bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of WWP1 is associated with the estrogen receptor and insulin‐like growth factor receptor 1 in breast carcinoma
Authors: Chen Ceshi , Zhou Zhongmei , Sheehan Christine E. , Slodkowska Elzbieta , Sheehan Christopher B. , Boguniewicz Ann , Ross Jeffrey S.
Published: January 2009

WWP1, a HECT type E3 ubiquitin ligase frequently amplified and overexpressed in breast cancer, has the potential to become a useful clinical biomarker and therapeutic target in breast cancer. Here, we performed immunohistochemical staining in formalin‐fixed and paraffin‐embedded tissue sections from 187 cases of primary invasive mammary carcinoma [137 ductal carcinomas (IDC) and 50 lobular carcinomas (ILC)] by using a monoclonal anti‐WWP1 antibody. The normal breast epithelium and adjacent benign epithelium are essentially negative for WWP1. Cytoplasmic WWP1 immunoreactivity was observed in 76/187 (40.6%) tumors and showed a positive correlation with ERα (p = 0.05) and IGF‐1R proteins (p = 0.001) in this cohort. The positive correlations between WWP1 and ER/IGF‐1R were also observed in a panel of 12 breast cancer cell lines by Western blot. Interestingly, the ER levels are decreased when WWP1 is silenced in ER positive MCF7 and T47D breast cancer cell lines. Finally, WWP1 ablation collectively inhibits cell proliferation with tamoxifen in MCF7 and T47D, as measured by 3H‐thymidine incorporation assays. These findings suggest that WWP1 may play an important role in ER positive breast cancer. © 2009 UICC
Construction of oncogenetic tree models reveals multiple pathways of oral cancer progression
Authors: Pathare Swapnali , Schäffer Alejandro A. , Beerenwinkel Niko , Mahimkar Manoj
Published: January 2009

Oral cancer develops and progresses by accumulation of genetic alterations. The interrelationship between these alterations and their sequence of occurrence in oral cancers has not been thoroughly understood. In the present study, we applied oncogenetic tree models to comparative genomic hybridization (CGH) data of 97 primary oral cancers to identify pathways of progression. CGH revealed the most frequent gains on chromosomes 8q (72.4%) and 9q (41.2%) and frequent losses on 3p (49.5%) and 8p (47.5%). Both mixture and distance‐based tree models suggested multiple progression pathways and identified +8q as an early event. The mixture model suggested two independent pathways namely a major pathway with −8p and a less frequent pathway with +9q. The distance‐based tree identified three progression pathways, one characterized by −8p, another by −3p and the third by alterations +11q and +7p. Differences were observed in cytogenetic pathways of node‐positive and node‐negative oral cancers. Node‐positive cancers were characterized by more non‐random aberrations (n= 11) and progressed via −8p or −3p. On the other hand, node‐negative cancers involved fewer non‐random alterations (n= 6) and progressed along −3p. In summary, the tree models for oral cancers provided novel information about the interactions between genetic alterations and predicted their probable order of occurrence. © 2009 UICC
Functional evidence for Eme1 as a marker of cisplatin resistance
Authors: Tomoda Yoshitaka , Katsura Mari , Okajima Miyuki , Hosoya Noriko , Kohno Nobuoki , Miyagawa Kiyoshi
Published: January 2009

The ability to predict cisplatin sensitivity in tumors has been expected to greatly improve the outcome of cancer therapy, because the drug is frequently used in a variety of tumors. Although ERCC1 and other repair proteins have been investigated as markers of cisplatin resistance, reliable markers are still needed. Here, we demonstrate that Eme1 levels can predict cisplatin sensitivity more accurately than ERCC1 or Rad51 levels in a variety of human cancer cell lines. Eme1 forms a heterodimeric protein complex with Mus81 and functions as a structure‐specific endonuclease. Haploinsufficiency of Eme1 led to hypersensitivity to cisplatin in the colon cancer cell line HCT116. On the basis of this finding, we examined the relationships between levels of proteins involved in the repair of interstrand cross‐links and cisplatin sensitivity in human tumor cell lines with a variety of origins. Although ERCC1, Rad51 and Mus81 levels correlated with sensitivity to some extent, the clearest correlation was observed with Eme1. Tumors with low Eme1 levels were more sensitive to the drug than tumors with high levels. This suggests that the measurement of Eme1 in tumors may be more informative for cisplatin‐based chemotherapy than that of the currently available markers. © 2009 UICC
A novel mechanism for anti‐EGFR antibody action involves chemokine‐mediated leukocyte infiltration
Authors: Hoffmann Thomas K. , Schirlau Kerstin , Sonkoly Enikö , Brandau Sven , Lang Stephan , Pivarcsi Andor , Balz Vera , Müller Anja , Homey Bernhard , Boelke Edwin , Reichert Torsten , Friebe‐Hoffmann Ulrike , Greve Jens , Schuler Patrick , Scheckenbach Kathrin , Schipper Jörg , Bas Murat , Whiteside Theresa L. , Bier Henning
Published: January 2009

