bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of left atrial size and function on P‐wave dispersion: A study in patients with paroxysmal atrial fibrillation
Authors: Tüukek Tufan , Akkaya Vakur , Atilgan Dursun , Demirel Şsleref , ÖZCAN Mustafa , Güuven Özen , Korkut Ferruh
Published: February 2009

Background: Paroxysmal atrial fibrillation (PAF), a common arrhythmia, is caused by the fractionated and nonhomo‐geneous propagation of sinus impulse.

Hypothesis: This study was undertaken to examine the effect of left atrial (LA) dimension and function on P‐wave dispersion (ΔP) in unselected patients with PAF and healthy controls.

Method: In this study, 62 consecutive patients with PAF (32 men, 30 women, mean age 55 ± 11 years) and 62 age‐ and gender‐matched healthy controls (33 men, 29 women, mean age 52 ± 13 years) were studied to compare the effect of LA size, volume, and function on ΔP (difference between maximum and minimum P‐wave duration on 12‐lead electrocardiogram).

Results: P‐wave dispersion in patients with PAF and normal LA diastolic diameter (LAD) was longer than that in controls with normal LA size (53 ± 8 vs. 34 ± 8 ms, p < 0.001). P‐wave dispersion increased in patients with PAF (62 ± 12 vs. 53 ± 8 ms, p = 0.003) and controls (40 ± 7 vs. 34 ± 8 ms, p = 0.005) with increased LAD. Presence or absence of PAF did not interact with LAD for their effect on ΔP (2 × 2 analysis of variance test p = 0.20). In the PAF group, ΔP correlated with LAD (r = 0.43, p = 0.002), LA diastolic volume (r = 0.6, p < 0.001), and LA ejection fraction (AEF) (r=‐0.33, p = 0.05). The AEF was preserved when LAD increased in the patients without PAF (0.52 ± 0.07 vs. 0.57 ± 0.10, p = NS), however was significantly decreased in the PAF group (0.37 ±0.12 vs. 0.49 ± 0.10, p = 0.01). On multivariate logistic regression analysis, only δP retained significance on development of PAF.

Conclusion: It was concluded that δP increased in patients with PAF and normal LA size. In controls with increased LA size, δP increased but did not reach the levels attained in patients with PAF. The AEF was decreased in patients with PAF but was preserved in those without PAF. These findings can be explained by the changes in LA microarchitecture which concurrently decreased atrial myocardial contraction, increased δP, and predisposed to PAF.
Coronary heart disease associated with the use of human immunodeficiency virus (HTV)‐1 protease inhibitors: Report of four cases and review
Authors: Duong Michel , Buisson Marielle , Cottin Yves , Piroth Lionel , Lhuillier Isabelle , Grappin Michele , Chavanet Pascal , Wolff Jean‐Eric , Portier Henri
Published: February 2009

Four cases of human immunodeficiency virus (HlV)‐infected patients who developed coronary heart disease (CHD) while under treatment with a protease inhibitor (PI) are described, and the epidemiologic and clinical features of 18 cases reported in the literature are analyzed. Cardiac manifestations mostly included myocardial infarctions. Smoking and hyperlipidemia were the most common risk factors for CHD, reported in 72 and 81% of the patients, respectively. Hypercholesterolemia was observed in 75% of the cases at the time of the cardiovascular event. Ninety percent of the patients with pretreatment normal lipid values experienced a rise in the plasma lipid levels during PI therapy. Although a definite relationship between the development of CHD and HIV Pis can not be made, this analysis suggests that Pi‐induced hyperlipidemia may play a role in accelerating coronary atherosclerosis in patients with concomitant risk factors. Evaluation and control of risk factors for CHD should be performed in each patient for whom treatment with a PI is indicated.
Left ventricular geometry and operative mortality in patients undergoing mitral valve replacement
Authors: Gomez‐Doblas Juan Jose , Schor John , Vignola Paul , Weinberg Denis , Traad Ernest , Carrillo Rogerio , Williams Donald , Lamas Gervasio A.
Published: February 2009

Background: Distortion of left ventricular (LV) shape is often associated with LV dysfunction and is thought to be an independent predictor of survival in patients with coronary disease.

Hypothesis: The purpose of this study was to examine the relationship between LV geometry and hospital mortality in patients with mitral regurgitation (MR) undergoing mitral valve surgery.

Methods: A consecutive series of patients (aged 68 ± 12 years, 47% men) (n = 149) with MR who underwent cardiac catheterization, left ventriculography, and mitral valve surgery from 1995 to 1996 at Mount Sinai Medical Center was studied. Left ventriculograms, clinical records, and hemodynamics were reviewed. Left ventricular volumes and ejection fraction were calculated using standard techniques. Left ventricular shape in diastole and systole was evaluated using the sphericity index, which is defined as the end‐systolic LV volume (X 100) divided by the volume of a sphere whose diameter is equal to the LV long axis.

Results: In the patients studied, the etiology of mitral insufficiency was mitral valve prolapse in 40.9%, ischemic heart disease in 40.3%, rheumatic heart disease in 11.4%, and prosthetic valvular dysfunction in 7.4%. The average ejection fraction was 65% ± 17. Systolic sphericity index (SSI) was 36% ± 15 in patients who died, compared with 25% ± 11 in patients who lived (p < 0.001). A multivariate model was constructed using hemodynamic and angiographic indices derived during preoperative cardiac catheterization. Systolic sphericity index (odds ratio = 1.6 for each point increase, p < 0.01) was found to be an independent predictor of postoperative survival in the global population, as well as in patients with coronary disease (p<0.01).

