bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of mechanical ventilation at low lung volume on respiratory mechanics and nitric oxide exhalation in normal rabbits
Authors: D'Angelo Edgardo , Pecchiari Matteo , Valle Patrizia Della , Koutsoukou Antonia , Milic-Emili Joseph
Published: March 2005

Lung mechanics, exhaled NO (NOe), and TNF-α in serum and bronchoalveolar lavage fluid were assessed in eight closed and eight open chest, normal anesthetized rabbits undergoing prolonged (3–4 h) mechanical ventilation (MV) at low volume with physiological tidal volumes (10 ml/kg). Relative to initial MV on positive end-expiratory pressure (PEEP), MV at low volume increased lung quasi-static elastance (+267 and +281%), airway (+471 and +382%) and viscolelastic resistance (+480 and +294%), and decreased NOe (−42 and −25%) in closed and open chest rabbits, respectively. After restoration of PEEP, viscoelastic resistance returned to control, whereas airway resistance remained elevated (+120 and +31%) and NOe low (−25 and −20%) in both groups of rabbits. Elastance remained elevated (+23%) only in closed-chest animals, being associated with interstitial pulmonary edema, as reflected by increased lung wet-to-dry weight ratio with normal albumin concentration in bronchoalveolar lavage fluid. In contrast, in 16 additional closed- and open-chest rabbits, there were no changes of lung mechanics or NOe after prolonged MV on PEEP only. At the end of prolonged MV, TNF-α was practically undetectable in serum, whereas its concentration in bronchoalveolar lavage fluid was low and similar in animals subjected or not subjected to ventilation at low volume (62 vs. 43 pg/ml). These results indicate that mechanical injury of peripheral airways due to their cyclic opening and closing during ventilation at low volume results in changes in lung mechanics and reduction in NOe and that these alterations are not mediated by a proinflammatory process, since this is expressed by TNF-α levels.
Central cell nuclear-cytoplasmic incongruity:a mechanism for segregation distortion in advanced backcross and selfed generations of (Allium cepa L. × Allium fistulosum L.) × A. cepa interspecific hybrid derivatives
Authors: Mangum P.D. , Peffley E.B.
Published: March 2005

A model is presented as an explanation for an anomaly observed in germination and establishment and isozyme segregation patterns in Allium cepa × A. fistulosum F2BC3 populations generated in an introgression-breeding program. The F1BC3 parent of these populations was selected for its heterozygous PGI phenotype, Pgi-12/3; Pgi-12 was inherited from an A. cepa (Ac) seed parent and Pgi-13 from an A. fistulosum (Af) pollen parent. Germination and establishment was recorded for the F2BC3 progeny population. Segregation of Ac and Af Pgi-1 alleles was investigated in F2BC3 seeds and embryo and endosperm tissue was isolated and tested for isozyme expression. A pooled goodness-of-fit test of the segregation of Pgi-1 alleles in the populations to the expected Mendelian 1:2:1 ratio using the chi-square statistic gave a χ2 = 185.9, well beyond the accepted limits at 2 degrees of freedom. The 1:2:1 ratio expected for simple Mendelian inheritance was rejected, while a pooled chi-square goodness-of-fit test of the segregation of Pgi-1 alleles in the populations fit a 1:1 ratio with a χ2 = 0.203, based on the incongruity model. We present here the central cell nuclear-cytoplasmic incongruity hypothesis to explain the observed anomalies.
Laboratory Markers of Severe Acute Pancreatitis
Authors: Rau B. , Schilling M.K. , Beger H.G.
Published: March 2005

Background: A large array of parameters has been proposed for the biochemical stratification of severity and prediction of complications in acute pancreatitis. However, the number of accurate and readily available variables for routine application is still limited. Methods: The literature was reviewed for laboratory markers of acute pancreatitis with special regard to their clinical usefulness and test performance for stratifying severity and monitoring disease progression. Results: Several parameters, such as trypsinogen and procarboxypeptidase B activation peptide, PMN-elastase, interleukin-6 (IL-6) and 8 (IL-8), serum amyloid A (SAA), and procalcitonin (PCT), can differentiate between mild and severe acute pancreatitis within 48 h of disease onset with favorable diagnostic accuracy. Because fully automated assays have become available, IL-6, IL-8, PCT, and SAA are the most interesting parameters in this respect. For monitoring disease progression beyond 48 h, acute-phase proteins, IL-6, IL-8, and PCT are valuable markers. PCT is the first biochemical variable for predicting severe pancreatic infections and overall prognosis throughout the course of acute pancreatitis with high sensitivity and specificity. Conclusions: Among all the biochemical variables available, C-reactive protein is still the standard for a fast, reliable, and cost-effective assessment of severity in acute pancreatitis. PCT substantially contributes to an improved stratification of patients at risk to develop major complications and deserves routine application.
Bladder Carcinoma during Pregnancy
Authors: Spahn M. , Bader P. , Westermann D. , Echtle D. , Frohneberg D.
Published: March 2005

