bluuebunny/crossref_metadata_2025 huggingface dataset:
A PHILOSOPHICAL FOUNDATION FOR UNIFICATION OF DYNAMIC MODELING METHODS BASED ON HIGHER-ORDER POTENTIALITIES AND THEIR REDUCERS
Authors: BOSSE TIBOR , TREUR JAN
Published: January 2009

In the development of disciplines addressing dynamics, a major role was played by the assumption that processes can be modeled by introducing state properties, called potentialities, anticipating in which respect a next state will be different. A second assumption often made is that these state properties can be related to other state properties, called reducers. This paper proposes a philosophical framework in terms of potentialities and their reducers, which can be used to obtain a common philosophical foundation for methods in AI, cognitive science and beyond to model dynamics. Based on this framework a metamodel for dynamic modeling approaches is described. The philosophical framework and the metamodel together provide a unified foundation for numerical, symbolic, and hybrid dynamic modeling approaches used in a large variety of disciplines.
TARTARUS AND FRACTAL GENE REGULATORY NETWORKS WITH INPUTS
Authors: ZAHADAT P. , KATEBI S. D.
Published: January 2009

Tartarus is a benchmark problem used to evaluate artificial intelligence techniques for solving problems in the field of non-Markovian agent motion planning. In this paper a fractal gene regulatory network with inputs is evolved to act as a virtual robot controller in the Tartarus environment. The proposed technique is compared and contrasted with other previously reported techniques and it is shown that the gene regulatory network that includes input information provides an excellent performance without using any explicit memory or environmental modeling. Detailed experimental studies are presented to illustrate the effectiveness and superiority of the proposed approach.
GENETIC ALGORITHMS WITH DYNAMIC MUTATION RATES AND THEIR INDUSTRIAL APPLICATIONS
Authors: CHAN K. Y. , FOGARTY T. C. , AYDIN M. EMIN , LING S. H. , IU H. H. C.
Published: January 2009

This paper presents a method on how to estimate main effects of gene representation. This estimate can be used not only to understand the domination of genes in the representation but also to design the mutation rate in genetic algorithms (GAs). A new approach of dynamic mutation rate is proposed by integrating the information of the main effects into the genes. By introducing the proposed method in GAs, both solution quality and solution stability can be improved in solving a set of parametrical test functions. The algorithm was applied to two illustrative applications to evaluate the performance of the proposed method, where the first application is on solving uncapacitated facility location problems and the next is on optimal power flow problems, which are employed. Results indicate that the proposed method yields significantly better results than the existing methods.
Skeletal changes associated with the onset of type 2 diabetes in the ZDF and ZDSD rodent models
Authors: Reinwald Susan , Peterson Richard G. , Allen Matt R. , Burr David B.
Published: January 2009

The incidence and prevalence of type 2 diabetes (T2D) continue to escalate at an unprecedented rate in the United States, particularly among populations with high rates of obesity. The impact of T2D on bone mass, geometry, architecture, strength, and resistance to fracture has yet to be incontrovertibly characterized because of the complex and heterogeneous nature of this disease. This study utilized skeletally mature male diabetic rats of the commonly used Zucker diabetic fatty (ZDF) and Zucker diabetic Sprague-Dawley (ZDSD) strains as surrogate models to assess alterations in bone attributable to T2D-like states. After the animals were euthanized, bone data were collected using dual-energy X-ray absorptiometry, peripheral quantitative tomography, and micro-CT imaging modalities and via three-point bending or compression mechanical testing methods. ZDF and ZDSD diabetic rats exhibited lower bone mineral densities, which coincided with declines in structural strength and increased fragility at the femoral midshaft and the L4 vertebral body in response to monotonic loading. Vertebral trabecular morphology was compromised in both diabetic rodent strains, and ZDSD diabetic rats exhibited additional phenotypic impairments to bone material properties at the spine. Because the metabolic origin of the T2D-like state that develops in the ZDSD rat strain is highly relevant to adult-onset diabetes, it is a particularly attractive novel model for future preclinical research.
Saccade Adaptation Specific to Visual Context
Authors: Herman James P. , Harwood Mark R. , Wallman Josh
Published: January 2009

When saccades consistently overshoot their targets, saccade amplitudes gradually decrease, thereby maintaining accuracy. This adaptive process has been seen as a form of motor learning that copes with changes in physical parameters of the eye and its muscles, brought about by aging or pathology. One would not expect such a motor-repair mechanism to be specific to the visual properties of the target stimulus. We had subjects make saccades to sudden movements of either of two targets—a steadily illuminated circle or a flickering circle—one of which stepped back during each saccade it elicited, simulating the effect of a hypermetric saccade. Saccade gain (saccade amplitude/target amplitude) decreased by 15% for the target that stepped back versus 6% for the target that did not step back. Most of the change in gain between successive blocks of trials of each type occurred on the first saccade of the block, decreasing by 0.12 on the first trial of a step-back block and increasing by 0.1 on the first trial of a no-step-back block. The differential adaptation of the two targets required postsaccadic feedback of both target types, as shown in a separate experiment, in which saccades to only one target received feedback, and the gain did not differ between the two target types. This demonstration that a context defined by a visual stimulus can serve as an effective cue for switching saccade gain between states suggests that saccade adaptation may have a heretofore unsuspected dimension of adaptability.
Antitumor Effects of a Combined 5-Aza-2′Deoxycytidine and Valproic Acid Treatment on Rhabdomyosarcoma and Medulloblastoma in Ptch Mutant Mice
Authors: Ecke Ines , Petry Frauke , Rosenberger Albert , Tauber Svantje , Mönkemeyer Sven , Hess Ina , Dullin Christian , Kimmina Sarah , Pirngruber Judith , Johnsen Steven A. , Uhmann Anja , Nitzki Frauke , Wojnowski Leszek , Schulz-Schaeffer Walter , Witt Olaf , Hahn Heidi
Published: January 2009

