bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in cerebellar activation pattern during two successive sequences of saccades
Authors: Stephan Thomas , Mascolo Andrea , Yousry Tarek A. , Bense Sandra , Brandt Thomas , Dieterich Marianne 
Published: August 2002

AbstractThe changes in the cerebellar activation pattern of two successive fMRI scanning runs were determined for visually guided to‐and‐fro saccades in 12 healthy volunteers familiar with the study paradigm. Group and single subject‐analyses revealed a constant activation of the paramedian cerebellar vermis (uvula, tonsils, tuber, folium/declive), which reflects constant ocular motor activity in both runs. A significant decrease in activation of the cerebellar hemispheres found in the second run is best explained by either a decrease in attention or the effects of motor optimization and learning. The significant, systematic changes of the cerebellar activation pattern in two successive runs were not expected, because the ocular motor task was simple, familiar, and highly automated. These findings indicate that similar effects may bias other cerebellar activation studies, in which sensorimotor tasks are repeated in a single session. Hum. Brain Mapping 16:63–70, 2002. © 2002 Wiley‐Liss, Inc.
Reaction with hydrazonoyl halides. Part 32 [1]: Reaction of C‐acyl‐N‐(3‐phenyl‐5‐pyrazolyl)hydrazonoyl chlorides with potassium thiocyanate and synthesis of some new 2,3‐dihydro‐1,3,4‐thiadiazoles and slenadiazoles
Authors: Abdelhamid Abdou O. , Sallam M. M. M. , Amer S. A. 
Published: August 2002

AbstractC‐acyl‐N‐(3‐phenyl‐5‐pyrazolyl)hydrazonoyl chlorides 1a,b react with potassium thiocyanate and potassium selenocyanate to give 5‐acyl‐2,3‐dihydro‐2‐imino‐3‐(3′‐phenyl)pyrazol‐5′‐yl)‐1,3,4‐thiadiazoles 2a,b and 5‐acetyl‐2,3‐dihydro;‐2‐imino‐3‐(3′‐phenyl)pyrazol‐5′‐yl)‐1,3,4‐selenadiazole 10a,b. Also, 2‐[mercapto‐(methylthio)methylene]indan‐1,3‐dione 16 reacts with hydrazonoyl halides 15 and 22–25 to afford 2,3‐dihydro‐1,3,4‐thiadiazoles 19 and 26–29, respectively. Structures of the newly synthesized compounds are elucidated on the basis of spectral data, chemical transformations, and alternative synthesis methods. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:468–474, 2001
Syntheses of optically active 2‐(2‐benzothiazolylimino)‐heterazolidines
Authors: Cruz Alejandro , Gayosso Martha , Contreras Rosalinda 
Published: August 2002

AbstractThe syntheses of compounds 4R, 5R‐2‐[2‐benzothiazolylimino]‐3‐hydro‐4‐methyl‐5‐phenylthiazolidine (5a), 4S,5S‐2‐[2‐benzothiazolylimino]‐3,4‐dimethyl‐5‐phenylthiazolidine (5b), 4R,5S‐[2‐benzothiazolylimino]‐3‐hydro‐4‐methyl‐5‐phenyloxazolidine (5c), 4R,5S‐2‐[2‐benzothiazolyl‐imino]‐3,4‐dimethyl‐5‐phenyloxazolidine (5d), and 4R,5S‐2‐[2‐benzothiazolylimino]‐1,3,4‐trimethyl‐5‐phenylimidazolidine (5e) are reported. The stereochemistry of the reaction products and the X‐ray diffraction analyses of compounds 5a–d are discussed. Compounds 5a–d present planar structures. We have found short distances between the thiazolidine S1 atom and the benzothiazole N9 atom for 5a and 5b (2.782 and 2.824 Å, respectively) and the distance between the oxazolidine O1 and the benzothiazole S7 for 5d (2.721 Å). These distances are shorter than the sum of the van der Waals radii. These distances, together with the coplanarity of the heterocycles, seem to indicate the existence of a weak coordination bonding from sp2 oxygen or nitrogen atoms towards the sulfur atom. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:586–593, 2001
Wait‐and‐see policy for the N0 neck in early‐stage oral and oropharyngeal squamous cell carcinoma using ultrasonography‐guided cytology: Is there a role for identification of the sentinel node?
Authors: Nieuwenhuis Eline J. C. , Castelijns Jonas A. , Pijpers Rik , van den Brekel Michiel W. M. , Brakenhoff Ruud H. , van der Waal Isaac , Snow Gordon B. , Leemans Charles R. 
Published: August 2002