Overexpression of the epidermal growth factor receptor (EGFR) is a hallmark of squamous cell carcinoma of the head and neck (SCCHN). Monoclonal antibodies (mAbs) against EGFR are currently used for therapy of recurrent or metastatic disease; however, their mode of action is not completely understood. To investigate the immunological effects of anti‐EGFR mAb, we generated a three‐dimensional spheroid model of EGFR‐expressing SCCHN and used this model to study the effect of anti‐EGFR mAb on leukocyte migration toward tumors. Pretreatment with the blocking anti‐EGFR mAb EMD 72000, its F(ab′)2 fragments or an EGFR tyrosine kinase inhibitor led to substantially increased leukocyte infiltration into EGFR overexpressing tumor spheroids, but not into those with low EGFR expression. Nonblocking anti‐EGFR mAb or fibroblast‐specific mAb did not affect leukocyte infiltration, suggesting that the observed increase in leukocyte infiltration depends on interference with EGFR activation. Using a human cytokine macroarray, we demonstrated that the blockade of EGFR by anti‐EGFR mAb in EGFR‐overexpressing SCCHN cells leads to differential expression of several cytokines and chemokines, including the chemokine MCP‐1/CCL‐2. The significant upregulation of MCP‐1/CCL2 on exposure to anti‐EGFR mAb was confirmed by quantitative PCR and enzyme‐linked immunospot analyses. Moreover, blocking anti‐MCP‐1 antibody inhibited leukocyte migration toward tumor cells induced by anti‐EGFR mAb, pointing to an important role of MCP‐1/CCL2 in anti‐EGFR mAb‐induced leukocyte migration. Our findings demonstrate that anti‐EGFR mAb induces leukocyte infiltration to tumor spheroids by upregulating chemokine expression. This novel mechanism for anti‐EGFR mAb action may contribute to the antitumor effects of anti‐EGFR mAb in vivo. © 2009 Wiley‐Liss, Inc.
Young children's responses to September 11th: The New York City experience
Authors: Klein Tovah P. , Devoe Ellen R. , Miranda‐Julian Claudia , Linas Keri
Published: January 2009

Although the knowledge base regarding very young children's responses to trauma has been expanding, descriptions of their responses to terrorism remain sparse. Yet, their vulnerability makes this an important group to study. Recent events in the United States (9/11, Hurricane Katrina) make this question highly relevant. This study aims to provide extensive descriptions of how children 5 years or younger on September 11th who were living in close proximity to Ground Zero responded that day and in the following months. Sixty‐seven New York City parents (with 104 children) participated in focus groups between November 2001 and May 2002. Focus groups also provided a foundation for an in‐depth study examining young children's adaptation following 9/11 and changes in parenting behaviors after the disaster. Findings on children's behavioral and emotional reactions on 9/11 and in the 8 months after as well as their need to return to normalcy are reported. Consistent with current understanding of trauma symptoms in young children, parents reported behaviors including chronic sleep disruptions, fearful reactions, development of new fears, and increased clinginess and separation anxiety following the disaster. On the actual day, children's responses were described as ranging from calm and cooperative to difficult and panicky. Implications for working with parents and young children affected by terrorism or community‐level trauma and directions for future research are discussed.
Neonatal physiological regulation is associated with perinatal factors: A study of neonates born to healthy African American women living in poverty
Authors: Jacob Suma , Byrne Michelle , Keenan Kate
Published: January 2009

Maternal mental health and prenatal stress are linked with neurobehavioral differences in the offspring. The majority of studies documenting this effect have been conducted using either predominantly European American infants or minority infants exposed to teratogens in utero. In this study, we focus on healthy African American women from low‐income environments to investigate the earliest individual differences in biobehavioral regulation, including resting heart rate and variability (HRV). In 87 neonates, HRV was significantly lower in those born to mothers reporting past major depressive disorder (p = .01). The number of maternal life stressors also was associated with lower neonatal HRV (p = .03). Obstetrical complications were not associated with significant differences, but breast‐ versus bottle‐feeding in the first few days of life was related to higher HRV (p = .04). Early variation in physiological regulation may be linked to subsequent individual differences in response to stress. Thus, identifying the earliest point in development when such differences can be reliably measured may result in opportunities for prevention of later deficits in regulating response to stress.
Distinct actions of Akt1 and Akt2 in skeletal muscle differentiation
Authors: Rotwein Peter , Wilson Elizabeth M.
Published: January 2009

Differentiation, maturation, and repair of skeletal muscle requires ongoing cooperation between signaling cascades activated by hormones and growth factors, and intrinsic regulatory programs controlled by myogenic transcription factors. The insulin‐like growth factor—phosphatidylinositol‐3 kinase—Akt pathway has been implicated in muscle growth and regeneration after injury, in counteracting sarcopenia during aging, and in maintaining muscle cell viability. Here we present evidence for distinct roles for Akt1 and Akt2 in different phases of muscle differentiation. Targeted knockdown of either Akt had no effect on C2 myoblast proliferation, even though Akt1 concentrations are markedly higher than Akt2 levels under growth‐promoting conditions. Akt2 concentrations rose by nearly an order of magnitude during muscle differentiation, while Akt1 levels remained constant, yet loss of either protein did not increase myoblast death. Rather, knockdown or genetic knockout of Akt1 blocked differentiation at its earliest stages, preventing induction of muscle‐specific proteins and inhibiting formation of multinucleated myofibers, while myoblasts lacking Akt2 differentiated normally, although resultant myofibers were thinner and incorporated fewer nuclei than controls. Forced expression of knockdown‐resistant Akt1 partially reversed the deficit in differentiation seen in myoblasts lacking Akt1. Our results define isoform‐specific Akt actions in muscle cells, and demonstrate that both Akts are necessary for full myoblast differentiation and maturation. J. Cell. Physiol. 219: 503–511, 2009. © 2009 Wiley‐Liss, Inc.
H‐Ras and PI3K are required for the formation of circular dorsal ruffles induced by low‐power laser irradiation
Authors: Gao Xuejuan , Xing Da , Liu Lei , Tang Yonghong
Published: January 2009

