bluuebunny/crossref_metadata_2025 huggingface dataset:
On the use of the T‐REx™ tetracycline‐inducible gene expression system in vivo
Authors: Dobrovolsky Vasily N. , Heflich Robert H.
Published: April 2007

Components of the commercially available T‐REx™ system were used to create two types of transgenic mice. The first contained the tetracycline‐repressor transgene under the control of the CMV promoter/enhancer; the second type contained a green fluorescent protein (GFP) reporter transgene under the control of the CMV promoter/enhancer with a tetracycline repressor operator sequence. Transgene expression was unpredictable in animals containing the individual transgenes. Animals with the reporter transgene expressed GFP in only some tissues (e.g., pancreas, kidney), and one line of reporter transgenic animals developed kidney disease, presumably due to expression of the transgene. The two types of transgenic animals were crossbred to produce double‐transgenic animals with the object of regulating the expression of the reporter in vivo. When a similar double‐transgenic system was constructed in cultured cells, the repressor protein suppressed the transcription of the reporter transgene. The presence of the repressor in double‐transgenic animals had no effect on the expression of the reporter; double transgenic animals developed the same kidney disease that was seen in singly transgenic mice with the reporter. Our results indicate that transgenes under the control of the CMV promoter in the T‐REx system express somewhat unpredictably and in only a limited number of tissues, making the use of this system for the development of in vivo models problematical. Biotechnol. Bioeng. 2007;98:719–723. © 2007 Wiley Periodicals, Inc.
Corporate social responsibility and policy making: what role does communication play?
Authors: Mathis Arno
Published: April 2007

Communication is of central importance for business and public authorities to make substantial progress on the sustainability ladder. Corporate social responsibility (CSR) is about the contribution of business to sustainability, and stakeholder theory is an integral concept of CSR. The literature regularly associates stakeholder management with good CSR schemes and practices. Proactive companies are assumed to interact at a certain level with their affected stakeholders through their business activities. It is quite common to find studies that show a direct connection between stakeholder management and business success, especially with regard to financial success. However, this study, based on an in‐depth case study on Campina, the second largest dairy company in the Netherlands, has its primary focus not on direct financial implications of stakeholder management, but on the impact proactive stakeholder management has on the interaction between companies and public authorities. The study argues that CSR pro‐active companies are better positioned in their sectors, especially when relating with public authorities, and that such companies are better able to influence the policy‐making process compared with their competitors. Copyright © 2007 John Wiley & Sons, Ltd and ERP Environment.
Feasibility and clinical impact of transcatheter closure of interatrial communications after a fenestrated Fontan procedure: Medium‐term outcomes
Authors: Pihkala Jaana , Yazaki Satoshi , Mehta Rohit , Lee Kyong‐Jin , Chaturvedi Rajiv , McCrindle Brian W. , Arsdell Glen Van , Benson Lee N.
Published: April 2007

Objective:

This study was to review an institutional experience with transcatheter closure of Fontan fenestrations and its impact on clinical care.

Background:

An interatrial fenestration improves postoperative outcomes in high‐risk children undergoing a Fontan repair. While technical feasibility has been well defined, the clinical impact of subsequent closure is not well defined.

Methods:

Transcatheter closure of a surgically created or additional interatrial communication was attempted in 152 children at a median interval of 13.8 months after surgery. The clinical records were reviewed for demographic and anatomical characteristics, previous surgeries; catheterization data, and status at latest follow‐up.

Results:

Mean oxygen saturation and right atrial pressure increased acutely from 87% ± 5% to 96% ± 3% (P < 0.001) and 12 ± 2 mm Hg to 13 ± 3 mm Hg (P < 0.001), respectively. Higher systemic venous atrial pressures after occlusion correlated with higher pulmonary artery pressures (P = 0.05) before the Fontan procedure and with higher right (P < 0.001) and left atrial (P = 0.001) and ventricular end‐diastolic pressures (P < 0.001) immediately before occlusion. Complications included device malposition in 2 children, 1 child each had an air embolism and post‐procedural bleeding, and each self‐limiting and 1 child had acute ST elevation in inferior ECG leads because of occlusion of the acute marginal branch which was treated with angioplasty and placement of a stent. At follow‐up (median 4.5 years), the mean oxygen saturation was 95% ± 3%. Residual interatrial leaks were noted echocardiographically in 9%. Two children developed protein‐losing enteropathy after fenestration closure. No deaths or strokes were observed in follow‐up.

Conclusions:

Transcatheter occlusion of Fontan fenestrations is safe with acute and persistent improvements in oxygen saturations. © 2007 Wiley‐Liss, Inc.
Access site hematoma requiring blood transfusion predicts mortality in patients undergoing percutaneous coronary intervention: Data from the National Heart, Lung, and Blood Institute Dynamic Registry
Authors: Yatskar Leonid , Selzer Faith , Feit Fredrick , Cohen Howard A. , Jacobs Alice K. , Williams David O. , Slater James
Published: April 2007

Objective:

To determine both the etiology of and outcomes associated with access site hematoma requiring transfusion (HRT) in patients undergoing percutaneous coronary intervention (PCI).

Background:

Access site hematoma in the setting of PCI is the most frequent periprocedural complication (2–12%). Antiplatelet and antithrombin therapy is designed to lower the incidence of adverse ischemic events while maintaining an acceptable rate of hemorrhagic complications.

Methods:

This was a prospective, multi‐center, cohort study of consecutive patients undergoing PCI during 3 NHLBI Dynamic Registry recruitment waves (1997–2002). The primary endpoints included the incidence of HRT, in‐hospital death, and death at 1‐year.