Patched (Ptch) heterozygous mice develop medulloblastoma (MB) and rhabdomyosarcoma (RMS) resembling the corresponding human tumors. We have previously shown that epigenetic silencing of the intact Ptch allele contributes to tumor formation in this model. Here, we investigated whether targeting of epigenetic silencing mechanisms could be useful in the treatment of Ptch-associated cancers. A reduction of endogenous DNA methyltransferase1 (Dnmt1) activity significantly reduced tumor incidence in heterozygous Ptch knockout mice. A combined treatment with the Dnmt inhibitor 5-aza-2′deoxycytidine (5-aza-dC) and the histone deacetlyase (HDAC) inhibitor valproic acid (VPA) efficiently prevented MB and RMS formation, whereas monotherapies with either drug were less effective. Wild-type Ptch expression was efficiently reactivated in tumors by 5-aza-dC/VPA combination therapy. This was associated with reduced methylation of the Ptch promoter and induction of histone hyperacetylation suggesting inhibition of HDACs in vivo. However, the treatment was not effective in clinically overt, advanced stage tumors. This is a first in vivo demonstration that targeting of Dnmt and HDAC activities is highly effective in preventing formation of Ptch-associated tumors. The results suggest a novel clinical strategy for consolidation therapy of corresponding tumors in humans after completion of conventional treatment. Our data also suggest that epigenetic therapy may be less effective in treating advanced stages of tumors, at least in this tumor model. [Cancer Res 2009;69(3):887–95]
Smad Ubiquitination Regulatory Factor 2 Promotes Metastasis of Breast Cancer Cells by Enhancing Migration and Invasiveness
Authors: Jin Chaoyang , Yang Yu-an , Anver Miriam R. , Morris Nicole , Wang Xiangchun , Zhang Ying E.
Published: January 2009

Controlled protein degradation mediated by ubiquitin/proteasome system (UPS) plays a crucial role in modulating a broad range of cellular responses. Dysregulation of the UPS often accompanies tumorigenesis and progression. Here, we report that Smad ubiquitination regulatory factor 2 (Smurf2), a HECT-domain containing E3 ubiquitin ligase, is up-regulated in certain breast cancer tissues and cells. We show that reduction of Smurf2 expression with specific short interfering RNA in metastatic breast cancer cells induces cell rounding and reorganization of the actin cytoskeleton, which are associated with a less motile and invasive phenotype. Overexpression of Smurf2 promotes metastasis in a nude mouse model and increases migration and invasion of breast cancer cells. Moreover, expression of Smurf2CG, an E3 ligase–defective mutant of Smurf2, suppresses the above metastatic behaviors. These results establish an important role for Smurf2 in breast cancer progression and indicate that Smurf2 is a novel regulator of breast cancer cell migration and invasion. [Cancer Res 2009;69(3):735–40]
Membrane Microvesicles as Actors in the Establishment of a Favorable Prostatic Tumoral Niche: A Role for Activated Fibroblasts and CX3CL1-CX3CR1 Axis
Authors: Castellana Donatello , Zobairi Fatiha , Martinez Maria Carmen , Panaro Maria Antonietta , Mitolo Vincenzo , Freyssinet Jean-Marie , Kunzelmann Corinne
Published: January 2009

Tumor microenvironment is enriched in plasma membrane microvesicles (MV) shed from all cell types that constitute the tumor mass, reflecting the antigenic profile of the cells they originate from. Fibroblasts and tumor cells mutually communicate within tumor microenvironment. Recent evidences suggest that tumor-derived MVs (TMV) exert a broad array of biological functions in cell-to-cell communication. To elucidate their role in cancer-to-fibroblast cell communication, TMV obtained from two prostate carcinoma cell lines with high and weak metastatic potential (PC3 and LnCaP, respectively) have been characterized. TMV exhibit matrix metalloproteinases (MMP) and extracellular MMP inducer at their surface, suggesting a role in extracellular matrix degradation. Moreover, TMV not only induce the activation of fibroblasts assessed through extracellular signal-regulated kinase 1/2 phosphorylation and MMP-9 up-regulation, increase motility and resistance to apoptosis but also promote MV shedding from activated fibroblasts able in turn to increase migration and invasion of highly metastatic PC3 cells but not LnCaP cells. PC3 cell chemotaxis seems, at least partially, dependent on membrane-bound CX3CL1/fractalkine ligand for chemokine receptor CX3CR1. The present results highlight a mechanism of mutual communication attributable not only to soluble factors but also to determinants harbored by MV, possibly contributing to the constitution of a favorable niche for cancer development. [Cancer Res 2009;69(3):785–93]
ADP-Ribosylation Factor 6 Regulates Glioma Cell Invasion through the IQ-Domain GTPase-Activating Protein 1-Rac1–Mediated Pathway
Authors: Hu Bo , Shi Binhai , Jarzynka Michael J. , Yiin Jia-Jean , D'Souza-Schorey Crislyn , Cheng Shi-Yuan
Published: January 2009