The formation of circular dorsal ruffles upon growth factor stimulation facilitates the static cells for subsequent motility. Low‐power laser irradiation (LPLI) has been shown to exert some promotive effects on migration and proliferation in various cell types. It is unclear whether LPLI could induce the formation of circular ruffles. In this study, using confocal fluorescence microscope, we for the first time demonstrated that LPLI could induce the production of circular ruffle structures in COS‐7 cells. These structures were proved to be actin‐based and originated from membrane microdomains enriched in cholesterol. Ras was shown to be activated by LPLI and expression of YFP‐H‐Ras (N17), a dominant negative H‐Ras, blocked the generation of circular ruffles induced by LPLI. Wortmannin, PI3K inhibitor, potently suppressed the formation of LPLI‐induced circular ruffles in a dose‐dependent manner. However, blocking the activation of PKC, which was activated during LPLI‐induced cell proliferation in our previous study, had no effect on the formation of circular ruffles. Thus, both H‐Ras and PI3K were required for the formation of circular ruffles induced by LPLI and the generation of circular ruffles provides new information for the mechanisms of biological effects of LPLI. J. Cell. Physiol. 219: 535–543, 2009. © 2009 Wiley‐Liss, Inc.
Low‐power laser irradiation promotes cell proliferation by activating PI3K/Akt pathway
Authors: Zhang Lingling , Xing Da , Gao Xuejuan , Wu Shengnan
Published: January 2009

Low‐power laser irradiation (LPLI) can stimulate cell proliferation through a wide network of signals. Akt is an important protein kinase in modulating cell proliferation. In this study, using real‐time single‐cell analysis, we investigated the activity of Akt and its effects on cell proliferation induced by LPLI in African green monkey SV40‐transformed kidney fibroblast cells (COS‐7). We utilized a recombinant fluorescence resonance energy transfer (FRET) Akt probe (BKAR) to dynamically detect the activation of Akt after LPLI treatment. Our results show that LPLI induced a gradual and continuous activation of Akt. Moreover, the activation of Akt can be completely abolished by wortmannin, a specific inhibitor of PI3K, suggesting that the activation of Akt caused by LPLI is a PI3K‐dependent event. Src family is involved in Akt activation as demonstrated by the part inhibition of Akt activity in samples treated with PP1 (an inhibitor of Src family). In contrast, loading Gö 6983, a PKC inhibitor, did not affect this response. Further experiments performed using GFP‐Akt fluorescence imaging and Western blot analysis demonstrate that, the activation of Akt is a multi‐step process in response to LPLI, involving membrane recruitment, phosphorylation, and membrane detachment. LPLI promotes cell proliferation through PI3K/Akt activation since the cell viability was significantly inhibited by PI3K inhibitor. All these studies create a concernful conclusion that PI3K/Akt signaling pathway is well involved in LPLI triggered cell proliferation that acts as a time‐ and dose‐dependent manner. J. Cell. Physiol. 219: 553–562, 2009. © 2009 Wiley‐Liss, Inc.
Oxidative stress promotes ocular neovascularization
Authors: Dong Aling , Xie Bing , Shen Jikui , Yoshida Tsunehiko , Yokoi Katsutoshi , Hackett Sean F. , Campochiaro Peter A.
Published: January 2009

Mice deficient in superoxide dismutase 1 (Sod1−/− mice) develop many features seen in patients with age‐related macular degeneration (AMD) including choroidal neovascularization (NV). We sought to determine if the absence of SOD1 contributes to the pro‐angiogenic environment in the subretinal space or whether it is completely secondary to other changes in Bruch's membrane and the retinal pigmented epithelium (RPE) that precede the development of choroidal NV. In an ischemic retinopathy model or a transgenic model in which the rhodopsin promoter drives expression of vascular endothelial growth factor (VEGF) in photoreceptor there was significantly more NV in Sod1−/− compared to Sod1+/+ mice. The compromised antioxidant defense system in Sod1−/− mice contributes to the pro‐angiogenic environment, because treatment of Sod1−/− mice with a mixture of antioxidants caused a significant reduction in ischemia‐induced retinal NV. Wild‐type mice treated with the same antioxidants also showed reduced ischemia‐induced retinal NV, reduced VEGF‐induced subretinal NV, and reduced choroidal NV at Bruch's membrane rupture sites. These data suggest that reactive oxygen species contribute to several types of ocular NV. This could explain why in the Age‐Related Eye Disease Trial, antioxidant treatment reduced conversion from non‐neovascular to neovascular AMD and severe vision loss, and suggest that potent antioxidants should be considered for other diseases complicated by ocular NV. J. Cell. Physiol. 219: 544–552, 2009. © 2009 Wiley‐Liss, Inc.
Biodiesel production from Jerusalem artichoke (Helianthus Tuberosus L.) tuber by heterotrophic microalgae Chlorella protothecoides
Authors: Cheng Yun , Zhou Wenguang , Gao Chunfang , Lan Kenneth , Gao Yang , Wu Qingyu
Published: January 2009

BACKGROUND: As a potential source of biomass, Jerusalem artichoke has been studied for bioethanol production; however, thus far it has not been investigated for the production of other liquid biofuels, such as biodiesel. This work aims to develop a novel approach for biodiesel production from Jerusalem artichoke tuber using heterotrophic microalgae.

RESULTS: In this study, Chlorella protothecoides utilized hydrolysate of Jerusalem artichoke tuber as carbon source and accumulated lipid in vivo, with lipid content as high as 44% by dry mass, and a carbon source to lipid conversion ratio of about 25% in a 4‐day scale cultivation. The lipids were extracted and then converted into biodiesel by transesterification. Cetane acid methyl ester, linoleic acid methyl ester and oleic acid methyl ester were the dominating components of the biodiesel produced. Unsaturated fatty acids methyl ester constituted over 82% of the total biodiesel content.