Results:

The incidence of HRT was 1.8% and femoral access was common. Older age, lower BMI, female sex, concomitant renal, cerebrovascular, peripheral vascular, and pulmonary disease were significantly associated with HRT. Glycoprotein IIb/IIIa inhibitors, thrombolytic therapy, and postprocedure heparin were more commonly used in HRT patients, but there was no difference in thienopiridiene use. Attempted lesions in patients developing HRT were more often calcified, thrombotic, located in an ostial location, or class B2 or C. In‐hospital mortality and 1‐year death rate was 9 and 4.5 times higher in HRT patients respectively. Following adjustment, HRT remained independently associated with in‐hospital mortality (OR 3.59, 95% CI 1.66–7.77) and 1‐year death (hazard ratio [HR] 1.65, 95% CI 1.01–2.70, P = 0.048). Independent predictors of HRT included age, female sex, IIb/IIIa inhibitors, thrombolytic agents, and concomitant conditions.

Conclusions:

Access site complications, especially HRT, remain a very important predictor of adverse procedural success and patient outcome. © 2007 Wiley‐Liss, Inc.
Closure of guide wire‐induced coronary artery perforation with a two‐component fibrin glue
Authors: Störger Hans , Ruef Johannes
Published: April 2007

Perforation or rupture of a coronary artery with subsequent pericardial effusion and cardiac tamponade is a potentially life‐threatening complication of percutaneous coronary intervention (PCI). Several emergency treatment strategies exist to close the perforation including reversal of anticoagulation, prolonged balloon inflation, implantation of stent grafts, local injection of thrombogenic molecules, placement of microcoils, or open heart surgery. Here we report on a 66‐year‐old patient who underwent urgent PCI for acute stent thrombosis in the proximal LAD. The artery was reopened, a new stent implanted successfully, and a GPIIb/IIIa‐antagonist was given. Shortly thereafter the patient suffered from cardiac tamponade requiring pericardiocentesis and pericardial drainage. The coronary angiogram indicated a severe guide wire‐induced perforation and pericardial effusion originating from a distal diagonal branch segment. Prolonged balloon inflation did not stop the leakage. Therefore the monorail balloon was exchanged for an over‐the‐wire balloon. A two‐component commercial fibrin glue consisting of fibrinogen and thrombin was rapidly but separately injected through the wire channel of the balloon into the distal segment of the diagonal branch. The coronary leak was successfully closed and the patient recovered quickly. In comparison with the previously reported cases of thrombin injection important differences should be noticed: (1) a two‐component hemostatic seal was used without reversal of anticoagulation, (2) rapid injection instead of prolonged infusion of the hemostatic drugs was performed, and (3) the rescue technique was applied in a cath lab that routinely uses monorail catheter systems. Therefore we consider this a novel and effective approach for closure of coronary ruptures. © 2007 Wiley‐Liss, Inc.
Pre‐existing left pulmonary artery stenosis and other anomalies associated with device occlusion of patent ductus arteriosus
Authors: Javois Alexander J. , Patel Dhaval , Roberson David , Husayni Tarek
Published: April 2007

A retrospective analysis was performed on 200 consecutive patients who underwent cardiac catheterization for occlusion of Patent Ductus Arteriosus (PDA) at a single center by a single operator. Four significant anomalies were observed: pre‐existing Left Pulmonary Artery (LPA) stenosis, left recurrent laryngeal nerve (LRLN) injury, electrocardiogram (EKG) changes, and aorto‐pulmonary (AP) collateral arteries. The observation of pre‐existing LPA stenosis, marked EKG changes, and permanent LRLN injury have not been previously reported. Incidence, etiology, and clinical significance of these anomalies are discussed with specific new recommendations for the prevention of LRLN injury and occlusion of AP collaterals. © 2007 Wiley‐Liss, Inc.
Coronary artery fistulas: How to manage them
Authors: Latson Larry A.
Published: April 2007

Coronary artery fistulas are rare persisting vascular connections from a coronary artery to a cardiac chamber or major central blood vessel. The true incidence is difficult to discern because at least 75% may be asymptomatic and clinically undetectable until an echocardiogram or coronary arteriogram is performed. Small coronary artery fistulas that are not clinically detectable are not clearly associated with significant long term complications. Medium or large fistulas are associated with significant long term problems including angina, arrhythmias, myocardial infarction, endocarditis, and progressive dilation. Treatment options include surgical and catheter approaches to significant fistulas. The long term outlook after fistula closure is not well defined and deserves further study. © 2007 Wiley‐Liss, Inc.
Three‐dimensional modeling of double‐stent techniques at the left main coronary artery bifurcation using micro‐focus X‐ray computed tomography
Authors: Murasato Yoshinobu , Horiuchi Masataka , Otsuji Yutaka
Published: April 2007

Background:

Various double‐stent techniques using drug‐eluting stents have been proposed to treat the left main coronary artery (LMCA) bifurcation. However, use of these techniques is frequently associated with focal restenosis at the ostium of the left circumflex coronary artery (LCX).

Objectives:

To examine the results of double‐stent techniques, using a silicon model of the LMCA bifurcation and three‐dimensional (3D) reconstruction images created with micro‐focus X‐ray computed tomography (MFCT).

Methods:

Crush, kissing, and modified T stentings were performed with bare metal stents in a LMCA bifurcation model. The stents were then inspected using MFCT at a minimal resolution of 0.06 mm.