AbstractBackgroundManagement of the N0 neck in patients with head and neck squamous cell carcinoma (SCC) remains controversial. We describe the outcome of patients who underwent transoral tumor excision and a wait‐and‐see policy for the neck staged N0 by ultrasonography‐guided cytology (USgFNAC). Because selection of lymph nodes for USgFNAC is currently based on size criteria, we investigated the additional value of sentinel node (SN) identification.MethodsThe outcome of 161 patients with T1–T2 oral/oropharyngeal SCC was determined. In a subgroup of 39 patients the SN was identified and aspirated in addition.ResultsSN identification and aspiration was possible in 38 of 39 patients but without decreasing the false‐negative rate of USgFNAC. During follow‐up (12–99 months) 34 of 161 (21%) patients developed lymph node metastases. After therapeutic neck dissection and postoperative radiotherapy, 27 of 34 (79%) could be salvaged (88% regional control).ConclusionsWait‐and‐see seems justified in case of negative USgFNAC. Strict follow‐up with USgFNAC is required. SN identification and aspiration is feasible but did not improve lymph node selection. © 2002 Wiley Periodicals, Inc. Head Neck 24: 282–289, 2002; DOI 10.1002/hed.10018
Omental free flap reconstruction in complex head and neck deformities
Authors: Losken Albert , Carlson Grant W. , Culbertson John H. , Scott Hultman C. , Kumar Ajay V. , Jones Glyn E. , Bostwick John , Jurkiewicz Maurice J. 
Published: August 2002

AbstractBackgroundMicrovascular free flaps continue to revolutionize coverage options in head and neck reconstruction. This article reviews our 25‐year experience with omental free tissue transfers.MethodsAll patients who underwent free omental transfer to the head and neck region were reviewed.ResultsFifty‐five patients were included with omental transfers to the scalp (25%), craniofacial (62%), and neck (13%) region. Indications were tumor resections, burn wound, hemifacial atrophy, trauma, and moyamoya disease. Average follow‐up was 3.1 years (range, 2 months–13 years). Donor site morbidities included abdominal wound infection, gastric outlet obstruction, and postoperative bleeding. Recipient site morbidities included partial flap loss in four patients (7%) total flap loss in two patients (3.6%), and three hematomas.ConclusionsThe omental free flap has acceptable abdominal morbidity and provides sufficient soft tissue coverage with a 96.4% survival. The thickness \and versatility of omentum provide sufficient contour molding for craniofacial reconstruction. It is an attractive alternative for reconstruction of large scalp defects and badly irradiated tissue. © 2002 Wiley Periodicals, Inc. Head Neck 24: 326–331, 2002; DOI 10.1002/hed.10082
Beyond health care cost containment: creating collaborative arrangements among the stakeholders
Authors: Young David W. , McCarthy Sheila M. , Barrett Diana , Kenagy John W. , Pinakiewicz Diane C. 
Published: August 2002

