bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of plaque calcium on neointimal hyperplasia following bare metal and drug‐eluting stent implantation
Authors: Shimada Yoshihisa , Kataoka Toru , Courtney Brian K. , Morino Yoshihiro , Bonneau Heidi N. , Yock Paul G. , Grube Eberhard , Honda Yasuhiro , Fitzgerald Peter J.
Published: May 2006

Objectives:

To examine the influence of vessel wall calcium on neointimal hyperplasia (NIH) following bare metal stent (BMS) and drug‐eluting stent (DES) implantation.

Background:

While procedural complications with coronary stenting in calcified lesions are well reported, little is known about subsequent NIH on plaque calcium following either BMS or DES implantation.

Methods:

In the Study to COmpare REstenosis Rate between QueST and QuaDDS‐QP2 (SCORE) trial, 6 months follow‐up volumetric intravascular ultrasound data were available for 41 lesions (BMS, 19; DES, 22). NIH thicknesses on superficial, deep, and noncalcified plaque were calculated at every 0.5 mm intervals over the stented segment. Calcified and less‐calcified cross‐sections were defined as those containing arcs of plaque calcium ≥90° and <90°, respectively.

Results:

In BMS, mean NIH thickness on both superficial (0.24 ± 0.23 mm) and deep calcium (0.25 ± 0.21 mm) was significantly smaller than that of noncalcified plaque (0.31 ± 0.22 mm) (P < 0.0005). NIH area was significantly smaller in calcified cross‐sections compared to less‐calcified cross‐sections (2.1 ± 1.2 mm2 vs. 3.1 ± 1.9 mm2, P < 0.0001). While in contrast, in DES, mean NIH thickness was similar, irrespective of the presence or location of calcium (0.03 ± 0.05 mm vs. 0.03 ± 0.06 mm vs. 0.03 ± 0.05 mm, superficial vs. deep vs. noncalcified plaque, P = NS). NIH area was also similar between calcified and less‐calcified cross‐sections (0.3 ± 0.6 mm2 vs. 0.3 ± 0.6 mm2, P = NS).

Conclusions:

These results suggest that while plaque calcium may influence NIH following BMS implantation, NIH suppression using DES does not appear to be affected by the presence or location of calcium. © 2006 Wiley‐Liss., Inc.
Successful percutaneous closure of paraprosthetic aorto‐right ventricular leak using the Amplatzer duct occluder
Authors: Dussaillant Gastón R. , Romero Leopoldo , Ramírez Alfredo , Sepúlveda Luis
Published: May 2006

A 55‐year‐old male with persisting aorto‐right ventricular paraprosthetic leak after mitroaortic valve replacement was hospitalized for recurrent heart failure. Depressed left ventricular ejection fraction and severe pulmonary hypertension with increased right and left ventricular filling pressures were associated with significant left to right shunting through the leak. Elective closure of the leak was obtained with a 6–4 mm Amplatzer duct occluder. No complications were observed, and the patient experienced complete resolution of heart failure symptoms, with NYHA class I heart failure 12 months after discharge. © 2006 Wiley‐Liss, Inc.
Successful thrombus extraction with the Rescue™ thrombus management system during acute percutaneous coronary intervention improves flow but does not necessarily restore optimal myocardial tissue perfusion
Authors: Vijayalakshmi Kunadian , Kunadian Babu , Wright Robert A. , Sutton Andrew G.C. , Hall James A. , de Belder Mark A.
Published: May 2006

We determined the effectiveness of the Rescue™ device in restoring flow and achieving optimal tissue perfusion during percutaneous coronary intervention (PCI) in thrombus‐laden coronary arteries. Methods: A total of 30 patients with an acute coronary syndrome underwent PCI using the Rescue device. Results: The mean age was 65.5 ± 9.8 years. Although the Rescue device could not be passed across the lesion in 6 (20%) cases, debris was aspirated in 26 (87%). The uncorrected TIMI frame count improved following the use of the Rescue device and improved further at the completion of PCI (92.2 ± 23.9 pre‐PCI vs. 38.7 ± 31.3 post‐Rescue vs. 21.96 ± 24 post‐PCI, P < 0.0001). The thrombus score improved from 4 ± 0 to 2.2 ± 1.29 to 0.86 ± 1.4 (P < 0.0001). TIMI flow grade (TFG) 3 was restored in 60% of cases following the Rescue device and in 87% after PCI. Myocardial blush grade 3 occurred in only 13% of patients following the Rescue device and 37% of patients after PCI. Conclusion: These data suggest that the Rescue device can aspirate considerable amounts of debris in the majority of patients and significantly improves the angiographic epicardial coronary blood flow. How effective such a device is in improving tissue perfusion and, thereby, clinical outcomes for patients remains to be seen. © 2006 Wiley‐Liss Inc.
Failure of transradial approach during coronary interventions: Anatomic considerations
Authors: Valsecchi Orazio , Vassileva Angelina , Musumeci Giuseppe , Rossini Roberta , Tespili Maurizio , Guagliumi Giulio , Mihalcsik Laurian , Gavazzi Antonello , Ferrazzi Paolo
Published: May 2006

