bluuebunny/crossref_metadata_2025 huggingface dataset:
CD8+-T-Cell-Dependent Control ofTrypanosoma cruziInfection in a Highly Susceptible Mouse Strain after Immunization with Recombinant Proteins Based on Amastigote Surface Protein 2
Authors: Araújo Adriano F. S. , de Alencar Bruna C. G. , Vasconcelos José Ronnie C. , Hiyane Meire I. , Marinho Cláudio R. F. , Penido Marcus L. O. , Boscardin Silvia B. , Hoft Daniel F. , Gazzinelli Ricardo T. , Rodrigues Mauricio M.
Published: August 2005

We previously described that DNA vaccination with the gene encoding amastigote surface protein 2 (ASP-2) protects approximately 65% of highly susceptible A/Sn mice against the lethalTrypanosoma cruziinfection. Here, we explored the possibility that bacterial recombinant proteins of ASP-2 could be used to improve the efficacy of vaccinations. Initially, we compared the protective efficacy of vaccination regimens using either a plasmid DNA, a recombinant protein, or both sequentially (DNA priming and protein boosting). Survival after the challenge was not statistically different among the three mouse groups and ranged from 53.5 to 75%. The fact that immunization with a recombinant protein alone induced protective immunity revealed the possibility that this strategy could be pursued for vaccination. We investigated this possibility by using six different recombinant proteins representing distinct portions of ASP-2. The vaccination of mice with glutathioneS-transferase fusion proteins representing amino acids 261 to 500 or 261 to 380 of ASP-2 in the presence of the adjuvants alum and CpG oligodeoxynucleotide 1826 provided remarkable immunity, consistently protecting 100% of the A/Sn mice. Immunity was completely reversed by the in vivo depletion of CD8+T cells, but not CD4+T cells, and was associated with the presence of CD8+T cells specific for an epitope located between amino acids 320 and 327 of ASP-2. We concluded that a relatively simple formulation consisting of a recombinant protein with a selected portion of ASP-2, alum, and CpG oligodeoxynucleotide 1826 might be used to cross-prime strong CD8+-T-cell-dependent protective immunity againstT. cruziinfection.
Genome-Wide Expression Profiling in Malaria Infection Reveals Transcriptional Changes Associated with Lethal and Nonlethal Outcomes
Authors: Schaecher Kurt , Kumar Sanjai , Yadava Anjali , Vahey Maryanne , Ockenhouse Christian F.
Published: August 2005

High-density oligonucleotide microarrays are widely used to study gene expression in cells exposed to a variety of pathogens. This study addressed the global genome-wide transcriptional activation of genes in hosts infected in vivo, which result in radically different clinical outcomes. We present an analysis of the gene expression profiles that identified a set of host biomarkers which distinguish between lethal and nonlethal blood stage
Plasmodium yoelii
malaria infections. Multiple biological replicates sampled during the course of infection were used to establish statistically valid sets of differentially expressed genes. These genes that correlated with the intensity of infection were used to identify pathways of cellular processes related to metabolic perturbations, erythropoiesis, and B-cell immune responses and other innate and cellular immune responses. The transcriptional apparatus that controls gene expression in erythropoiesis was also differentially expressed and regulated the expression of target genes involved in the host's response to malaria anemia. The biological systems approach provides unprecedented opportunities to explore the pathophysiology of host-pathogen interactions in experimental malaria infection and to decipher functionally complex networks of gene and protein interactions.
Complement Receptor 3 Binds theBorrelia burgdorferiOuter Surface Proteins OspA and OspB in an iC3b-Independent Manner
Authors: Garcia Rodolfo C. , Murgia Rossella , Cinco Marina
Published: August 2005

Persistence of borreliae within the vertebrate host depends on the fate of interactions between the spirochetes and target cells. The present work demonstrates the direct binding of theBorrelia burgdorferiouter surface proteins OspA and OspB to CR3 and that this binding is independent of iC3b.
The
Mycobacterium tuberculosis
ESAT-6 Homologue in
Listeria monocytogenes
Is Dispensable for Growth In Vitro and In Vivo
Authors: Way Sing Sing , Wilson Christopher B.
Published: August 2005

ESAT-6 is a virulence determinant in
Mycobacterium tuberculosis
and a member of a conserved group of proteins in a variety of other bacteria. A targeted deletion of the homologous gene in
Listeria
was generated, and in contrast to that observed for mycobacteria, this locus was not required for
Listeria
virulence.
Role of Toll-Like Receptor 4 in the Proinflammatory Response to
Vibrio cholerae
O1 El Tor Strains Deficient in Production of Cholera Toxin and Accessory Toxins
Authors: Haines G. Kenneth , Sayed Blayne Amir , Rohrer Melissa S. , Olivier Verena , Satchell Karla J. Fullner
Published: August 2005

Following intranasal inoculation,
Vibrio cholerae
KFV101 (Δ
ctxAB
Δ
hapA
Δ
hlyA
Δ
rtxA
) colonizes and stimulates tumor necrosis factor alpha and interleukin 1β (IL-1β) in mice, similar to what occurs with isogenic strain P4 (Δ
ctxAB
), but is less virulent and stimulates reduced levels of IL-6, demonstrating a role for accessory toxins in pathogenesis. Morbidity is enhanced in C3H/HeJ mice, indicating that Toll-like receptor 4 is important for infection containment.
The Protective Effect of Antibody in Immunity to Murine Chlamydial Genital Tract Reinfection Is Independent of Immunoglobulin A
Authors: Morrison Sandra G. , Morrison Richard P.
Published: August 2005