AbstractThe causes of escalating healthcare costs in the United States and many other industrial countries are well documented. Less evident are the structural factors that underlie the increases and their implications for the future. This paper discusses these structural factors, puts them in the context of the healthcare marketplace, and proposes a way to address them using a collaborative arrangement among all stakeholders in a healthcare system, called value‐based partnering. To be successful, the effort must include not only final purchasers (such as employers or Medicare in the USA) but all stakeholders in a healthcare system. Each stakeholder must develop a value equation in terms that are meaningful to the others, and must identify opportunities for value‐enhancing partnerships. The paper also identifies some of the impediments to value‐based partnering and discusses ways to overcome them, including the need for senior management intervention within some stakeholder groups, and the importance of collaborative discussions among all stakeholders. Copyright © 2001 John Wiley & Sons, Ltd.
A non‐conventional watershed partitioning method for semi‐distributed hydrological modelling: the package ALADHYN
Authors: Menduni Giovanni , Pagani Alessandro , Rulli Maria Cristina , Rosso Renzo 
Published: August 2002

AbstractThe extraction of the river network from a digital elevation model (DEM) plays a fundamental role in modelling spatially distributed hydrological processes. The present paper deals with a new two‐step procedure based on the preliminary identification of an ideal drainage network (IDN) from contour lines through a variable mesh size, and the further extraction of the actual drainage network (AND) from the IDN using land morphology. The steepest downslope direction search is used to identify individual channels, which are further merged into a network path draining to a given node of the IDN. The contributing area, peaks and saddles are determined by means of a steepest upslope direction search. The basin area is thus partitioned into physically based finite elements enclosed by irregular polygons. Different methods, i.e. the constant and variable threshold area methods, the contour line curvature method, and a topologic method descending from the Hortonian ordering scheme, are used to extract the ADN from the IDN. The contour line curvature method is shown to provide the most appropriate method from a comparison with field surveys. Using the ADN one can model the hydrological response of any sub‐basin using a semi‐distributed approach. The model presented here combines storm abstraction by the SCS‐CN method with surface runoff routing as a geomorphological dispersion process. This is modelled using the gamma instantaneous unit hydrograph as parameterized by river geomorphology. The results are implemented using a project‐oriented software facility for the Analysis of LAnd Digital HYdrological Networks (ALADHYN). Copyright © 2002 John Wiley & Sons, Ltd.
Impact of human bladder cancer cell architecture on autologous T‐lymphocyte activation
Authors: Dangles Virginie , Validire Pierre , Wertheimer Mireille , Richon Sophie , Bovin Christophe , Zeliszewski Dominique , Vallancien Guy , Bellet Dominique 
Published: August 2002

AbstractTo investigate the influence of tumor cell architecture on T‐cell activation, we used an autologous human model based on 2 bladder tumor cell lines as targets for cytotoxic tumor‐infiltrating lymphocytes (TILs). These tumor cell lines were grown in vitro as either standard 2‐dimensional (2D) monolayers or 3‐dimensional (3D) spheroids. T‐cell activation was determined by measuring the production of three major cytokines (tumor necrosis factor, granulocyte/macrophage colony‐stimulating factor and interferon‐γ), known to be secreted by most activated TILs. Changes in the architecture of target cells from 2D to 3D induced a dramatic decrease in their capacity for stimulating TILs. Interestingly, neither TIL infiltration nor MHC class I, B7.1 costimulatory or lymphocyte function‐associated factor‐3 adhesion molecule downregulation played a major role in this decrease. These findings demonstrate that tumor architecture has a major impact on T‐cell activation and might be implicated in the escape of tumor cells from the immune system. © 2001 Wiley‐Liss, Inc.
Bcl‐XL is a chemoresistance factor in human melanoma cells that can be inhibited by antisense therapy
Authors: Heere‐Ress Elisabeth , Thallinger Christiane , Lucas Trevor , Schlagbauer‐Wadl Hermine , Wacheck Volker , Monia Brett P. , Wolff Klaus , Pehamberger Hubert , Jansen Burkhard 
Published: August 2002