The anatomy of the radial artery has yet to be systematically studied from the perspective of using it as a route for catheter access. We prospectively performed angiography of the arteries of the upper limb to delineate the anatomic features of the radial artery as a way to determine the feasibility of using it as a route for coronary intervention. We studied 2,211 consecutive patients submitted to transradial cardiac catheterization. In all patients, an angiography of the upper limb arteries was performed before and after procedure. Radial puncture was successful in 98.9% of patients. At angiography, anatomic variations of upper limb arteries were noted in 505 patients (22.8%) and included tortuous configurations (3.8%), stenosis (1.7%), hypoplasias (7.7%), radioulnar loop (0.8%), abnormal origin of the radial artery (8.3%), and lusoria subclavian artery (0.45%). Overall procedural success by transradial approach was 97.5%. Patients with anatomic variations of radial artery had a significantly lower puncture (96.2% vs 99.7%, P < 0.0001) and procedural (93.1% vs 98.8%, P < 0.0001) success. The procedure was successfully performed by radial approach in 98.8% of patients with tortuous configurations, 91.9% of radial stenosis, 93.9% of hypoplastic radial artery, 83.3% of radioulnar loop, 96.7% of radial axillary origin, and 60% of lusoria subclavian artery setting. Anatomic variations of the radial artery are not rare. However, they do not represent an important limitation in transradial approach if they are well documented previously. © 2006 Wiley‐Liss., Inc.
Development of a novel catheter preventing the outflow of debris and thrombus on percutaneous transluminal angioplasty for hemodialysis access fistulas
Authors: Horita Yuki , Namura Masanobu , Matsumura Masami
Published: May 2006

If a large amount of debris or thrombus dislodges from a lesion because of dilation of the stenotic or occluded lesion in the hemodialysis access fistula when angioplasty is performed, it may move into the pulmonary artery via the central vein, resulting in pulmonary embolism. A novel sheath has been developed to prevent the outflow of debris or thrombus to the central vein. The catheter consists of a 5 F sheath introducer and a silicone balloon attached at the tip of the sheath. The silicon balloon is inflated via small inflation lumen on the shaft wall of the sheath. In the case of percutaneous transluminal angioplasty (PTA), the silicone balloon is inflated to block the blood flow by a mixture of contrast medium and physiological saline, and then dilate a stenotic or occluded lesion by PTA balloon. Next, the debris and thrombus are aspirated using the flush‐lumen of this device. Finally, the silicone balloon is deflated and the dilation of the lesion is confirmed. A case of hemodialysis access fistula graft with massive thrombotic occlusion was presented. This device enabled Fogarty procedure using PTA balloon and the blood flow of the graft was completely improved and a large amount of thrombus was removed. This novel device is useful to prevent the embolic complication of the intervention for hemodialysis access fistula. © 2006 Wiley‐Liss, Inc.
Bifurcation stenting with drug eluting stents: Illustration of the crush technique
Authors: Sianos Georgios , Vaina Sofia , Hoye Angela , Serruys Patrick W.
Published: May 2006

A number of percutaneous stenting techniques have been proposed for optimal treatment of bifurcation lesions. However, to date the most favorable interventional approach still remains controversial, since bifurcation lesions are associated with high procedural complication and restenosis rates. In the era of drug‐eluting stents, crush stenting technique simplified the procedure, concurrently allowing full lesion coverage. The purpose of the present report is to review three cases treated with crush stenting and to describe in detail the technique and its variations. © 2006 Wiley‐Liss., Inc.
Perforation complicating carotid artery stenting: The use of a covered stent
Authors: Dieter Robert S. , Ikram Sohail , Satler Lowell F. , Babrowicz Joseph C. , Reddy Bhagat , Laird John R.
Published: May 2006

Carotid artery angioplasty and stenting has emerged as an effective strategy for the treatment of significant carotid artery stenosis. Perforation during carotid artery stenting is a very rare potential complication of the procedure. We describe a case of carotid artery perforation that occurred during postdilation of the carotid artery stent. In our case this potentially serious complication was successfully treated with a covered stent‐graft. © 2006 Wiley‐Liss, Inc.
Successful utilization of a novel aspiration thrombectomy catheter (Pronto) for the treatment of patients with stent thrombosis
Authors: Siddiqui Danish S. , Choi C. Joon , Tsimikas Sotirios , Mahmud Ehtisham
Published: May 2006

Stent thrombosis is a rare but catastrophic complication of percutaneous coronary intervention (PCI). Thrombolytic therapy is ineffective for the treatment of patients with stent thrombosis, while primary PCI in such patients is limited by a high thrombus burden in the culprit vessel often leading to distal embolization and extensive tissue infarction. We present three patients with stent thrombosis successfully treated with the adjunctive use of a novel and new aspiration thrombectomy device (Pronto). © 2006 Wiley‐Liss., Inc.
Extreme coronary guide catheter support: Report of two cases of a novel telescopic guide catheter system
Authors: Stys Adam T. , Lawson William , Brown David
Published: May 2006

Extra support of the guiding catheter is required in selected cases of percutaneous coronary intervention (PCI). We describe two successful cases of PCI of very calcified and tortuous right coronary arteries in which a novel telescopic guide system was devised. The system utilizes a long sheath that “armors” the guide catheter. The operator can adjust the support of the guiding system from soft up to extremely stiff. © 2006 Wiley‐Liss, Inc.
Use of a branch wire to anchor stents for exact placement proximal to bifurcation stents: The reverse Szabo technique
Authors: Lo Henry , Kern Morton J.
Published: May 2006

This report describes a technique for correct positioning of a stent proximal to a bifurcation lesion treated with V‐stents. A second wire passed through the first cell of a stent, the opposite end of the anchor wire technique as first described by Szabo et al, facilitated precise stent placement and eliminated erroneous positioning inside or outside the treated bifurcation lesion. © 2006 Wiley‐Liss, Inc.
Transgenic mice expressing tamoxifen‐inducible Cre for somatic gene modification in renal epithelial cells
Authors: Lantinga‐van Leeuwen Irma S. , Leonhard Wouter N. , van de Wal Annemieke , Breuning Martijn H. , Verbeek Sjef , de Heer Emile , Peters Dorien J.M.
Published: May 2006

