institutions. The VCHILL not only expands the education experience provided by the radar system, but also stimulates the development of innovative research applications for atmospheric remote sensing. The VCHILL is being used by several universities for research and education.
Detectability and Configuration of Tropical Cyclone Eyes over the Western North Pacific in TRMM PR and IR Observations
Authors: Kodama Yasu-Masa , Yamada Takuya
Published: August 2005

Statistics for 138 cases from 61 tropical cyclones over the western North Pacific during the five years from 1998 to 2002 were used to determine the detectability and configuration of tropical cyclone (TC) eyes and to reveal relations with TC intensity and life stages in satellite-based infrared (IR) and precipitation radar (PR) observations from the Tropical Rainfall Measuring Mission (TRMM). Tropical cyclone eyes were detectable in PR data in 89% of cases and in IR data in 37% of cases. Maximum sustained wind speeds in TCs were much greater when the eye was detected in both IR and PR data than in cases when the eye was detected only in PR data or when no eye was detected in either PR or IR data. An eye was detectable in both IR and PR data in the developing stage of only 18% of TCs although an eye was present in the PR data in 90% of cases. An eye was detected in both IR and PR data in 51% of the TCs during the mature stage. During the decaying stage, an eye was detected in both IR and PR data in 31% of cases. Eye diameter determined from PR observations was larger during the later stages. Most TCs had an eye less than 82.5 km in diameter during the developing stage. Tropical cyclone eyes embedded within concentric eyewalls appeared more frequently in the mature and decaying stages; this is consistent with findings from previous studies. In most cases, eye diameter was smaller in IR observations than in PR observations because an upper cloud shield extending from the eyewall partially covered the eye. For several TCs with concentric eye walls, however, eye diameter was smaller in PR observations. A shallow inner eyewall in the PR data and a deep outer eyewall in both IR and PR data characterized these cases.
Toward an Understanding of Decision Making on Complementary and Alternative Medicine Use in Poorer Countries: The Case of Cancer Care in Pakistan
Authors: Tovey Philip , Chatwin John , Ahmad Salma
Published: August 2005

During the past 2 decades, the study of complementary and alternative medicine (CAM) in general, and the sociological study of CAM in particular, have developed apace in richer countries. In addition to data on use levels and the nature of provision, there is now increasing research on issues such as motivation for use, decision-making processes, and so on. The integration of nonorthodox therapies into cancer care has been an important focus for such work. However, this interest has yet to be matched by work in poorer countries. While the nature of traditional medicine (TM) has long been of interest to anthropologists, the new context (marked by the globalized nature of CAMs existing alongside TM and allopathic treatment) has yet to be examined in any depth. In this article, the authors discuss the structural and cultural context of the first sociological research to be conducted into the role ofCAMandTMin cancer care in Pakistan. They identify some potentially important processes (ie, those identified in the limited existing literature and in anecdotal commentary), which are being tested by the new empirical study. The specific foci of the work are outlined. It is argued that research in poorer countries is essential both to ensure that an existing academic imbalance is addressed and to underpin more informed policy making in complex medically pluralistic (poorer) countries.