bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular‐targeting therapies for treatment of malignant disease
Authors: Siemann Dietmar W. , Chaplin David J. , Horsman Michael R. 
Published: May 2004

AbstractBACKGROUNDTumor endothelium represents a valuable target for cancer therapy. The vasculature plays a critical role in the survival and continued growth of solid tumor masses; in addition, the inherent differences between tumor blood vessels and blood vessels associated with normal tissue make the tumor vasculature a unique target on which to base the design of novel therapeutics, which may allow highly selective treatment of malignant disease. Therapeutic strategies that target and disrupt the already formed vessel networks of growing tumors are actively being pursued. The goal of these approaches is to induce a rapid and catastrophic shutdown of the vascular function of the tumor so that blood flow is arrested and tumor cell death due to the resulting oxygen and nutrient deprivation and buildup of waste products occurs.METHODSBiologic approaches and small‐molecule drugs that can be used to damage tumor vasculature have been identified. Physiologic, histologic/morphologic, and immunohistochemical assessments have demonstrated that profound disruption of the tumor vessel network can be observed minutes to hours after treatment. The small‐molecule agents that have made the greatest advances in the clinical setting (5,6‐dimethylxanthenone‐4‐acetic acid [DMXAA], combretastatin A4 disodium phosphate [CA4DP], and ZD6126) are the focus of the current review.RESULTSLoss of patent blood vessels, decreased tumor blood flow, extensive necrosis, and secondary ischemia‐induced tumor cell death have been well documented in a variety of preclinical tumor models treated with agents such as DMXAA, CA4DP, and ZD6126. The use of such agents in conjunction with irradiation and other chemotherapeutic agents has led to improved treatment outcomes.CONCLUSIONSThe targeting of tumors' supportive blood vessel networks could lead to improvements in cancer cure rates. It is likely that this approach will prove to be most efficacious when used in concert with conventional treatment strategies. Cancer 2004. © 2004 American Cancer Society.
The changing pattern of Kaposi sarcoma in patients with HIV, 1994–2003
Authors: Mocroft Amanda , Kirk Ole , Clumeck Nathan , Gargalianos‐Kakolyris Panaglotis , Trocha Hanna , Chentsova Nelly , Antunes Francisco , Stellbrink Hans‐Jürgen , Phillips Andrew N. , Lundgren Jens D. 
Published: May 2004

AbstractBACKGROUNDThe introduction of highly active antiretroviral therapy (HAART) has radically changed the clinical course of human immunodeficiency virus (HIV) infection. The goals of the current study were to assess the change in the incidence of Kaposi sarcoma (KS) among European patients with HIV since the introduction of HAART and to identify the factors associated with the development of KS among patients receiving HAART.METHODSThe incidence of KS and the factors associated with the development of this malignancy in patients receiving HAART were evaluated using Poisson regression. Patients examined in the current study were among the 9803 individuals with HIV who were enrolled in the EuroSIDA study, a pan‐European multicenter investigation.RESULTSThere was an estimated annual reduction of 39% (95% confidence interval [CI], 35–43%; P < 0.0001) in the incidence of KS between 1994 and 2003. The proportion of acquired immunodeficiency syndrome (AIDS) diagnoses made due to KS during prospective follow‐up ranged from 4.1% to 7.5%, and there was no significant change over time in this figure (P = 0.97). Four thousand fourteen patients began receiving HAART during prospective follow‐up; 41 of these 4014 were subsequently diagnosed with KS (1.0%). After adjustment in multivariate analyses, patients with higher current CD4 counts were found to have a decreased incidence of KS (incidence rate ratio [IRR], 0.60; 95% CI, 0.53–0.68; P < 0.0001), as were those for whom more time had elapsed since the initiation of HAART (IRR, 0.77; 95% CI, 0.60–0.98; P = 0.037). In contrast, homosexual men were found to have a significantly increased incidence of KS (IRR, 2.12; 95% CI, 1.00–4.54; P = 0.050)CONCLUSIONSThe current incidence of KS among patients with HIV is less than 10% of the incidence reported in 1994; the proportion of AIDS diagnoses made on the basis of KS diagnoses remains near 6%. Most individuals who developed KS while receiving HAART began treatment with low CD4 cell counts and developed KS within 6 months of the initiation of HAART. There continues to be an increased incidence of KS among homosexual men and a greatly reduced incidence of KS among patients with higher CD4 counts. Cancer 2004. © 2004 American Cancer Society.
Paramagnetic Chloro‐, Alkoxo‐, or Azidovanadium(IV) Complexes Supported by an [ONNO]‐Type Amine Bis(phenolate) Ligand
Authors: Wolff Fabien , Lorber Christian , Choukroun Robert , Donnadieu Bruno 
Published: May 2004