The resolution of primary and secondary chlamydial genital infection in immunoglobulin A (IgA)-deficient (IgA−/−) mice was not different from that in IgA+/+mice. Furthermore, depletion of either CD4+or CD8+T cells prior to reinfection of IgA+/+or−/−mice had limited impact on immunity to reinfection. Thus, although antibody contributes importantly to immunity to chlamydial genital tract reinfection, IgA antibodies are not an absolute requirement of that protective response.
Characterization of FimH Adhesins Expressed by
Salmonella enterica
Serovar Gallinarum Biovars Gallinarum and Pullorum: Reconstitution of Mannose-Binding Properties by Single Amino Acid Substitution
Authors: Kisiela Dagmara , Sapeta Anna , Kuczkowski Maciej , Stefaniak Tadeusz , Wieliczko Alina , Ugorski Maciej
Published: August 2005

Recombinant FimH adhesins of type 1 fimbriae from
Salmonella enterica
serovar Gallinarum biovars Gallinarum and Pullorum, in contrast to those of
Salmonella enterica
serovar Typhimurium, did not bind to high-mannose oligosaccharides or to human colon carcinoma HT-29 cells. However, mutated FimH proteins from biovar Gallinarum and biovar Pullorum, in which the isoleucine at position 78 was replaced by the threonine found in
S. enterica
serovar Typhimurium, bound well to glycoproteins carrying high-mannose oligosaccharides and colon carcinoma cells. The loss of sugar-binding properties by biovar Gallinarum and biovar Pullorum FimH adhesins, which are a part of the type 1 fimbriae, is most probably the result of a single T78I mutation, as was proven by site-directed mutagenesis of FimH proteins.
AFTER LEGAL CONSCIOUSNESS
Authors: Silbey Susan S.
Published: August 2005

▪ Abstract  Legal consciousness as a theoretical concept and topic of empirical research developed to address issues of legal hegemony, particularly how the law sustains its institutional power despite a persistent gap between the law on the books and the law in action. Why do people acquiesce to a legal system that, despite its promises of equal treatment, systematically reproduces inequality? Recent studies have both broadened and narrowed the concept's reach, while sacrificing much of the concept's critical edge and theoretical utility. Rather than explaining how the different experiences of law become synthesized into a set of circulating schemas and habits, the literature tracks what particular individuals think and do. Because the relationships among consciousness and processes of ideology and hegemony often go unexplained, legal consciousness as an analytic concept is domesticated within what appear to be policy projects: making specific laws work better for particular groups or interests.
Changes in guinea pig gallbladder smooth muscle Ca2+homeostasis by acute acalculous cholecystitis
Authors: Gomez-Pinilla Pedro J. , Morales Sara , Camello-Almaraz Cristina , Moreno Rosario , Pozo María J. , Camello Pedro J.
Published: August 2005

Impaired smooth muscle contractility is a hallmark of acute acalculous cholecystitis. Although free cytosolic Ca2+([Ca2+]i) is a critical step in smooth muscle contraction, possible alterations in Ca2+homeostasis by cholecystitis have not been elucidated. Our aim was to elucidate changes in the Ca2+signaling pathways induced by this gallbladder dysfunction. [Ca2+]iwas determined by epifluorescence microscopy in fura 2-loaded isolated gallbladder smooth muscle cells, and isometric tension was recorded from gallbladder muscle strips. F-actin content was quantified by confocal microscopy. Ca2+responses to the inositol trisphosphate (InsP3) mobilizing agonist CCK and to caffeine, an activator of the ryanodine receptors, were impaired in cholecystitic cells. This impairment was not the result of a decrease in the size of the releasable pool. Inflammation also inhibited Ca2+influx through L-type Ca2+channels and capacitative Ca2+entry induced by depletion of intracellular Ca2+pools. In addition, the pharmacological phenotype of these channels was altered in cholecystitic cells. Inflammation impaired contractility further than Ca2+signal attenuation, which could be related to the decrease in F-actin that was detected in cholecystitic smooth muscle cells. These findings indicate that cholecystitis decreases both Ca2+release and Ca2+influx in gallbladder smooth muscle, but a loss in the sensitivity of the contractile machinery to Ca2+may also be responsible for the impairment in gallbladder contractility.
Critical mass hypothesis revisited: role of dynamical wave stability in spontaneous termination of cardiac fibrillation
Authors: Qu Zhilin
Published: August 2005

The tendency of atrial or ventricular fibrillation to terminate spontaneously in finite-sized tissue is known as the critical mass hypothesis. Previous studies have shown that dynamical instabilities play an important role in creating new wave breaks that maintain cardiac fibrillation, but its role in self-termination, in relation to tissue size and geometry, is not well understood. This study used computer simulations of two- and three-dimensional tissue models to investigate qualitatively how, in relation to tissue size and geometry, dynamical instability affects the spontaneous termination of cardiac fibrillation. The major findings are as follows: 1) Dynamical instability promotes wave breaks, maintaining fibrillation, but it also causes the waves to extinguish, facilitating spontaneous termination of fibrillation. The latter effect predominates as dynamical instability increases, so that fibrillation is more likely to self-terminate in a finite-sized tissue. 2) In two-dimensional tissue, the average duration of fibrillation increases exponentially as tissue area increases. In three-dimensional tissue, the average duration of fibrillation decreases initially as tissue thickness increases as a result of thickness-induced instability but then increases after a critical thickness is reached. Therefore, in addition to tissue mass and geometry, dynamical instability is an important factor influencing the maintenance of cardiac fibrillation.
Glial-specific ablation of angiotensinogen lowers arterial pressure in renin and angiotensinogen transgenic mice
Authors: Sherrod Mikhiela , Davis Deborah R. , Zhou Xizhou , Cassell Martin D. , Sigmund Curt D.
Published: August 2005