A common pathobiological feature of malignant gliomas is the insidious infiltration of single tumor cells into the brain parenchyma, rendering these deadly tumors virtually incurable with available therapies. In this study, we report that ADP-ribosylation factor 6 (ARF6), a Ras superfamily small GTPase, is abundantly expressed in invasive human glioma cells. Cellular depletion of ARF6 by small interfering RNA decreased Rac1 activation, impaired HGF-stimulated and serum-stimulated glioma cell migration in vitro, and markedly decreased the invasive capacity of invasive glioma in the brain. Furthermore, ectopic expression of ARF6 in glioma cells promoted cell migration via the activation of Rac1. Upon stimulation of glioma cells with HGF, we show that IQ-domain GTPase-activating protein 1 (IQGAP1) is recruited and overlaps with ARF6 at the leading edge of migrating cells. However, cellular depletion of ARF6 abrogated this recruitment of IQGAP1 and attenuated the formation of surface protrusions. ARF6 forms complexes with Rac1 and IQGAP1 in glioma cells upon HGF stimulation, and knockdown of IQGAP1 significantly inhibits ARF6-induced Rac1 activation and cell migration. Taken together, these data suggest that ARF6-mediated Rac1 activation is essential for glioma cell invasion via a signaling pathway that requires IQGAP1. [Cancer Res 2009;69(3):794–801]
β1 Integrin Adhesion Enhances IL-6–Mediated STAT3 Signaling in Myeloma Cells: Implications for Microenvironment Influence on Tumor Survival and Proliferation
Authors: Shain Kenneth H. , Yarde Danielle N. , Meads Mark B. , Huang Mei , Jove Richard , Hazlehurst Lori A. , Dalton William S.
Published: January 2009

The bone marrow microenvironmental components interleukin (IL)-6 and fibronectin (FN) individually influence the proliferation and survival of multiple myeloma (MM) cells; however, in vivo, these effectors most likely work together. We examined signaling events, cell cycle progression, and levels of drug response in MM cells either adhered to FN via β1 integrins, stimulated with IL-6, or treated with the two combined. Although G1-S cell cycle arrest associated with FN adhesion was overcome when IL-6 was added, the cell adhesion–mediated drug resistance (CAM-DR) was maintained in the presence of IL-6. Concomitant exposure of MM cells to IL-6 and FN adhesion revealed a dramatic increase in signal transducers and activators of transcription 3 (STAT3) phosphorylation, nuclear translocation, and DNA binding, compared with either IL-6 or FN adhesion alone in four MM cell lines. Importantly, this increase in STAT3 activation correlated with a novel association between STAT3 and gp130 in cells adhered to FN before stimulation with IL-6, relative to nonadherent cells. Taken together, these results suggest a mechanism by which collaborative signaling by β1 integrin and gp130 confers an increased survival advantage to MM cells. [Cancer Res 2009;69(3):1009–15]
Longitudinal Diffusion Tensor Magnetic Resonance Imaging Study of Radiation-Induced White Matter Damage in a Rat Model
Authors: Wang Silun , Wu Ed X. , Qiu Deqiang , Leung Lucullus H.T. , Lau Ho-Fai , Khong Pek-Lan
Published: January 2009

Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (λ//), and radial diffusivity (λ⊥) can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in λ// from 4 to 40 weeks postradiation, and an increase in λ⊥ with return to baseline in λ// at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in λ// correlated with reactive astrogliosis (P < 0.01) and λ⊥ correlated with demyelination (P < 0.01). Higher radiation dose (30 Gy) induced earlier and more severe histologic changes than lower radiation dose (25 Gy), and these differences were reflected by the magnitude of changes in λ// and λ⊥. DTI indices reflected the histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage. [Cancer Res 2009;69(3):1190–8]
Senescent Stromal-Derived Osteopontin Promotes Preneoplastic Cell Growth
Authors: Pazolli Ermira , Luo Xianmin , Brehm Sarah , Carbery Kelly , Chung Jun-Jae , Prior Julie L. , Doherty Jason , Demehri Shadmehr , Salavaggione Lorena , Piwnica-Worms David , Stewart Sheila A.
Published: January 2009

Alterations in the tissue microenvironment collaborate with cell autonomous genetic changes to contribute to neoplastic progression. The importance of the microenvironment in neoplastic progression is underscored by studies showing that fibroblasts isolated from a tumor stimulate the growth of preneoplastic and neoplastic cells in xenograft models. Similarly, senescent fibroblasts promote preneoplastic cell growth in vitro and in vivo. Because senescent cells accumulate with age, their presence is hypothesized to facilitate preneoplastic cell growth and tumor formation in older individuals. To identify senescent stromal factors directly responsible for stimulating preneoplastic cell growth, we carried out whole-genome transcriptional profiling and compared senescent fibroblasts with their younger counterparts. We identified osteopontin (OPN) as one of the most highly elevated transcripts in senescent fibroblasts. Importantly, reduction of OPN protein levels by RNA interference did not affect senescence induction in fibroblasts; however, it dramatically reduced the growth-promoting activities of senescent fibroblasts in vitro and in vivo, showing that OPN is necessary for paracrine stimulation of preneoplastic cell growth. In addition, we found that recombinant OPN was sufficient to stimulate preneoplastic cell growth. Finally, we show that OPN is expressed in senescent stroma within preneoplastic lesions that arise following 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate treatment of mice, suggesting that stromal-derived OPN-mediated signaling events affect neoplastic progression. [Cancer Res 2009;69(3):1230–9]
Loss of Rad51c Leads to Embryonic Lethality and Modulation of Trp53-Dependent Tumorigenesis in Mice
Authors: Kuznetsov Sergey G. , Haines Diana C. , Martin Betty K. , Sharan Shyam K.
Published: January 2009