AbstractThe reactions between V(N3)2(NMe2)2 or V(OiPr)4 and the chelating dianionic bis(phenoxy)amine ligand [ONNO]H2 afford complexes formulated as [V(N3)2{ONNO}] (1) and [V(OiPr)2{ONNO}] (2). When refluxed in toluene with an excess of Me3SiCl, compound 2 leads to mono‐ or dichloro derivatives [V(Cl)(OiPr){ONNO}] (3) and [VCl2{ONNO}] (4) depending on the experimental conditions. The crystal structures of complexes 1−4 were solved and show in all cases an [ONNO] ligand that has phenolate groups in a trans configuration, with both amino‐nitrogen donor atoms of the ligand coordinated to the octahedral vanadium center. Complexes 1−4 were further characterized by EPR spectroscopy and susceptibility measurement studies typical of d1‐paramagnetic VIV species. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Ruthenium(II) Octaphenylporphyrazine Complexes with Mixed Axial Ligands: Peculiarities of Their Formation and Spectral Properties
Authors: Vagin Sergej , Ziener Ulrich , Hanack Michael , Stuzhin Pavel A. 
Published: May 2004

AbstractA series of new axially bis‐coordinated (octaphenylporphyrazinato)ruthenium(II) complexes {[(Ph8Pz)RuL2], L = cyclohexyl isocyanide, CyNC, (1b); 4,4′‐bipyridine, bpy, (2c); N‐methylimidazole, CH3Im, (3a)} was prepared and characterized. The reaction of the bis‐isocyanide adducts [(Ph8Pz)Ru(tBuNC)2] (1a) or [(Ph8Pz)Ru(CyNC)2] (1b) with monodentate N‐heterocycles gave, under certain conditions, the mixed‐ligand complexes [(Ph8Pz)Ru(Py)(tBuNC)] (4a), [(Ph8Pz)Ru(Py)(CyNC)] (4b) and [(Ph8Pz)Ru(CH3Im)(CyNC)] (3b). The reaction of 1a or 1b with an excess of bidentate 4,4′‐bipyridine under the same conditions resulted in the formation of the corresponding dimeric species [(Ph8Pz)Ru(tBuNC)]2(μ‐bpy) (2a) and [(Ph8Pz)Ru(CyNC)]2(μ‐bpy) (2b) in high yield. The structures of all the complexes were unambiguously proved by 1H NMR spectroscopy, and the possibility of their self‐assembly is discussed. All mixed‐ligand compounds were also characterized by UV/Vis and IR spectroscopy, as well as elemental analysis. The 1H NMR spectra of these compounds are discussed in detail. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Specific cerebellar activation during Braille reading in blind subjects
Authors: Gizewski Elke R. , Timmann Dagmar , Forsting Michael 
Published: May 2004