Angiotensinogen (AGT) is mainly expressed in glial cells in close proximity to renin-expressing neurons in the brain. We previously reported that glial-specific overexpression of ANG II results in mild hypertension. Here, we tested the hypothesis that glial-derived AGT plays an important role in blood pressure regulation in hypertensive mice carrying human renin (hREN) and human AGT transgenes under the control of their own endogenous promoters. To perform a glial-specific deletion of AGT, we used an AGT transgene containing loxP sites (hAGTflox), so the gene can be permanently ablated in the presence of cre-recombinase expression, driven by the glial fibrillary acidic protein (GFAP) promoter. Triple transgenic mice (RAC) containing a: 1) systemically expressed hREN transgene, 2) systemically expressed hAGTfloxtransgene, and 3) GFAP-cre-recombinase were generated and compared with double transgenic mice (RA) lacking cre-recombinase. Liver and kidney hAGT mRNA levels were unaltered in RAC and RA mice, as was the level of hAGT in the systemic circulation, consistent with the absence of cre-recombinase expression in those tissues. Whereas hAGT mRNA was present in the brain of RA mice (lacking cre-recombinase), it was absent from the brain of RAC mice expressing cre-recombinase, confirming brain-specific elimination of AGT. Immunohistochemistry revealed a loss of AGT immunostaining glial cells throughout the brain in RAC mice. Arterial pressure measured by radiotelemetry was significantly lower in RAC than RA mice and unchanged from nontransgenic control mice. These data suggest that there is a major contribution of glial-AGT to the hypertensive state in mice carrying systemically expressed hREN and hAGT genes and confirm the importance of a glial source of ANG II substrate in the brain.
Effect of renal medullary H2O2 on salt-induced hypertension and renal injury
Authors: Taylor Norman E. , Cowley Allen W.
Published: August 2005

Dahl salt-sensitive (SS) and consomic, salt-resistant SS-13BN rats possess substantial differences in blood pressure salt-sensitivity even with highly similar genetic backgrounds. The present study examined whether increased oxidative stress, particularly H2O2, in the renal medulla of SS rats contributes to these differences. Blood pressure was measured using femoral arterial catheters in three groups of rats: 1) 12-wk-old SS and consomic SS-13BN rats fed a 0.4% NaCl diet, 2) SS rats fed a 4% NaCl diet and chronically infused with saline or catalase (6.9 μg·kg−1·min−1) directly into the renal medulla, and 3) SS-13BN fed high salt (4%) and infused with saline or H2O2 (347 nmol·kg−1·min−1) into the renal medullary interstitium. After chronic blood pressure measurements, renal medullary interstitial H2O2 concentration ([H2O2]) was collected by microdialysis and analyzed with Amplex red. Blood pressure and [H2O2] were both significantly higher in SS (126 ± 3 mmHg and 145 ± 17 nM, respectively) vs. SS-13BN rats (116 ± 2 mmHg and 56 ± 14 nM) fed a 0.4% diet. Renal interstitial catalase infusion significantly decreased [H2O2] (96 ± 41 vs. 297 ± 52 nM) and attenuated the hypertension (146 ± 2 mmHg catalase vs. 163 ± 4 mmHg saline) in SS rats after 5 days of high salt (4%). H2O2 infused into the renal medulla of consomic SS-13BN fed high salt (4%) for 7 days accentuated the salt sensitivity (145 ± 2 mmHg H2O2 vs. 134 ± 1 mmHg saline). [H2O2] was also increased in the treated group (83 ± 1 nM H2O2 vs. 44 ± 9 nM saline). These data show that medullary production of H2O2 may contribute to salt-induced hypertension in SS rats and that chromosome 13 of the Brown Norway contains gene(s) that protect against renal medullary oxidant stress.
Demogenetic Study of Three Populations within a Region with Strong Founder Effects
Authors: Lavoie Eve-Marie , Tremblay Marc , Houde Louis , Vézina Hélène
Published: August 2005

Objectives: The population of the Saguenay-Lac-St-Jean (SLSJ) region (Quebec, Canada) is known to have a relatively high prevalence of certain hereditary disorders, which can be explained by the consequences of founder effects. This study aims at providing new insights on the origins and subregional stratification of these founder effects. Methods: The genealogies of 300 individuals were reconstructed and analyzed using the BALSAC population register. Results: Inbreeding and kinship levels are higher in Lower Saguenay than in Upper Saguenay and Lac-St-Jean. The population of Lower Saguenay also distinguishes itself because of a fewer number of distinct ancestors. Conclusion: Beyond the genetic features that characterize the whole region, SLSJ also displays intraregional variability. Thus it is important to take into account the settlement patterns and the demographic history of this population for a better appraisal of its contemporary genetic structure.
Attitudes about Genetics in Underserved, Culturally Diverse Populations
Authors: Catz Diana S. , Green Nancy S. , Tobin Jonathan N. , Lloyd-Puryear Michele A. , Kyler Penny , Umemoto Ann , Cernoch Jennifer , Brown Roxane , Wolman Fredericka
Published: August 2005