Results:

Gaps in stent apposition to the vessel were observed at the site of stent overlap in the distal LMCA with all stenting techniques. In crush stenting, when the left anterior descending artery stent overlapped the LCX stent, the latter was crushed on the myocardial side of the vessel, and a gap was observed on the nonmyocardial side, at the LCX ostium. When the overlap was reversed, the LCX stent was crushed on the nonmyocardial side and a gap was observed on the myocardial side. In the case of kissing stents, stent overlap created a gap beneath the overlapped portion of the stents. In modified T‐stenting, correct positioning of the LCX stent was difficult and MFCT imaging revealed a nonmyocardial gap.

Conclusions:

Close apposition of the stent to the vessel at the ostium of the LCX is difficult to achieve at the LMCA bifurcation, regardless of which double‐stent technique is employed, due to the site's wide bifurcation angle and complex 3D structure. The distribution of plaque and the bifurcation angle should be considered before double‐stent deployment, to avoid leaving a gap over significant plaques. © 2007 Wiley‐Liss, Inc.
Role of radiotherapy in ductal (endometrioid) carcinoma of the prostate
Authors: Eade Thomas N. , Al‐Saleem Tahseen , Horwitz Eric M. , Buyyounouski Mark K. , Chen David Y.T. , Pollack Alan
Published: April 2007

BACKGROUND.

Ductal carcinoma of the prostate is a rare variant of prostate cancer that presents most commonly with obstructive urinary symptoms or hematuria. This case series of 6 patients is the first to report the outcome of ductal carcinoma treated with external beam radiotherapy.

METHODS.

A retrospective review was performed of patients treated between 1980 and 2006 at Fox Chase Cancer Center, Philadelphia, Penn. Six patients were identified with ductal carcinoma.

RESULTS.

Five of the 6 patients were treated definitively and the sixth patient was treated at recurrence 3 years after a radical prostatectomy. Patient ages ranged from 66–80 years and the initial prostate‐specific antigen (iPSA) ranged from 1.69–100.3 ng/mL. Three patients had a mixed acinar and ductal carcinoma, 2 with a Gleason score (GS) of 8 and 1 with a GS of 7. Of the patients treated definitively, 4 had clinical stage T2A‐T2C and 1 had clinical stage T1B. Definitive radiotherapy was delivered to the prostate with doses between 72 Gy and 78 Gy. Pelvic lymph nodes were treated in all patients. One patient was treated postradical prostatectomy to the prostate bed to a dose of 60 Gy. Adjuvant androgen deprivation was given in 5 of the patients. Two of the patients died from metastatic disease at 1.4 and 7.1 years after treatment. The remaining 4 patients remain alive between 3.2 and 4.8 years from treatment, with 3 patients biochemically without evidence of disease. No patients have developed a local recurrence.

CONCLUSIONS.

Ductal carcinoma of the prostate may be treated effectively with external beam radiotherapy. Aggressive management is indicated, even with low‐volume metastatic disease. Cancer 2007. © 2007 American Cancer Society.
Decaying modes for the wave equation in the exterior of an obstacle
Authors: Lax P. D. , Phillips R. S.
Published: April 2007

In this paper we study the dependence of the set of ‘exterior’ eigenvalues {λk} of Δ on the geometry of the obstacle 𝒪. In particular we show that the real eigenvalues, corresponding to purely decaying modes, depend monotonically on the obstacle 𝒪, both for the Dirichlet and Neumann boundary conditions. From this we deduce, by comparison with spheres—for which the eigenvalues {λk} can be determined as roots of special functions—upper and lower bounds for the density of the real {λk}, and upper and lower bounds for λ1, the rate of decay of the fundamental real decaying mode. We also consider the wave equation with a positive potential and establish an analogous monotonicity theorem for such problems. We obtain a second proof for the above Dirichlet problem in the limit as the potential becomes infinite on 𝒪.

Finally we derive an integral equation for the decaying modes; this equation bears strong resemblance to one appearing in the transport theory of mono‐energetic neutrons in homogeneous media, and can be used to demonstrate the existence of infinitely many modes.
Early change in maladaptive defence style and development of the therapeutic alliance
Authors: Ambresin Gilles , de Roten Yves , Drapeau Martin , Despland Jean‐Nicolas
Published: April 2007

This study examined the early change in maladaptive defence style (MDS), the development of the therapeutic alliance and the relationship between MDS and alliance in a short psychodynamic intervention. Sixty‐eight outpatients from a psychiatric clinic completed a four‐session psychodynamic intervention. Defence and alliance measures were collected at the intake and the final session. Patients who began the intervention with a poor alliance but ended with a good alliance (linear growth therapeutic alliance group) significantly decreased their use of maladaptive defences over the course of therapy, while patients in the high and low alliance groups did not. Results showed that at the end of the intervention, MDS and alliance were related across all patients. This relation concerned particularly the linear growth therapeutic alliance profile. These results suggest that the developing therapeutic alliance might reflect the collaborative work between the patient and the therapist as they try to understand the causes of the crisis. This understanding might help reduce maladaptive defences that were initially activated to ward off anxiety and distress. Copyright © 2007 John Wiley & Sons, Ltd.
Cyto‐histological correlations inprimary, recurrent, and metastatic bone and soft tissue osteosarcoma. Institut Curie's experience
Authors: Klijanienko Jerzy , Caillaud Jean‐Michel , Orbach Daniel , Brisse Hervé , Lagacé Réal , Sastre‐Gareau Xavier
Published: April 2007

To determine diagnostic cytomorphologic features of osteosarcoma on fine‐needle aspiration materials, we reviewed the cytologic material and corresponding histologic slides of 126 tumors in 107 patients. Fifty‐five (43.6%) tumors were primary, 31 (24.6%) were recurrent, and 40 (31.8%) were metastatic. Review of original cytology reports revealed that 120 (95.3%) tumors were diagnosed as malignant. Six (4.7%) cases were reported as suspicious, false‐negative, or unsatisfactory samples.