RecA/Rad51 protein family members (Rad51, Rad51b, Rad51c, Rad51d, Xrcc2, and Xrcc3) are essential for DNA repair by homologous recombination, and their role in cancers has been anticipated. Here we provide the first direct evidence for a tumor suppressor function for a member of the Rad51 family. We show that Rad51c deficiency leads to early embryonic lethality, which can be delayed on a Trp53-null background. To uncover the role of Rad51c in tumorigenesis, we have exploited the fact that Rad51c and Trp53 are both closely located on the mouse chromosome 11. We have generated double heterozygous (DH) mice carrying mutant alleles of both genes either on different (DH-trans) or on the same chromosome (DH-cis), the latter allowing for a deletion of wild-type alleles of both genes by loss of heterozygosity. DH-trans mice, in contrast to DH-cis, developed tumors with latency and spectrum similar to Trp53 heterozygous mice. Strikingly, Rad51c mutation in DH-cis mice promoted the development of tumors of specialized sebaceous glands and suppressed tumors characteristic of Trp53 mutation. In addition, DH-cis females developed tumors significantly earlier than any other group. [Cancer Res 2009;69(3):863–72]
Limits to Thymidylate Synthase andTP53Genes as Predictive Determinants for Fluoropyrimidine Sensitivity and Further Evidence for RNA-Based Toxicity as a Major Influence
Authors: Brody Jonathan R. , Hucl Tomas , Costantino Christina L. , Eshleman James R. , Gallmeier Eike , Zhu Heng , van der Heijden Michiel S. , Winter Jordan M. , Wikiewicz Agnieszka K. , Yeo Charles J. , Kern Scott E.
Published: January 2009

The major determinants of 5-flurouracil (5-FU) response would seem, based on accumulated literature, to be thymidylate synthase (TYMS, TS) expression levels, TS gene modifications, and TP53 status. We tested 5-FU sensitivity in yeast and human cancer cell models in which TS or TP53 alleles and expression were varied. Polymorphic TS tandem repeat status, TS expression levels reported, TS intragenic mutations, and TP53 status in outbred and experimental cancer cell lines did not predict 5-FU sensitivity or resistance. Novel observations included a dose-resistant persistence of unbound TS protein in many cancers and, upon 5-FU treatment of the colon cancer cell line, HCT116, evidence of allelic switching favoring transcripts of the mutant TS allele. The reported alleles having an intragenic mutation could not be causally associated with major degrees of 5-FU sensitivity. In yeast, TS protein was altered upon treatment with FdUMP, but 5-FU toxicity seemed to be largely RNA-based, being rescued by uridine rather than by thymidine. Cancer cell lines were also rescued from 5-FU toxicity with uridine rather than thymidine. Additionally, a TS (CDC21) knockout yeast strain, obviating any potential role for TS protein as a target, was hypersensitive to 5-FU. When denatured proteins from cancer cells treated with radiolabeled 5-FU were labeled, species with alternative molecular weights other than TS were visualized, providing further evidence for alternative 5-FU protein targets. These data emphasize that TS and TP53 status do not consistently explain the variance in responses of fluoropyrimidine-treated cancer cells, in part due to RNA-based toxicity. [Cancer Res 2009;69(3):984–91]
A γ-Tocopherol–Rich Mixture of Tocopherols Inhibits Colon Inflammation and Carcinogenesis in Azoxymethane and Dextran Sulfate Sodium–Treated Mice
Authors: Ju Jihyeung , Hao Xingpei , Lee Mao-Jung , Lambert Joshua D. , Lu Gang , Xiao Hang , Newmark Harold L. , Yang Chung S.
Published: January 2009

We investigated the effects of a γ-tocopherol–rich mixture of tocopherols (γ-TmT, containing 57% γ-T, 24% δ-T, and 13% α-T) on colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)–treated mice. In experiment 1, 6-week-old male CF-1 mice were given a dose of AOM (10 mg/kg body weight, i.p.), and 1 week later, 1.5% DSS in drinking water for 1 week. The mice were maintained on either a γ-TmT (0.3%)–enriched or a standard AIN93M diet, starting 1 week before the AOM injection, until the termination of experiment. In the AOM/DSS–treated mice, dietary γ-TmT treatment resulted in a significantly lower colon inflammation index (52% of the control) on day 7 and number of colon adenomas (9% of the control) on week 7. γ-TmT treatment also resulted in higher apoptotic index in adenomas, lower prostaglandin E2, leukotriene B4, and nitrotyrosine levels in the colon, and lower prostaglandin E2, leukotriene B4, and 8-isoprostane levels in the plasma on week 7. Some of the decreases were observed even on day 7. In experiment 2 with AOM/DSS– treated mice sacrificed on week 21, dietary 0.17% or 0.3% γ-TmT treatment, starting 1 week before the AOM injection, significantly inhibited adenocarcinoma and adenoma formation in the colon (to 17-33% of the control). Dietary 0.3% γ-TmT that was initiated after DSS treatment also exhibited a similar inhibitory activity. The present study showed that γ-TmT effectively inhibited colon carcinogenesis in AOM/DSS–treated mice, and the inhibition may be due to the apoptosis-inducing, anti-inflammatory, antioxidative, and reactive nitrogen species–trapping activities of tocopherols.
Transrectal Ultrasound as Diagnostic Tool for the Detection of Local Recurrence following Cystectomy and Urinary Diversion
Authors: Simon J. , Bartsch Jr. G. , Rinnab L. , Hautmann R.E. , Volkmer B.G.
Published: January 2009