Introduction: We report 3 cases of bladder cancer during pregnancy and give a review of the literature in an attempt to evaluate tumor at presentation, characteristics, maternal and fetal outcome. Materials and Methods: The case history of 3 pregnant women treated for bladder cancer in 2001 together with the results of a MEDLINE search from 1966 to 2003. Results: Out of 27 cases of nonbilharzial bladder carcinoma, 74% presented with transitional cell carcinoma. Five patients had muscle-invasive tumors. Major symptom was hematuria in 81%, which was initially mistaken as vaginal bleeding in 22%. Only half of the tumors were identified by ultrasonography. Although superficial bladder carcinoma was transurethrally resected alone, outcome and prognosis are good. But the prognosis of locally advanced bladder carcinoma is poor. None of the fetuses delivered before 30 weeks of gestation survived. Two of the 5 patients died from the disease and follow-up is only short in the rest. Conclusion: Any doubtful genital bleeding during pregnancy without definite proof of vaginal/cervical origin should be investigated by both ultrasonography of the upper urinary tract and urethrocystoscopy. Superficial bladder tumors can be most effectively treated by transurethral resection followed by cystoscopy, whereas the prognosis of muscle-invasive bladder carcinoma is poor and demands more radical treatment, depending on the stage of pregnancy.
Effects of Micronised Purified Flavonoid Fraction on Pain, Spermiogram and Scrotal Color Doppler Parameters in Patients with Painful Varicocele
Authors: Kiliç Süleyman , Güneş Ali , Ipek Deniz , Dusak Abdurrahim , Güneş Gülsen , Balbay Mevlana Derya , Baydinç Yaşar Can
Published: March 2005

Purpose: Micronised purified flavonoid fraction (MPFF) is a phlebotropic drug improving venous tone, elasticity and lymphatic drainage, decreasing venous distensibility, venous emptying times, reflux time of venous blood and capillary hyperpermeability, and having antioxidant activities. Since varicocele is a venous pathology, we evaluated the effects of MPFF on pain, spermiogram and color Doppler parameters in patients with painful varicocele. Material and Methods: Semen analyses and Doppler sonography were performed in 16 patients (aged 20–62 years, mean 31.2 ± 10.9) before and after 1,000 mg/day MPFF treatment. Pain change was assessed with visual analogue scale scored between 0 and 10. Patient satisfaction with outcome and side effects were recorded. Results: Mean pain scores at 1, 3, and 6 months were 1.25 ± 1.34, 0.25 ± 0.68, and 0.12 ± 0.34, respectively, all being significantly lower (p < 0.001 for each) than baseline (4.93 ± 1.77). Mean score at 12 months (0.93 ± 1.06) was still lower than baseline (p < 0.001) but higher than at 6 months (p = 0.019). Respectively, 14 (87.5%) and 2 (12.5%) patients reported complete and very significant resolution of pain at the 6th month. All patients were very satisfied with the outcome. While semen volume, total sperm count, sperm concentration and morphology did not change significantly, motility increased significantly (p = 0.009) due to decrease of grade 0 sperms (p = 0.006) and increase of grade 3 + 4 sperms (p < 0.001). Reflux time of left spermatic vein during the Valsalva maneuver decreased significantly (p = 0.003). No significant change occurred in reflux time of the right spermatic vein. No side effect was recorded. Conclusions: Results of this preliminary study suggest the safety and efficacy of MPFF in the treatment of varicocele-associated pain. However, no recommendation for the use of MPFF in the treatment of pain associated with varicocele can be made before these preliminary results are confirmed by a randomized placebo-controlled trial.
Bilateral Perirenal Lymphangioma: A Conservative Approach
Authors: Praz Valentin , Müntener Michael , Oechslin Erwin , Weishaupt Dominik , Hauri Dieter , John Hubert
Published: March 2005

The lymphangioma is a well-recognized benign tumor most frequently encountered in infancy and childhood. The kidneys are rarely involved. Despite its benign nature, most of the patients were treated by partial or radical nephrectomy. We describe a case of bilateral perirenal lymphangioma in a 33-year-old man for whom we chose a conservative approach.
Transverse Testicular Ectopia Associated with Persistent Müllerian Duct Syndrome
Authors: Tiryaki Tuğrul , Hücümenoğlu Sema , Atayurt Halil
Published: March 2005

Transverse testicular ectopia (TTE) associated with persistent Müllerian duct syndrome (PMDS) is a rare genitourinary anomaly. The clinical and operative findings and treatment are discussed. It is very important to perform a careful exploration in TTE when the testes are undescended, in order to exclude the presence of PMDS. Transseptal orchidopexy is the surgical treatment of choice.
Development of the Embryonic Porcine Neuroretina in vitro
Authors: Engelsberg Karl , Johansson Kjell , Ghosh Fredrik
Published: March 2005

Purpose: The objective of this study was to investigate the survival and morphology of embryonic porcine full-thickness neuroretina in culture. Methods: Porcine fetuses were taken out by cesarian section, and the eyes were enucleated. Neuroretinas were explanted on culture plate inserts and were kept for 0–42 days in vitro under standard culture conditions. Green nucleic acid (Sytox) was used for measuring the extent of cell death, and 4,6-diaminidine-2-phenylindoldihydrochloride was used as a marker for the cellular layers. The explants were examined as whole-mount preparations and vertical sections. Sectioned tissue was stained with hematoxylin-eosin and labeled for immunohistochemistry with photoreceptor-specific antibodies raised against transducin and recoverin. Results: In explants kept for 0–5 days in vitro, the developing retina consisted of multiple rows of neuroblastic cells and a more defined, but multilayered ganglion cell layer (GCL). Older explants revealed a more differentiated appearance with ultimately all normal retinal layers present, even after 42 days in vitro. Transducin- and recoverin-labeled photoreceptors were seen in these specimens, but no outer segments were found. The whole-mount preparation revealed extensively Sytox-labeled cells in the GCL at 2 days in vitro, but very few cells were labeled in older explants. Conclusion: This study shows that cultured fetal porcine full-thickness neuroretina can survive and develop according to its intrinsic timetable for at least 6 weeks in vitro. The in vitro system for culturing of the full-thickness retina may be useful in experiments involving retinal transplantation.
Thymoma-Associated Neuromyotonia with Antibodies against Voltage-Gated Potassium Channels Presenting as Chronic Intestinal Pseudo-Obstruction
Authors: Viallard Jean-François , Vincent Angela , Moreau Jean-François , Parrens Marie , Pellegrin Jean-Luc , Ellie Emmanuel
Published: March 2005