AbstractMalignant melanoma is a tumor that responds poorly to a variety of apoptosis‐inducing treatment modalities, such as chemotherapy. The expression of genes that regulate apoptotic cell death plays an important role in determining the sensitivity of tumor cells to chemotherapeutic intervention. Bcl‐xL is an antiapoptotic member of the Bcl‐2 family and is universally expressed in human melanoma. To evaluate the Bcl‐xL protein as a potential therapeutic target in melanoma, the influence of Bcl‐xL expression levels on the chemoresistance of human melanoma cells was investigated. Overexpression of Bcl‐xL in stably transfected human melanoma Mel Juso cells significantly reduced sensitivity to cisplatin‐induced apoptosis (p ≤ 0.05). In a parallel approach, reduction of Bcl‐xL protein by specific AS oligonucleotide (ISIS 16009) treatment enhanced the chemosensitivity of Mel Juso cells by 62% compared to cells treated with MM control oligonucleotide (ISIS 16967) as well as chemotherapy‐induced apoptosis. These data suggest that Bcl‐xL is an important factor contributing to the chemoresistance of human melanoma. Reduction of Bcl‐xL expression by AS oligonucleotides provides a rational and promising approach that may help to overcome chemoresistance in this malignancy. © 2002 Wiley‐Liss, Inc.
Comparison of aluminium (III) phthalocyanine tetrasulfonate‐ and meta‐tetrahydroxyphenylchlorin‐monoclonal antibody conjugates for their efficacy in photodynamic therapy in vitro
Authors: Vrouenraets Maarten B. , Visser Gerard W.M. , Stigter Marÿke , Oppelaar Hugo , Snow Gordon B. , van Dongen Guus A.M.S. 
Published: August 2002

AbstractA challenge in photodynamic therapy (PDT) is to improve the tumour selectivity of the photosensitizers by using monoclonal antibodies (MAbs). With this aim, we developed MAb‐conjugates with the hydrophobic photosensitizer meta‐tetrahydroxyphenylchlorin (mTHPC) and with the hydrophilic sensitizer aluminium (III) phthalocyanine tetrasulfonate (AlPcS4). The capacity of these photoimmunoconjugates for selective targeting of squamous cell carcinoma (SCC) in vivo was demonstrated previously in SCC‐bearing nude mice. Preliminary in vitro PDT studies with the vulvar SCC cell line A431 showed promising phototoxicity with both sensitizers when coupled to the internalizing MAb 425. To rank the photosensitizers for their potential in photoimmunotherapy, we herein describe an extensive in vitro evaluation of mTHPC‐MAb and AlPcS4‐MAb conjugates. Both classes of conjugates were directly compared using 5 different SCC cell lines as target and 3 different MAbs (BIWA 4, E48 and 425) for tumour cell targeting. In contrast to free AlPcS4 (IC50 ≥ 700 nM), MAb‐conjugated AlPcS4 was found to be highly phototoxic in PDT in all 5 cell lines. AlPcS4‐BIWA 4 was most consistently effective with IC50 values ranging from 0.06–5.4 nM. mTHPC‐MAb conjugates were in general hardly effective. Phototoxicity (log IC50) of the AlPcS4‐MAb conjugates was found to be strongly correlated with their total cell binding capacity (internalized and surface bound) and to be less correlated with their internalization capacity. In conclusion, these data show a high potential of AlPcS4‐MAb conjugates in comparison to mTHPC‐MAb conjugates for use in PDT. © 2002 Wiley‐Liss, Inc.
Molecular classification of borderline ovarian tumors using hierarchical cluster analysis of protein expression profiles
Authors: Alaiya Ayodele A. , Franzén Bo , Hagman Anders , Dysvik Bjarte , Roblick Uwe J. , Becker Susanne , Moberger Birgitta , Auer Gert , Linder Stig 
Published: August 2002