Objective: Routine follow-up after cystectomy for bladder cancer detect patients with local recurrence late in the course of disease. We set out to determine the value of transrectal ultrasound (TRUS) as diagnostic tool to diagnose local failure. Patients and Methods: Between 1986 and 2003, radical cystectomy for bladder cancer with orthotopic diversion was performed in 642 male patients. We identified all patients that simultaneously had transabdominal ultrasound, digital rectal examination, TRUS and CT/MRI of the pelvis at the diagnosis of local recurrence. Results: Mean follow-up was 59.4 months. 83/642 patients (13%) had local failure of bladder cancer during follow-up. In 48/642 patients (7.5%) the local recurrence was the first site of recurrence. 35/642 patients (5.5%) developed local failure with concomitant distant disease. 31/83 patients met the inclusion criteria. The median time between cystectomy and diagnosis of local recurrence was 13 months (2–51 months). Routine follow-up detected local recurrence in 1 asymptomatic patient. 25/31, 3/31 and 2/31 patients had pain in the lower extremities/pelvis, hematuria and urinary retention, respectively. Digital rectal examination, transabdominal ultrasound, TRUS, and CT/MRI of the pelvis were suspicious for local recurrence in 9, 7, 26, and 29 patients, respectively. Conclusions: TRUS is a highly sensitive tool in detecting local recurrence following cystectomy. It is easy to perform and inexpensive. We recommend TRUS in short intervals in all patients with high risk for local recurrence in order to detect cancer early.
Nephron-Sparing Surgery: The Effect of Surface Cooling and Temporary Renal Artery Occlusion on Renal Function
Authors: Bakirtas Hasan , Eroglu Muzaffer , Naldoken Seniha , Akbulut Ziya , Tekdogan U. Yener
Published: January 2009

Aims: To evaluate whether transient renal artery clamping and external renal hypothermia cause any detrimental effect on the remaining renal parenchyma after nephron-sparing surgery with the use of 99mTc-DMSA-SPECT. Methods: Twenty-eight patients with a unilateral renal mass but a normal contralateral kidney underwent nephron-sparing surgery. Serum biochemistry, 24-hour urinary creatinine clearance and absolute uptakes of the injected dose (%ID) of both kidneys as measured by renal 99mTc-DMSA-SPECT were compared preoperatively and in the 3rd postoperative month. 99mTc-DMSA uptakes in the contralateral kidney were used as controls. Results: The average tumor size and mean renal artery clamping time were 37.4 ± 11.3 (range 25–68) mm and 53.7 ± 13 (range 38–90) min, respectively. Pre- and postoperative mean absolute uptakes of %ID in the remaining parenchyma of the operated kidneys were 15.13 ± 3.30 and 14.74 ± 3.38%, respectively (p = 0.052). In the contralateral kidneys, there was also no significant difference between the two studies (18.82 ± 6.26 vs. 19.14 ± 7.19%, respectively; p = 0.546). Likewise, there was no statistically significant difference between pre- and postoperative serum creatinine (p = 0.179) and creatinine clearance values (p = 0.108). Conclusion: Renal artery clamping and external cooling during nephron-sparing surgery have no demonstrable harmful effects on the renal parenchyma as measured by 99mTc-DMSA-SPECT analysis.
Alterations of Urine TGF-β1 and bFGF following Bladder Outlet Obstruction: A Predictor for Detrusor Contractibility?
Authors: Shi Benkang , Zhu Yaofeng , Laudon Vincent , Ran Lingxia , Liu Yuqiang , Xu Zhishun
Published: January 2009

Objectives: To investigate the alterations of urine transforming growth factor-β1 (TGF-β1) and basic fibroblast growth factor (bFGF) following bladder outlet obstruction (BOO) in rats and to determine their correlation with the impaired detrusor contractibility. Methods: Wistar rats were divided into control, 2-week BOO 6-week and BOO groups. Impaired detrusor contractibility was quantified by measuring detrusor contraction force (DCF) of detrusor strip stimulated by carbachol. The enzyme-linked immunosorbent assay method was used to determine the urine levels of the 2 factors. Correlation analysis was conducted between DCF and urine levels of the 2 factors to see if there was an association between them after BOO. Results: DCF was found to be significantly lower in the 6-week BOO group than in the 2-week BOO and control groups. There is no significant difference regarding urine TGF-β1 between the 2-week BOO and control groups (p > 0.05). Urine TGF-β1 level in the 6-week BOO group was significantly higher than in the 2-week BOO (p < 0.05) and control groups (p < 0.05). There existed a negative correlation between DCF and urine TGF-β1 (p < 0.05). Conclusions: In an animal model, our results have suggested the potential role of urine TGF-β1 as a noninvasive biomarker to predict detrusor contractibility after BOO.
Prostate Cancer-Producing Granulocyte Colony-Stimulating Factor
Authors: Matsuoka Yoh , Arai Gaku , Okada Yume , Aida Junko
Published: January 2009

An 86-year-old man with a serum prostate-specific antigen level of 93.33 ng/ml was diagnosed as having cT3aN0M0 prostatic adenocarcinoma of Gleason score 9. Although the serum prostate-specific antigen responded well to combined androgen blockade, the cancer spread and lead to death 6 months after diagnosis. The patient had leukocytosis during the clinical course with no sign of localized infection, especially after manipulation of the prostate. Enzyme immunoassay demonstrated elevated serum levels of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor. To our knowledge, this is the first case of prostate cancer with G-CSF production, which was confirmed immunohistochemically.
Collagen Graft Interposition in Vesicovaginal Fistula Treatment
Authors: Robles J.E. , Saiz A. , Rioja J. , Brugarolas X. , Berian J.M.
Published: January 2009