Chronic intestinal pseudo-obstruction can occur as a paraneoplastic disorder, and several cases have been reported in association with thymoma or small-cell lung cancer. Autoantibodies against voltage-gated potassium channels (VGKCs) are found in acquiredneuromyotonia (Isaac’s syndrome), and have been reported in one case of slow transit constipation without apparent neurological disease. We describe a patient with VGKC antibodies, acquired neuromyotonia and thymoma, who first presented with a severe slow-transit constipation and in whom the gastrointestinal symptoms responded well to plasmapheresis. We suggest that VGKC antibodies might be helpful in patients with possible paraneoplastic chronic intestinal pseudo-obstruction, and a positive result should stimulate the search for a thymoma or other tumour and raise the possibility of immunotherapy.
Obesity and Clomiphene Challenge Test as Predictors of Outcome of in vitro Fertilization and Intracytoplasmic Sperm Injection
Authors: van Swieten Esther C.A.M. , van der Leeuw-Harmsen Loes , Badings Erik A. , van der Linden Paul J.Q.
Published: March 2005

One hundred and sixty-two consecutive patients undergoing in vitro fertilization (IVF) or IVF/intracytoplasmic sperm injection (ICSI) were studied to determine the effect of obesity on the outcome of this treatment and to evaluate the prognostic value of the Clomiphene Challenge Test (CCT) in controlled ovarian hyperstimulation. In this prospective clinical study, we assessed the mean number of stimulation days, the mean gonadotropin level/day, cancellation rate, the mean thickness of the endometrium, the mean number of oocytes retrieved, the fertilization rate, the clinical pregnancy rate/embryo transfer and the abortion rate. Obese women had a doubled risk of cancellation due to poor response, although this was not statistically significant. Furthermore, they showed up to 45% lower fertilization rates compared to women of normal weight. The CCT was a good predictor of IVF and IVF/ICSI outcome. Women with an abnormal CCT needed more days of stimulation and higher doses of gonadotropins to reach an adequate stimulation, but still overall results were less than in women with a normal CCT. We conclude that obesity negatively affects IVF and IVF/ICSI outcome, and that CCT is a useful prognosticator of response to ovarian stimulation. Obese patients show a tendency to experience more cancellation due to poor response and lower fertilization rates. Obese women should be counseled on their possible poor performance in IVF and IVF/ICSI programs.
Development of the Right Ventricular Inflow Tract and Moderator Band
Authors: Jongbloed M.R.M. , Wijffels M.C.E.F. , Schalij M.J. , Blom N.A. , Poelmann R.E. , van der Laarse A. , Mentink M.M.T. , Wang Z. , Fishman G.I. , Gittenberger-de Groot A.C.
Published: March 2005

Atriofascicular accessory bundles with AV-node like conduction properties can sustain atrioventricular (AV) re-entrant tachycardia (Mahaim tachycardia). During early embryogenesis, the AV canal is situated above the primitive left ventricle (LV), and a right AV connection has not been achieved yet. We studied the formation of the right ventricular (RV) inflow tract in relation to the developing cardiac conduction system and hypothesized a morphological explanation for functional atriofascicular bypass tracts. Analysis of lacZ-expression during sequential stages of cardiogenesis was performed in CCS-lacZ transgenic mice (E9.5 to 15.5). Embryos were stained for β-galactosidase activity and the myocardial marker HHF35. At early stages CCS-lacZ expression was observed in a ring surrounding the AV canal, which connected at the inner curvature to the primary fold. The first sign of formation of the (CCS-lacZ negative) RV inlet component was a groove in the CCS-lacZ positive tissue of the primary fold. Outgrowth of the RV inlet tract resulted in division of the primary fold in a septal part, the trabecula septomarginalis and a lateral part, the moderator band, which extended laterally up to the right AV ring. Electrophysiological measurements in embryonic hearts (E15.5) in which the right atrium (RA) and RV were isolated from the left atrium (LA) and LV supported the functionality of this AV-connection via the moderator band, by demonstrating sequential atrial and ventricular activation in both RA/RV and LA/LV preparations. In conclusion, our observations may provide a possible morphological and functional explanation for atriofascicular accessory pathways via the moderator band, underlying Mahaim tachycardia.
SDF-1α/CXCR4 Axis Is Instrumental in Neointimal Hyperplasia and Recruitment of Smooth Muscle Progenitor Cells
Authors: Zernecke Alma , Schober Andreas , Bot Ilze , von Hundelshausen Philipp , Liehn Elisa A. , Möpps Barbara , Mericskay Mathias , Gierschik Peter , Biessen Erik A. , Weber Christian
Published: March 2005