CONCLUSION: This work suggests the feasibility of an alternative method of producing biodiesel from Jerusalem artichoke tuber using microalgae cultivation, and a cost reduction of carbon source feed in algal oil production can be expected. Copyright © 2009 Society of Chemical Industry
Modern MALDI time‐of‐flight mass spectrometry
Authors: Vestal Marvin L.
Published: January 2009

This paper focuses on development of time‐of‐flight (TOF) mass spectrometry in response to the invention of matrix‐assisted laser desorption/ionization (MALDI). Before this breakthrough ionization technique for nonvolatile molecules, TOF was generally considered as a useful tool for exotic studies of ion properties but was not widely applied to analytical problems. Improved TOF instruments and software that allow the full potential power of MALDI to be applied to difficult biological applications are described. A theoretical approach to the design and optimization of MALDI‐TOF instruments for particular applications is presented. Experimental data are provided that are in excellent agreement with theoretical predictions of resolving power and mass accuracy. Data on sensitivity and dynamic range using kilohertz laser rates are also summarized. These results indicate that combinations of high‐performance MALDI‐TOF and TOF‐TOF with off‐line high‐capacity separations may ultimately provide throughput and dynamic range several orders of magnitude greater than those currently available with electrospray LC‐MS and MS‐MS. Copyright © 2009 John Wiley & Sons, Ltd.
CE with direct sample injection for the determination of metformin in plasma for type 2 diabetic mellitus: An adequate alternative to HPLC
Authors: Wei Shao‐Yun , Yeh Hsin‐Hua , Liao Fen‐Fen , Chen Su‐Hwei
Published: January 2009

We developed a simple and selective CE with UV detection at 233 nm for the analysis of metformin in plasma based on direct sample injection without any pretreatment. The sample was employed with an electrokinetic injection of 10 kV for 100 s. CE separation of metformin from biological matrix was performed at 25°C using a BGE consisting of 25 mM Tris buffer at pH 4.0. The linear range of the CE method for the determination of metformin in plasma was over the range of 0.1–2.0 μg/mL; the LOD of the drug in plasma (S/N = 3; injection 10 kV, 100 s) was 30 ng/mL. Data by CE were compared with the results obtained by a validated HPLC method. CE assay of metformin exhibited a very good correlation (r2 = 1) with respect to HPLC. CE determination of metformin is a robust, sensitive, and reproducible method with the advantage over HPLC of being fast, without prior extraction, or precipitation of proteins, also enabling quick assessment of metformin for pharmacokinetic and clinical studies.
Separation of fatty alcohol ethoxylates by capillary zone electrophoresis and micellar electrokinetic chromatography
Authors: Koike Ryo , Kitagawa Fumihiko , Otsuka Koji
Published: January 2009

Separation methods based on capillary zone electrophoresis and micellar electrokinetic chromatography were developed to characterize the distribution of ethylene oxide (EO) homologues in the fatty alcohol ethoxylates (FAEs). Prior to the separation, the FAEs were derivatized with 2‐fluoro‐1‐methylpyridinium p‐toluenesulfonate (FMPTS) to allow CZE separation and UV detection. To prevent adsorption of cationic analytes onto the inner surface of the capillary and formation of micelles in CZE analysis, a lower pH background solution (BGS) containing a high concentration of acetonitrile was employed. Under optimal conditions, FMPTS‐derivatized FAEs with an average EO number of 6 were completely separated within 11 min. For MEKC analysis of the FAEs, dodecyltrimethylammonium chloride (DTAC) was added to the BGS. In the presence of 30 mM DTAC in 10 mM phosphate buffer (pH 2.5) containing 20% (v/v) acetonitrile, superior oligomer separation of the FAEs containing up to 50 EO groups was achieved within 30 min with good analytical reproducibilities. Furthermore, the developed method was applied to the analysis of the FAEs in commercial products such as laundry detergent and fabric softener.
Simple and rapid genotyping ofD‐amino acid oxidase gene recognizing a crucial variant in the ddY strain using microchip electrophoresis
Authors: Tojo Yosuke , Hamase Kenji , Konno Ryuichi , Koyanagi Satoru , Ohdo Shigehiro , Zaitsu Kiyoshi
Published: January 2009

A rapid genotyping method ofD‐amino acid oxidase (DAO), an enzyme that catalyzes the oxidative degradation of most of theD‐amino acids in mammals, has been established. This method employs a one‐step PCR, restriction enzyme digestion and rapid microchip electrophoresis (MCE), and the DAO genotype of the living individual mice was definitely determined within a day by clearly separating the 95 and 107 bpHpaII digested DNA fragments. For verification of the method, the DAO activity in the kidney of individual mice was also determined, and the obtained values completely matched the estimated genotypes (DAO+/+, DAO+/–, and DAO–/–). The intrinsic amounts ofD‐Pro in the serum and kidney of mice with three DAO genotypes were compared for the first time, and demonstrated that theD‐amino acid amounts in the DAO+/+mice (1.93 ± 0.66 nmol/mL serum, not detectable in the kidney) and DAO+/–mice (1.50 ± 0.24 nmol/mL serum, not detectable in the kidney) were almost the same. The present method should be a powerful tool to establish various pathologic‐model animals under the complete care of their intrinsic DAO activity, which are useful for the screening ofD‐amino acids having physiological activity and/or diagnostic values.
A capillary holder for scanning detection of capillary isoelectric focusing with laser‐induced fluorescence
Authors: Takahashi Katsuyoshi , Maruo Yuji , Kitamori Takehiko , Shimura Kiyohito
Published: January 2009