Gene inactivation often leads to an embryonic‐lethal phenotype. In focal diseases like renal cell carcinomas and polycystic kidney disease, somatic gene inactivation in subsets of cells is likely to occur at later stages. We generated a transgenic mouse line with an inducible form of Cre recombinase for conditional gene modifications in kidney epithelial cells. To this end a 1.4‐kb promoter fragment of the kidney‐specific cadherin gene (KspCad) was cloned upstream of a tamoxifen‐inducible Cre recombinase (CreERT2) encoding sequence. Expression and activity of Cre was evaluated using reverse transcriptase polymerase chain reaction (RT‐PCR) analysis and by crossbreeding to Z/EG reporter mice. One KspCad‐CreERT2 line showed kidney‐specific Cre expression and mediated recombination upon tamoxifen treatment in Z/EG reporter mice. No reporter gene expression was detected in untreated animals or in extrarenal tissues upon treatment. Within the kidneys, enhanced green fluorescent protein (EGFP) fluorescence was observed in epithelial cells in several nephronic segments. In addition, the system successfully recombined a floxed Pkd1 gene. genesis 44:225–232, 2006. © 2006 Wiley‐Liss, Inc.
Temporal regulation of Cre recombinase activity in neural stem cells
Authors: Imayoshi Itaru , Ohtsuka Toshiyuki , Metzger Daniel , Chambon Pierre , Kageyama Ryoichiro
Published: May 2006

Neural stem cells are known to give rise to distinct subtypes of neurons and glial cells over time by changing their competency. However, precise characterization of neural stem cells at various developmental stages remains to be performed. For such analysis, a tool to manipulate neural stem cells at different time points is necessary. Here, we generated transgenic mice that express Cre‐ERT2 in the ventricular zone of the developing nervous system under the control of the nestin promoter and enhancer (Nes‐CreERT2). In mice expressing Cre‐ERT2 at appropriate levels, Cre recombinase activity was mostly inactive but efficiently activated by tamoxifen within 1 day. When such mice were crossed with the ROSA‐26 or Z/EG reporter mice, neural stem cells were permanently labeled after administration of tamoxifen. Thus, Nes‐CreERT2 mice offer a powerful tool to manipulate neural stem cells genetically at desired time points. genesis 44:233–238, 2006. © 2006 Wiley‐Liss, Inc.
Inducible gene deletion in astroglia and radial glia—A valuable tool for functional and lineage analysis
Authors: Mori Tetsuji , Tanaka Kohichi , Buffo Annalisa , Wurst Wolfgang , Kühn Ralf , Götz Magdalena
Published: May 2006

Astrocytes are thought to play a variety of key roles in the adult brain, such as their participation in synaptic transmission, in wound healing upon brain injury, and adult neurogenesis. However, to elucidate these functions in vivo has been difficult because of the lack of astrocyte‐specific gene targeting. Here we show that the inducible form of Cre (CreERT2) expressed in the locus of the astrocyte‐specific glutamate transporter (GLAST) allows precisely timed gene deletion in adult astrocytes as well as radial glial cells at earlier developmental stages. Moreover, postnatal and adult neurogenesis can be targeted at different stages with high efficiency as it originates from astroglial cells. Taken together, this mouse line will allow dissecting the molecular pathways regulating the diverse functions of astrocytes as precursors, support cells, repair cells, and cells involved in neuronal information processing. © 2006 Wiley‐Liss, Inc.
Synergetic effects of quetiapine and venlafaxine in preventing the chronic restraint stress‐induced decrease in cell proliferation and BDNF expression in rat hippocampus
Authors: Xu Haiyun , Chen Zhong , He Jue , Haimanot Samson , Li Xiaokun , Dyck Lillian , Li Xin‐Min
Published: May 2006

Clinical studies show better response rates of patients with depression and schizophrenia to combinations of atypical antipsychotics and antidepressants, compared to responses to either type of drugs alone. Animal studies demonstrate that some antipsychotics and antidepressants increase neurogenesis and BDNF expression in the hippocampus, which is reduced in volume in patients with depression or schizophrenia. We hypothesized that the better therapeutic effects of combined treatment seen in schizophrenia and depression patients are related to the additive or synergistic effects of combined treatment on hippocampal neurogenesis and BDNF expression. To test this hypothesis, we investigated the effects of chronic administration of quetiapine, venlafaxine, and their combination, on hippocampal cell proliferation and BDNF expression in rats, when subjected to chronic restraint stress (CRS) during the last 2 weeks of a 3‐week drug administration period. We found (1) CRS decreased hippocampal cell proliferation and BDNF expression; (2) chronic administration of quetiapine or venlafaxine dose‐dependently prevented these decreases in hippocampal cell proliferation and BDNF expression caused by CRS (6 h/day for 14days); (3) the combination of lower doses of quetiapine (5mg/kg) and venlafaxine (2.5mg/kg) increased hippocampal cell proliferation and prevented BDNF decrease in stressed rats, whereas each of the drugs exerted mild or no effects; (4) individual higher doses of quetiapine (10mg/kg) or venlafaxine (5mg/kg) exerted effects comparable to those produced by their combination. These results support our hypothesis and can lead to future studies to develop new therapeutic approaches for treatment‐resistant depression and the negative symptoms of schizophrenia. © 2006 Wiley‐Liss, Inc.
Minced cartilage without cell culture serves as an effective intraoperative cell source for cartilage repair
Authors: Lu Yiling , Dhanaraj Sridevi , Wang Ziwei , Bradley Dino M. , Bowman Steven M. , Cole Brian J. , Binette Francois
Published: May 2006