Recent evidence infers a contribution of smooth muscle cell (SMC) progenitors and stromal cell-derived factor (SDF)-1α to neointima formation after arterial injury. Inhibition of plaque area and SMC content in apolipoprotein E-deficient mice repopulated with LacZ
+
or CXCR4
−/−
BM or lentiviral transfer of an antagonist reveals a crucial involvement of local SDF-1α and its receptor CXCR4 in neointimal hyperplasia via recruitment of BM-derived SMC progenitors. After arterial injury, SDF-1α expression in medial SMCs is preceded by apoptosis and inhibited by blocking caspase-dependent apoptosis. SDF-1α binds to platelets at the site of injury, triggers CXCR4- and P-selectin-dependent arrest of progenitor cells on injured arteries or matrix-adherent platelets, preferentially mobilizes and recruits c-kit
−
/platelet–derived growth factor receptor (PDGFR)-β
+
/lineage
−
/sca-1
+
progenitors for neointimal SMCs without being required for their differentiation. Hence, the SDF-1α/CXCR4 axis is pivotal for vascular remodeling by recruiting a subset of SMC progenitors in response to apoptosis and in concert with platelets, epitomizing its importance for tissue repair and identifying a prime target to limit lesion development.
A Novel Form of Short QT Syndrome (SQT3) Is Caused by a Mutation in the
KCNJ2
Gene
Authors: Priori Silvia G. , Pandit Sandeep V. , Rivolta Ilaria , Berenfeld Omer , Ronchetti Elena , Dhamoon Amit , Napolitano Carlo , Anumonwo Justus , di Barletta Marina Raffaele , Gudapakkam Smitha , Bosi Giuliano , Stramba-Badiale Marco , Jalife José
Published: March 2005

Short QT syndrome (SQTS) leads to an abbreviated QTc interval and predisposes patients to life-threatening arrhythmias. To date, two forms of the disease have been identified: SQT1, caused by a gain of function substitution in the HERG (
I
Kr
) channel, and SQT2, caused by a gain of function substitution in the KvLQT1 (
I
Ks
) channel. Here we identify a new variant, “SQT3”, which has a unique ECG phenotype characterized by asymmetrical T waves, and a defect in the gene coding for the inwardly rectifying Kir2.1 (
I
K1
) channel. The affected members of a single family had a G514A substitution in the
KCNJ2
gene that resulted in a change from aspartic acid to asparagine at position 172 (D172N). Whole-cell patch-clamp studies of the heterologously expressed human D172N channel demonstrated a larger outward
I
K1
than the wild-type (
P
<0.05) at potentials between −75 mV and −45 mV, with the peak current being shifted in the former with respect to the latter (WT, −75 mV; D172N, −65 mV). Coexpression of WT and mutant channels to mimic the heterozygous condition of the proband yielded an outward current that was intermediate between WT and D172N. In computer simulations using a human ventricular myocyte model the increased outward
I
K1
greatly accelerated the final phase of repolarization, and shortened the action potential duration. Hence, unlike the known mutations in the two other SQTS forms (N588K in HERG and V307L in KvLQT1), simulations using the D172N and WT/D172N mutations fully accounted for the ECG phenotype of tall and asymmetrically shaped T waves. Although we were unable to test for inducibility of arrhythmia susceptibility due to lack of patients’ consent, our computer simulations predict a steeper steady-state restitution curve for the D172N and WT/D172N mutation, compared with WT or to HERG or KvLQT1 mutations, which may predispose SQT3 patients to a greater risk of reentrant arrhythmias.
Analysis of phosphorylation of human heat shock factor 1 in cells experiencing a stress
Authors: Guettouche Toumy , Boellmann Frank , Lane William S , Voellmy Richard
Published: March 2005

Background

Heat shock factor (HSF/HSF1) not only is the transcription factor primarily responsible for the transcriptional response of cells to physical and chemical stress but also coregulates other important signaling pathways. The factor mediates the stress-induced expression of heat shock or stress proteins (HSPs). HSF/HSF1 is inactive in unstressed cells and is activated during stress. Activation is accompanied by hyperphosphorylation of the factor. The regulatory importance of this phosphorylation has remained incompletely understood. Several previous studies on human HSF1 were concerned with phosphorylation on Ser303, Ser307 and Ser363, which phosphorylation appears to be related to factor deactivation subsequent to stress, and one study reported stress-induced phosphorylation of Ser230 contributing to factor activation. However, no previous study attempted to fully describe the phosphorylation status of an HSF/HSF1 in stressed cells and to systematically identify phosphoresidues involved in factor activation. The present study reports such an analysis for human HSF1 in heat-stressed cells.

Results

An alanine scan of all Ser, Thr and Tyr residues of human HSF1 was carried out using a validated transactivation assay, and residues phosphorylated in HSF1 were identified by mass spectrometry and sequencing. HSF1 activated by heat treatment was phosphorylated on Ser121, Ser230, Ser292, Ser303, Ser307, Ser314, Ser319, Ser326, Ser344, Ser363, Ser419, and Ser444. Phosphorylation of Ser326 but none of the other Ser residues was found to contribute significantly to activation of the factor by heat stress. Phosphorylation on Ser326 increased rapidly during heat stress as shown by experiments using a pSer326 phosphopeptide antibody. Heat stress-induced DNA binding and nuclear translocation of a S326A substitution mutant was not impaired in HSF1-negative cells, but the mutant stimulated HSP70 expression several times less well than wild type factor.

Conclusion

Twelve Ser residues but no Thr or Tyr residues were identified that were phosphorylated in heat-activated HSF1. Mutagenesis experiments and functional studies suggested that phosphorylation of HSF1 residue Ser326 plays a critical role in the induction of the factor's transcriptional competence by heat stress. PhosphoSer326 also contributes to activation of HSF1 by chemical stress. To date, no functional role could be ascribed to any of the other newly identified phosphoSer residues.
Searching QTL by gene expression: analysis of diabesity
Authors: Brown Aaron C , Olver William I , Donnelly Charles J , May Marjorie E , Naggert Jürgen K , Shaffer Daniel J , Roopenian Derry C
Published: March 2005

Background

Recent developments in sequence databases provide the opportunity to relate the expression pattern of genes to their genomic position, thus creating a transcriptome map. Quantitative trait loci (QTL) are phenotypically-defined chromosomal regions that contribute to allelically variant biological traits, and by overlaying QTL on the transcriptome, the search for candidate genes becomes extremely focused.