Conclusion: Left ventricular geometry is an independent angiographic risk factor for survival following mitral valve replacement. Sphericity index is a simple method for assessing LV geometry which should be calculated in patients as part of risk stratification.
Effects of acute exercise on hemorheological, endothelial, and platelet markers in patients with chronic heart failure in sinus rhythm
Authors: Gibbs Christopher R. , Blann Andrew D. , Edmunds Mrcpath, Eiry , Watson Robert D. S. , Lip Gregory Y. H.
Published: February 2009

Background: Chronic heart failure (CHF) is associated with an increased risk of thrombosis and thromboembolic events, including stroke and venous thromboembolism, which may be related to a prothrombotic or hypercoagulable state. Acute vigorous exercise has been associated with activation of hemostasis, and this risk may well be particularly increased in patients with CHF.

Hypothesis: The study was undertaken to determine whether acute exercise would adversely affect abnormalities of hemorheological (fibrinogen, plasma viscosity, hematocrit), endothelial (von Willebrand factor), and platelet markers (soluble P selectin) in patients with CHF.

Methods: We studied 22 ambulant outpatients (17 men; mean age 65 ± 9 years) with stable CHF (New York Heart Association class II—HI and a left ventricular ejection fraction of ≤ 40%) who were exercised to exhaustion on a treadmill. Results were compared with 20 hospital controls (patients with vascular disease, but free of CHF) and 20 healthy controls.

Results: Baseline von Willebrand factor (p = 0.01) and soluble P‐selectin (p=0.006) levels were significantly elevated in patients with CHF when compared with controls. In the patients with CHF who were exercised, plasma viscosity, fibrinogen, and hematocrit levels increased significantly, both immediately post exercise and at 20 min into the recovery period (repeated measures analysis of variance, all p < 0.05). There was a positive correlation between exercise workload and the maximal changes in plasma viscosity in the patients with CHF (Spearman r = 0.5, p = 0.02). Plasma viscosity levels increased with exercise in the hospital control group, although no other exercise‐induced changes were noted in this group.

Conclusion: The present study indicates that the hemorheological indices, fibrinogen, and hematocrit specifically increase during acute exercise in patients with CHF. Although moderate exercise should be encouraged in patients with CHF, vigorous exercise should probably be avoided in view of its potential prothrombotic effects in this high‐risk group of patients.
Identification of patients with coronary artery disease by assessing diastolic abnormalities during isometric exercise
Authors: Manolas Jan , Chrysochoou Christina , Kastelanos Stamatis , Aggeli Konstantina , Panagiotakos Demosthenes B. , Stefanadis Christodoulos , Toutouzas Pavlos
Published: February 2009

Background: Previous clinical studies using invasive and noninvasive methods have shown handgrip‐induced diastolic abnormalities in patients with coronary artery disease (CAD).

Hypothesis: The study was undertaken to determine the utility of Doppler echo‐ and pressocardiography during handgrip in discriminating patients with coronary artery disease (CAD) and in those with normal coronary arteries.

Methods: Both methods were obtained in 96 patients with suspected CAD within 24 h before coronary angiography. An abnormal handgrip‐Doppler was defined by an early (E) to late (A) transmittal flow velocities ratio (E/A) < 1 during handgrip and a positive handgrip pressocardiographic test (HAT) by an abnormal increase in the A wave/total excursion or prolongation of the absolute or relative (heart‐rate corrected) total relaxation time during isometric exercise.

Results: Of the 96 patients studied, 23 had normal coronary arteries and 73 showed CAD. In patients with normal coronary arteries, handgrip‐Doppler showed an abnormal average E/A at rest and during handgrip, whereas all variables of HAT were within normal limits. In patients with CAD, handgrip‐Doppler showed only a moderate handgrip‐induced increase in average A (+ 19%, p < 0.001), whereas HAT showed a significant (p < 0.001) increase in mean A wave/total excursion (+ 60%) and decrease in the relative total relaxation time (‐17%). Furthermore, handgrip‐Doppler and HAT were abnormal in 15 of 23 (65%, specificity 35%) and the HAT in 5 of 23 (22%, specificity 78%) patients with normal coronary arteries, as well as in 57 of 73 (sensitivity 78%) and 69 of 73 (95%) patients with CAD.

Conclusions: Our study demonstrates that these noninvasive stress tests can become a useful new diagnostic modality for detecting patients with unknown or suspected CAD.
Should functional cardiac murmurs be diagnosed by auscultation or by doppler echocardiography?
Authors: Bloch Antoine , Crittin Jean , Jaussi Andres
Published: February 2009

Background: For many years, cardiac auscultation has been the only available method for distinguishing between functional and organic murmurs; however, a more reliable differential diagnosis can now be achieved with Doppler echocardiography. The question remains as to whether a Doppler echocardiogram needs to be routinely recorded in the presence of a heart murmur or whether the auscultatory diagnosis of a functional murmur is sufficient.

Hypotltesis: This prospective study attempts to answer this important question at a time when medical costs have to be curbed.

Methods: The three cardiologists involved in this study saw 516 new patients in their private practice over a 10‐month period; of these, 321 (63.6%) underwent Doppler echocardiography. All patients underwent careful auscultation prior to echocardiography. At the end of their examinations, the cardiologists noted whether they considered the murmur to be of functional or organic origin. Minimal mitral or aortic regurgitations of short duration and low velocity occurring on non‐thickened valves were considered functional.