Traumatic articular cartilage injuries heal poorly and may predispose patients to the early onset of osteoarthritis. One current treatment relies on surgical delivery of autologous chondrocytes that are prepared, prior to implantation, through ex vivo cell expansion of cartilage biopsy cells. The requirement for cell expansion, however, is both complex and expensive and has proven to be a major hurdle in achieving a widespread adoption of the treatment. This study presents evidence that autologous chondrocyte implantation can be delivered without requiring ex vivo cell expansion. The proposed improvement relies on mechanical fragmentation of cartilage tissue sufficient to mobilize embedded chondrocytes via increased tissue surface area. Our outgrowth study, which was used to demonstrate chondrocyte migration and growth, indicated that fragmented cartilage tissue is a rich source for chondrocyte redistribution. The chondrocytes outgrown into 3‐D scaffolds also formed cartilage‐like tissue when implanted in SCID mice. Direct treatment of full‐thickness chondral defects in goats using cartilage fragments on a resorbable scaffold produced hyaline‐like repair tissue at 6 months. Thus, delivery of chondrocytes in the form of cartilage tissue fragments in conjunction with appropriate polymeric scaffolds provides a novel intraoperative approach for cell‐based cartilage repair. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
MRI analysis of in vivo meniscal and tibiofemoral kinematics in ACL‐deficient and normal knees
Authors: Shefelbine Sandra J. , Ma C. Benjamin , Lee Keh‐Yang , Schrumpf Mark A. , Patel Priyesh , Safran Marc R. , Slavinsky John P. , Majumdar Sharmila
Published: May 2006

The objectives of this study were to analyze simultaneously meniscal and tibiofemoral kinematics in healthy volunteers and anterior cruciate ligament (ACL)‐deficient patients under axial load‐bearing conditions using magnetic resonance imaging (MRI). Ten healthy volunteers and eight ACL‐deficient patients were examined with a high‐field, closed MRI system. For each group, both knees were imaged at full extension and partial flexion (∼45°) with a 125N compressive load applied to the foot. Anteroposterior and medial/lateral femoral and meniscal translations were analyzed following three‐dimensional, landmark‐matching registration. Interobserver and intraobserver reproducibilities were less than 0.8 mm for femoral translation for image processing and data analysis. The position of the femur relative to the tibia in the ACL‐deficient knee was 2.6 mm posterior to that of the contralateral, normal knee at extension. During flexion from 0° to 45°, the femur in ACL‐deficient knees translated 4.3 mm anteriorly, whereas no significant translation occurred in uninjured knees. The contact area centroid on the tibia in ACL‐deficient knees at extension was posterior to that of uninjured knees. Consequently, significantly less posterior translation of the contact centroid occurred in the medial tibial condyle in ACL‐deficient knees during flexion. Meniscal translation, however, was nearly the same in both groups. Axial load‐bearing MRI is a noninvasive and reproducible method for evaluating tibiofemoral and meniscal kinematics. The results demonstrated that ACL deficiency led to significant changes in bone kinematics, but negligible changes in the movement of the menisci. These results help explain the increased risk of meniscal tears and osteoarthritis in chronic ACL deficient knees. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Soluble nickel inhibits HIF‐prolyl‐hydroxylases creating persistent hypoxic signaling in A549 cells
Authors: Davidson Todd L. , Chen Haobin , Di Toro Dominic M. , D'Angelo Gisela , Costa Max
Published: May 2006

Soluble nickel compounds are carcinogenic to humans although the mechanism by which they cause cancer remains unclear. One major consequence of exposure to nickel is the stabilization of hypoxia inducible factor‐1α (HIF‐1α), a protein known to be overexpressed in a variety of cancers. In this study, we report a persistent stabilization of HIF‐1α by nickel chloride up to 72 h after the removal of nickel from the culture media. In addition, we show that the HIF‐prolyl hydroxylases (PHD's) are inhibited when cells are exposed to nickel and that they remain repressed for up to 72 h after nickel is removed. We then show that nickel can inhibit purified HIF‐PHD's 2 in vitro, through direct interference with the enzyme. Through theoretical calculations, we also demonstrate that nickel may be able to replace the iron in the active site of this enzyme, providing a plausible mechanism for the persistent inhibition of HIF‐PHD's by nickel. The data presented suggest that nickel can interfere with HIF‐PHD directly and does not inhibit the enzyme by simply depleting cellular factors, such as iron or ascorbic acid. Understanding the mechanisms by which nickel can inhibit HIF‐PHD's and stabilize HIF‐1α may be important in the treatment of cancer and ischemic diseases. © 2006 Wiley‐Liss, Inc.
Persistent infection of hepatitis B virus is involved in high rate of p16 methylation in hepatocellular carcinoma
Authors: Jicai Zhang , Zongtao Yu , Jun Lu , Haiping Li , Jianmin Wu , Lihua Hu
Published: May 2006

High rate of chronic hepatitis B virus (HBV) infection and p16 promoter methylation were found in the majority of hepatocellular carcinoma (HCC). To investigate the potential linkage between high rate of p16 methylation and HBV infection, p16 methylation was detected with methylation‐specific polymerase chain reaction (PCR), and HBV markers were examined with real‐time PCR and immunologic method. p16 methylation was detected in 5.5% of patients with hepatitis B, 9.1% of noncancerous liver, 36.6% of cirrhotic liver tissue, and 70.5% of cancerous tissue of HCC, primarily in cirrhotic (46.7%) and cancerous tissue (90.6%) with HBV infection. In noncancerous tissue, p16 methylation could only be detected in samples with HBV infection, although no significant difference, the frequency of p16 methylation in noncancerous tissue with HBV infection was higher than those without it. The results showed that, in cancerous, cirrhotic, or noncancerous tissues, the frequency of p16 methylation in samples with HBV infection was higher than those without it, suggesting possible association between HBV infection and p16 methylation. The result of HBV‐DNA analysis showed that 96.1% (49/51) samples with p16 methylation also showed detectable HBV‐DNA; it signifies that replication and/or integration of HBV may contribute to high rate of p16 methylation in hepatocarcinogenesis. Generally, these results indicate that persistent HBV infection may be associated with high rate of p16 methylation, and involved in development of HCC through this way. © 2006 Wiley‐Liss, Inc.
Cross reactivity between many anti‐human antibodies for their hamster homologs provide the tools to study the signal transduction pathway activated by asbestos and SV40 in the malignant mesothelioma model
Authors: Kroczynska Barbara , Carbone Michele
Published: May 2006