Our findings showed that osteoblastic roundish cells, spindle‐shaped cells, reactive giant cells, and osteoid were the most consistent features representative of osteosarcoma. Periosteal reactions, fractures with callous formation, giant cells of osteoclastic type in various conditions, chondrosarcoma with enchondral ossification are entities to consider in the differential diagnosis. Diagn. Cytopathol. 2007;35:270–275. © 2007 Wiley‐Liss, Inc.
Cytomorphological correlates of epidermal growth factor receptor mutations in lung carcinoma
Authors: Brachtel Elena F. , Iafrate A. John , Mark Eugene J. , Deshpande Vikram
Published: April 2007

The initial diagnosis of lung carcinoma is frequently made by fine‐needle aspiration biopsy. Novel therapeutic strategies of this disease include tyrosine kinase inhibitors (TKI), such as gefitinib (Iressa®) or erlotinib (Tarceva®), which target the kinase domain of epidermal growth factor receptor (EGFR). Somatic mutations of this region have been shown to predict a therapeutic response of lung carcinomas to TKI. EGFR mutations have been described in adenocarcinomas of the lung, especially the bronchioloalveolar subtype, which has both cytopathologic and histopathologic definitions. This study investigates whether tumors with EGFR mutations display a characteristic phenotype on fine‐needle aspiration biopsy. We identified 37 fine‐needle aspiration biopsy of lung masses on which molecular analysis for EGFR mutations was available. Molecular analysis was performed on DNA isolated from formalin‐fixed, paraffin‐embedded, or frozen tissue from the corresponding core biopsies/cell blocks or resection specimens followed by PCR with primers for the tyrosine kinase region exons 18–24 and nucleotide sequence analysis by gel electrophoresis. Two observers who were blinded to the mutational data assessed several cytomorphological parameters. A semiquantitative analysis included predominant tissue pattern (flat or overlapping), nuclear features (nucleoli, intranuclear inclusions, grooves), cytoplasmic qualities, and extracellular material. All cases were adenocarcinomas primary in the lung. Thirteen cases showed EGFR mutations in exons 18, 19, 20, or 21 of the tyrosine kinase domain. The 24 cases negative for the relevant mutation served as the control group. Tumors with EGFR mutations were statistically more likely to demonstrate a predominantly flat, monolayer architecture (P = 0.04) with nuclear inclusions (P = 0.014) and the absence of macronucleoli (P = 0.001). The predominance of flat monolayers in conjunction with the absence of extracellular mucin and macronucleoli indicated the presence of EGFR mutations with a positive predictive value of 69% and a negative predictive value of 92%. All four cases with extracellular mucin were negative for the examined mutations. Some of the traditional cytomorphological features of bronchioloalveolar carcinoma, i.e., flat monolayers, intranuclear inclusions, and the absence of macronucleoli, statistically correlated with the presence of mutations within the tyrosine kinase region of EGFR. Cytomorphological features could serve as an adjunctive predictive marker of response to TKIs and possibly to other new therapies in development. Diagn. Cytopathol. 2007;35:257–262. © 2007 Wiley‐Liss, Inc.
A metastatic renal carcinoid tumor presenting as breast mass: A diagnostic dilemma
Authors: Hasteh Farnaz , Pu Robert , Michael Claire W.
Published: April 2007

We present clinicopathological and cytological findings of a well‐defined breast mass in a patient with history of primary renal carcinoid tumor. Fine‐needle aspiration (FNA) cytology showed monotonous tumor cells with plasmacytoid appearance arranged singly and in small clusters. Occasional tumor cells were arranged in acinar architecture resembling glandular differentiation. Tumor cells showed fine speckled chromatin. The unusual location for metastasis of this rare type of carcinoid tumor and overlapping cytological features with primary mammary carcinoma led to an erroneous preliminary cytological diagnosis of primary breast carcinoma with plasmacytoid features. Tumor cells in the corresponding cell block showed strong diffuse positivity for synapthophysin and pan‐cytokeratin with weak focal positivity for chromogranin markers. These patterns of immunostaining were similar to the original renal carcinoid tumor. To the best of our knowledge, a few cases of carcinoid tumor metastatic to the breast have been reported in the literature and more than half of these cases were initially misdiagnosed as primary breast carcinoma causing unnecessary surgical treatment. This is a first reported case of metastatic renal carcinoid tumor into breast diagnosed with FNA biopsy. This report highlights the cytological features of well‐differentiated neuroendocrine tumor (carcinoid tumor) and its potential diagnostic pitfalls. Diagn. Cytopathol. 2007;35:306–310. © 2007 Wiley‐Liss, Inc.
Coupling cellular oscillators: A mechanism that maintains synchrony against developmental noise in the segmentation clock
Authors: Ishimatsu Kana , Horikawa Kazuki , Takeda Hiroyuki
Published: April 2007