AbstractOvarian tumors range from benign to aggressive malignant tumors, including an intermediate class referred to as borderline carcinoma. The prognosis of the disease is strongly dependent on tumor classification, where patients with borderline tumors have much better prognosis than patients with carcinomas. We here describe the use of hierarchical clustering analysis of quantitative protein expression data for classification of this type of tumor. An accurate classification was not achieved using an unselected set of 1,584 protein spots for clustering analysis. Different approaches were used to select spots that were differentially expressed between tumors of different malignant potential and to use these sets of spots for classification. When sets of proteins were selected that differentiated benign and malignant tumors, borderline tumors clustered in the benign group. This is consistent with the biologic properties of these tumors. Our results indicate that hierarchical clustering analysis is a useful approach for analysis of protein profiles and show that this approach can be used for differential diagnosis of ovarian carcinomas and borderline tumors. © 2002 Wiley‐Liss, Inc.
Nuclear PTEN expression and clinicopathologic features in a population‐based series of primary cutaneous melanoma
Authors: Whiteman David C. , Zhou Xiao‐Ping , Cummings Margaret C. , Pavey Sandra , Hayward Nicholas K. , Eng Charis 
Published: August 2002

AbstractGermline mutations of the PTEN tumor‐suppressor gene, on 10q23, cause Cowden syndrome, an inherited hamartoma syndrome with a high risk of breast, thyroid and endometrial carcinomas and, some suggest, melanoma. To date, most studies which strongly implicate PTEN in the etiology of sporadic melanomas have depended on cell lines, short‐term tumor cultures and noncultured metastatic melanomas. The only study which reports PTEN protein expression in melanoma focuses on cytoplasmic expression, mainly in metastatic samples. To determine how PTEN contributes to the etiology or the progression of primary cutaneous melanoma, we examined cytoplasmic and nuclear PTEN expression against clinical and pathologic features in a population‐based sample of 150 individuals with incident primary cutaneous melanoma. Among 92 evaluable samples, 30 had no or decreased cytoplasmic PTEN protein expression and the remaining 62 had normal PTEN expression. In contrast, 84 tumors had no or decreased nuclear expression and 8 had normal nuclear PTEN expression. None of the clinical features studied, such as Clark's level and Breslow thickness or sun exposure, were associated with cytoplasmic PTEN expressional levels. An association with loss of nuclear PTEN expression was indicated for anatomical site (p = 0.06) and mitotic index (p = 0.02). There was also an association for melanomas to either not express nuclear PTEN or to express p53 alone, rather than both simultaneously (p = 0.02). In contrast with metastatic melanoma, where we have shown previously that almost two‐thirds of tumors have some PTEN inactivation, only one‐third of primary melanomas had PTEN silencing. This suggests that PTEN inactivation is a late event likely related to melanoma progression rather than initiation. Taken together with our previous observations in thyroid and islet cell tumors, our data suggest that nuclear–cytoplasmic partitioning of PTEN might also play a role in melanoma progression. © 2002 Wiley‐Liss, Inc.
Suberoylanilide hydroxamic acid (SAHA) overcomes multidrug resistance and induces cell death in P‐glycoprotein‐expressing cells
Authors: Ruefli Astrid A. , Bernhard David , Tainton Kellie M. , Kofler Reinhard , Smyth Mark J. , Johnstone Ricky W. 
Published: August 2002

AbstractMultidrug resistance (MDR) mediated by the ATP‐dependent efflux protein P‐glycoprotein (P‐gp) is a major obstacle to the successful treatment of many cancers. In addition to effluxing toxins, P‐gp has been shown to protect tumor cells against caspase‐dependent apoptosis mediated by Fas and tumor necrosis factor receptor (TNFR) ligation, serum starvation and ultraviolet (UV) irradiation. However, P‐gp does not protect against caspase‐independent cell death mediated by granzyme B or pore‐forming proteins (perforin, pneumolysin and activated complement). We examined the effects of the chemotherapeutic hybrid polar compound suberoylanilide hydroxamic acid (SAHA) on P‐gp‐expressing MDR human tumor cell lines. In the CEM T‐cell line, SAHA, a histone deacetylase inhibitor, induced equivalent death in P‐gp‐positive cells compared with P‐gp‐negative cells. Cell death was marked by the caspase‐independent release of cytochrome c, reactive oxygen species (ROS) production and Bid cleavage that was not affected by P‐gp expression. However, consistent with our previous findings, SAHA‐induced caspase activation was inhibited in P‐gp‐expressing cells. These data provide evidence that P‐gp inhibits caspase activation after chemotherapeutic drug treatment and demonstrates that SAHA may be of value for the treatment of P‐gp‐expressing MDR cancers. © 2002 Wiley‐Liss, Inc.
Optimized intensity‐modulated arc therapy for prostate cancer treatment
Authors: Ma Lijun , Yu Cedric X. , Earl Matthew , Holmes Tim , Sarfaraz Mehrdad , Li X. Allen , Shepard David , Amin Pradip , DiBiase Steven , Suntharalingam Mohan , Mansfield Carl 
Published: August 2002