The aim of this study was to test the possibility of using human antibodies to study the pathogenic mechanism of SV40 and asbestos in a hamster mesothelioma model. The cellular lysates from human and hamster primary mesothelial cells were tested by Western blot analysis. All of the antibodies we tested (HGF, Notch, VEGF, Sp1, p53, PP2A, p‐ERK1, p‐c‐jun, Fra1, Fra2, MMP1, MMP9, NFκB p65, IκB, GAPDH) cross‐reacted with their hamster counterparts. These data indicate that hamster mesothelioma model and more in general hamster experimental model, can be used for functional studies because many mouse, rabbit, and goat monoclonal antibodies prepared against human antigens cross‐react with their hamster counterparts. © 2006 Wiley‐Liss, Inc.
Thimerosal induces apoptosis and G2/M phase arrest in human leukemia cells
Authors: Woo Kyung Jin , Lee Tae‐Jin , Bae Jae Hoon , Jang Byeong‐Churl , Song Dae‐Kyu , Cho Jae‐We , Suh Seong‐Il , Park Jong‐Wook , Kwon Taeg Kyu
Published: May 2006

Thimerosal is an organomercury compound with sulfhydryl‐reactive properties. The ability of thimerosal to act as a sulfhydryl group is related to the presence of mercury. Due to its antibacterial effect, thimerosal is widely used as preservatives and has been reported to cause chemically mediated side effects. In the present study, we showed that the molecular mechanism of thimerosal induced apoptosis in U937 cells. Thimerosal was shown to be responsible for the inhibition of U937 cells growth by inducing apoptosis. Treatment with 2.5–5 µM thimerosal but not thiosalicylic acid (structural analog of thimerosal devoid of mercury) for 12 h produced apoptosis, G2/M phase arrest, and DNA fragmentation in a dose‐dependent manner. Treatment with caspase inhibitor significantly reduced thimerosal‐induced caspase 3 activation. In addition, thimerosal‐induced apoptosis was attenuated by antioxidant Mn (III) meso‐tetrakis (4‐benzoic acid) porphyrin (Mn‐TBAP). These data indicate that the cytotoxic effect of thimerosal on U937 cells is attributable to the induced apoptosis and that thimerosal‐induced apoptosis is mediated by reactive oxygen species generation and caspase‐3 activation. © 2006 Wiley‐Liss, Inc.
Molecular targets for the cancer preventive activity of tea polyphenols
Authors: Yang Chung S. , Lambert Joshua D. , Hou Zhe , Ju Jihyeung , Lu Gang , Hao Xinpei
Published: May 2006

Inhibition of carcinogenesis by tea and tea polyphenols has been demonstrated in many animal models. The mechanisms of action have been extensively investigated mostly in cell culture systems with (‐)‐epigallocatechin‐3‐gallate (EGCG), the most active and major polyphenolic compound from green tea. However, the mechanisms of cancer preventive activity by tea and tea polyphenols are not clearly understood. This article discusses some of the reported mechanisms and possible targets for the action of EGCG. The difficulties and major issues in extrapolating data from studies in cancer cell lines to cancer prevention mechanisms are discussed. Activities observed in cell culture with high concentrations of EGCG may not be relevant because of the limited systemic bioavailability of EGCG. In addition, possible artifacts due to the auto‐oxidation of EGCG may complicate this issue. Some recent studies revealed high‐affinity EGCG binding proteins as possible direct targets for the action of EGCG. Validating the related cancer preventive mechanisms found in in vitro studies in animal models and human samples would be exciting. © 2006 Wiley‐Liss, Inc.
p53 and its downstream proteins as molecular targets of cancer
Authors: Sun Yi
Published: May 2006

The p53 tumor suppressor gene plays a key role in prevention of tumor formation through transcriptional dependent and independent mechanisms. Transcriptional‐dependent mechanisms are mainly mediated by p53 regulation of downstream targets, leading to growth arrest and apoptosis. Mutational inactivation of the p53 gene is detected in more than 50% of human cancers. Mutation of p53 renders cancer cells more resistant to current cancer therapies due to lack of p53‐mediated apoptosis. Extensive studies have been conducted to identify small molecules that manipulate p53, including restoration of mutant p53 conformation to wild‐type, disruption of murine double minute‐2 (Mdm2)‐p53 binding to increase p53 level and inhibition of Mdm2 E3 ubiquitin ligase activity to prevent p53 degradation. Another approach was to identify and validate “drugable” target(s) in p53 signaling pathways that modulate p53‐induced apoptosis. We profiled a p53 temperature‐sensitive lung cancer cell model with the Affymetrix human HG‐U133 GeneChip, covering the entire human transcriptome. We identified thousands of unique genes that were either induced or repressed in response to p53‐induced apoptosis. A follow‐up study characterized a p53‐repressed gene, SAK, a polo‐like kinase (PLK) family member, as an appealing cancer drug target. Snk/Plk‐akin kinase (SAK) silencing via small interfering RNA (siRNA) induced apoptosis, whereas SAK overexpression attenuated p53‐induced apoptosis. Thus, SAK repression by p53 contributes to p53‐induced apoptosis. Future work is directed at determining the normal cell response to SAK silencing. If a therapeutic window is obtained, a SAK inhibitor identified from high throughput screening (HTS) could serve as a lead compound for development of a novel class of apoptosis‐inducing anticancer drugs. © 2006 Wiley‐Liss, Inc.
Congenital dysgranulopoietic neutropenia
Authors: Olcay Lale , Yetgin Sevgi , Erdemli Esra , Germeshausen Manuela , Aktaş Dilek , Büyükaşık Yahya , Okur Hamza
Published: May 2006