Results

We used our novel data mining tool, ExQuest, to select genes within known diabesity QTL showing enriched expression in primary diabesity affected tissues. We then quantified transcripts in adipose, pancreas, and liver tissue from Tally Ho mice, a multigenic model for Type II diabetes (T2D), and from diabesity-resistant C57BL/6J controls. Analysis of the resulting quantitative PCR data using the Global Pattern Recognition analytical algorithm identified a number of genes whose expression is altered, and thus are novel candidates for diabesity QTL and/or pathways associated with diabesity.

Conclusion

Transcription-based data mining of genes in QTL-limited intervals followed by efficient quantitative PCR methods is an effective strategy for identifying genes that may contribute to complex pathophysiological processes.
Ethmoidal osteoid osteoma with orbital and intracranial extension – a case report
Authors: Pai S Balaji , Harish K , Venkatesh MS , Udayshankar  , Jermely Deepthi
Published: March 2005

Background

Osteoid osteoma is a benign bone neoplasm which is seen in the long bones of appendicular skeleton. It is rarely seen in the cranium. Skull base osteoid osteoma is extremely rare and has been anecdotally reported.

Case presentation

The authors report a case of a large osteoid osteoma of the ethmoid with intraorbital and intracranial extension in a 33 year old male patient. He presented with loss of vision in the left eye. The intra-cranial extension was excised through a single burr-hole fronto-orbitotomy. The ethmoid and orbital portions were approached and excised through a Weber-Ferguson incision and inferior orbitotomy. Radical excision of the tumor could thus be achieved through a craniofacial approach.

Conclusion

Although benign and rare, skull base osteoid osteoma can present with neurological deficit due to its mass effect and involvement of vital structures. A multispeciality team approach is advisable in such cases if radical excision is to be achieved. A craniofacial approach made radical single stage excision of this multicompartmental osteoid osteoma possible with an uneventful postoperative period.
Human Mineralocorticoid Receptor Expression Renders Cells Responsive for Nongenotropic Aldosterone Actions
Authors: Grossmann Claudia , Benesic Andreas , Krug Alexander W. , Freudinger Ruth , Mildenberger Sigrid , Gassner Birgit , Gekle Michael
Published: March 2005

The steroid hormone aldosterone is important for salt and water homeostasis as well as for pathological tissue modifications in the cardiovascular system and the kidney. The mechanisms of action include a classical genomic pathway, but physiological relevant nongenotropic effects have also been described. Unlike for estrogens or progesterone, the mechanisms for these nongenotropic effects are not well understood, although pharmacological studies suggest a role for the mineralocorticoid receptor (MR). Here we investigated whether the MR contributes to nongenotropic effects. After transfection with human MR, aldosterone induced a rapid and dose-dependent phosphorylation of ERK1/2 and c-Jun NH2-terminal kinase (JNK) 1/2 kinases in Chinese hamster ovary or human embryonic kidney cells, which was reduced by the MR-antagonist spironolactone and involved cSrc kinase as well as the epidermal growth factor receptor. In primary human aortic endothelial cells, similar results were obtained for ERK1/2 and JNK1/2. Inhibition of MAPK kinase (MEK) kinase but not of protein kinase C prevented the rapid action of aldosterone and also reduced aldosterone-induced transactivation, most probably due to impaired nuclear-cytoplasmic shuttling of MR. Cytosolic Ca2+ was increased by aldosterone in mock- and in human MR-transfected cells to the same extend due to Ca2+ influx, whereas dexamethasone had virtually no effect. Spironolactone did not prevent the Ca2+ response. We conclude that some nongenotropic effects of aldosterone are MR dependent and others are MR independent (e.g. Ca2+), indicating a higher degree of complexity of rapid aldosterone signaling. According to this model, we have to distinguish three aldosterone signaling pathways: 1) genomic via MR, 2) nongenotropic via MR, and 3) nongenotropic MR independent.
αvβ3 Integrins and Pyk2 Mediate Insulin-Like Growth Factor I Activation of Src and Mitogen-Activated Protein Kinase in 3T3-L1 Cells
Authors: Sekimoto Hiroko , Eipper-Mains Jodi , Pond-Tor Sunthorn , Boney Charlotte M.
Published: March 2005

IGF-I stimulates cell growth through interaction of the IGF receptor with multiprotein signaling complexes. However, the mechanisms of IGF-I receptor-mediated signaling are not completely understood. We have previously shown that IGF-I-stimulated 3T3-L1 cell proliferation is dependent on Src activation of the ERK-1/2 MAPK pathway. We hypothesized that IGF-I activation of the MAPK pathway is mediated through integrin activation of Src-containing signaling complexes. The disintegrin echistatin decreased IGF-I phosphorylation of Src and MAPK, and blocking antibodies to αv and β3 integrin subunits inhibited IGF-I activation of MAPK, suggesting that αvβ3 integrins mediate IGF-I mitogenic signaling. IGF-I increased ligand binding to αvβ3 as detected by immunofluorescent staining of ligand-induced binding site antibody and stimulated phosphorylation of the β3 subunit, consistent with inside-out activation of αvβ3 integrins. IGF-I increased tyrosine phosphorylation of the focal adhesion kinase (FAK) Pyk2 (calcium-dependent proline-rich tyrosine kinase-2) to a much greater extent than FAK, and increased association of Src with Pyk2 but not FAK. The intracellular calcium chelator BAPTA prevented IGF-I phosphorylation of Pyk2, Src, and MAPK, suggesting that IGF-I activation of Pyk2 is calcium dependent. Transient transfection with a dominant-negative Pyk2, which lacks the autophosphorylation and Src binding site, decreased IGF-I activation of MAPK, but no inhibition was seen with transfected wild-type Pyk2. These results indicate that IGF-I signaling to MAPK is dependent on inside-out activation of αvβ3 integrins and integrin-facilitated multiprotein complex formation involving Pyk2 activation and association with Src.
Doob: A Half-Century on
Authors: Bingham N. H.
Published: March 2005