A holder for a 12 cm long capillary was designed for scanning LIF detection of CIEF. The polyimide coat of a fused‐silica capillary has been removed, and 1.5 mm diameter flanges have been attached near both ends. The holder is fixed on the stage of a fluorescence microscope via a translational stage, and a capillary guide is directly fixed on the microscope stage. The guide has a groove and a pressure plate for the capillary to slide in. The holder has two pulling plates with slits of 1 mm to accept the capillary just inside the flanges. The slits and the groove of the guide have been aligned. The motion of the translational stage brings the pulling plate into contact with the flange at the pulled side, and slides the capillary through the guide. The other end of the capillary is free and produces no strain on the capillary. When the motion of the stage is reversed, an unstrained contact is achieved at the other end. The baseline noise from scanning was only 50% larger than that without scanning. The fluorescence‐signal variation during scanning was about 4% of the total signal, which was about twice that without scanning.
Semiconductor disk lasers for the generation of visible and ultraviolet radiation
Authors: Calvez S. , Hastie J.E. , Guina M. , Okhotnikov O.G. , Dawson M.D.
Published: January 2009

Recent developments in semiconductor disk lasers (SDLs) generating visible or ultraviolet light are reviewed. After an introduction on potential applications, we discuss how the combination of vertical‐emitting semiconductor GaAs‐based structures and intra‐cavity nonlinear conversion techniques can be successfully exploited to uniquely meet demands for continuous‐wave radiation in the visible and ultraviolet spectral range. To do so, an overview of the device operating principles and performance is presented highlighting the underlying material considerations, semiconductor structural designs, thermal management techniques and suitable cavity configurations. This summary is completed by a presentation of new developments in the field, with a particular focus on the trends towards miniaturization.
Robotic laser tissue welding of sclera using chitosan films
Authors: Garcia Pablo , Mines Michael J. , Bower Kraig S. , Hill J. , Menon J. , Tremblay Eric , Smith Benjamin
Published: January 2009

Purpose

To demonstrate the feasibility of scleral wound closure using a novel adhesive made of chitosan film.

Methods

Five‐millimeter scleral lacerations were created in enucleated pig eyes. Casted chitosan films were sized to 7×7 mm patches. Lacerations were sealed with chitosan film alone (7 eyes) or chitosan film followed by laser irradiation using a near infrared laser (1,455 nm) at 350 mW for 6 minutes (7 eyes). Seven eyes were closed with 9‐0 nylon suture for comparison (7 eyes). Outcome measures included watertight closure, closure time, and leak pressure. Leak pressure was measured with a pressure transducer attached to tubing continuously monitored intraocular pressure during saline infusion. Watertight closure testing was performed immediately following closure (n = 3 per group) and after 24 hours (n = 3 per group). One eye in each group was fixed in formalin for histology.

Results

All wounds were watertight for each closure method. Mean closure time with unlasered chitosan film was 2.24 minutes (range 1.80–3.26, 7 eyes) with a mean leak pressure of 303 mm Hg (range 217–364, 3 eyes). Mean closure time with lasered chitosan was 12.47 minutes (range 11.45–14.15, 7 eyes) with a mean leak pressure of 454.7 mm Hg (range 152–721, 3 eyes). Suture closure required a mean of 4.83 minutes (range 4.03–7.30, 7 eyes) and resulted in a mean leak pressure of 570.3 mm Hg (range 460–646, 3 eyes). Both lasered and unlasered chitosan eyes remained watertight after 24 hours. Histology revealed minimal laser tissue damage in lasered eyes.

Conclusions

In this preliminary study chitosan film successfully closed scleral lacerations with and without the application of laser energy. While laser appears to strengthen the closure, it significantly increases the closure time. Chitosan based adhesives hold promise as a scleral wound closure technique. Lasers Surg. Med. 41:59–67, 2009. © 2009 Wiley‐Liss, Inc.
Percutaneous laser discectomy guided with stereotactic computer‐assisted surgical navigation
Authors: von Jako Ronald A. , Cselik Zsolt
Published: January 2009

Background and Objective

Percutaneous laser discectomy at various wavelengths has been used for minimally invasive surgery of herniated intervertebral discs. Using a high‐intensity diode laser at 980‐nm wavelength, we aimed to improve the safe insertion of the laser trocar with the aid of a stereotactic computer‐assisted surgical navigation system.

Study Design/Materials and Methods

The experiments were performed on ex vivo porcine spines with intact soft tissue. Before laser irradiation, each specimen was imaged by computed tomography (CT) with fiduciary markers. The Digital Imaging and Communications in Medicine (DICOM standard) data sets were retrieved into the GE Healthcare Surgery InstaTRAK®3500 Plus computer‐assisted surgical navigation platform via the hospital Ethernet using a picture archiving and communication system. A special trocar with quartz waveguide connected to the navigation system was inserted into a total of 12 lumbar discs of two fresh intact porcine specimens. Various laser energies (200–700 J) with different exposure times were delivered. Pre‐ and post‐irradiation magnetic resonance (MR) imaging and postoperative macroscopic and histologic studies were carried out.

Results

A navigation system accuracy of better than 2 mm was achieved. Tracking of the instrument from pre‐acquired formatted CT reconstructed images reduced overall radiation exposure by limiting the need for continuous intraoperative C‐arm fluoroscopy. The use of surgical navigation by CT images enhanced the precision insertion of the laser trocar. Irradiation with the 980‐nm wavelength diode laser resulted in tissue evaporation changes of the intervertebral disc material as demonstrated by comparing pre‐ and post‐irradiation changes of MR images and macro‐ and microscopic changes of the dissected disc material.