We investigated a 15‐year‐old female with congenital dysgranulopoietic neutropenia (CDN) and her non‐neutropenic mother who had recurrent stomatitis. In both patients, cells of the neutrophilic, eosinophilic, monocytic, megakaryocytic, and basophilic series were dysmorphic. Plasmacytoid lymphocytes and mild megaloblastic erythroid precursors were present. Bleeding times of both patients were prolonged. The mother had a secondary aggregation defect; the number of the plasmacytoid lymphocytes, dense granules of platelets, and dysmorphic neutrophils, neutrophil chemotaxis, and myeloperoxidase content fluctuated according to the presence or not of aphthae. The daughter's karyotype revealed 46,XX/46,XX, t(1;8). No ELA2 or G‐CSFR mutation was detected. These findings support stem cell involvement in CDN. Pediatr Blood Cancer 2008;50:115–119. © 2006 Wiley‐Liss, Inc.
Hypertension and prehypertension in long‐term survivors of childhood and adolescent cancer
Authors: Haddy Theresa B. , Mosher Revonda B. , Reaman Gregory H.
Published: May 2006

Background

Hypertension as a late effect following childhood and adolescent cancer has received little attention. Since obesity, a known risk factor for hypertension, is increased following some childhood cancers, it seems likely that significant numbers of survivors would have hypertension.

Procedures

The records of patients seen in the Long Term Follow Up Clinic of Children's National Medical Center were examined for a single institution, retrospective study of blood pressure in survivors of childhood and adolescent cancer. Of 103 consecutive survivors who attended the clinic from January 1 through June 30, 2004, 51 (49.5%) were female and 52 (50.5%) were male. Their mean age was 14.6 years. Systolic and diastolic blood pressures for children and adolescents under 18 years of age were evaluated for hypertension and prehypertensive according to standards for age, sex, and height. Blood pressures for adults 18 years of age and older were evaluated according to standard adult values. Children and adolescents were evaluated for obesity and overweight according to body mass index (BMI) standards for age and sex. Adults were evaluated according to standard adult values.

Results

Twenty‐nine patients (28.2%) were hypertensive or prehypertensive, and 74 (71.8%) were normal. Thirty‐eight patients (36.9%) were obese or overweight, and 65 (63.1%) were non‐obese. Most Wilms tumor patients, 7 of 10 (70.0%), had hypertension or prehypertension, but only 4 of 10 (40.0%) were obese or overweight.

Conclusion

Careful follow‐up of their blood pressure status is warranted for long‐term survivors of childhood and adolescent cancer, especially for those with an initial diagnosis of Wilms tumor. Pediatr Blood Cancer 2007;49:79–83. © 2006 Wiley‐Liss, Inc.
Maxillary ameloblastic carcinoma in a child
Authors: Yazıcı Nalan , Karagöz Begül , Varan Ali , Yılmaz Taner , Öztürk Arzu , Usubütün Alp , Büyükpamukçu Münevver
Published: May 2006

We report an extremely rare occurrence of ameloblastic carcinoma located in the maxilla of a pediatric patient. Wide surgical resection was done along with adjuvant radiotherapy because of involved surgical margins. Histopathological diagnosis was established with morphological features of both ameloblastoma and carcinoma. Pediatr Blood Cancer 2008;50:175–176. © 2006 Wiley‐Liss, Inc.
Response to rituximab in a child with neuroblastoma and opsoclonus‐myoclonus
Authors: Bell Jessica , Moran Cassandra , Blatt Julie
Published: May 2006

Opsoclonus‐myoclonus (OM) is a paraneoplastic syndrome of probable autoimmune origin. Despite current therapies aimed at decreasing autoantibody formation, OM is difficult to control and may impact long‐term neurologic outcome. We present a case of a 19‐month‐old patient who initially presented with OM, neuroblastoma and a constitutional cytogenetic abnormality t(5;12)(q11.2;q15). The patient's OM was recalcitrant to conventional therapies, but showed significant improvement following treatment with rituximab. Pediatr Blood Cancer 2008;50:370–371. © 2006 Wiley‐Liss, Inc.
Radiation effects on SBR–EPDM blends: A correlation with blend morphology
Authors: Dubey K. A. , Bhardwaj Y. K. , Chaudhari C. V. , Bhattacharya Shovit , Gupta S. K. , Sabharwal S.
Published: May 2006

The effect of γ radiation on the morphological and physical properties of Styrene–butadiene rubber (SBR) and Ethylene–propylene–diene monomer (EPDM) blends has been investigated. An attempt has been made to establish a correlation between various parameters like Gordon–Taylor parameter (k), hydrodynamic interaction parameter (Δ[η]mix), chemical shift factor (b), Charlesby–Pinner parameter (p0/q0) and polymer–polymer interaction parameter (χ). The results showed a close dependence of mechanical and physical properties of irradiated blends on these parameters. The probability of spur overlap has been found to increase with the increase in EPDM content in the blends, which in turn results in significant improvement in the mechanical properties of the irradiated SBR–EPDM blends with higher EPDM fraction. The efficiency of four multifunctional acrylates as crosslinking aid for the radiation‐induced vulcanization of SBR–EPDM blend was also studied. The results established lower efficiency of methacrylates over acrylates in the process and indicated that among the crosslinking agents studied trimethylolpropane triacrylate is the most efficient one. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 1676–1689, 2006
Urban schools' teachers enacting project‐based science
Authors: Tal Tali , Krajcik Joseph S. , Blumenfeld Phyllis C.
Published: May 2006