Probability theory, and its dynamic aspect stochastic process theory, is both a venerable subject, in that its roots go back to the mid-seventeenth century, and a young one, in that its modern formulation happened comparatively recently - well within living memory. The year 2003 marked the seventieth anniversary of Kolmogorov'sGrundbegriffe der Wahrscheinlichkeitsrechnung, usually regarded as having inaugurated modern (measure-theoretic) probability theory. It also marked the fiftieth anniversary of Doob'sStochastic Processes. The profound and continuing influence of this classic work prompts the present piece.
Gillis' Random Walks on Graphs
Authors: Guillotin-Plantard Nadine
Published: March 2005

We consider a random walker on a d-regular graph. Starting from a fixed vertex, the first step is a unit step in any one of the d directions, with common probability 1/d for each one. At any later step, the random walker moves in any one of the directions, with probability q for a reversal of direction and probability p for any other direction. This model was introduced and first studied by Gillis (1955), in the case when the graph is a d-dimensional square lattice. We prove that the Gillis random walk on a d-regular graph is recurrent if and only if the simple random walk on the graph is recurrent. The Green function of the Gillis random walk will be also given, in terms of that of the simple random walk.
Novel Stable Silicon-Based π-Electron Systems: Synthesis, Unique Structure, and Properties of Cyclic, Spiroconjugated, and Cumulative Silicon–Silicon Doubly-Bonded Compounds
Authors: Iwamoto Takeaki
Published: March 2005

In this account, the synthesis, structure, and reactions of cyclic, spiro-conjugated, and cumulative silicon–silicon doubly-bonded compounds are described. Photochemical and thermal interconversion among Si4R6 isomers including cyclotetrasilene 1, cyclotrisilene 2, and bicyclo[1.1.0]tetrasilane 7 occur without apparent participation of the corresponding tetrasila-1,3-diene, in contrast to the related interconversion among C4H6 isomers. Whereas parent spiropentadiene, the simplest spiroconjugation system, is known to survive only below −100 °C, spiropentasiladiene 3 is thermally very stable and shows remarkable spiroconjugation between the two ring π systems. The skeleton of isolable trisilaallene 4, the first stable silicon compound with tetracoordinate divalent (formally sp-hybridized) silicon atom, is not linear but remarkably bent. The considerable conjugation between two cumulative Si=Si double bonds was observed. The structural feature of 4 is quite different from that of carbon-based allenes having linear structure without conjugation between two π-bonds.
Hydration Structure around a Formyl-Hydrogen Atom Studied by Neutron Diffraction with H/D Isotopic Substitution Method
Authors: Kameda Yasuo , Sayama Atsunari , Sasaki Motoya , Amo Yuko , Usuki Takeshi
Published: March 2005

Time-of-Flight (TOF) neutron diffraction measurements were carried out for 12 mol% *HCOO7Li solutions in D2O. The H/D isotopic substitution technique was applied to the formyl-hydrogen atom of the formate ion in order to determine both the hydration structure around the formyl-hydrogen atom and the intramolecular structure of HCOO− in the aqueous solution. The hydration structure around the formyl-hydrogen atom was analyzed by applying a least-squares refinement procedure to the observed intermolecular difference function. The intramolecular distances within the formate ion were determined to be r(Hf–C) = 1.072(2) Å and r(Hf···Of) = 2.015(8) Å.
Orientation Behavior of Polyelectrolyte in Solution under an External Electric Field. A Coarse Grain Molecular Dynamics Simulation Study
Authors: Ueda Kazuyoshi , Iizumi Nobu , Sakomura Masaru
Published: March 2005

A coarse grain molecular dynamics simulation method was applied to polystyrenesulfonate in aqueous solution to investigate the conformational and orientational behavior of flexible polyion under an external electric field. When the electric field was applied, the deviation of the counter-ion distribution and the rotational orientation of the polyion toward the direction of the electric field were observed. The orientation behavior of flexible polyelectrolytes depended on the field strength, and two typical orientational motions were detected. That is, at low electric field strength, elongation of the whole polyion chain conformation occurs at first stage and subsequently rotationally orients toward the field direction. On the other hand, segment orientation occurs at the high field because of the fast displacement of the counter ions on each polymer segment. The ionic polarization of the flexible polyion was evaluated by the component analysis of the counter-ion deviation. Results showed that the loosely-bound counter ions contribute largely to the ionic polarization.
Application of Chiral Pyrromethene–BF2 Complex Dye as a Fluorescent Labeling Reagent
Authors: Matsui Masaki , Funabiki Kazumasa , Nakaya Ken-ichi
Published: March 2005