Objective: New medical discoveries regarding genetic susceptibility to common chronic diseases, and the decoding of the human genome have increased public attention to genetics. What information is understood and what attitudes exist towards genetics and genetic research have not been well examined in underserved, culturally diverse communities. Methods: To better understand attitudes and beliefs towards genetics and genetic testing in these groups, we conducted eight focus groups with 55 patients and health care workers in New York City and Westchester, N.Y., in English, Spanish, and Chinese. Results: Focus group participants had limited understanding about genetics or genetic testing. Newborn screening was the least-known genetic issue, even among health care workers. Regardless of their cultural group, most participants expressed a desire for more information about genetics and genetic tests. Latinos and Chinese participants generally expressed positive attitudes towards genetic studies and genetic testing, with the possibility of preventing diseases cited as the main advantage. Black Americans and Non-Hispanic Whites reported mixed feelings about genetic research and genetic testing. Concerns expressed included: anxiety before receiving test results or waiting for a disease to develop, fear of genetic discrimination by health and life insurance companies and employers, not having the financial means to deal with genetic diseases in themselves or a sick child, concern that children and adults are having too many tests. Black Americans expressed the most concern for possibly harmful use of genetic information. Conclusions: Minority populations of diverse cultures have limited knowledge about genetics and genetic testing, would like to have more information, and are not well reached by the current educational approaches. Participants knew the least about newborn screening, a test that is mandatory in the New York State. While genetic knowledge by minority populations was perhaps not different from the level of knowledge of consumers in general, minority populations are at particular risk of being left behind because of historically poor access to information and services.
In utero Repair of an Experimental Neural Tube Defect in a Chronic Sheep Model Using Biomatrices
Authors: Eggink A.J. , Roelofs L.A.J. , Feitz W.F.J. , Wijnen R.M.H. , Mullaart R.A. , Grotenhuis J.A. , van Kuppevelt T.H. , Lammens M.M.Y. , Crevels A.J. , Hanssen A. , van den Berg P.P.
Published: August 2005

Objective: Persistent exposure of the unprotected spinal cord to amniotic fluid and the uterine wall can lead to progressive damage of neural tissue in case of a myelomeningocele (two-hit hypothesis). The aim of this study was to evaluate whether in utero repair of an experimental neural tube defect in a fetal lamb could protect neural tissue from secondary injury and save neurologic functions after birth. Methods:In 19 fetal lambs, a neural tube defect was created at 79 days’ gestation. In 12 lambs the defect was covered either with a novel, molecular defined collagen-based biocompatible and biodegradable matrix (UMC) or with a small intestinal submucosa (SIS) biomatrix (Cook®) or by closing the skin over the defect. Results: All lambs with the defect covered showed no or minor neurologic morbidity in contrast to the lambs with the defect uncovered in which major neurologic morbidity was seen. Conclusions:These results demonstrate that long-term exposure of the open spinal cord to the intrauterine environment can lead to damage of neural tissue and, consequently loss of neurologic functions and that coverage of the defect can lead to a better neurologic outcome. Furthermore, we could show that a UMC biomatrix and an SIS biomatrix are useful for in utero coverage of a surgically created neural tube defect in our model.
Omphalocoele-Exstrophy-Imperforate Anus-Spinal Defects Complex in Dizygotic Twins
Authors: Noack Frank , Sayk Friedhelm , Gembruch Ulrich
Published: August 2005

OEIS complex refers to a combination of defects consisting of omphalocoele, exstrophy of the cloaca, imperforate anus, and spinal defects. The incidence of the OEIS complex is very rare, estimated to occur in 1 of 200,000–400,000 pregnancies. The aetiology of the OEIS complex is still unclear, single defects in blastogenesis and mutations in homeobox genes, such as HLXB9, have been suggested to be responsible for the development of the OEIS complex. Moreover, higher incidence of OEIS in monozygotic twins suggests a possible genetic contribution to the occurrence of this multisystem defect. We here report the peculiar case of OEIS complex in a dizygotic twin pregnancy. Prenatal diagnosis of OEIS by ultrasound examination is possible but difficult. Sonographic detection of an omphalocoele in the presence of an open neural tube defect should prompt a search of OEIS-associated defects. Accurate prenatal diagnosis by ultrasound and/or diagnosis of the OEIS complex at autopsy are important for detailed counselling of the parents and perinatal management.
Predicting Outcome in Primary Fetal Hydrothorax
Authors: Klam Stephanie , Bigras Jean-Luc , Hudon Lynda
Published: August 2005

Objective: This study examines the role of serial ultrasound in predicting fetal outcomes based on progress, resolution or stability of pleural effusions in primary fetal hydrothorax (PFHT). Methods: Records from consecutive cases of fetal pleural effusions referred to the fetal echocardiography unit over a 12-year period were reviewed. Study patients underwent thorough investigation to rule out secondary causes of pleural effusions. The clinical course was monitored with serial ultrasound studies every 2 weeks until delivery. Pleurocentesis and pleuroamniotic shunts were performed in select cases of PFHT. Fetal survival was the primary outcome variable. Results: Eighteen of 44 patients referred for perinatal evaluation of fetal pleural effusions met the study criteria for PFHT. Diagnosis was made at 28 ± 7 weeks and fetuses delivered at 35 ± 3 weeks’ gestational age. Overall survival was 78%. Effusion progression, greater effusion ratios, earlier gestational age at delivery, and lower Apgar scores at birth were associated with poor outcome. Conservative management was appropriate for most cases. Conclusions: Serial ultrasound studies to evaluate the clinical course of the pleural effusions are essential in the management of PFHT. Expectant management of stable and resolving effusions was appropriate in all cases.
Effects of Cafedrine/Theodrenaline, Etilefrine and Ephedrine on Uterine Blood Flow during Epidural-Induced Hypotension in Pregnant Sheep
Authors: Strümper D. , Gogarten W. , Durieux M.E. , Hartleb K. , van Aken H. , Marcus M.A.E.
Published: August 2005