Vesicovaginal fistula (VVF) is a quite rare complication of gynecological surgery. The first attempt to repair the fistulous tract offers the best opportunity for cure. We report the successful repair of VVF in 2 patients using a combined anterior vaginal approach and porcine dermal collagen grafting as interposition tissue. Favorable results confirm technical simplicity, safety and efficacy of this procedure.
A New Modified Renal Vein Anastomosis in Unilateral Dual Renal Transplantation
Authors: Wang Daohu , Li Heng-ai , Deng Suxiong , Chen Wei , Chen Lingwu
Published: January 2009

Transplantation of renal allografts inadequate to meet the recipient’s metabolic needs has been proposed as a cause of chronic allograft failure. Dual renal transplant is a novel idea to transplant enough nephron mass to solve this problem. According to the current literature, graft renal veins are anastomosed to the external iliac vein or inferior vena cava as venous drainage in the setting of dual renal transplantation. In the presented case, renal blood was returned through one of the grafts back to the systematic circulation through the other renal vein graft. This provides a feasible option for unilateral dual renal transplantation to accomplish renal vein anastomosis in some difficult situations.
Insulin-Like Growth Factor I and Growth Responses during the First Year of Growth Hormone Treatment in KIGS Patients with Idiopathic Growth Hormone Deficiency, Acquired Growth Hormone Deficiency, Turner Syndrome and Born Small for Gestational Age
Authors: Cutfield Wayne S. , Lundgren Frida
Published: January 2009

Background and Methods: We assessed the value of in- sulin-like growth factor I (IGF-I) monitoring during growth hormone (GH) treatment by retrospectively examining the relationships between (1) GH dose and IGF-I response, (2) baseline serum IGF-I concentration and growth response and (3) serum IGF-I response and growth response after 1 year of GH treatment among patients in the Pfizer International Growth Study database (KIGS). KIGS patients were eligible for the study if they were classified as having idiopathic GH deficiency, acquired GH deficiency, Turner syndrome or were born small for gestational age. Results: Correlations between GH dose and IGF-I response and between pretreatment IGF-I values and first-year growth response were weak across all groups. Correlations between the IGF-I response and growth response after 1 year of treatment were greater than those between baseline serum IGF-I values and first-year growth response. Pre- and posttreatment clinical characteristics were consistently different across all groups, but the numerous technical factors affecting these relationships are remediable. Conclusions: IGF-I monitoring during GH therapy is a valuable tool to monitor compliance and ensure that IGF-I levels do not exceed the normal range for extended periods. IGF-I monitoring may help clinicians increase GH doses as needed during puberty to achieve normal serum IGF-I values and normal or enhanced growth.
Evaluation of Right Ventricular Systolic and Diastolic Function in Patients with Newly Diagnosed Obstructive Sleep Apnea Syndrome without Hypertension
Authors: Tugcu Aylin , Guzel Deniz , Yildirimturk Ozlem , Aytekin Saide
Published: January 2009

Objectives: We investigated right ventricular (RV) structural and functional cardiac alterations in obstructive sleep apnea (OSA) independent of systemic hypertension and their correlation to the severity of OSA. Methods: Forty-one moderate-to-severe OSA but otherwise healthy patients and 30 body mass index-matched control subjects were included. All subjects underwent 24-hour ambulatory blood pressure monitoring, standard and tissue Doppler imaging of the RV. Results: The OSA group had increased RV wall thickness, impaired right ventricular outflow tract fractional shortening (RVOT fs), tricuspid annular plane systolic excursion (TAPSE), RV myocardial performance index (MPI) and RV myocardial acceleration during isovolumic contraction (IVA) (p < 0.001). Apnea hypopnea index (AHI) and mean pulmonary artery (PA) pressure were correlated with all these indices (p < 0.01 for all). RV free wall thickness (p < 0.001) and IVA (p = 0.006) remained significant predictors of AHI after adjusting for age, body mass index, mean PA pressure, RVOT fs, TAPSE and MPI in a multiple stepwise linear regression model. Conclusions: OSA is associated with impaired RV function despite normal systemic blood pressures. The level of RV dysfunction has a direct relationship with the severity of OSA. RV free wall thickness and IVA are independent predictors of AHI in uncomplicated OSA patients.
Plasma B-Type Natriuretic Peptide as a Marker of Myocardial Asynchrony
Authors: Ciuraszkiewicz Katarzyna , Janion Marianna , Dudek Dariusz , Gawor Zenon
Published: January 2009