A unique feature of vertebrate segmentation is its strict periodicity, which is governed by the segmentation clock consisting of numerous cellular oscillators. These cellular oscillators, driven by a negative‐feedback loop of Hairy transcription factor, are linked through Notch‐dependent intercellular coupling and display the synchronous expression of clock genes. Combining our transplantation experiments in zebrafish with mathematical simulations, we review how the cellular oscillators maintain synchrony and form a robust system that is resistant to the effects of developmental noise such as stochastic gene expression and active cell proliferation. The accumulated evidence indicates that the segmentation clock behaves as a “coupled oscillators,” a mechanism that also underlies the synchronous flashing seen in fireflies. Developmental Dynamics 236:1416–1421, 2007. © 2007 Wiley‐Liss, Inc.
Characteristics and key findings for ‘Early erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants’
Authors: van Dalen Elvira , Kremer Leontien
Published: April 2007

These are the characteristics and key findings for a Cochrane review, published in this issue of EBCH, first published as: Ohlsson A, Aher SM. Early erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD004863. DOI: 10.1002/14651858.CD004863.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying EBCH Summary and Commentary articles. Copyright © 2007 John Wiley & Sons, Ltd.
Tips and tricks for understanding and using SR results. No 5: Prospective Trial Registers
Authors: Hooft Lotty , Offringa Martin , Chan An‐Wen
Published: April 2007

This fifth article for ‘Tips and tricks for understanding and using SR results’ in Evidence‐Based Child Health is, like the previous ones, aimed at helping readers to interpret the results of systematic reviews and to use the results in clinical practice. This time, we focus on the development of (inter)national prospective trial registers and their relevance for systematic reviews. The information in this article is based on published papers on the topic and the experience of the authors in trial registration. Copyright © 2007 John Wiley & Sons, Ltd.
Summary of ‘Breastfeeding or breast milk for procedural pain in neonates’
Authors: Milne Andrea
Published: April 2007

This is a summary of a Cochrane review, published in this issue of EBCH, first published as: Shah PS, Aliwalas LL, Shah V. Breastfeeding or breast milk for procedural pain in neonates. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD004950. DOI: 10.1002/14651858.CD004950.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Commentary and Characteristics and Key Findings Tables articles. Copyright © 2007 John Wiley & Sons, Ltd.
Commentary on reviews of erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants
Authors: Bassler Dirk , Poets Christian F.
Published: April 2007

This is a commentary on three Cochrane reviews, published in this issue of EBCH, first published as: Ohlsson A, Aher SM. Early erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD004863. DOI: 10.1002/14651858.CD004863.pub2; Aher S, Ohlsson A. Late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD004868. DOI: 10.1002/14651858.CD004868.pub2; and Aher SM, Ohlsson A. Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD004865. DOI: 10.1002/14651858.CD004865.pub2.

Further information for these Cochrane reviews (early, late, and early vs late) is available in this issue of EBCH in the accompanying EBCH Summary (early, late, and early vs late) and Characteristics and Key Findings Tables (early, late, and early vs late) articles. Copyright © 2007 John Wiley & Sons, Ltd.
Allelic imbalances and microdeletions affecting the PTPRD gene in cutaneous squamous cell carcinomas detected using single nucleotide polymorphism microarray analysis
Authors: Purdie Karin J. , Lambert Sally R. , Teh Muy‐Teck , Chaplin Tracy , Molloy Gael , Raghavan Manoj , Kelsell David P. , Leigh Irene M. , Harwood Catherine A. , Proby Charlotte M. , Young Bryan D.
Published: April 2007

Cutaneous squamous cell carcinomas (SCC) are the second most commonly diagnosed cancers in fair‐skinned people; yet the genetic mechanisms involved in SCC tumorigenesis remain poorly understood. We have used single nucleotide polymorphism (SNP) microarray analysis to examine genome‐wide allelic imbalance in 16 primary and 2 lymph node metastatic SCC using paired non‐tumour samples to counteract normal copy number variation. The most common genetic change was loss of heterozygosity (LOH) on 9p, observed in 13 of 16 primary SCC. Other recurrent events included LOH on 3p (9 tumors), 2q, 8p, and 13 (each in 8 SCC) and allelic gain on 3q and 8q (each in 6 tumors). Copy number‐neutral LOH was observed in a proportion of samples, implying that somatic recombination had led to acquired uniparental disomy, an event not previously demonstrated in SCC. As well as recurrent patterns of gross chromosomal changes, SNP microarray analysis revealed, in 2 primary SCC, a homozygous microdeletion on 9p23 within the protein tyrosine phosphatase receptor type D (PTPRD) locus, an emerging frequent target of homozygous deletion in lung cancer and neuroblastoma. A third sample was heterozygously deleted within this locus and PTPRD expression was aberrant. Two of the 3 primary SCC with PTPRD deletion had demonstrated metastatic potential. Our data identify PTPRD as a candidate tumor suppressor gene in cutaneous SCC with a possible association with metastasis. © 2007 Wiley‐Liss, Inc.
Theoretical study of the reaction mechanism and solvent effect on the regioselectivity of 1,3‐dipolar cycloaddition reaction between azide and acetylene derivatives
Authors: Li Xi‐Bo , Song Qin‐Hua
Published: April 2007