Introduction:Maternal hypotension is a major concern in obstetric anesthesia, and concerns have been raised about standard vasopressor therapy with ephedrine. Therefore, we evaluated the maternal and fetal hemodynamic effects of two potential alternatives to ephedrine. Methods: Hypotension was induced by epidural administration of lidocaine in 6 chronically instrumented pregnant ewes (at 118–122 days of gestation, term 145 days). Three treatments were studied: 25 mg ephedrine, 5 mg etilefrine and 100 mg cafedrine/5 mg theodrenaline (C/T) intravenously. Mean fetal and maternal blood pressure and heart rate, uterine blood flow, as well as fetal and maternal arterial blood gases were recorded for 60 min. Results:All three vasopressors increased maternal blood pressure, accompanied by a significant increase in uterine blood flow. C/T caused marked maternal tachycardia, whereas ephedrine decreased maternal heart rate. Maternal and fetal blood gases did not change during any of the three treatment regimens. Conclusion:All three vasopressors restored maternal blood pressure and uterine blood flow after epidurally induced maternal hypotension. However, restoration of uterine perfusion was delayed and less pronounced with C/T.
Diagnosis and Management of Rh Alloimmunization
Authors: Matijevic Ratko , Grgic Ozren , Klobucar Ante , Miskovic Berivoj
Published: August 2005

Objective: To assess the current problem of alloimmunization in a tertiary referral center in Croatia. The results obtained were compared to data published worldwide. Methods: Retrospective case analysis included women with Rhesus (Rh) alloimmunization treated in our department from January 1997 to January 2003. Data of interest included the incidence, prevention, diagnosis and treatment, with the final point being perinatal mortality and morbidity. Results: 23 pregnant women with alloimmunization were identified. The incidence was 0.138% of deliveries in the same time period. The median gestational age at diagnosis/referral was 22 (range 9–37) weeks. Anti-D antigen, alone or in combination with the other antigens, was responsible for more than 90% of the alloimmunization cases included. A defined protocol for prevention of Rh D immunization after previous delivery was not followed properly in 9/19 cases. A particular problem was prophylaxis after previous pregnancy termination (TOP), whereby only 1/14 woman received adequate prophylaxis and only after 2 of 5 TOPs. Regarding fetal treatment, 9/23 women had a total of 24 intrauterine intravascular blood transfusions. Overall, perinatal mortality was 13%, and the median gestational age at delivery was 34 (range 31–40) weeks. In all there were 31 fetal exchange transfusions after delivery performed in 14/20 newborns. Conclusion: Despite precise diagnostic criteria and modern therapeutic options, alloimmunization remains a problem in Croatia. It is still related with a high perinatal mortality and morbidity. The main problem is inadequate prevention.
Development of a New Model to Investigate the Fetal Nociceptive Pathways
Authors: Houfflin Debarge Véronique , Bresson Sophie , Jaillard Sophie , Elbaz Frédéric , Riou Yvon , Dalmas Serge , Deruelle Philippe , Ducloy Anne Sophie , Puech Francis , Storme Laurent
Published: August 2005

Objective: The aim of the study was to develop an experimental model to investigate the fetal nociceptive pathways and fetal analgesia. Methods: We tested the electromyographic (EMG) response from the biceps femoris to electrical stimulation of the sural nerve in chronically-prepared fetal lambs with and without sufentanil. Results: An EMG response could be recorded 140 ms after the electrical stimulation above a threshold of current’s intensity. The response presents the characteristics of a nociceptive flexion reflex. The reflex magnitude increased with the stimulus intensity. Sufentanil decreased the response. Bradycardia was noted 10 s after the stimulation and was not observed after sufentanilinfusion. Catecholamine concentrations were not altered by the stimulation. Conclusion: Our study shows that a nociceptive flexion reflex can be recorded in the ovine fetus. We suggest that this reflex can be used as a new tool to study the ontogenesis of the nociceptive pathways and the effects of analgesic drugs during fetal life.
The Role of RCAS1 and Oxytocinase in Immune Tolerance during Pregnancy
Authors: Wicherek L. , Dutsch-Wicherek M. , Mak P. , Klimek M.
Published: August 2005

Objectives: To determine and compare the level of RCAS1 (receptor-binding cancer antigen expressed in SiSo cells) in placentas at term as well as oxytocinase/cystine amino peptidase (CAP) serum level a few days before labor in order to evaluate their possible role in the regulation of maternal immune response during pregnancy and in initiation of labor. Methods: We estimated the RCAS1 content in 44 placental tissue samples, using Western blot method. We also assessed CAP serum level by its enzymatic activity, using L-cystine-di-β-naphthylamide as a synthetic substrate. The statistical analysis was performed using Shapiro-Wilk procedure. Student’s t test was applied to compare the differences between parametric data. A value of p < 0.05 was considered significant. Results: RCAS1 was found in all placental tissue samples examined. The differences in the RCAS1 relative amount depended on the onset of labor, with the highest level in induced labor and the lowest in spontaneous labor. The differences were also observed in the CAP serum level with the highest level in pregnant women whose labor was induced. Conclusions: We have observed a link between the expression of the two proteins examined and the onset of the labor. Therefore, we posit that RCAS1 and CAP may play a role in the downregulation of the maternal immune response during pregnancy and may participate in the initiation of the labor.
Fetal Intravascular Transfusion for Hydropic Disease due to Rhesus Isoimmunization
Authors: Mesogitis Spiros , Daskalakis George , Pilalis Athanasios , Papantoniou Nikolaos , Antsaklis Aris
Published: August 2005