Results: The results for cardiac auscultation and Doppler echocardiography were considered to be concordant, that is, both techniques diagnosed either a functional or organic murmur in 250 of 321 patients (77.9%). The results for cardiac auscultation and Doppler echocardiography showed a major discordance in just six cases (1.9%). All were mitral regurgitations of moderate severity.

Conclusion: The prevalence of cardiac murmurs in the general population is very high. As echocardiography currently represents a significant proportion of cardiac medical expenditure, it would be wise to limit the use of this technique to essential indications. This study confirms that both cardiac auscultation and Doppler echocardiography possess important limitations. Nevertheless, it also shows that well‐trained cardiologists can identify the vast majority of functional murmurs on auscultation. Better training of nonspecialist physicians in cardiac auscultation may help in containing medical expenses.
Correlates of bundle‐branch block in patients undergoing primary angioplasty for acute myocardial infarction
Authors: Sugiura Tetsuro , Yamasaki Fumiyasu , Hatada Kengo , Nakamura Seishi , Iwasaka Toshiji
Published: February 2009

Background: Early reperfusion therapy has reduced the infarct size and mortality rate in patients with acute myocardial infarction (AMI). The occurrence of bundle‐branch block in AMI is related to the amount of myocardial damage and the insult to the conduction system.

Hypothesis: To evaluate the clinical and angiographic factors related to the occurrence of bundle‐branch block (BBB) in patients with primary percutaneous transluminal coronary angioplasty (PTCA), we investigated consecutive series of patients with their first Q‐wave AMI and successful PTCA.

Methods: Coronary angiogram at the time of admission, electrocardiogram, and echocardiogram were evaluated in 279 patients with their first Q‐wave AMI and successful PTCA.

Results: Bundle‐branch block was detected in 26 patients (9%) 16 patients had transient and 10 patients had persistent block, while 16 patients had bifascicular block and 10 patients had right BBB. The patients with BBB had a significantly larger number of left ventricular asynergic segments, higher incidence of total occlusion of infarct‐related artery, angiographic no reflow, and pericardial rub than those without BBB. When the multivariate analysis was performed using five clinical markers of infarct severity, angiographic no reflow (F = 20.2, p < 0.001) and total occlusion of infarct‐related artery (F = 4.2, p = 0.04) were found to be the significant variables related to BBB.

Conclusions: Despite successful primary PTCA, absence of antegrade flow in the infarct‐related artery at the onset of AMI and/or angiographic no reflow resulted in more severe transmural myocardial damage and, hence, the occurrence of BBB.
Right ventricular electrocardiographic leads for detection of brugada syndrome in sudden unexplained death syndrome survivors and their relatives
Authors: Sangwatanaroj Somkiat , Prechawat Somchai , Sunsaneewitayakul Buncha , Sitthisook Surapun , Tosukhowong Piyarat , Tungsanga Kriang
Published: February 2009

Background: Sudden unexplained death syndrome (SUDS) is a sudden death syndrome in previously healthy Southeast Asian young adults without any structural causes of death. Many SUDS survivors show electrocardiographic (ECG) evidence of RSR' and ST elevation in leads V1 to V3, which is similar to the ECG pattern in Brugada syndrome. However, in many cases transient normalization of the ECG does not make diagnosis with standard 12‐lead ECG possible.

Hypothesis: To overcome this problem, we utilized the new right ventricular ECG leads to detect the Brugada syndrome in SUDS survivors.

Methods: The subject was a Thai male patient who presented with a SUDS‐like syncopal attack. He had cardiac arrest due to idiopathic ventricular fibrillation.

Results: Post‐resuscitation standard 12‐lead ECG showed no diagnostic features of Brugada syndrome. However, ECG patterns of RSR' and ST elevations typical for Brugada syndrome could be detected at the higher intercostal space leads V1 to V3. We observed similar findings in 2 of the other 10 SUDS survivors and 4 of 23 healthy family members.

Conclusions: Our data suggest that these new right ventricular leads ECG may be helpful in detecting Brugada syndrome in SUDS survivors and their relatives.
Morphology, binding behavior and MR‐properties of paramagnetic collagen‐binding liposomes
Authors: Sanders H. M. H. F. , Strijkers G. J. , Mulder W. J. M. , Huinink H. P. , Erich S. J. F. , Adan O. C. G. , Sommerdijk N. A. J. M. , Merkx M. , Nicolay K.
Published: February 2009

Collagen is an important component of the extracellular matrix (ECM) and plays an important role in normal tissue maturation and in pathological processes such as atherosclerosis and myocardial infarction. The diagnostics of the latter diseases using MRI could strongly benefit from the use of collagen‐specific contrast agents. The current study aimed to develop a bimodal liposomal MR contrast agent that was functionalized with CNA35, a collagen adhesion protein of the Staphylococcus aureus bacterium. The liposomes were characterized in terms of CNA35 protein conjugation and loading. The overall morphology was assessed with DLS and cryo‐TEM, while cryo‐TEM tomography was used to visualize the protein coverage of the liposomes. The binding properties of the contrast agent were investigated using a fluorescence assay based on the rhodamine content of the liposomes. The bulk relaxivity was determined using regular relaxometry while the MR‐properties of liposomes in their bound state were studied using NMR depth profiling. This CNA35 functionalized contrast agent and the set of in vitro experiments we performed indicate the potential of this technology for in vivo molecular imaging of collagen. Copyright © 2009 John Wiley & Sons, Ltd.
HPV detection rate in discordant Pap tests between cytotechnologists and pathologists
Authors: Chhieng David C. , Bakdounes K. , Connolly Mary , Gallaspy Sandra , Roberson Janie , Eltoum Isam
Published: February 2009