AbstractThe traditional view that the cerebellum is involved only in the control of movements has been changed recently. It has been suggested that the human cerebellum is involved in cognition and language. Likewise, besides cortical activity in sensorimotor and visual areas, an increased global activation of the cerebellum has been revealed during Braille reading in blind subjects. Our purpose was to investigate whether there is cerebellar activation during Braille reading by blind subjects other than sensorimotor activation related to finger movements. Early blind and normal sighted subjects were studied with functional magnetic resonance imaging (fMRI) during Braille reading, tactile discrimination of nonsense dots, dots forming symbols, and finger tapping. The experiments were done in block design. Echo planar imaging sequences were carried out on a 1.5‐T MR scanner. All blind individuals reading Braille showed robust activation of the posterior and lateral aspects of cerebellar hemispheral lobules Crus I bilaterally but more predominately on the right side. Additionally, activation was present in the medial cerebellum within lobules IV, V, and VIIIA, predominantly on the right. Discriminating nonsense dots did not reveal any activation of Crus I, but did reveal activation within the medial part of lobules IV, V, and VIIIA, predominately on the right. Analysis of sighted subjects during reading of printed text revealed activation of the posterolateral cerebellar hemisphere in Crus I bilaterally, predominantly on the right. Tactile analysis of dots representing symbols revealed an activation in lobules IV and VIII and in right Crus II but not in Crus I. In conclusion, parts of cerebellar activation during Braille reading in blind subjects (i.e., within lobules IV, V, and VIII) overlap with the known hand representation within the cerebellum and are likely related to the sensorimotor part of the task. Cerebellar activation during Braille reading within bilateral Crus I may be due to language processes or inner speech similar to those found during text reading in normal sighted subjects. Object recognition did not account for Crus I activation. Hum. Brain Mapp. 22:229–235, 2004. © 2004 Wiley‐Liss, Inc.
Executive processes in Parkinson's disease: FDG‐PET and network analysis
Authors: Lozza Catherine , Baron Jean‐Claude , Eidelberg David , Mentis Marc J. , Carbon Maren , Marié Rose‐Marie 
Published: May 2004

AbstractIt is assumed widely that the clinical expression of Parkinson's Disease (PD), both motor and cognitive, is subtended by topographically distributed brain networks. However, little is known about the functional neuroanatomy of executive dysfunction in PD. Our objective was to validate further in a PD group the use of network analysis to assess the relationship between executive processes and pathological disorganization of frontostriatal networks. We studied 15 patients with idiopathic PD, and 7 age‐matched normal controls, using resting [18F]fluorodeoxyglucose (FDG) and high‐resolution positron emission tomography (PET). We carried out network analysis on regional metabolic data to identify specific covariation patterns associated with motor and executive dysfunction. We detected two independent patterns relating respectively to the two clinical abnormalities. The first pattern (principal component 1) was topographically similar to that described previously in other PD populations. Subject scores for this pattern discriminated patients from controls and correlated significantly with bradykinesia ratings (P = 0.013, r = 0.655) in PD patients. The second pattern (principal component 2) was characterized by relative ventromedial frontal, hippocampal, and striatal hypometabolism, associated with mediodorsal thalamic hypermetabolism. In the PD group, scores from this pattern correlated with scores on the conditional associative learning (CAL; P = 0.01, r = 0.690) and the Brown Peterson paradigm (BPP; P = 0.017, r = −0.651) tests, respectively assessing strategy and planning, and working memory. According to these findings, the networks subserving bradykinesia and executive dysfunction in PD seems to be topographically distinct and to involve different aspects of subcortico‐cortical processing. Hum. Brain Mapping 22:236–245, 2004. © 2004 Wiley‐Liss, Inc.
Autoradiographic distribution of serotonin transporters and receptor subtypes in human brain
Authors: Varnäs Katarina , Halldin Christer , Hall Håkan 
Published: May 2004

AbstractSeveral neurochemical in vitro and in vivo imaging studies have been aimed at characterizing the localization of serotonin receptors and transporters in the human brain. In this study, a detailed comparison of the distribution of a number of 5‐HT receptor subtypes and the 5‐HT transporter was carried out in vitro using human postmortem brain tissue. Anatomically adjacent whole hemisphere sections were incubated with specific radioligands for the 5‐HT1A, 5‐HT1B, 5‐HT2A, 5‐HT4 receptors and the 5‐HT transporter. The autoradiograms revealed different laminar and regional distribution patterns in the isocortex, where 5‐HT1A and 5‐HT4 receptor binding showed highest densities in superficial layers and 5‐HT2A receptor binding was most abundant in middle layers. In cortical regions, 5‐HT transporters were concentrated to several limbic lobe structures (posterior uncus, entorhinal, cingulate, insular and temporal polar regions). 5‐HT1A receptor densities were also high in limbic cortical regions (hippocampus, posterior entorhinal cortex, and subcallosal area) compared to the isocortex. Subregionally different distribution patterns were observed in the basal ganglia with a trend toward higher levels in ventral striatal (5‐HT1B receptors) and pallidal (5‐HT transporters and 5‐HT1B receptors) regions. The localization in regions belonging to limbic cortico‐striato‐pallido‐thalamic circuits is in line with the documented role of 5‐HT in modulation of mood and emotion, and the suggested involvement of this system in pathophysiology of various psychiatric disorders. The qualitative and quantitative information reported in this study might provide important complements to in vivo neuroimaging studies of the 5‐HT system. Hum. Brain Mapping 22:246–260, 2004. © 2004 Wiley‐Liss, Inc.
High‐dose superselective intra‐arterial cisplatin and concomitant radiation (radplat) for advanced head and neck cancer
Authors: Balm Alfons J. M. , Rasch Coen R. N. , Schornagel Jan H. , Hilgers Frans J. M. , Keus Ronald B. , Schultze‐Kool Leo , Ackerstaff Annemieke H. , Busschers Wim , Tan I. Bing 
Published: May 2004