Objective: To evaluate the management of hydropic fetuses, due to rhesus isoimmunization, with fetal intrauterine intravascular transfusions. Material and Methods: This is a retrospective analysis of 18 rhesus-negative pregnant women presenting at our hospital with fetal hydrops during a 7-year period. All cases were managed with serial intrauterine intravascular transfusions with the goal of delivery by cesarean section beyond 33 weeks of gestation. All patients received prophylactic ampicillin and ritodrine for 4 days after the procedure. Results: There were 11 mildly and 7 severely hydropic fetuses. All fetuses with mild hydrops and 5 of the 7 with severe hydrops were delivered alive after 32 weeks of gestation in a good condition. Two fetuses both with severe hydrops died in utero, at 28 weeks of gestation. Intrauterine reversal of hydrops occurred in 90.9% of fetuses with mild hydrops and in 57.1% of severely hydropic fetuses. Conclusions: The survival rate for the hydropic fetuses in our study was 88.9% and it was associated with the severity of fetal hydrops.
Fetal Hydrocephalus and Intrauterine Cerebral Ventriculoscopy: An Animal Model
Authors: de Keersmaecker B. , Vloeberghs M. , Ville Y.
Published: August 2005

Objective: The aim of this study was to create an animal model of obstructive ventriculomegaly in the fetal lamb at 78 days of gestation by injecting maternal blood into the lateral ventricles under ultrasound guidance. Methods: An endoscope of 1.2 mm housed in a 1.6-mm trocar was introduced into the dilated lateral ventricle. The lambs were sacrificed after delivery. Results: All fetuses diagnosed with ventriculomegaly on ultrasound showed dilatation on the anatomical sections. The ventricles had a dilated aspect when compared to the controls. In 1 fetus the septum between the two ventricles was completely ruptured. Microscopically the ependymal cells were flattened and the cellular lining was disruptured. Conclusion: The model proved suitable for ventriculoscopic examination at 128 days of gestation. This should allow to elaborate further on therapeutic studies in this controversial area.
Congenital Cystic Adenomatoid Malformation in the Fetus: A Hypothesis of Its Development
Authors: Kulwa Ema , Tharakan Tessie , Baxi Laxmi
Published: August 2005

We present a case of congenital cystic adenomatoid malformation of the lung diagnosed at 34 weeks of gestation in the setting of polyhydramnios. The fetus had CCAM in the L lung, with mediastinal shift to the right and ascites. The neonate underwent drainage of cysts and subsequent left lung lobar resection with improvement in respiratory function. The pathology of CCAM is reviewed in detail. We speculate the role of alcohol as a teratogen through retinoic acid at 8–10 weeks of gestation when fetal lungs are actively developing.
Infiltrative Breast Cancer during Pregnancy and Conservative Surgery
Authors: Annane Kadour , Bellocq Jean-Pierre , Brettes Jean-Philippe , Mathelin Carole
Published: August 2005

Mastectomy is considered as the standard therapy for gestational breast cancer. Since radiation therapy is harmful for the fetus, conservative surgery is rarely used during pregnancy. Among 16 patients with gestational breast cancer, 10 and 6 were treated with conservative surgery and mastectomy, respectively. No local recurrences occurred with a median follow-up time of 87 months. Among the 10 patients treated with conservative surgery, 3 chose therapeutic abortion and 7 opted to continue their pregnancy. Concerning these 7 fetuses, there were no congenital anomalies, nor growth restriction. All children were normal physically and neurologically. We concluded that conservative breast surgery may be an alternative to mastectomy in the treatment of gestational breast cancer and is safe for the fetus.
Uterine Rupture during Second Trimester Abortion with Misoprostol
Authors: Nayki Umit , Taner Cuneyt Eftal , Mizrak Tolga , Nayki Cenk , Derin Gulsen
Published: August 2005

Background: Data are limited regarding the use of misoprostol in the midtrimester, therefore few cases with uterine rupture during the second trimester with a previous uterine scar have been reported in the literature. Case Report: A 23-year-old woman with a prior low transverse cesarean section presented at 26 weeks’ gestation for pregnancy termination for a fetal abnormality. She was given 200 µg misoprostol intravaginally every 3 h until regular contractions began. After the fourth dose, she had vaginal bleeding and severe contractions. She aborted completely 2 h later after the last dose. Uterine rupture was diagnosed at the previous cesarean section scar by manual vaginal examination. She underwent emergency laparotomy and the uterus was repaired. Conclusion: Misoprostol use in the second trimester in a woman with a uterine scar can trigger severe contractions that can lead to uterine rupture.
Renal Handling of NH3/NH4+: Recent Concepts
Authors: Karim Zoubida , Szutkowska Marta , Vernimmen Catherine , Bichara Maurice
Published: August 2005

To be appropriately excreted in urine, NH4+, the major component of urinary acid excretion, must be synthesized by proximal tubular cells, secreted into the proximal tubular fluid, reabsorbed by the medullary thick ascending limb (MTAL) to be accumulated in the medullary interstitium, and finally secreted in medullary collecting ducts. Several targets have been identified to account at the gene expression level for the adaptation of renal NH4+ synthesis and transport in response to a chronic acid load. These targets are the key enzymes of ammoniagenesis (mitochondrial glutaminase and glutamate dehydrogenase) and gluconeogenesis (phosphoenolpyruvate carboxykinase) and the Na+/H+( NH4+) exchanger NHE3 in the proximal tubule, the apical Na+-K+(NH4+)-2Cl– cotransporter of the MTAL, the basolateral Na+-K+(NH4+)-2Cl– cotransporter, and likely the epithelial Rh B and C glycoproteins in the collecting ducts. An acid pH per se appears to be a major factor in the control of the expression of these genes during metabolic acidosis probably through activation of pH sensors. Glucocorticoids may also act in concert with an acid pH to coordinate the adaptation of various tubular cell types. The present review focuses on some new aspects of NH3/ NH4+ transport and of regulations of gene expression that have recently emerged.
Statin Monotherapy Attenuates Renal Injury in a Salt-Sensitive Hypertension Model of Renal Disease
Authors: Vieira Jr. J.M. , Rodrigues L.T. , Mantovani E. , Dellê H. , Mattar A.L. , Malheiros D.M.A.C. , Noronha I.L. , Fujihara C.K. , Zatz R.
Published: August 2005