When a Pap test is referred for pathologist review, it is accompanied by the cytotechnologist's provisional interpretation. Discordant interpretations between pathologists and cytotechnologists are sometimes noted. The objective is to correlate HPV detection rate with both estimated false‐negative fraction (EFNF) and ASC to SIL ratio among discordant ASC cases. ThinPrep Pap tests in which the cytotechnologists' provisional interpretations were up‐ or down‐graded by pathologists to ASC were retrieved between January and December 2006. HPV DNA testing was performed using hybrid capture technique. EFNFs and ASC to SIL ratio were estimated for cytotechnologists and pathologists, respectively. Overall, the EFNF ratio was 3.4% and the high‐risk HPV DNA detection rates in cases that were “over‐” or “under‐” interpreted by technologists were 0.71 and 0.40, respectively. The overall ASC to SIL ratio was 1.41 and the high‐risk HPV DNA detection rates in cases that were upgraded or downgraded to ASC were 0.40 and 0.71, respectively. In conclusion, our ASC to SIL ratios and EFNF were within acceptable range. We did not observe any association between ASC to SIL ratio and HPV detection rate in cases that were upgraded or downgraded to ASC by pathologists or between EFNF ratio and HPV detection rate in cases that were “over‐interpreted” (or “under‐interpreted”) by cytotechnologists. The HPV detection rates for ASC cases that were originally “over‐interpreted” by cytotechnologists were comparable to the HPV detection rates for LSIL, whereas those that were underinterpreted were comparable to the HPV detection rate for ASC. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
Cytologic diagnosis of osseous lesions: A review with emphasis on the diagnosis of primary neoplasms of bone
Authors: Layfield Lester J.
Published: February 2009

Fine‐needle aspiration has been utilized as the initial diagnostic technique at a large number of body sites for over three quarters of a century. As early as the 1930s, fine‐needle aspiration (FNA) was used to investigate lesions of the musculoskeletal system. In many early reports, FNA was most frequently and successfully used for the diagnosis of metastatic disease to bone. Less emphasis was placed on its utility for the investigation of primary neoplasms of bone and soft tissue. Current utilization of FNA continues to de‐emphasize its application to the diagnosis of primary lesions of the musculoskeletal system.

Recent advances in imaging techniques, immunohistochemistry, and molecular diagnostics along with an increasing familiarity among pathologists with the cytologic appearance of primary osseous tumors has led to reevaluation of the technique for investigation of these tumors. The diagnostic accuracy of FNA along with its relatively low cost and high degree of safety makes it a desirable technique for the investigation of primary lesions of the musculoskeletal system. This article reviews issues of diagnostic accuracy, optimal practice procedures, and benefits of the technique including cost reduction.

The article will review criteria for selection of appropriate tissue targets for FNA to reduce the number of unsatisfactory specimens. Cytomorphologic features of the more common primary neoplasms of bone will be summarized along with recommendations for the utilization of immunohistochemistry and molecular diagnostics in the work‐up of primary neoplasms of bone. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
Use of streamed Internet video for cytology training and education: www.PathLab.org
Authors: Poller David , Ljung Britt‐Marie , Gonda Peter
Published: February 2009

An Internet‐based method is described for submission of video clips to a website editor to be reviewed, edited, and then uploaded onto a video server, with a hypertext link to a website. The information on the webpages is searchable via the website sitemap on Internet search engines. A survey of video users who accessed a single 59‐minute FNA cytology training cytology video via the website showed a mean score for usefulness for specialists/consultants of 3.75, range 1–5, n = 16, usefulness for trainees mean score was 4.4, range 3–5, n = 12, with a mean score for visual and sound quality of 3.9, range 2–5, n = 16. Fifteen out of 17 respondents thought that posting video training material on the Internet was a good idea, and 9 of 17 respondents would also consider submitting training videos to a similar website.

This brief exercise has shown that there is value in posting educational or training video content on the Internet and that the use of streamed video accessed via the Internet will be of increasing importance. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
Cervical intraepithelial neoplasia and aneusomy of TERC: Assessment of liquid‐based cytological preparations
Authors: Ramsaroop Reena , Oei Paul , Ng Daniel , Kumar Nirup , Cotter Philip D.
Published: February 2009

The implementation of effective screening programs has decreased the incidence and mortality of cervical carcinoma. However, single screening tests are subjective and carry a significant false‐negative rate. Therefore, supplementary tests to support the Papanicolaou (PAP) smear are being developed. Human papillomavirus (HPV) testing has increased the specificity of the PAP smear, but has high sensitivity rate. This has proven unhelpful in low‐grade lesions and in young women.

Cervical carcinogenesis is a multifactorial disorder. In addition to exposure to oncogenic HPV, which is regarded as the initiator, there must be a promoter to eventuate in invasive disease. The promoter factor appears to be the acquisition of extra copies of chromosome 3q and has been shown to be a constant recurrence in cervical carcinoma (squamous and adenocarcinomas). The 3q region contains the RNA sequence of the human telomerase gene TERC. Recent studies have shown a strong correlation between high‐grade cervical lesions and abnormalities of TERC.