Conclusion

This preclinical study demonstrates the clinical utility of a 980‐nm diode laser delivered through a fiber‐optic waveguide trocar in which precise insertion was enabled by the use of surgical navigation. This in turn decreases the exposure to ionizing radiation during the procedure. Lasers Surg. Med. 41:42–51, 2009. © 2008 Wiley‐Liss, Inc.
810 nm Wavelength light: An effective therapy for transected or contused rat spinal cord
Authors: Wu Xingjia , Dmitriev Anton E. , Cardoso Mario J. , Viers‐Costello Angela G. , Borke Rosemary C. , Streeter Jackson , Anders Juanita J.
Published: January 2009

Background and Objectives

Light therapy has biomodulatory effects on central and peripheral nervous tissue. Spinal cord injury (SCI) is a severe central nervous system trauma with no effective restorative therapies. The effectiveness of light therapy on SCI caused by different types of trauma was determined.

Study Design/Materials and Methods

Two SCI models were used: a contusion model and a dorsal hemisection model. Light (810 nm) was applied transcutaneously at the lesion site immediately after injury and daily for 14 consecutive days. A laser diode with an output power of 150 mW was used for the treatment. The daily dosage at the surface of the skin overlying the lesion site was 1,589 J/cm2 (0.3 cm2 spot area, 2,997 seconds). Mini‐ruby was used to label corticospinal tract axons, which were counted and measured from the lesion site distally. Functional recovery was assessed by footprint test for the hemisection model and open‐field test for the contusion model. Rats were euthanized 3 weeks after injury.

Results

The average length of axonal re‐growth in the rats in the light treatment (LT) groups with the hemisection (6.89±0.96 mm) and contusion (7.04±0.76 mm) injuries was significantly longer than the comparable untreated control groups (3.66±0.26 mm, hemisection; 2.89±0.84 mm, contusion). The total axon number in the LT groups was significantly higher compared to the untreated groups for both injury models (P<0.05). For the hemisection model, the LT group had a statistically significant lower angle of rotation (P<0.05) compared to the controls. For contusion model, there was a statistically significant functional recovery (P<0.05) in the LT group compared to untreated control.

Conclusions

Light therapy applied non‐invasively promotes axonal regeneration and functional recovery in acute SCI caused by different types of trauma. These results suggest that light is a promising therapy for human SCI. Lasers Surg. Med. 41:36–41, 2009. © 2008 Wiley‐Liss, Inc.
A preliminary report about treatment of bisphosphonate related osteonecrosis of the jaw with Er:YAG laser ablation
Authors: Stübinger Stefan , Dissmann Jan‐Philipp , Pinho Nicole Chambron , Saldamli Belma , Seitz Oliver , Sader Robert
Published: January 2009

Background and Objectives

This preliminary report describes a new laser‐assisted treatment option for the emerging complication of bisphosphonate related osteonecrosis (BON) of the jaw.

Materials and Methods

In eight tumour patients (three women, five men) ten bony lesions in the maxilla and mandible in the course of intravenous bisphosphonate therapy were treated with a variable square pulsed (VSP) Er:YAG laser. For the treatment, the Er:YAG laser was applied with a pulse energy of 1,000 mJ, a pulse duration of 300 microseconds, and a frequency of 12 Hz (energy density 157 J/cm2). The spot size was 0.9 mm and the handpiece was kept at a distance of about 10 mm from the bone surface. The diseased bone was ablated exclusively with the Er:YAG laser by subsequently sweeping the bone surface in a well directed scanning mode.

Results

The surgical procedure and postoperative wound healing were without any complications and a complete soft tissue recovering was achieved within 4 weeks. During follow‐up examinations over 12 months soft tissue conditions were stable. The pulsed laser ablation caused a characteristic microstructured and craggy bone surface without a condensation or a smear layer on the laser rims.

Conclusion

The bone ablation technique using a VSP Er:YAG laser yielded promising clinical results without impairment of wound healing. A further analyse of the chemical, physical and pharmacological aspects of laser assisted treatment of BON lesions is necessary to get a safe and reliable treatment protocol for bisphosphonate‐related osteonecrosis of the jaw. Lasers Surg. Med. 41:26–30, 2009. © 2008 Wiley‐Liss, Inc.
Bipolar fractional radiofrequency treatment induces neoelastogenesis and neocollagenesis
Authors: Hantash Basil M. , Ubeid Anan Abu , Chang Hong , Kafi Reza , Renton Bradley
Published: January 2009

Background

We recently introduced Renesis™, a novel minimally invasive radiofrequency (RF) device, for the treatment of human skin. The wound healing response post‐fractional RF (FRF™) treatment was examined in human subjects.

Study Design

The FRF system delivered RF energy directly within the dermis via 5 micro‐needle electrode pairs. Tissue temperature was held at 72°C for 4 seconds using an intelligent feedback system. The wound healing response was evaluated histologically and by RT‐PCR up to 10 weeks post‐RF treatment. Neoelastogenesis and the role of heat shock proteins (HSPs) were assessed by immunohistochemistry.

Results

FRF treatment generated a RF thermal zone (RFTZ) pattern in the reticular dermis that consisted of zones of denatured collagen separated by zones of spared dermis. RFTZs were observed through day 28 post‐treatment but were replaced by new dermal tissue by 10 weeks. HSP72 expression rapidly diminished after day 2 while HSP47 expression increased progressively through 10 weeks. Reticular dermal volume, cellularity, hyaluronic acid, and elastin content increased. RT‐PCR studies revealed an immediate increase in IL‐1β, TNF‐α, and MMP‐13 while MMP‐1, HSP72, HSP47, and TGF‐β levels increased by 2 days. We also observed a marked induction of tropoelastin, fibrillin, as well as procollagens 1 and 3 by 28 days post‐treatment.