Objectives: Myocardial asynchrony in postinfarction patients with intraventricular conduction defects (IVCD) may influence plasma levels of B-type natriuretic peptide (BNP). The aim of the study is to evaluate asynchrony parameters in postinfarction patients with IVCD and to define the relationship between plasma levels of BNP and echocardiographic parameters of asynchrony. Methods: The study included 158 patients 6 months after myocardial infarction (MI): 126 patients with IVCD and 32 patients without IVCD. Plasma levels of BNP were measured using an immunoenzymatic method. Left ventricular (LV) function was evaluated in echocardiography. Results: In patients with post-MI IVCD, the mean plasma level of BNP was 280.2 ± 340.2 versus 181.7 ± 270.4 pg/ml (p < 0.001) and they had significantly higher parameters of interventricular asynchrony as compared with subjects without postinfarction IVCD. Multifactorial regression analysis showed that in patients with an ejection fraction (EF) ≥50%, interventricular asynchrony and intraventricular delay significantly influenced the BNP level. In patients with an EF <50%, BNP levels were correlated with the magnitude of the EF. Conclusion: Plasma levels of BNP 6 months after MI depend not only on parameters of LV function but also on LV asynchrony and may serve as its marker in patients with IVCD and preserved LV systolic function.
Increased Serum 90K and Galectin-3 Expression Are Associated with Advanced Stage and a Worse Prognosis in Diffuse Large B-Cell Lymphomas
Authors: Kim Seok Jin , Lee Seung Jin , Sung Hwa Jung , Choi In Keun , Choi Chul Won , Kim Byung Soo , Kim Jun Suk , Yu Woosung , Hwang Hee Sang , Kim In Sun
Published: January 2009

The role of 90K and galectin-3 in cell-to-extracellular matrix adhesion and tumor metastasis has been reported, but little is known about their role in the prognosis and extranodal involvement of diffuse large B-cell lymphomas (DLBCL). Thus, we measured serum 90K concentration by enzyme-linked immunosorbent assay and tissue expression of galectin-3 by immunohistochemistry in newly diagnosed DLBCL patients. The mean serum 90K concentration was higher in DLBCL than in healthy controls (1,408.81 ± 89.45 vs. 980.94 ± 58.69 ng/ml, p = 0.036). High serum 90K (median value ≥1,249.50 ng/ml) and high galectin-3 expression (grade 3 positive staining in >75% of cells) showed a significant association with stage III/IV, ≥2 extranodal involvements and risk of high/high-intermediate international prognostic index (p < 0.05). The complete response (CR) rate (86.9%, 20/23) in the low 90K group was higher than in the high 90K group (56.5%, 13/23). Among 14 patients with high galectin-3 expression, only 6 patients showed CR (42.9%). The time to progression and overall survival were shorter in the group with high 90K and galectin-3 expression (p < 0.05). In conclusion, serum 90K and galectin-3 expression might be useful markers to indicate the extent of lymphoma involvement and prognosis in DLBCL.
A Case of Amyoplasia in a Monochorionic Twin Pregnancy: A Sequela from Twin-Twin Transfusion Syndrome?
Authors: Wong H.S. , Kidd A. , Zuccollo J. , Parker S. , Richardson V. , Tait J. , Pringle K.C.
Published: January 2009

Objective: To present and discuss the sonographic and clinical findings in one twin of a monochorionic pair affected by amyoplasia. Methods: On ultrasound examination at 21 weeks in a monochorionic twin pregnancy, twin I was smaller, hydropic, with multiple contractures consistent with amyoplasia and oligohydramnios. Twin II was anatomically normal with polyhydramnios. Results: The twins were delivered at 28 weeks’ gestation. The clinical findings were consistent with twin-twin transfusion syndrome (TTTS). Conclusion: It is postulated that TTTS may be a causative factor in the excessive incidence of amyoplasia in monozygotic twin pregnancy.
Increased Risk of Anastomotic Leakage with Diclofenac Treatment after Laparoscopic Colorectal Surgery
Authors: Klein Mads , Andersen Lars Peter Holst , Harvald Thomas , Rosenberg Jacob , Gögenur Ismail
Published: January 2009

Background: Over a period our department experienced an unexpected high frequency of anastomotic leakages. After diclofenac was removed from the postoperative analgesic regimen, the frequency dropped. This study aimed to evaluate the influence of diclofenac on the risk of developing anastomotic leakage after laparoscopic colorectal surgery. Methods: This was a retrospective case-control study based on 75 consecutive patients undergoing laparoscopic colorectal resection with primary anastomosis. In period 1, patients received diclofenac 150 mg/day. In period 2, diclofenac was withdrawn and the patients received an opioid analgesic instead. The primary outcome parameter was clinically significant anastomotical leakage verified at reoperation. Results: 1/42 patients in the no-diclofenac group compared with 7/33 in the diclofenac group had an anastomotic leakage after operation (p = 0.018). In a multivariate regressional analysis, none of the recorded factors were significantly associated with the frequency of anastomotical leakages when diclofenac treatment was omitted from the model. Conclusions: We found an increased number of clinically significant anastomotic leakages in patients receiving oral diclofenac for postoperative analgesia. There is an urgent need to test our hypothesis in prospective randomized clinical trials and to examine whether our findings can be extended to open surgery and to other NSAIDs.
Embolization as Treatment of Choice for Bleeding Peptic Ulcers in High-Risk Patients
Authors: van Vugt Raoul , Bosscha Koop , van Munster Ivo P. , de Jager Cornelis P.C. , Rutten Matthieu J.C.M.
Published: January 2009