This study supports the previous studies and examines the status of the TERC gene in low and high‐grade cervical intraepithelial lesions, diagnosed on cytology. ASC‐H smears are also examined in an attempt to categorize lesions that are more likely to progress. Potentially this may help identify women in need of close clinical follow‐up and early treatment. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
Cytologic diagnosis of pulmonary adenocarcinoma with micropapillary pattern: Does it correlate with the histologic findings?
Authors: Rudomina Dorota E. , Lin Oscar , Moreira Andre L.
Published: February 2009

Micropapillary adenocarcinoma is associated with poor‐prognosis in several organs including the lung. The presence of small tight balls of neoplastic cells devoid of fibrovascular core in cytological preparations (micropapillary tufts) has been described as characteristic of micropapillary adenocarcinoma. In the lung, however, this criterion has not been validated. The cytological material of 46 cases of histologically proven pulmonary adenocarcinoma with a micropapillary component was compared to 33 cases with no micropapillary component to determine the specificity of micropapillary tufts for the histologic diagnosis of micropapillary adenocarcinoma. Other histologic patterns of invasive pulmonary adenocarcinomas (acinar, papillary, and solid) were also compared with patterns of neoplastic cell aggregates in cytological preparations. There were no significant differences in the distribution of micropapillary clusters between the two groups. The positive predictive value for the cytologic diagnosis of a micropapillary component in lung adenocarcinomas was of 64%. Similar findings were observed for other invasive patterns. Therefore, the detection of micropapillary tufts in cytology is not specific for the diagnosis of a pulmonary micropapillary adenocarcinoma in the lung. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
The Allantoic Core Domain: New insights into development of the murine allantois and its relation to the primitive streak
Authors: Downs Karen M. , Inman Kimberly E. , Jin Dexter X. , Enders Allen C.
Published: February 2009

The whereabouts and properties of the posterior end of the primitive streak have not been identified in any species. In the mouse, the streak's posterior terminus is assumed to be confined to the embryonic compartment, and to give rise to the allantois, which links the embryo to its mother during pregnancy. In this study, we have refined our understanding of the biology of the murine posterior primitive streak and its relation to the allantois. Through a combination of immunostaining and morphology, we demonstrate that the primitive streak spans the posterior extraembryonic and embryonic regions at the onset of the neural plate stage (∼7.0 days postcoitum, dpc). Several hours later, the allantoic bud emerges from the extraembryonic component of the primitive streak (XPS). Then, possibly in collaboration with overlying allantois‐associated extraembryonic visceral endoderm, the XPS establishes a germinal center within the allantois, named here the Allantoic Core Domain (ACD). Microsurgical removal of the ACD beyond headfold (HF) stages resulted in the formation of allantoic regenerates that lacked the ACD and failed to elongate; nevertheless, vasculogenesis and vascular patterning proceeded. In situ and transplantation fate mapping demonstrated that, from HF stages onward, the ACD's progenitor pool contributed to the allantois exclusive of the proximal flanks. By contrast, the posterior intraembryonic primitive streak (IPS) provided the flanks. Grafting the ACD into TC/TC hosts, whose allantoises are significantly foreshortened, restored allantoic elongation. These results revealed that the ACD is essential for allantoic elongation, but the cues required for vascularization lie outside of it. On the basis of these and previous findings, we conclude that the posterior primitive streak of the mouse conceptus is far more complex than was previously believed. Our results provide new directives for addressing the origin and development of the umbilical cord, and establish a novel paradigm for investigating the fetal/placental relationship. Developmental Dynamics 238:532–553, 2009. © 2009 Wiley‐Liss, Inc.
Hoxb13 regulatory elements mediate transgene expression during prostate organogenesis and carcinogenesis
Authors: McMullin Ryan P. , Mutton Laura N. , Bieberich Charles J.
Published: February 2009

The prostate requires androgens for development and homeostasis. Prostate cancer shares this dependence, however progression to androgen‐independence is common after androgen deprivation. There is considerable interest in achieving therapeutic gene expression after androgen ablation using prostate‐specific promoters. Paradoxically, known prostate‐restricted cis‐regulatory elements are androgen dependent. Hoxb13 expression is restricted in adults to the prostate and colon, and robust Hoxb13 expression persists after castration. To locate regulatory elements conferring this expression pattern, a lacZ reporter was inserted into the Hoxb13 locus on a mouse genomic bacterial artificial chromosome. In transgenic mice, this construct recapitulated the Hoxb13 expression pattern, including expression after castration. Reporter gene activity was maintained during carcinogenesis in a prostate cancer model. Hoxb13 cis‐regulatory elements provide a powerful tool to achieve androgen‐independent transgene expression in the prostate and distal colon‐specific expression in the gastrointestinal tract. These data establish a framework for high‐resolution analyses of factors regulating Hoxb13. Developmental Dynamics 238:664–672, 2009. © 2009 Wiley‐Liss, Inc.
Aph‐1 is required to regulate Presenilin‐mediated γ‐secretase activity and cell survival in Drosophila wing development
Authors: Cooper Emilie , Deng Wu‐Min , Chung Hui‐Min
Published: February 2009