A chiral pyrromethene–BF2 complex dye, showing absorption (λmax) and emission maxima (λem) at 499 and 518 nm in acetonitrile, respectively, was synthesized. Racemic mexiletine smoothly reacted with this reagent in the presence of EDC to preferentially produce the corresponding diastereomeric amides, which were nicely separated by a non-chiral reverse phase column. The detection limit (S/N > 3) of mexiletine was ca. 0.3 pmol.
Formation of Coumarins by Palladium(II)-Catalyzed Reaction of Phenols with Ethyl Acrylates
Authors: Aoki Shinya , Oyamada Juzo , Kitamura Tsugio
Published: March 2005

The reaction of phenols with ethyl acrylates in the presence of a Pd(OAc)2 catalyst in trifluoroacetic acid did not yield dihydrocoumarins but gave coumarins, in contrast to the reaction of phenols with propiolates. The addition of K2S2O8 as an oxidant increased the yield of coumarins. The reaction of several phenols with ethyl cinnamate, ethyl crotonate, or ethyl acrylate gave the corresponding coumarin derivatives in moderate to good yields. The coumarin formation competed with the oxidative coupling of electron-rich phenols, which reduced the product yield.
Static and Dynamic Stereochemistry of Tris(9-triptycyl)stannane Derivatives
Authors: Yamamoto Gaku , Ohta Shozo , Kaneko Megumi , Mouri Kaoru , Ohkuma Miki , Mikami Ryo , Uchiyama Yosuke , Minoura Mao
Published: March 2005

Static and dynamic stereochemistry of several tris(9-triptycyl)stannane derivatives Tp3SnX (X = H, halogens, and alkyl groups) were studied. X-ray crystallography of the bromo and methyl compounds showed that the Sn atom was fundamentally tetrahedral and that the three Tp groups meshed with each other like bevel gears and formed a near-C3 chiral conformation. The rate constants for enantiomerization of the chiral conformation in solution could be obtained by the lineshape analysis of the aromatic proton signals, even when a direct probe for enantiomerization such as a benzyl group was absent. The energy barrier to enantiomerization decreased as the substituent X became bulkier, suggesting that the ground state is more destabilized than the transition state upon introduction of a bulkier group.
Self-Assembly of Gold Nanoparticles Utilizing a Charge-Transfer Interaction between Carbazolyl and Dinitrophenyl Units
Authors: Naka Kensuke , Itoh Hideaki , Chujo Yoshiki
Published: March 2005

Colloidal gold nanoparticles self-assembled into macroscopic aggregates by a charge-transfer interaction between a 9-carbazolyl unit as an electron-donor immobilized on the surface of the gold nanoparticles and a bivalent linker containing two dinitrophenyl units as electron-acceptors. Transmission electron microscopy and scanning electron microscopy images showed spherical aggregates consisting of the gold nanoparticles.
Recycling of Wastewater Containing Iron-Complex Cyanides Using UV Photodecomposition and UV Ozone Oxidation in Combination with an Ion-Exchange Resin Method
Authors: Wada Hiromutsu , Yanaga Kazuko , Kuroda Yasuhiro , Hanela Sergio , Hirayama Yoshio
Published: March 2005

Wastewater contaminated with iron-complex cyanides was processed by UV photodecomposition accompanied by an iron elimination process using an iron-adsorbent. The wastewater processed by UV photodecomposition was oxidized by ozone combined with UV irradiation. The treated water was deionized by an ion-exchange resin method. This combined processes further increased the production of the pure water volume compared to a single process using an ion-exchange resin. The technique developed in this study can be summarized as follows. First, the iron-complex cyanides in plating wastewater were converted into aquapentacyanoferrate(III) [Fe(CN)5(H2O)]3− ion. Following the application of UV irradiation, it was decomposed into iron and cyanide (CN−) ion. The iron was removed from the water in the form of Fe(OH)3 by processing the wastewater with ozone and an iron-adsorbent. The CN− ion was oxidized to the cyanate (OCN−) form by UV ozone oxidation in a relatively short time. The processed water was de-ionized by passing through cation and anion-exchange resins. The deionized water could be reused as rinsing water in a plating process. The results reported here suggest that wastewater contaminated with chemically stable iron-complex cyanides can be effectively recycled.
Isotopic evidence for age‐related variation in diet from Isola Sacra, Italy
Authors: Prowse Tracy L. , Schwarcz Henry P. , Saunders Shelley R. , Macchiarelli Roberto , Bondioli Luca
Published: March 2005

This study examines collagen (N = 105) and apatite (N = 65) data from an Imperial Roman skeletal sample from the necropolis of Isola Sacra (Rome, Italy). This paper explores correlations between the isotopic composition of bone samples and the inferred age and sex of these individuals (aged 5–45+ years). The collagen of males, and older individuals in general, was significantly enriched in15N but not13C. Bone carbonate was somewhat depleted in13C in some older individuals, suggesting increased consumption of olive oil and possibly wine. Subadults (>5 years) in the sample appear to have consumed an almost exclusively terrestrial diet. This study demonstrates a clear trend in dietary patterns between adult age groups, as well as between adults and children within a population. Am J Phys Anthropol 128:2‐13, 2005. © 2005 Wiley‐Liss, Inc.
Cytostatic Activity of 1,10‐Phenanthroline Derivatives Generated by the Clip‐Phen Strategy
Authors: Pitié Marguerite , Croisy Alain , Carrez Danièle , Boldron Christophe , Meunier Bernard
Published: March 2005