Background/Aim: Peptic ulcers are the most common cause of acute upper gastrointestinal bleedings in the digestive tract. Most patients are poor surgical candidates. The aim was to describe the efficacy of embolization as the treatment of choice for bleeding peptic ulcers in high-risk patients when endoscopic treatment failed. Methods: All patients who underwent a selective embolization of branches of the superior mesenteric artery and/or branches of the gastroduodenal artery for a bleeding peptic ulcer in the period January 2004 until December 2007 were included in this retrospective descriptive study. We examined the known risk factors for surgery and mortality in upper gastrointestinal bleeding due to peptic ulcers and describe the clinical course and outcome. Primary endpoints were the primary technical success and the clinical success rates. The secondary endpoint was the 30-day mortality. Results: 16 patients were included. All patients had at least two risk factors for surgery and mortality. The clinical success rate was 81% (13/16). The first embolization failed in 3 patients, 1 was successful re-embolized and 2 were operated upon without re-embolization. The primary technical success rate, i.e. bleedings controlled by radiologic intervention, was 88% (14/16). 6 patients died due to non-embolization-related problems; 5 of them developed upper gastrointestinal bleeding during a stay in the hospital. Conclusion: Embolization was a successful, minimal invasive alternative for surgical intervention in high-risk patients with upper gastrointestinal bleeding after failure of endoscopic treatment.
Plasma Homocysteine Levels and Different Forms of Vascular Disease in Patients with Dementia and Other Psychogeriatric Diseases
Authors: Nilsson Karin , Gustafson Lars , Hultberg Björn
Published: January 2009

Background: Total plasma homocysteine (tHcy) concentration is elevated in patients with psychogeriatric disease. There are many different determinants of plasma tHcy concentration, including the presence of vascular disease. Method: We investigated plasma tHcy levels in several different subgroups of vascular disease and also the relation between plasma tHcy and renal function in patients with psychogeriatric disease. Results: All different groups of patients with vascular disease exhibited an elevated level of plasma tHcy compared to patients without vascular disease even after exclusion of patients with folate/cobalamin deficiency. Patients with elevated serum creatinine with or without vascular disease exhibited significantly increased plasma tHcy compared to the respective groups of patients without elevated serum creatinine. Patients with vascular dementia and Alzheimer’s disease with concomitant vascular disease exhibited significantly increased plasma tHcy levels compared to patients without vascular disease. Conclusion: The presence of vascular disease increases the level of plasma tHcy and renal impairment further increases the elevated plasma tHcy level. Furthermore, the findings suggest similar influence on plasma tHcy turnover irrespective of whether the vascular disease is of cerebral or extracerebral origin or only manifests itself as arrhythmia or hypertension.
Coexpression of GABABR1 and GABABR2 Receptor Subunits in the Rat Vestibular Nucleus
Authors: Lai C.H. , Ng K.Y. , Yung K.K.L. , Shum D.K.Y. , Chan Y.S.
Published: January 2009

The expression patterns of the two subunits of the metabotropic GABAB receptor, GABABR1 and GABABR2, vary among various neural regions and their relative expression in the rat central vestibular system remains unknown. To identify the expression patterns of these two subunits of the metabotropic GABAB receptor in the vestibular nucleus of adult rats, double immunofluorescence experiments were performed. GABABR1 or GABABR2 immunoreactivity was observed in neurons and neuropilar elements of the vestibular nuclear complex and its subgroups x and y. These neurons were oval, multipolar, fusiform or triangular in shape. In contrast to other brain regions, individual neurons or neuropil within the various vestibular subnuclei and subgroups displayed comparable levels of GABABR1 and GABABR2 immunoreactivity. Double immunofluorescence experiments further demonstrated the coexpression of GABABR1 and GABABR2 receptor subunits in individual central vestibular neurons. The present findings provide histological evidence of the heterodimeric nature of GABAB receptors that mediate inhibitory neurotransmission in the rat vestibular nuclei.
Surgical Outcome and Long-Term Follow-Up after Segmental Colorectal Resection in Women with a Complete Obstruction of the Rectosigmoid due to Endometriosis
Authors: de Jong M.J.H. , Mijatovic V. , van Waesberghe J.H.T.M. , Cuesta M.A. , Hompes P.G.A.
Published: January 2009

Introduction: Intestinal involvement is reported in up to 12% of women with endometriosis. Complete large bowel obstruction is a rare complication of intestinal endometriosis. It is estimated to occur in less than 1% of the cases. Objective: The aim of this study is to evaluate the surgical outcome and long-term follow-up after segmental colorectal resection in women with a complete obstruction of the rectosigmoid due to endometriosis. In addition, the diagnostic work-up is described and discussed in view of the current literature. Patients and Methods: We present a case series of 5 patients with a complete obstruction of the rectosigmoid due to endometriosis who were finally treated in our hospital within a multidisciplinary endometriosis team. We retrospectively analyzed all patients with this condition who were referred in the period January 2000 to December 2006. Results: All patients (mean age 31.8 years, range 25–43 years) underwent emergency surgery resulting in a diverting colostomy before referral to our hospital. The principal diagnostic tool used was magnetic resonance imaging which demonstrated in all patients multiorgan endometriosis with complete obstruction of the rectosigmoid. Thereafter, all patients underwent a segmental colorectal resection by re-laparotomy. The diagnosis intestinal endometriosis was histologically confirmed in all cases. After surgery no major complications occurred. During a follow-up of 18–36 months, residual symptoms such as chronic constipation, deep dyspareunia and chronic pelvic pain were reported in 2 patients. No recurrences of intestinal endometriosis occurred. Conclusion: In our case series, segmental colorectal resection showed a favorable surgical outcome with no major complications. In the long-term follow-up, a limited number of residual symptoms were reported and no recurrences occurred. Intestinal endometriosis as a cause of bowel obstruction is often a diagnostic challenge mimicking a broad spectrum of diseases. It should be included in the differential diagnosis in women of reproductive age presenting with any symptoms of bowel obstruction. Magnetic resonance imaging is recommended as the primary imaging technique in such cases. In our opinion, these patients should be treated in a multidisciplinary setting.