The reaction mechanism and solvent‐dependant regioselectivity of 1,3‐dipolar cycloaddition reactions between azide and acetylene derivatives have been studied using computational methods. The two possible reaction transition states were located. Geometry and NBO analysis found that the reactions take place along a synchronous and concerted mechanism for TS1 and an asynchronous and less concerted mechanism for TS2. SCRF analysis found that TS2 is more sensitive to the polarity of solvent. In less polar solvent such as CCl4, the difference of activation barriers of the two transition states is small. However, when the reactions were conducted in water, the activation barriers for TS2 increase which leads to the observed regioselectivity. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:203–207, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20236
Synthesis and anti‐HIV activity of new chiral 1,2,4‐triazoles and 1,3,4‐thiadiazoles
Authors: Akhtar Tashfeen , Hameed Shahid , Al‐Masoudi Najim A. , Khan Khalid M.
Published: April 2007

5‐substituted 4‐(4‐chlorophenyl)‐4H‐1,2,4‐triazol‐3‐thiones 3 and 2‐substituted 5‐(4‐chlorophenylamino)‐1,3,4‐thiadiazoles 4 were prepared from the intermediate thiosemicarbazides 2 under basic and acidic conditions, respectively. The thiosemicarbazides, in turn, were prepared by the reaction of hydrazides 1 with 4‐chlorophenylisothiocyanate in MeOH. Some of the new synthesized compounds were assayed against HIV‐1 and HIV‐2 in MT‐4 cells. All the compounds were inactive except 3f, which showed an EC50 value of 23.9 μg/mL and 9.9 μg/mL against HIV‐1 and HIV‐2 with a therapeutic index of 3 and 7, respectively. It means that compound 3f was cytotoxic to MT‐4 cells at CC50 of 72.7 μg/mL in both strains. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:316–322, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20282
Synthesis of α‐fluoro‐β‐trifluoromethyl alka‐2,4‐dienes
Authors: Shen Yanchang , Wang Guoping
Published: April 2007

The palladium/copper(I) iodide cocatalyzed coupling reaction of (Z)‐α‐fluoro‐β‐trifluoromethylstannanes (1) with vinyl iodides (2) has been explored giving substituted α‐fluoro‐β‐trifluoromethyl dienes (3) in 33–95% yields. In studies we have conducted so far, a larger number of the configurations of the products remained unchanged (cases 3a, 3e–h), though in several cases (cases 3b–d) two configurations of the products were obtained. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:208–211, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20284
One‐pot synthesis of novel 2′‐deoxyuridine derivatives containing α‐aminophosphonate moieties
Authors: Shang Zhi‐Qiang , Chen Ru‐Yu , Huang You
Published: April 2007

A series of α‐aminophosphonate derivatives of 2′‐deoxyuridine (8a–k) have been prepared from 5′‐O‐tert‐butyldimethylsilyl‐3′‐amino‐2′, 3′‐dideoxyuridine in good yields. The structures of all the products were confirmed by 1H NMR, 31P NMR, 31C NMR, and IR spectroscopy, and mass spectrometry and elemental analyses. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:230–235, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20288
A convenient synthesis of thiamacrocyclic dilactams
Authors: Abbas Ashraf A. , Girgis Adel S.
Published: April 2007

A convenient synthesis of 26‐ to 28‐membered thiamacrocyclic dilactams 8 was achieved via base‐catalyzed condensation reaction of bis‐2‐cyanoacetamides 4 with dialdehyde derivatives 7. The reaction was assumed to be geometrically stereoselective, affording E, E′‐configuration as the only isolable isomer. N, N′‐[Alkanediylbis(thia‐2,1‐phenylene)]bis[2‐cyanoacetamides] 4 were obtained by the reaction of cyanoacetic acid with the corresponding diamine hydrochlorides 3. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:249–254, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20292
Fatty acid hydrazides in heterocyclic synthesis: Synthesis of 1,2‐diazepine and pyridazine derivatives
Authors: Zaki Magdi E. A. , Yousef Elham A. A. , Hassanien Abu Zeid A.
Published: April 2007

1,2‐Diazepinone derivatives 6a–d, 8a,b, and 10a–c were synthesized from the reaction of olefines carrying EWG as ethoxymethylene malononitrile, ethoxymethylene cyanoacetate, and tetracyanoethylene with 1a–f respectively. Also, 5‐alkyl‐6‐oxotetrahydropyridazine‐4,4‐dicarboxylate derivatives 12a–c were afforded via the reaction of 1d–f with diethyl ethoxymethylene malonate. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:259–264, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20294
Synthesis and interconversion of isomeric pyrrolotriazolopyrimidines
Authors: Desai Nirmal D.
Published: April 2007

4‐Hydrazino‐7H‐pyrrolo[2,3‐d]pyrimidines 4 were cyclocondensed with formic acid or triethyl orthoformate to give 7H‐pyrrolo[3,2‐e][1,2,4]triazolo[1,5‐c]pyrimidines 6 and 7H‐pyrrolo[3,2‐e][1,2,4]triazolo[4,3‐c]pyrimidines 7, respectively. The [4,3‐c] isomers 7 were rearranged into thermodynamically more stable [1,5‐c] isomers 6. The identical compounds 6 were prepared using another route by reacting 3‐amino‐4‐imino‐7H‐pyrrolo[2,3‐d]pyrimidines 3 with formic acid or triethyl orthoformate. The reaction of 2‐amino‐3‐cyanopyrroles 1 with triethyl orthoformate gave N‐ethoxymethylene‐2‐amino‐3‐cyanopyrroles 2. Further reaction with an equivalent of hydrazine hydrate provided 3‐amino‐4‐imino‐7H‐pyrrolo[2,3‐d]pyrimidines 3, whereas treatment with excess of hydrazine hydrate, 3 rearranged to 4‐hydrazino‐7H‐pyrrolo[2,3‐d]pyrimidines 4. Compounds 4 were also obtained by the treatment of N‐ethoxymethylene‐2‐amino‐3‐cyanopyrroles 2 in excess of hydrazine hydrate. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:265–273, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20295
Synthesis and antiviral screening of some novel pyridazine and triazolopyridazine nucleosides
Authors: Rashad Aymn E. , Shamroukh Ahmed H. , Ali Mohamed A. , Abdel‐Motti Faiza M.
Published: April 2007