AbstractBackground.The purpose of this study was to study the effect of intensive targeted chemoradiation in a group of patients with head and neck cancer with stage IV inoperable disease.Methods.We examined 79 patients with inoperable stage IV head and neck cancer receiving intra‐arterial infusion of high‐dose cisplatin (150 mg/m2) on days 2, 9, 16, and 23 concomitant with delivery of external beam radiotherapy (total dose, 70 Gy; 2 Gy, 35 fractions; 1 fraction/day for 7 weeks). Sodium thiosulfate was administered intravenously to provide effective cisplatin neutralization.Results.Four patients were not assessable. Complete local tumor response was achieved in 72 patients (91%) and a partial response in three patients. The complete response rate of neck node metastases was 90%. The 1‐ and 2‐year locoregional control rates were 82% and 69%, respectively. The median overall survival time was 2.2 years, with a 3‐year overall survival probability of 43%. Acute toxicities were as follows: grade III/IV hematologic toxicity (22%/16%), grade III/IV nephrotoxicity (0%), grade III mucositis (43%), grade III skin reactions (24%), grade III toxicity of the upper gastrointestinal tract (57%), grade III nausea (20%), and grade III subjective hearing loss (10%). Grade V toxicity (treatment‐related deaths) was 3.8%. Six (18%) of 33 patients with complete remission needed tube feeding 2 years after treatment without intercurrent salvage surgery.Conclusions.Supradose superselective intra‐arterial cisplatin and concomitant radiation is an effective organ‐preserving therapy in an unfavorable group of patients. Our series confirms encouraging results reported previously. This regimen is justified in unresectable patients despite the substantial toxicity. © 2004 Wiley Periodicals, Inc. Head Neck 26: 485–493, 2004
A pilot study of a randomized controlled trial to evaluate the effects of progressive resistance exercise training on shoulder dysfunction caused by spinal accessory neurapraxia/neurectomy in head and neck cancer survivors
Authors: McNeely Margaret L. , Parliament Matthew , Courneya Kerry S. , Seikaly Hadi , Jha Naresh , Scrimger Rufus , Hanson John 
Published: May 2004

AbstractBackground.Shoulder dysfunction remains a frequent complication after neck dissection procedures for head and neck cancer.Methods.We conducted a pilot study to evaluate the effects of progressive resistance exercise training (PRET) on shoulder dysfunction caused by spinal accessory neurapraxia/neurectomy in patients with head and neck cancer. Twenty patients (mean age, 61 ± 7.7 years) were randomly assigned to PRET or standard care intervention. Subjects assigned to the PRET group exercised three times per week for 12 weeks. The goal of the exercise program was to enhance scapular stability and strength of the upper extremity. The resistance‐training program was progressive in terms of number of sets and repetitions performed, as well as the amount of weight lifted, depending on performance status.Results.The completion rate for the trial was 85% (17 of 20). The exercise group completed 93% of scheduled exercise sessions. Significant improvements were found in favor of the PRET group in active shoulder external rotation (p = .001), shoulder pain (p = .038), and overall score for shoulder pain and disability (p = .045).Conclusions.The study results demonstrate a high rate of completion and adherence with our PRET program among patients with head and neck cancer. The preliminary findings, although limited, also suggest a potential therapeutic role for resistance exercise as an adjunct to standard physical therapy treatment. © 2004 Wiley Periodicals, Inc. Head Neck 26: 518–530, 2004
Transcription factor NF‐κB activation after in vivo perforant path LTP in mouse hippocampus
Authors: Freudenthal Ramiro , Romano Arturo , Routtenberg Aryeh 
Published: May 2004