AbstractWe recently implemented intensity‐modulated arc therapy (IMAT) at our institution. In this study, we evaluate the dosimetric merits of the application of this technique to the treatment of prostate cancer. Each IMAT treatment plan incorporated bilateral overlapping arcs. The dose from each beam segment was computed using the three‐dimensional dose model of a clinical treatment planning system (Render Plan 3.5, Precision Therapy). The weights assigned to the individual arc segments were optimized using a gradient search method. For 12 patients, comparisons were made between the IMAT treatment plans and corresponding plans using fixed cone‐beam intensity‐modulated radiotherapy (IMRT) from a commercial inverse planning system (CORVUS, NOMOS Corp.). We found that the optimized IMAT treatments produced similar dose distributions to the IMRT deliveries. Compared with the IMRT treatments, the IMAT treatments produced slightly less target dose homogeneity with consistently greater sparing of the rectum in regions of lower dose. The trade‐off between target dose conformity and rectum sparing can be adjusted in both optimization procedures. Because the total beam‐on time for IMAT delivery is 1 to 2 minutes with approximately 5–6 minutes of patient setup time, the delivery efficiency of the IMAT treatment was significantly better than the multiple‐beam IMRT treatment. © 2001 Wiley‐Liss, Inc.
Melphalan availability in hypoxia‐inducible factor‐1α+/+ and factor‐1α–/– tumors is independent of tumor vessel density and correlates with melphalan erythrocyte transport
Authors: Wildiers Hans , Guetens Gunter , de Boeck Gert , Landuyt Willy , Verbeken Eric , Highley Martin , de Bruijn Ernst A. , van Oosterom Allan T. 
Published: August 2002

AbstractMany tumors are impervious to anticancer agents. Resistance due to lack of cytotoxic penetration into the tumor is often overlooked but can play a significant role in undermining therapy. Insufficient and irregular vascularization of tumors is a possible barrier to drug delivery, but there are others, e.g., impaired vessel permeability and poor interstitial transport. We evaluated the importance of tumor vessel density in the availability of melphalan to tumors. A nude mouse tumor model with different vascularization due to a single‐gene deletion of hypoxia‐inducible factor 1α (HIF‐1α+/+ and HIF‐1α–/– embryonic stem cell–derived tumors) was used. The availability of melphalan to HIF‐1α+/+ (n = 20) and HIF‐1α–/– (n = 23) tumors was not significantly different (p = 0.12). Furthermore, in the various subgroup analyses accentuating the difference in vessel density, no significant correlation between vessel density and melphalan availability was found. In the second part of the study, melphalan, was demonstrated to be transported in blood in mice with a distribution of 24% in erythrocytes vs. 76% in plasma. A strong correlation (r = 0.93, p < 0.000001) between melphalan concentrations in plasma and erythrocytes was found, indicating an equilibrium between these 2 compartments. Plasma and erythrocyte concentrations of melphalan are correlated with the tumor availability of melphalan (r = 0.66 and 0.64, respectively, both p < 0.001). These data suggest that tumor vessel density is not an important predictor of the tumor availability of small cytotoxic drugs such as melphalan and indicate the importance of erythrocytes in the transport of melphalan. © 2002 Wiley‐Liss, Inc.