Background: Several salutary biological effects of statins have been described. We sought to investigate more closely the anti-inflammatory and antiproliferative effects of simvastatin (SIMV) in a model of hypertension and progressive renal disease, as well as its effects on the cyclin-cdk inhibitors p21 and p27. Methods: Munich-Wistar rats received the nitric oxide (NO) synthase inhibitor L-NAME (25 mg/kg/day p.o.) for 20 days accompanied by a high-salt diet (HS, 3% Na) and then were kept on HS for 60 days. Animals were then divided into two groups: vehicle (VH) or SIMV 2 mg/kg/day p.o. Albuminuria and tail-cuff pressure were determined at 30 and 60 days. RT-PCR was done to assess renal expression of TGF-β1, collagen I and III, fibronectin, p27, p21 and monocyte chemoattractant protein-1 (MCP-1). Renal protein expression was assessed by Western blot (proliferating cell nuclear antigen (PCNA)) and immunostaining (macrophage, lymphocyte, PCNA). Results: SIMV did not prevent the development of severe hypertension or albuminuria. SIMV-treated animals had less severe renal interstitial inflammation and cell proliferation. MCP-1 expression was significantly diminished in the SIMV-treated animals (55.4 ± 7.3 vs. 84.4 ± 8.2 OD, p = 0.02). mRNA renal expression for p27 and TGF-β did not change between groups, but p21 mRNA renal expression, highly induced in this model, significantly decreased with SIMV treatment (31.6 ± 6.6 vs. 50.2 ± 5.8 OD, p < 0.05). The interstitial fibrosis score significantly decreased with SIMV (2.46 ± 0.40 vs. 4.07 ± 0.38%, p < 0.01), which was confirmed by a decrease in renal collagen I and fibronectin expression. Serum cholesterol level did not change with SIMV. Conclusion: SIMV attenuated interstitial fibrosis associated with this model of hypertensive renal disease. The mechanism involved MCP-1 downregulation. SIMV treatment was also associated with a p21 downregulation in the kidney, which might be involved in the protection of renal scarring.
Biology of Vascular Calcification in Renal Disease
Authors: Farzaneh-Far Afshin , Shanahan Catherine M.
Published: August 2005

The high rates of atherosclerotic vascular disease in patients with end-stage renal disease (ESRD) cannot be fully explained by the excess of traditional risk factors. Interest has therefore arisen in the possible role of vascular calcification, which is increased in these patients and may effect plaque stability and have detrimental hemodynamic consequences. Considerable evidence has accumulated recently pointing to the regulated nature of the calcification process. The initiation of calcium crystal formation appears to require the presence of small membrane bound vesicles released by living or apoptotic cells. The cellular release, content and phagocytosis of these vesicles appear to be important regulatory pathways in vascular calcification. Better understanding of these mechanisms may have therapeutic potential in reducing the adverse cardiovascular event rates in patients with (ESRD).
p47phox-Dependent NADPH Oxidase Regulates Flow-Induced Vascular Remodeling
Authors: Castier Yves , Brandes Ralf P. , Leseche Guy , Tedgui Alain , Lehoux Stéphanie
Published: August 2005

Chronic alterations in blood flow elicit an adaptive response that tends to normalize shear stress, involving nitric oxide (NO) and matrix metalloproteinases (MMPs). To evaluate the role of NADPH oxidase in this process, we developed a new model of mouse arteriovenous fistula (AVF) connecting the right common carotid artery (RCCA) with the jugular vein, which does not affect blood pressure. Mice deficient for gp91phox and p47phox subunits of NADPH and wild-type controls were used. AVF greatly increased RCCA blood flow (0.78±0.12 to 4.71±0.78 mL/min;
P
<0.01), producing an abrupt rise in shear stress (35±1 to 261±17 dynes/cm
2
;
P
<0.01) within 24 hours. RCCA diameter (460±14 μm) gradually enlarged 1 and 3 weeks after AVF (534±14 μm and 627±19 μm;
P
<0.01), reducing shear stress (173±13 and 106±10 dynes/cm
2
, respectively). In gp91phox
−/−
mice, changes in RCCA caliber and shear stress matched controls. However, p47phox
−/−
mouse RCCAs enlarged only marginally, such that shear stress remained high (199±8 dynes/cm
2
at 3 weeks). Likewise, remodeling was minimal in endothelial NO synthase (eNOS)
−/−
mice. In both control and gp91phox
−/−
animals, reactive oxygen species (ROS) production and MMP induction was enhanced by AVF, whereas in p47phox
−/−
and eNOS
−/−
mice such response was negligible. Similarly, nitrotyrosine staining, indicating peroxynitrite formation, was more pronounced in control and gp91phox
−/−
mice than in p47phox
−/−
and eNOS
−/−
mice. Hence, shear stress induces vascular NADPH oxidase comprising p47phox but not gp91phox. Generated ROS interact with NO to produce peroxynitrite, which in turn activates MMPs, facilitating vessel remodeling. Our study provides the first evidence that ROS play a fundamental role in flow-induced vascular enlargement.
Transgenic Overexpression of Vascular Endothelial Growth Factor-B Isoforms by Endothelial Cells Potentiates Postnatal Vessel Growth In Vivo and In Vitro
Authors: Mould Arne W. , Greco Sonia A. , Cahill Marian M. , Tonks Ian D. , Bellomo Daniela , Patterson Carol , Zournazi Anna , Nash Andrew , Scotney Pierre , Hayward Nicholas K. , Kay Graham F.
Published: August 2005