What teaching practices foster inquiry and promote students to learn challenging subject matter in urban schools? Inquiry‐based instruction and successful inquiry learning and teaching in project‐based science (PBS) were described in previous studies (Brown & Campione, 1990; Crawford, 1999; Krajcik, Blumenfeld, Marx, Bass, & Fredricks, 1998; Krajcik, Blumenfeld, Marx, & Solloway, 1994; Minstrell & van Zee, 2000). In this article, we describe the characteristics of inquiry teaching practices that promote student learning in urban schools. Teaching is a major factor that affects both achievement of and attitude of students toward science (Tamir, 1998). Our involvement in reform in a large urban district includes the development of suitable learning materials and providing continuous and practiced‐based professional development (Fishman & Davis, in press; van Es, Reiser, Matese, & Gomez, 2002). Urban schools face particular challenges when enacting inquiry‐based teaching practices like those espoused in PBS. In this article, we describe two case studies of urban teachers whose students achieved high gains on pre‐ and posttests and who demonstrated a great deal of preparedness and commitment to their students. Teachers' attempts to help their students to perform well are described and analyzed. The teachers we discuss work in a school district that strives to bring about reform in mathematics and science through systemic reform. The Center for Learning Technologies in Urban Schools (LeTUS) collaborates with the Detroit Public Schools to bring about reform in middle‐school science. Through this collaboration, diverse populations of urban‐school students learn science through inquiry‐oriented projects and the use of various educational learning technologies. For inquiry‐based science to succeed in urban schools, teachers must play an important role in enacting the curriculum while addressing the unique needs of students. The aim of this article is to describe patterns of good science teaching in urban school. © 2006 Wiley Periodicals, Inc. J Res Sci Teach 43: 722–745, 2006
Creating contextually authentic science in a “low‐performing” urban elementary school
Authors: Buxton Cory A.
Published: May 2006

This article reports on a 2½‐year collaborate project to reform the teaching and learning of science in the context of Mae Jemison Elementary, the lowest performing elementary school in the state of Louisiana. I outline a taxonomy of authentic science inquiry experiences and then use the resulting framework to focus on how project participants interpreted and enacted ideas about collaboration and authenticity. The resulting contextually authentic science inquiry model links the strengths of a canonically authentic model of science inquiry (grounded in the Western scientific canon) with the strengths of a youth‐centered model of authenticity (grounded in student‐generated inquiry), thus bringing together relevant content standards and topics with critical social relevance. I address the question of how such enactments may or may not promote doing science together and consider the implications of this model for urban science education. © 2006 Wiley Periodicals, Inc. J Res Sci Teach 43: 695–721, 2006
Reproductive life history of South African cheetahs (Acynonyx jubatus jubatus) at the San Diego Zoo Wild Animal Park, 1970–2005
Authors: Augustus Paula , Casavant Kelly , Troxel Natalie , Rieches Randy , Bercovitch Fred
Published: May 2006

We analyzed 35 years of data from a captive breeding program of cheetahs to determine basic reproductive life history characteristics of females. Breeding females ranged in age from 2.7–10.5 years. Sixteen females and over 13 males produced 129 cubs in 36 litters, with an average litter size of 3.6. Older females produced significantly fewer cubs per litter than younger females, but cub survivorship was comparable across female ages. Sex ratio was balanced at birth and 71% of infants survived the weaning period. Given that the reproductive output of captive cheetahs in our study is similar to that in other zoologic institutions and to cheetahs in the wild, we suggest that reproductive deficits in captive cheetahs arise from the inability of some pairs to breed, due to a lack of mating preference, rather than from a species‐wide problem. Zoo Biol 0:1–8, 2006. © 2006 Wiley‐Liss, Inc.
Word form access dyslexia: Understanding the basis of visual reading errors
Authors: Crutch Sebastian J. , Warrington Elizabeth K.
Published: May 2006

We report the case of a patient V.E.M. who exhibits the infrequently described syndrome of visual dyslexia. V.E.M. read many single words accurately and rapidly; however, when words were read inaccurately, the majority of responses were alternate real words bearing a strong visual relationship to the target items. A series of observational and experimental investigations of her reading skills revealed that response accuracy was strongly affected by word frequency and mildly affected by concreteness but not influenced by word length, orthographic neighbourhood size, or semantic priming. It is argued that V.E.M.'s visual dyslexia results from a deficit of the visual word form system. More specifically, we propose that this deficit has an “access” quality, with visual word form representations remaining relatively intact despite an impairment in the processes by which these representations are activated. Taking the results of this study together with previous reports of dyslexic patients who make a high proportion of visual paralexic errors, we also suggest that visual dyslexia represents a multicomponent dyslexic syndrome for which phonological impairment and not semantic impairment may be a necessary condition.
A mitotic topoisomerase II checkpoint in budding yeast is required for genome stability but acts independently of Pds1/securin
Authors: Andrews Catherine A. , Vas Amit C. , Meier Brian , Giménez-Abián Juan F. , Díaz-Martínez Laura A. , Green Julie , Erickson Stacy L. , VanderWaal Kristyn E. , Hsu Wei-Shan , Clarke Duncan J.
Published: May 2006