Some novel cyclic and acyclic pyridazine and triazolopyridazine nucleoside derivatives were prepared. Some of the prepared products were selected and tested for antiviral activity against herpes simplex virus type‐1 (HSV‐1) and hepatitis‐A virus (HAV, MBB‐cell culture adapted strain). Plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with test compounds. Compound 15 showed the highest effect on the HAV than the other tested compounds. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:274–282, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20296
A theoretical study on C2HXSi silylenes (X = H, CN, NH2, and OMe)
Authors: Kassaee M. Z. , Musavi S. M. , Ghambarian M.
Published: April 2007

Relative stabilities and structural characters of 30 silylenic C2HXSi species (X = H, NH2, CN, and OMe), with singlet (s) and/or triplet (t) states, are calculated at six levels of theory: HF/6‐311++G**, MP3/6‐31G*, B1LYP/6‐311++G**, B3LYP/6‐311++G**, MP2/6‐311++G**, and MP4(SDTQ)/6‐311++G**. The four possible isomers considered for C2SiHX are (i) 3‐X‐1‐silacyclopropenylidene (1s‐X and 1t‐X), (ii) X‐vinilydensilylene (2s‐X and 2t‐X), (iii) ethynyl‐X‐silylene (3s‐X and 3t‐X), and (iv) (X‐ethynyl)silylene (4s‐X and 4t‐X). The GIAO–NICS calculations show that singlet cyclic structures, 1s‐X, are considerably more aromatic than benzene. Conversely, triplet cyclic C2HCNSi breaks down through optimization, and transforms into a novel high‐spin acyclic carbenosilylene minimum (1t‐CN). Singlet 3 and triplet 3 cross at a divalent angle (|XSiC) of 152°. This angle narrows to 137° for crossing of singlet 3s‐CN and triplet, 3t‐CN. The smallest |XSiC occurs at 132° for crossing of 3s‐H and 3t‐H. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:283–293, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20297
Cell cycle effects resulting from inhibition of hepatocyte growth factor and its receptor c-Met in regenerating rat livers by RNA interference
Authors: Paranjpe Shirish , Bowen William C. , Bell Aaron W. , Nejak-Bowen Kari , Luo Jian-Hua , Michalopoulos George K.
Published: April 2007

Hepatocyte growth factor (HGF) and its receptor c-Met are involved in liver regeneration. The role of HGF and c-Met in liver regeneration in rat following two-thirds partial hepatectomy (PHx) was investigated using RNA interference to silence HGF and c-Met in separate experiments. A mixture of 2 c-Met-specific short hairpin RNA (ShRNA) sequences, ShM1 and ShM2, and 3 HGF-specific ShRNA, ShH1, ShH3, and ShH4, were complexed with linear polyethylenimine. Rats were injected with the ShRNA/PEI complex 24 hours before and at the time of PHx. A mismatch and a scrambled ShRNA served as negative controls. ShRNA treatment resulted in suppression of c-Met and HGF mRNA and protein compared with that in controls. The regenerative response was assessed by PCNA, mitotic index, and BrdU labeling. Treatment with the ShHGF mixture resulted in moderate suppression of hepatocyte proliferation. Immunohistochemical analysis revealed severe suppression of incorporation of BrdU and complete absence of mitosis in rats treated with ShMet 24 hours after PHx compared with that in controls. Gene array analyses indicated abnormal expression patterns in many cell-cycle- and apoptosis-related genes. The active form of caspase 3 was seen to increase in ShMet-treated rats. The TUNEL assay indicated a slight increase in apoptosis in ShMet-treated rats compared with that in controls.

Conclusion:

The data indicated that

in vivo

silencing of c-Met and HGF mRNA by RNA interference in normal rats results in suppression of mRNA and protein, which had a measurable effect on proliferation kinetics associated with liver regeneration. (Hepatology 2007.)
Reduced anterior hippocampal formation volume in hyponatremic schizophrenic patients
Authors: Goldman M.B. , Torres I.J. , Keedy S. , Marlow‐O'Connor M. , Beenken B. , Pilla R.
Published: April 2007