Vascular endothelial growth factors (VEGFs) play significant roles in endothelial growth, survival, and function, and their potential use as therapeutic agents to promote the revascularization of ischemic tissues in being avidly explored. VEGF-A has received most attention, as it is a potent stimulator of vascular growth. Results in clinical trials of VEGF-A as a therapeutic agent have fallen short of high expectations because of serious edematous side effects caused by its activity in promoting vascular permeability. VEGF-B, a related factor, binds some of the VEGF-A receptors but not to VEGF receptor 2, which is implicated in the vascular permeability promoting activity of VEGF-A. Despite little in vitro evidence to date for the ability of Vegf-B to directly promote angiogenesis, recent data indicate that it may promote postnatal vascular growth in mice, suggesting that it may have potential therapeutic application. We have specifically studied the effects of VEGF-B on vascular growth in vivo and on angiogenesis in vitro by analyzing transgenic mice in which individual isoforms (
VEGFB
167
Tg and
VEGFB
186
Tg) of VEGF-B are overexpressed in endothelial cells.
VEGFB
167
Tg and
VEGFB
186
Tg mice displayed enhanced vascular growth in the Matrigel assay in vivo and during cutaneous wound healing. In the aortic explant assay, explants from
VEGFB
167
Tg and
VEGFB
186
Tg mice displayed elevated vascular growth, suggesting a direct effect of VEGF-B isoforms in potentiating angiogenesis. These data support the use of VEGF-B as a therapeutic agent to promote vascular growth, in part, by potentiating angiogenesis. Furthermore, the lack of vascular permeability activity associated with either transgenic overexpression of the VEGF-B gene in endothelial cells or application of VEGF-B protein to the skin of mice in the Miles assay indicates that use of VEGF-B as a therapy should not be associated with edematous side effects.
Factors Affecting the Accuracy of SHOWEX HF Radar Wave Measurements
Authors: Wyatt Lucy R. , Liakhovetski Guennadi , Graber Hans C. , Haus Brian K.
Published: August 2005

Ocean Surface Current Radar (OSCR) HF radar measurements of ocean waves and currents were made during the Shoaling Waves Experiment (SHOWEX) in the fall of 1999. During some periods, at some locations, good quality wave measurements were obtained. Limitations in the wave measurement capability due to OSCR hardware, deployment configuration, signal-to-noise ratio, and antenna sidelobes are identified and discussed. A short period of large currents in the presence of antenna pattern distortion is identified as the source of the main errors in the wave measurements.
Theoretical and Experimental Characterization of the Ultrafast Aircraft Thermometer: Reduction of Aerodynamic Disturbances and Signal Processing
Authors: Rosa Bogdan , Bajer Konrad , Haman Krzysztof E. , Szoplik Tomasz
Published: August 2005

The ultrafast aircraft thermometer, built for measuring temperature in clouds at flight speeds up to 100 m s−1, employs a 2.5-μm-thick platinum-coated tungsten wire as a sensing element. When temperature increases, the wire resistance increases. The changes are amplified by an electronic system. Temperature measurements made in a wind tunnel and during flights show noise that is related to the von Kármán vortex street generated behind the shield that protects the sensing element against the impact of cloud droplets. To reduce both the level of turbulence and the amount of water collected on the shield, suction is applied through the slits in its sides. The effect of suction on the flow field is twofold. First, at the Reynolds numbers that the thermometer is operated suction eliminates aerodynamic disturbances. Second, suction diverts the inner part of the boundary layer into the slit. This inner part is a region of strong shear and, therefore, a region where intensive viscous heating takes place. When the suction is on much of the air that is heated in the boundary layer in the front part of the shield is removed through the slits and never reaches the sensor. To study the role of the shield with suction and confirm its chosen shape, two-dimensional (2D) direct numerical simulations (DNSs) are performed of the airflow and of the trajectories of droplets of various sizes and initial positions. The influence on the temperature distribution of the irreversible dissipation of energy due to air viscosity is also examined. This is found to have a small but measurable effect. The effects associated with sampling and processing of the analog signal obtained from the sensing wire are discussed. The results herein quantitatively explain the nature of the measured aerodynamic noise.
Predictability of Total Ozone Using a Global Three-Dimensional Chemical Transport Model Coupled with the MRI/JMA98 GCM
Authors: Sekiyama T. T. , Shibata K.
Published: August 2005

A global three-dimensional chemical transport model is being developed for forecasting total ozone. The model includes detailed stratospheric chemistry and transport and couples with a dynamical module of the Meteorological Research Institute/Japan Meteorological Agency 1998 (MRI/JMA98) general circulation model, which can yield realistic atmospheric fields through a meteorological assimilation system. Its predictability on total ozone is investigated for up to 4 weeks from 1997 to 2000. Global root-mean-square errors (rmses) of a control run are approximately 10 DU (3% of total ozone) throughout a year; the control run results are used as initial values for hindcast experiments. Rmses of the hindcast experiments globally range from 10 to 30 DU. The anomaly correlation between the 5-day forecasts and satellite measurements is approximately 0.6 throughout a year in the mid- and high latitudes of both the Northern and Southern Hemispheres. Thus, the model has potential for utilization on total ozone forecasts up to 5 days. In the northern mid- and high latitudes, the model produces better total ozone forecasts than the persistence up to 2 weeks, indicating that the deterministic limit of the total ozone forecasts is durationally comparable to that of weather forecasts. Good correlations between changes in total ozone and 100-hPa geopotential height reveal that the predictability of the dynamical field in the lower stratosphere critically affects the predictability of total ozone.