Aph‐1 is a multipass transmembrane protein and an essential component of the Presenilin (Psn)‐mediated γ‐secretase complex. During protease assembly, Aph‐1 stabilizes the newly synthesized Psn holoprotein to facilitate generation of the active form of Psn, which is a Psn‐NTF/Psn‐CTF heterodimer produced through a Presenilinase‐initiated endoproteolytic cleavage of the Psn holoprotein. Although it is clear that loss of Aph‐1 activity leads to failure of Psn heterodimer formation, little is understood about whether Aph‐1 plays a role in regulating γ‐secretase activity in addition to assisting Psn maturation. Using various modified Psn forms that do not require endoproteolysis or have a large deletion of the cytosolic loop, we show that in Drosophila Aph‐1 is still required for γ‐secretase activity independent of its role in promoting Psn endoproteolysis. In addition, our results indicate that Aph‐1 is required to promote cell survival in the wing imaginal disc; aph‐1 mutant cells are lost either through cell death or because of a defect in cell proliferation. This function of Aph‐1 is independent of its role in regulating γ‐secretase activity, but possibly involves downregulating the activity of uncleaved Psn holoprotein. genesis 47:169–174, 2009. © 2009 Wiley‐Liss, Inc.
Decomposition and reconstruction of signal in real‐time spectral analysis
Authors: Nakatsuji Hideto , Omatu Sigeru
Published: February 2009

In recent years, wavelet transform which gives expression in the time–frequency domain has been adopted for a nonstationary process. The authors have proposed a new spectral analytical method in the time–frequency domain. In the conventional spectral analytical methods, the decomposition and the reconstruction of signals have been obtained analytically. The proposed method consists of two approaches. We call these approaches Approach 1 and Approach 2. In this paper, we show the decomposition and reconstruction of signals based on Approach 1. First, we show that the signal is decomposed to the signal elements. They are called the decomposition waves, and all of these decomposed waves are added to obtain the reconstructed wave. Next, we show the magnitude characteristic and the phase characteristic between the original signal and the reconstructed wave. Then the conditions between the signal and the reconstructed wave are derived to realize a sufficiently approximated wave. By a numeric calculation example, we show the approximation ability by the proposed method. © 2009 Wiley Periodicals, Inc. Electron Comm Jpn, 91(11): 37–45, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecj.10182
Classification of semiconductor defects using a small number of training data and qualitative knowledge
Authors: Shimomura Shohei , Igarashi Hajime , Hiroi Takashi , Hosoya Naoki , Nakagawa Yasuo
Published: February 2009

In semiconductor wafer manufacturing processes, defect candidates are usually extracted by an inspection system. The defect candidates are composed of true defects such as open circuits, contaminants, and bridges, as well as nondefect patterns, called nuisances, which predominate over true defects. The goal of this study is to classify the defect candidates as the various true defects and nuisances by using a small number of training data obtained by SEM inspection. It is shown that the accuracy of clustering is considerably improved by use of qualitative knowledge about the defects, given a priori by inspectors, in the clustering processes. © 2009 Wiley Periodicals, Inc. Electron Comm Jpn, 91(11): 46–54, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecj.10183
Development of an identification system for location of free metallic particles in GIS based on analysis of Lamb waves
Authors: Kozako Masahiro , Ohtsuka Shinya , Kaneko Shuhei , Okabe Shigemitsu , Hikita Masayuki
Published: February 2009

We investigated propagation properties of Lamb waves in a gas‐insulated switchgear (GIS) tank to diagnose insulation performance of GIS. The acoustic signals excited by a free metallic particle colliding with the tank sheath were measured using AE sensors. The wavelet transform was applied to decompose the wave data into its time–frequency components. As a result, difference of propagation properties of Lamb waves is clearly seen with different sizes of GIS tank. Based on the characteristics of Lamb waves, algorithms for location identification of a free metallic particle were examined in model GIS using two AE sensors. Herein, we propose a new system for location identification of a free metallic particle in GIS. Moreover, it is verified that the new identification system is suitable as a diagnostic technique for GIS. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 167(3): 28–35, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20676
The Magnetotransport Properties and a Neutron Diffraction Study of Sr2–xNdxFeMoO6 Double Perovskites
Authors: Retuerto María , Martínez‐Lope María Jesús , García‐Hernández Mar , Alonso José Antonio
Published: February 2009

New electron‐doped derivatives of the Sr2FeMoO6 double perovskite have been studied. We report on the synthesis of the Sr2–xNdxFeMoO6 (x = 0, 0.2, 0.4 and 0.6) perovskite series by a wet chemistry procedure and its characterization. The evolution of the crystal and magnetic structure has been analyzed from neutron powder diffraction data. The partial replacement of Sr2+ cations by higher valence Nd3+ cations induces an injection of electrons into the Fe/Mo sublattice. A bond‐valence study demonstrates that this electron‐injection preferentially affects the Mo orbitals. This substitution leads to a distortion of the structure from tetragonal (I4/m) to monoclinic (P21/n) at room temperature for x ≥ 0.4 and an increase of the disorder between Fe and Mo cations. This effect has severe consequences for the magnetic properties, notably a reduction of the saturation magnetization and a non‐monotonic behavior of the Curie temperature. Magnetotransport measurements show a significant increment of the magnetoresistance at low temperature for high values of x. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Hypercoordinate Silicon Complexes of (O,N,N′ vs. O,N,O′) Schiff Base Type N‐(2‐Carbamidophenyl)imines: Examples of Exclusively O‐Silylated Carbamides
Authors: Kämpfe Alexander , Kroke Edwin , Wagler Jörg
Published: February 2009