Topoisomerase II (Topo II) performs topological modifications on double-stranded DNA molecules that are essential for chromosome condensation, resolution, and segregation. In mammals, G2 and metaphase cell cycle delays induced by Topo II poisons have been proposed to be the result of checkpoint activation in response to the catenation state of DNA. However, the apparent lack of such controls in model organisms has excluded genetic proof that Topo II checkpoints exist and are separable from the conventional DNA damage checkpoint controls. But here, we define a Topo II-dependent G2/M checkpoint in a genetically amenable eukaryote, budding yeast, and demonstrate that this checkpoint enhances cell survival. Conversely, a lack of the checkpoint results in aneuploidy. Neither DNA damage-responsive pathways nor Pds1/securin are needed for this checkpoint. Unusually, spindle assembly checkpoint components are required for the Topo II checkpoint, but checkpoint activation is not the result of failed chromosome biorientation or a lack of spindle tension. Thus, compromised Topo II function activates a yeast checkpoint system that operates by a novel mechanism.
Monocytic leukemia zinc finger protein is essential for the development of long-term reconstituting hematopoietic stem cells
Authors: Thomas Tim , Corcoran Lynn M. , Gugasyan Raffi , Dixon Mathew P. , Brodnicki Thomas , Nutt Stephen L. , Metcalf Donald , Voss Anne K.
Published: May 2006

Monocytic leukemia zinc finger protein (MOZ), a transcriptional coactivator and member of the MYST family of histone acetyltransferases, is the target of recurrent translocations in acute myeloid leukemia. Since genes associated with translocations in leukemia are typically important regulators of blood formation, we investigated if Moz has a role in normal hematopoiesis. We generated mice carrying a mutation in the Moz gene. Homozygous Moz mutant mice died at birth. Moz mutant fetal liver hematopoietic cells were incapable of contributing to the hematopoietic system of recipients after transplantation. We observed profound defects in the stem cell compartment of Moz-deficient mice. Progenitors of all lineages were reduced in number. However, blood cell lineage commitment was unaffected. Together, these results show that Moz is essential for a fundamental property of hematopoietic stem cells, the ability to reconstitute the hematopoietic system of a recipient after transplantation and that Moz is specifically required in the stem cell compartment.
Functional coupling of RNAP II transcription to spliceosome assembly
Authors: Das Rita , Dufu Kobina , Romney Ben , Feldt Megan , Elenko Mark , Reed Robin
Published: May 2006

The pathway of gene expression in higher eukaryotes involves a highly complex network of physical and functional interactions among the different machines involved in each step of the pathway. Here we established an efficient in vitro system to determine how RNA polymerase II (RNAP II) transcription is functionally coupled to pre-mRNA splicing. Strikingly, our data show that nascent premessenger RNA (pre-mRNA) synthesized by RNAP II is immediately and quantitatively directed into the spliceosome assembly pathway. In contrast, nascent pre-mRNA synthesized by T7 RNA polymerase is quantitatively assembled into the nonspecific H complex, which consists of heterogeneous nuclear ribonucleoprotein (hnRNP) proteins and is inhibitory for spliceosome assembly. Consequently, RNAP II transcription results in a dramatic increase in both the kinetics of splicing and overall yield of spliced mRNA relative to that observed for T7 transcription. We conclude that RNAP II mediates the functional coupling of transcription to splicing by directing the nascent pre-mRNA into spliceosome assembly, thereby bypassing interaction of the pre-mRNA with the inhibitory hnRNP proteins.
SOX2 is a dose-dependent regulator of retinal neural progenitor competence
Authors: Taranova Olena V. , Magness Scott T. , Fagan B. Matthew , Wu Yongqin , Surzenko Natalie , Hutton Scott R. , Pevny Larysa H.
Published: May 2006

Approximately 10% of humans with anophthalmia (absent eye) or severe microphthalmia (small eye) show haploid insufficiency due to mutations in SOX2, a SOXB1-HMG box transcription factor. However, at present, the molecular or cellular mechanisms responsible for these conditions are poorly understood. Here, we directly assessed the requirement for SOX2 during eye development by generating a gene-dosage allelic series of Sox2 mutations in the mouse. The Sox2 mutant mice display a range of eye phenotypes consistent with human syndromes and the severity of these phenotypes directly relates to the levels of SOX2 expression found in progenitor cells of the neural retina. Retinal progenitor cells with conditionally ablated Sox2 lose competence to both proliferate and terminally differentiate. In contrast, in Sox2 hypomorphic/null mice, a reduction of SOX2 expression to <40% of normal causes variable microphthalmia as a result of aberrant neural progenitor differentiation. Furthermore, we provide genetic and molecular evidence that SOX2 activity, in a concentration-dependent manner, plays a key role in the regulation of the NOTCH1 signaling pathway in retinal progenitor cells. Collectively, these results show that precise regulation of SOX2 dosage is critical for temporal and spatial regulation of retinal progenitor cell differentiation and provide a cellular and molecular model for understanding how hypomorphic levels of SOX2 cause retinal defects in humans.
Dynamic regulatory interactions of Polycomb group genes: MEDEA autoregulation is required for imprinted gene expression in Arabidopsis
Authors: Baroux Célia , Gagliardini Valeria , Page Damian R. , Grossniklaus Ueli
Published: May 2006

The imprinted Arabidopsis Polycomb group (PcG) gene MEDEA (MEA), which is homologous to Enhancer of Zeste [E(Z)], is maternally required for normal seed development. Here we show that, unlike known mammalian imprinted genes, MEA regulates its own imprinted expression: It down-regulates the maternal allele around fertilization and maintains the paternal allele silent later during seed development. Autorepression of the maternal MEA allele is direct and independent of the MEA–FIE (FERTILIZATION-INDEPENDENT ENDOSPERM) PcG complex, which is similar to the E(Z)–ESC (Extra sex combs) complex of animals, suggesting a novel mechanism. A complex network of cross-regulatory interactions among the other known members of the MEA–FIE PcG complex implies distinct functions that are dynamically regulated during reproduction.