Conclusion

Our study revealed a vigorous wound healing response is initiated post‐treatment, with progressive increase in inflammatory cell infiltration from day 2 through 10 weeks. An active dermal remodeling process driven by the collagen chaperone HSP47 led to complete replacement of RFTZs with new collagen by 10 weeks post‐treatment. Furthermore, using both immunohistochemical and PCR studies, we successfully demonstrated for the first time evidence of profound neoelastogenesis following RF treatment of human skin. The combination of neoelastogenesis and neocollagenesis induced by treatment with the FRF system may provide a reliable treatment option for skin laxity and/or rhytids. Lasers Surg. Med. 41:1–9, 2009. © 2008 Wiley‐Liss, Inc.
Factors affecting carbon dioxide laser treatment for oral precancer: A patient cohort study
Authors: Hamadah O. , Thomson P.J.
Published: January 2009

Background

Although the benefits of CO2 laser surgery in oral precancer management have been evaluated, little consideration has been given to the factors which may influence treatment outcome, especially amongst patients developing recurrence or malignant transformation.

Study Design

Seventy eight patients (51 males, 27 females; mean age 57.8 years) undergoing CO2 laser excision of single, new dysplastic oral precancer lesions (OPLs) were followed up for a minimum of 2 years and the influence of clinico‐pathological parameters, socio‐demographic factors and the presence or absence of residual dysplasia in excision margins upon clinical outcome were examined.

Results

Seventy three percent of patients were smokers and 78% consumed alcohol regularly. The majority of lesions were leukoplakias arising in the floor of mouth and ventro‐lateral tongue and moderate or severe dysplasia accounted for 86% of histopathological diagnoses. Patient follow up ranged from 24 to 119 months (mean 58 months). Sixty four percent of patients were disease free at most recent clinical follow up, whilst 32% developed local recurrent dysplasia or new site dysplasia with 4% developing oral squamous cell carcinoma (but at sites distinct from their initial OPL). Excision margins were clear in 55% of cases, but 19% showed mild, 21% moderate and 5% severe dysplasia on histopathological examination. No statistically significant associations were seen between patients' age, gender, lesion appearance, site of origin, histopathological grading, presence of dysplasia in resection margins, or alcohol consumption and clinical outcome. Smokers, however, were at significantly higher risk of dysplasia recurrence compared to ex‐smokers or non‐smokers (P = 0.04).

Conclusions

In the absence of agreed treatment protocols for OPLs, we recommend CO2 laser surgery as an effective treatment modality offering precise lesion excision, full histopathological assessment, minimal post‐operative morbidity and a 64% disease free clinical outcome. Regular patient follow up is encouraged due to the persistence of field cancerisation effects. Lasers Surg. Med. 41:17–25, 2009. © 2008 Wiley‐Liss, Inc.
Low level laser therapy (LLLT): Attenuation of cholinergic hyperreactivity, β2‐adrenergic hyporesponsiveness and TNF‐α mRNA expression in rat bronchi segments in E. coli lipopolysaccharide‐induced airway inflammation by a NF‐κB dependent mechanism
Authors: Mafra de Lima F. , Costa M.S. , Albertini R. , Silva J.A. , Aimbire F.
Published: January 2009

Background and Objectives

It is unknown if the decreased ability to relax airways smooth muscles in asthma and other inflammatory disorders, such as acute respiratory distress syndrome (ARDS), can be influenced by low level laser therapy (LLLT) irradiation. In this context, the present work was developed in order to investigate if LLLT could reduce dysfunction in inflamed bronchi smooth muscles (BSM) in rats.

Study Design/Materials and Methods

A controlled ex vivo study was developed where bronchi from Wistar rat were dissected and mounted in an organ bath apparatus with or without a TNF‐α.

Results

LLLT administered perpendicularly to a point in the middle of the dissected bronchi with a wavelength of 655 nm and a dose of 2.6 J/cm2, partially decreased BSM hyperreactivity to cholinergic agonist, restored BSM relaxation to isoproterenol and reduced the TNF‐α mRNA expression. An NF‐κB antagonist (BMS205820) blocked the LLLT effect on dysfunction in inflamed BSM.

Conclusion

The results obtained in this work indicate that the LLLT effect on alterations in responsiveness of airway smooth muscles observed in TNF‐α‐induced experimental acute lung inflammation seems to be dependent of NF‐κB activation. Lasers Surg. Med. 41:68–74, 2009. © 2008 Wiley‐Liss, Inc.
Delineating melanoma using multimodal polarized light imaging
Authors: Tannous Zeina , Al‐Arashi Munir , Shah Sonali , Yaroslavsky Anna N.
Published: January 2009

Background and Significance

Melanoma accounts for 3% of all skin cancers but causes 83% of skin cancer deaths. The first step in treatment of melanoma is the removal of the lesions, usually by surgical excision. Currently most lesions are removed without intraoperative margin control. Post‐operative methods inspect 1–2% of the surgical margin and are prone to sampling errors. In this study we evaluate the use of reflectance and fluorescence polarization imaging for the demarcation of melanoma in thick fresh skin excisions.

Materials and Methods

Pigmented lesions clinically suspicious for melanoma were elliptically excised with proper margins. Elliptical surgical excisions were vertically bisected along the short axis of the specimen into two halves in the middle of the pigmented lesions. The vertically bisected tumor face was imaged. After that, one half of the sample was briefly stained in aqueous 2 mg/ml solution of tetracycline, whereas another half was stained in 0.2 mg/ml aqueous solution of methylene blue. Then both specimens were reimaged. Reflectance images were acquired in the spectral range between 390 and 750 nm. Fluorescence images of the tetracycline‐stained tissue were excited at 390 nm and registered between 450 and 700 nm. Fluorescence of the methylene blue‐stained samples was excited at 630 nm and registered between 650 and 750 nm. After imaging, the tissue was processed for standard H&E histopathology. The resulting histological and optical images were compared to each other.