Tridentate salphen‐type O,N,N′ chelators, upon acylation of the NH2 group, are capable of engaging an O,N,O′ coordination mode in addition to their inherent O,N,N′ donor character. In six‐coordinate silicon complexes of the type SiL2 [L = N‐(2‐carbamidophenyl)imine], these ligands were found to exclusively form SiN2O4 coordination spheres by engaging their tridentate O,N,O′ donor capability. Selected ligands L were also shown to preferably engage the O,N,O′ coordination mode when incorporated in five‐ and four‐coordinate silicon compounds of the type LSiPhX (X = Cl, F) and LSiPh2, respectively. The coordination modes of the herein presented six‐, five‐, and four‐coordinate silicon compounds represent the first examples of X‐ray structurally confirmed O‐silylated carbamides, which hence adopt structural features of C‐siloxyimines.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
A New Titanium Alkoxide–Thiolate Complex as a Versatile Heterofunctional Metalloligand
Authors: Fandos Rosa , Otero Antonio , Rodríguez Ana , Terreros Pilar , Aullón Gabriel , Álvarez Santiago
Published: February 2009

The titanium complex [TiCp*(OSBz)(OBzSH)] (1) has been synthesized by reaction of [TiCp*(Me)3] (Cp* = η5‐C5Me5) with 2‐mercaptobenzyl alcohol (H2OSBz). The reaction of complex 1 with H2O gives the dinuclear oxo‐bridged complex [{TiCp*(OSBz)}2(μ‐O)] (2). Complex 1 reacts with [M(μ‐OH)(cod)]2 (M = Rh, Ir) to yield the early–late heterobimetallic complexes [TiCp*(OSBz)2M(cod)] {M = Rh (3); Ir (4)}. Carbon monoxide easily replaces the cod ligand in 3 and 4, which leads to the corresponding dicarbonyl derivatives [TiCp*(OSBz)2M(CO)2] {M = Rh (5); Ir (6)}. Compound 5 reacts with PPh3 to yield the monocarbonyl complex [TiCp*(OSBz)2Rh(CO)(PPh3)] (7). The molecular structures of complexes 2 and 5 have been established by single‐crystal X‐ray diffraction studies. The structure of complex 1 and its coordination mode toward a rhodium moiety have been ascertained by means of calculations based on density functional theory. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Continuous Flow Hydrogenation of Functionalized Pyridines
Authors: Irfan Muhammed , Petricci Elena , Glasnov Toma N. , Taddei Maurizio , Kappe C. Oliver
Published: February 2009

The heterogeneous hydrogenation of substituted pyridines has been accomplished by employing a continuous flow hydrogenation device that incorporates in situ hydrogen generation by electrolysis of H2O and pre‐packed catalyst cartridges. In general, the hydrogenation reactions proceeded smoothly regardless of the supported precious metal catalyst (Pd/C, Pt/C, or Rh/C). By using 30–80 bar of hydrogen pressure at 60–80 °C full conversion was typically achieved in all cases at a flow rate of 0.5 mL min–1, providing the corresponding piperidines in high yields. For disubstituted pyridines, variations in stereoselectivity were observed depending on both the metal catalyst and the temperature/pressure of the hydrogenation reaction. For ethyl nicotinate the selectivity between partial and full hydrogenation could be tuned depending on the hydrogen pressure, solvent, and the choice of supported metal catalyst. Changing the hydrogen source from H2O to D2O allowed the preparation of deuteriated derivatives. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Cyclohexane‐1,2‐diamines: Efficient Catalysts for the Enantioselective Conjugate Addition of Ketones to Nitro Olefins
Authors: Rasappan Ramesh , Reiser Oliver
Published: February 2009

Simple monosulfonated cyclohexane‐1,2‐diamines are highly enantioselective organocatalysts for the conjugate addition of ketones to nitro olefins. By focusing on aromatic ketones as the most challenging substrates, selectivities of up to 98 % ee can be achieved for the title reaction. Moreover, a three‐component process between the primary amine catalyst, the nitroalkene, and the ketone, which results in the irreversible formation of pyrrols has been recognized as a reaction pathway for catalyst deactivation.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
A model for the 3D kinematic interaction analysis of pile groups in layered soils
Authors: Dezi Francesca , Carbonari Sandro , Leoni Graziano
Published: February 2009

The paper presents a numerical model for the analysis of the soil–structure kinematic interaction of single piles and pile groups embedded in layered soil deposits during seismic actions. A finite element model is considered for the pile group and the soil is assumed to be a Winkler‐type medium. The pile–soil–pile interaction and the radiation problem are accounted for by means of elastodynamic Green's functions. Condensation of the problem permits a consistent and straightforward derivation of both the impedance functions and the foundation input motion, which are necessary to perform the inertial soil–structure interaction analyses. The model proposed allows calculating the internal forces induced by soil–pile and pile‐to‐pile interactions. Comparisons with data available in literature are made to study the convergence and validate the model. An application to a realistic pile foundation is given to demonstrate the potential of the model to catch the dynamic behaviour of the soil–foundation system and the stress resultants in each pile. Copyright © 2009 John Wiley & Sons, Ltd.
Human bone marrow‐derived mesenchymal stem cells induce Th2‐polarized immune response and promote endogenous repair in animal models of multiple sclerosis
Authors: Bai Lianhua , Lennon Donald P. , Eaton Valerie , Maier Kari , Caplan Arnold I. , Miller Stephen D. , Miller Robert H.
Published: February 2009