The cytostatic activities of a series of twelve 1,10‐phenanthroline (Phen) derivatives and of their copper complexes were studied on L1210 murine leukemia cells. Large increases in the biological activity were observed for compounds of the 3‐Clip‐Phen series, in which two Phen moieties were bridged at their C3 positions by an alkoxy linker, the 3‐pentyl‐Clip‐Phen derivative showing an IC50 value of 130 nM while Phen shows an IC50 value of 2500 nM under the same conditions. IC50 values seemed to be modulated not only by the position, the nature, and the length of the linker of Clip‐Phen but also by hydrophobicity. Since copper complexes of Phen are chemical nucleases and nucleic acids are thus a potential target for these compounds, the corresponding copper complexes were also studied. Copper complexation of the 3‐Clip‐Phen ligands did not increase their biological activities. Attempts to vectorize 3‐Clip‐Phen derivatives with a DNA binder such as spermine or with a cell‐penetration peptide failed to increase their biological activity relative to the original 3‐Clip‐Phen series.
Adaptation of the Vogt–Mizaikoff F‐test to determine the number of principal factors responsible for a data matrix and comparison with other popular methods
Authors: Malinowski Edmund R.
Published: March 2005

The statistical method developed by Vogt and Mizaikoff for the purpose of determining the number of principal factors responsible for a given test vector is adapted to determine the rank of the data matrix, i.e. the number of principal factors responsible for the entire data matrix. The adapted method is compared with other well‐established methods, namely the IND function, the Malinowski F‐test and the Faber–Kowalski F‐test, using real chemical data as well as modeled data. Copyright © 2005 John Wiley & Sons, Ltd.
Application of SIC (simple interval calculation) for object status classification and outlier detection—comparison with regression approach
Authors: Rodionova Oxana Ye. , Esbensen Kim , Pomerantsev Alexey
Published: March 2005

We introduce a novel approach termed simple interval calculation (SIC) for classification of object status in linear multivariate calibration (MVC) and other data analytical contexts. SIC is a method that directly constructs an interval estimator for the predicted response. SIC is based on the single assumption that all errors involved in MVC arelimited. We present the theory of the SIC method and explain its realization by linear programming techniques. The primary SIC consequence is a radically new object classification that can be interpreted using a two‐dimensional object status plot (OSP), ‘SIC residual vs SIC leverage’. These two new measures of prediction quality are introduced in the traditional chemometric MVC context. Simple straight demarcations divide the OSP into areas which quantitatively discriminate all objects involved in modeling and prediction into four different types:boundary samples, which are the significant objects (for generating the entire data structure) within the training subset;insiders, which are samples that comply with the model;outsiders, which are samples that have large prediction errors; and finallyoutliers, which are those samples that cannot be predicted at all with respect to a given model. We also present detailed comparisons of the new SIC approach with traditional chemometric methods applied for MVC, classification and outlier detection. These comparisons employ four real‐world data sets, selected for their particular complexities, which serve as showcases of SIC application on intricate training and test set data structures. Copyright © 2005 John Wiley & Sons, Ltd.
Vibration of a space arc subject to a critical dynamic load
Authors: Tenek Lazarus Teneketzis
Published: March 2005

The present study concerns the dynamic behaviour of a space arc subject to a midarc vertical buckling load dynamically applied. The arc is discretized with a set of three‐dimensional beam finite elements and the non‐linear dynamic equation (large displacements) is solved by means of an unconditionally stable time‐dependent scheme over time. The vertical excitation gives rise to a very fast and erratic horizontal wave as the structure begins to vibrate in all directions. This horizontal wave has chaotic characteristics as its attractor indicates. Time–displacement curves are obtained for all components of the midarc point. Although the time algorithm was executed here for 2000 time steps, simulation over longer periods of time can reveal the vibration characteristics and even simulate structural failure under the imposed dynamic buckling load for the space arc structure. Copyright © 2004 John Wiley & Sons, Ltd.
The Sound Velocity in Ideal Liquid Mixtures from Thermal Volume Fluctuations
Authors: Pfeiffer Helge , Heremans Karel
Published: March 2005

The selection of the correct mixing rule for sound velocity in ideal liquid mixtures determines the interpretation of the sound velocity in real mixtures. This is especially important for the determination of apparent properties of solutes, such as their apparent compressibility. There are different approaches reported in the literature, and this article presents a new derivation of the mixing rule based on statistical mechanics. It is shown that the correlation of volume fluctuations between adjacent components has a crucial influence on the ideal mixing rule.
Analysis of virtual two‐dimensional gels based upon affinity capillary electrophoresis hyphenated to ion trap‐mass spectrometry
Authors: Machour Nadine , Place John , Tron François , Charlionet Roland , Mouchard Laurent , Morin Christophe , Desbène Annie , Desbène Paul‐Louis
Published: March 2005

Affinity capillary electrophoresis (ACE) is a robust tool for the study of noncovalent biomolecular interactions and to determine the binding constants. It is advantageous due to the speed of analysis, the high and reproducible separation efficiencies, the low consumption of analytes, the ability to study several interactions at the same time, and to cover a wide range of affinity. The use of an ion trap‐mass spectrometer as a sensitive and specific detector, coupled on‐line with a classical UV detector, permits extracting simultaneously the electropherograms corresponding to each ionic species. The mass spectra, acquired by scanning the results of a first separation due to ACE, were assimilated into a virtual two‐dimensional (2‐D) gel. We developed a software application, which was designed to create and analyze these virtual 2‐D gels. The validity of this new analytical tool for probing biomolecular interactions has been demonstrated on mixtures of antibiotics of the vancomycin group and several dipeptide substrates. Using the dynamic equilibrium affinity electrophoresis approach, we have shown that molecular components interacting with a low affinity are easily located on the virtual 2‐D gels, and that binding constants and stoichiometry of the interactions can be assessed. As the binding constants derived from ACE‐electrospray ionization‐mass spectrometry (ESI‐MS) are unreliable, they must only be determined with the UV detector.