Results and Conclusions

Our findings demonstrate that both tetracycline and methylene blue are suitable for imaging dysplastic and benign nevi. Melanoma is better delineated in the samples stained in methylene blue. Accurate and rapid delineation of melanoma in standard fresh surgical excisions appears feasible. Lasers Surg. Med. 41:10–16, 2009. © 2008 Wiley‐Liss, Inc.
Binary Interaction Parameters, Ternary Systems: Realistic Modeling of Liquid/Liquid Phase Separation
Authors: Wolf Bernhard A.
Published: January 2009

The phase behavior of ternary systems (either a polymer solution in a mixed solvent or a polymer blend in a single solvent) was modeled theoretically. The modeling considers two specific features of polymers explicitly: chain connectivity and the ability to respond to changes in the molecular environment by conformational reorientation. Previously, this approach has been applied to polymer solutions in single solvents. Here it is generalized and the number of parameters is reduced to two per binary system. The calculation of the Gibbs energies of the ternary mixtures accounts for the composition dependencies of the binary interaction parameters. The following phenomena are reproduced realistically for polymer solutions in a mixed solvent and for solutions of two polymers in a common solvent: simplicity, co‐solvency, and co‐non‐solvency. The results nourish the hope that the new approach is capable of modeling phase diagrams for ternary systems by means of binary interaction parameters only.

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Transcriptional processing of G4 DNA
Authors: Tornaletti Silvia
Published: January 2009

Genomic DNA sequences with the ability to assume non‐B form secondary structures have been recently shown to be particularly susceptible to genetic instability, an early contributing factor in human disease and cancer development. Transcription appears to play a central role in formation of these structures and in promoting instability at these sites. The subpathway of nucleotide excision DNA repair, transcription‐coupled DNA repair (TCR), removes transcription‐arresting damage from the transcribed strands of expressed genes, but little is known about how non‐canonical DNA structures are processed when encountered by the transcription machinery. If such structures arrest transcription, they may elicit “gratuitous” TCR in which the resulting reiterative and futile repair replication might generate a significant level of mutagenesis in a frequently transcribed gene because of faulty processing in the area of transcription arrest. Here we will describe our current understanding of how TCR may be elicited at non‐B DNA structures and summarize recent literature describing the behavior of RNA polymerases when encountering non‐canonical DNA structures, with particular emphasis on quadruplex DNA. © 2009 Wiley‐Liss, Inc.
Regulation of the hedgehog signaling by the mitogen‐activated protein kinase cascade in gastric cancer
Authors: Seto Motoko , Ohta Miki , Asaoka Yoshinari , Ikenoue Tsuneo , Tada Motohisa , Miyabayashi Koji , Mohri Dai , Tanaka Yasuo , Ijichi Hideaki , Tateishi Keisuke , Kanai Fumihiko , Kawabe Takao , Omata Masao
Published: January 2009

The hedgehog and mitogen‐activated protein kinase (MAPK) signaling pathways regulate growth in many tumors, suggesting cooperation between these two pathways in the regulation of cell proliferation. However, interactions between these pathways have not been extensively studied. We assessed cross‐talk between hedgehog and MAPK signaling in the regulation of cell proliferation in gastric cancer. We showed that PTCH expression was significantly correlated with extracellular signal‐regulated kinase (ERK) 1/2 phosphorylation (P = 0.016) as well as SHH expression (P = 0.034) in the 35 gastric cancers assessed by immunohistochemistry. Indeed, MAPK signaling increased the GLI transcriptional activity and induced the expression of hedgehog target genes in gastric cancer cells. The inductive effect of activated KRAS and mitogen‐activated protein/extracellular signal‐regulated kinase kinase (MEK) 1 was blocked by the suppressor of fused (SUFU), indicating that MAPK signaling regulates GLI activity via a SUFU‐independent process. Moreover, the deletion of the NH2‐terminal domain of GLI1 gene resulted in reduced response to MEK1 stimulation. Our results suggest that the KRAS‐MEK‐ERK cascade has a positive regulatory role in GLI transcriptional activity in gastric cancer. © 2009 Wiley‐Liss, Inc.
Resveratrol enhances cell‐mediated immune response to DMBA through TLR4 and prevents DMBA induced cutaneous carcinogenesis
Authors: Yusuf Nabiha , Nasti Tahseen H. , Meleth Sreelatha , Elmets Craig A.
Published: January 2009

Toll‐like receptors (TLRs) activate signals that are critically involved in innate immune responses and that contribute to the initiation of adaptive immune responses. Resveratrol (trans‐3,5,4‐trihydroxystilbene), a polyphenol found in red grapes and in several other plant sources, is an effective chemopreventive agent in cutaneous chemical carcinogenesis. In this study, we investigated whether TLR4 was required for the chemopreventive action of resveratrol in DMBA skin carcinogenesis. For this purpose, mice with normal and deficient TLR4 function were compared when pretreated with resveratrol and then subjected to a DMBA‐induced skin carcinogenesis protocol. There were fewer tumors/group (P < 0.001) in resveratrol treated TLR4 competent C3H/HeN mice than in TLR4 deficient C3H/HeJ mice. In addition, the size of tumors in C3H/HeN mice was reduced in vivo and their survival in vitro was inhibited by resveratrol to a significantly greater extent than in C3H/HeJ mice. Resveratrol inhibited angiogenesis to a much greater extent in the TLR4 competent mice than in TLR4 deficient mice. IFN‐γ and IL‐12 levels were also increased in TLR4 competent mice compared to TLR4 deficient mice, and TLR4 competent C3H/HeN mice exhibited a greater increase in the cell‐mediated immune response to DMBA. The results of this study indicate that TLR4 is an important mediator of resveratrol chemoprevention in DMBA skin tumorigenesis. Published 2009 Wiley‐Liss, Inc.