Cell‐based therapies are attractive approaches to promote myelin repair. Recent studies demonstrated a reduction in disease burden in mice with experimental allergic encephalomyelitis (EAE) treated with mouse mesenchymal stem cells (MSCs). Here, we demonstrated human bone marrow‐derived MSCs (BM‐hMSCs) promote functional recovery in both chronic and relapsing‐remitting models of mouse EAE, traced their migration into the injured CNS and assayed their ability to modulate disease progression and the host immune response. Injected BM‐hMSCs accumulated in the CNS, reduced the extent of damage and increased oligodendrocyte lineage cells in lesion areas. The increase in oligodendrocytes in lesions may reflect BM‐hMSC‐induced changes in neural fate determination, since neurospheres from treated animals gave rise to more oligodendrocytes and less astrocytes than nontreated neurospheres. Host immune responses were also influenced by BM‐hMSCs. Inflammatory T‐cells including interferon gamma producing Th1 cells and IL‐17 producing Th17 inflammatory cells and their associated cytokines were reduced along with concomitant increases in IL‐4 producing Th2 cells and anti‐inflammatory cytokines. Together, these data suggest that the BM‐hMSCs represent a viable option for therapeutic approaches. © 2009 Wiley‐Liss, Inc.
Microarray analyses reveal regional astrocyte heterogeneity with implications for neurofibromatosis type 1 (NF1)‐regulated glial proliferation
Authors: Yeh Tu‐Hsueh , Lee Da Yong , Gianino Scott M. , Gutmann David H.
Published: February 2009

Numerous studies have suggested that astrocytes in the central nervous system (CNS) exhibit molecular and functional heterogeneity. In this regard, astroglia from different CNS locations express distinct immune system, and neurotransmitter proteins, have varying levels of gap junction coupling and respond differently to injury. However, the relevance of these differences to human disease is unclear. As brain tumors in children arise in specific CNS locations, we hypothesized that regional astroglial cell heterogeneity might partly underlie the propensity for gliomas to arise in these areas. In this study, we performed high‐density RNA microarray profiling on astrocytes from postnatal day 1 optic nerve, cerebellum, brainstem, and neocortex. We showed that astroglia from each region are molecularly distinct, and we were able to develop gene expression patterns that distinguish astroglia, but not neural stem cells, from these different brain regions. We next used these microarray data to determine whether brain tumor suppressor genes were differentially expressed in these distinct populations of astroglia. Interestingly, neurofibromatosis type 1 (NF1) gene expression was decreased at both the RNA and protein levels in neocortical astroglia relative to astroglia from the other brain regions. To determine the functional significance of this finding, we found increased astroglial cell proliferation in optic nerve, brainstem, and cerebellum, but not neocortex, following Nf1 inactivation in vitro and in vivo. These findings provide molecular evidence for CNS astroglial cell heterogeneity, and suggest that differences in tumor suppressor gene expression might contribute to the regional localization of human brain tumors. © 2009 Wiley‐Liss, Inc.
Dual regulation of Ca2+‐dependent glutamate release from astrocytes: Vesicular glutamate transporters and cytosolic glutamate levels
Authors: Ni Yingchun , Parpura Vladimir
Published: February 2009

Vesicular glutamate transporters (VGLUTs) are responsible for vesicular glutamate storage and exocytotic glutamate release in neurons and astrocytes. Here, we selectively and efficiently overexpressed individual VGLUT proteins (VGLUT1, 2, or 3) in solitary astrocytes and studied their effects on mechanical stimulation‐induced Ca2+‐dependent glutamate release. Neither VGLUT1 nor VGLUT2 overexpression changed the amount of glutamate release, whereas overexpression of VGLUT3 significantly enhanced Ca2+‐dependent glutamate release from astrocytes. None of the VGLUT overexpression affected mechanically induced intracellular Ca2+ increase. Inhibition of glutamine synthetase activity by L‐methionine sulfoximine in astrocytes, which leads to increased cytosolic glutamate concentration, greatly increased their mechanically induced Ca2+‐dependent glutamate release, without affecting intracellular Ca2+ dynamics. Taken together, these data indicate that both VGLUT3 and the cytosolic concentration of glutamate are key limiting factors in regulating the Ca2+‐dependent release of glutamate from astrocytes. © 2009 Wiley‐Liss, Inc.
Imaging glioma cell invasion in vivo reveals mechanisms of dissemination and peritumoral angiogenesis
Authors: Winkler Frank , Kienast Yvonne , Fuhrmann Martin , Von Baumgarten Louisa , Burgold Steffen , Mitteregger Gerda , Kretzschmar Hans , Herms Jochen
Published: February 2009

Infiltration of cancer cells into normal tissue is a hallmark of malignant gliomas and compromises treatment options. A lack of appropriate models limits the study of this invasion in vivo, which makes it difficult to fully understand its anatomy and the role of dynamic interactions with structures of the normal brain. We developed a novel methodology by utilizing multiphoton laser scanning microscopy (MPLSM) to image the movement of glioma cells deep within the normal brain of live mice in real time. This allowed us to track the invasion of individual RFP‐expressing GL261 cells in relation to perfused vasculature or GFP‐labeled endothelial cells repetitively over days, up to a depth of 0.5 mm. Glioma cells moved faster and more efficiently when the abluminal site of a blood vessel was utilized for invasion. Cells that invaded perivascularly were frequently found next to (a) multiple capillary structures where microvessels run parallel to each other, (b) capillary loops or glomeruloid‐like bodies, and (c) dilated capillaries. Dynamic MPLSM for more than 48 h revealed that single invasive glioma cells induced intussusceptive microvascular growth and capillary loop formation, specifically at the microvascular site with which they had contact. As the main tumor grew by cooption of existing brain vessels, these peritumoral vascular changes may create a beneficial environment for glioma growth. In conclusion, our study revealed new mechanisms of peritumoral angiogenesis and invasion in gliomas, providing an explanation for their interdependence. © 2009 Wiley‐Liss, Inc.