Diminished hippocampal volume occurs in the anterior segment of some schizophrenic patients, and in the posterior segment in others. The significance of hippocampal pathology in general and these segmental differences in specific is not known. Several lines of evidence suggest anterior hippocampal pathology underlies the life‐threatening hyponatremia seen in a subgroup of patients with schizophrenia; therefore our goal was to determine if this region was preferentially diminished in hyponatremic patients. We studied seven polydipsic hyponatremic, ten polydipsic normonatremic, and nine nonpolydipsic normonatremic schizophrenic inpatients, as well as 12 healthy controls. All underwent structural scanning on a high resolution (3.0 T) magnetic resonance imaging (MRI) scanner. Hippocampal formation, amygdala, and third ventricle volumes were manually traced in each subject. The hippocampus was divided at the posterior extent of the uncus, and all structural volumes were corrected for whole brain volume and other significant recognized factors (i.e., age, gender, height, parental education). Despite being overhydrated, anterior hippocampal formation volume was diminished in those with polydipsia and hyponatremia relative to each of the other three groups. Third ventricle volume was larger in this group than in healthy controls but similar to the two patient groups. Posterior hippocampal and amygdala volumes did not differ between groups. Other potential confounds (e.g., water imbalance) either had no effect or accentuated these differences. We conclude the anterior hippocampal formation is smaller in hyponatremic schizophrenic patients, thereby linking an important and objective clinical feature of schizophrenia to a neural pathway that can be investigated in animal models. The findings strengthen the hypothesis that anterior hippocampal formation pathology disrupts functional connectivity with other limbic structures in schizophrenia. © 2007 Wiley‐Liss, Inc.
Estrous‐cycle‐dependent hippocampal levels of signaling proteins
Authors: Diao Wei‐Fei , Höger Harald , Chen Wei‐Qiang , Pollak Arnold , Lubec Gert
Published: April 2007

There is information that proteins are expressed in a hormone‐dependent manner but no systematic study on this subject has been carried out to the best of our knowledge. We therefore decided to investigate protein expression in a well‐studied brain area, the hippocampus, in female rats at various phases of the estrous cycle and in male rats. Male and female OFA Sprague‐Dawley rats were used in the studies and estrous phases were determined using vaginal smears and females were grouped according to PE, E, ME, and DE. Hippocampal tissue was taken, proteins extracted, run on two‐dimensional gel electrophoresis and proteins were identified by mass spectrometry methods (MALDI‐TOF‐TOF and nano‐LC‐ESI‐MS/MS). Individual signaling protein levels quantified by specific software were shown to depend on sex and phase of the estrous cycle. These include NG,NG‐dimethylarginine dimethylaminohydrolase for nitric oxide signaling, stathmin, SH3 domain protein 2A, SH3 domain protein 2B, S100 calcium binding protein B, calcyclin‐binding protein, Syndapin I, GTPase HRas, guanine nucleotide‐binding proteins, septin 8, G‐septin alpha, phosphtidylethanolamine‐binding protein, several protein phosphatases. Results from this study, although increasing complexity of protein knowledge, may help to design further investigations at the protein level and may assist to interpret literature on protein expression and brain protein levels. © 2007 Wiley‐Liss, Inc.
Influence of age on BDNF modulation of hippocampal synaptic transmission: Interplay with adenosine A2A receptors
Authors: Diógenes Maria J. , Assaife‐Lopes Natália , Pinto‐Duarte António , Ribeiro Joaquim A. , Sebastião Ana M.
Published: April 2007

We previously reported that adenosine, through A2A receptor activation, potentiates synaptic actions of brain‐derived neurotrophic factor (BDNF) in the hippocampus of infant (3–4 weeks) rats. Since A2A‐receptor‐mediated actions are more evident in old than in young rats and since the therapeutic potential for BDNF‐based strategies is greater in old subjects, we now evaluated synaptic actions of BDNF and the levels of TrkB receptors and of adenosine A2A receptors in the hippocampus of three groups of adult rats: young adults (10–16 weeks), old adults (36–38 weeks), and aged (70–80 weeks), as well as in one group of infant (3–4 weeks) rats. BDNF (20 ng/ml) enhances field excitatory postsynaptic potentials recorded from the hippocampus of young adults and aged rats, an action triggered by adenosine A2A receptor activation, since it was blocked by the A2A receptor antagonist, ZM 241385. In the other groups of animals BDNF (20 ng/ml) was virtually devoid of action on synaptic transmission. Western blot analysis of receptor density shows decreased amounts of TrkB receptors in old adults and aged rats, whereas A2A receptor levels assayed by ligand binding are enhanced in the hippocampus of old adults and aged rats. It is concluded that age‐related changes in the density of TrkB receptors and of adenosine A2A receptors may be responsible for a nonmonotonous variation of BDNF actions on synaptic transmission in the hippocampus. © 2007 Wiley‐Liss, Inc.
Improved short‐term engraftment of lentivirally versus gammaretrovirally transduced allogeneic canine repopulating cells
Authors: Neff Tobias , Gerull Sabine , Peterson Laura J. , Kiem Hans‐Peter
Published: April 2007

Gammaretroviral vectors require cell division for efficient transduction. Thus, extended cell culture times are necessary for efficient transduction with gammaretroviral vectors, which in turn can lead to stem cell loss and impaired engraftment. Lentiviral vectors transduce nondividing cells and are therefore able to transduce stem cells in short transduction protocols. Here, we compared the short‐term engraftment of lentivirally and gammaretrovirally transduced canine allogeneic DLA‐matched littermate cells. A reduced conditioning regimen of 400 cGy total body irradiation was used in preparation for clinical studies. Two dogs received a graft of gammaretrovirally transduced CD34‐selected cells. CD34+ cells were prestimulated for 30 h and then exposed twice to concentrated RD114 pseudotype vector. Three dogs received lentivirally transduced CD34‐selected cells. Cells were transduced overnight with concentrated VSV‐G pseudotype lentiviral vector. The animals in the lentiviral group showed a significantly faster granulocyte recovery. VNTR analysis 40–50 days after transplantation revealed higher donor chimerism for the lentiviral group compared to the retroviral group. These data suggest that short lentiviral transduction protocols may be superior to extended gammaretroviral transduction protocols with respect to engraftment potential of transduced CD34+ hematopoietic repopulating cells. Copyright © 2007 John Wiley & Sons, Ltd.