AbstractThere is increasing evidence that transcription factors (TFs) play a critical role in maintaining later phases of hippocampal long‐term potentiation (LTP). We have been led to study the role in synaptic plasticity of the powerful, yet generally unheralded, NF‐κB TF because it may serve as both a signaling molecule after its activation at the synapse and then a transcription initiator upon reaching the nucleus. In the present study, we show that LTP activates NF‐κB in the intact mouse hippocampus. Mice were sacrificed 15 min after one of three treatments: tetanization (high‐frequency stimulation [HFS]), low‐frequency stimulation (LFS), or no stimulated control animals (CT). In a first study, nuclear NF‐κB activity from hippocampus was estimated by electrophoretic mobility shift assays (EMSAs). A higher level of hippocampal TF binding to the NF‐κB recognition element was found in the HFS group compared with LFS or CT. In a second study, NF‐κB activity was evaluated by immunohistochemistry with a specific antibody that recognizes the activated form of NF‐κB. This antibody binds to the exposed nuclear location sequence on the p65 subunit of NF‐κB consequent to its dissociation from the inhibitory IκB molecule. In the four subfields of hippocampus examined—granule cell layer, hilus of the dentate gyrus, CA3 and CA1 pyramidal fields of the hippocampal gyrus—the highest levels of activated NF‐κB, statistically significant in all cases were found after HFS. In certain comparisons, LFS animals also showed significant elevation with respect to CT. These results support the role of NF‐κB as part of the synaptic signaling and transcriptional regulation mechanism required in long‐term plasticity, emphasizing the combinatorial nature of TF function. © 2004 Wiley‐Liss, Inc.
Thermal residual stresses near the interface between plasma‐sprayed hydroxyapatite coating and titanium substrate: Finite element analysis and synchrotron radiation measurements
Authors: Cofino B. , Fogarassy P. , Millet P. , Lodini A. 
Published: May 2004

AbstractPlasma‐sprayed hydroxyapatite (HA) coatings on titanium alloy are often used in prosthetic implants. The metallic substrate gives the implant good mechanical strength which is combined with good biocompatibility and osteointegration of the ceramic coating. However, the interface between the HA coating and titanium alloy substrate is an area of critical weakness when compared with the interlamellar cohesive strength of the HA coating structure. Knowledge of the stresses in materials near the interface seems to be an important step in understanding why failure occurs. Synchrotron radiation, using Beamline BM16 at the European Synchrotron Radiation Facility (Grenoble, France), has been used to determine local stresses near the interface, down to 10 μm in resolution, between a plasma‐sprayed HA coating and a titanium alloy substrate. This experimental determination of residual stresses is compared with the results found by a finite element analysis modeling the thermal effects of the plasma‐spraying process. Residual stresses have been found in deposited ceramic near the interface due to a thermal properties mismatch of the materials. If the plane stress state is assumed, meaning the perpendicular component of residual stress is ignored (σz = 0), then the synchrotron residual stress measurements should be interpreted as mainly compressive in the ceramic coating. This is in contradiction with the coefficient of thermal expansion mismatch; therefore, the simplified plane stresses assumption seems to be inappropriate for the deposited morphology characterized by pores and a network of microcracks. The detailed finite element analysis model, taking into account the real morphology of the coating and the real three‐dimensional stress field distribution, allowed the estimation of σz, leading to a more accurate interpretation of synchrotron measurements, which is validated by the experimental results. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 20–27, 2004
Preparation of poly(ethylene glycol)‐block‐poly(caprolactone) copolymers and their applications as thermo‐sensitive materials
Authors: Kim Moon Suk , Seo Kwang Su , Khang Gilson , Cho Sun Hang , Lee Hai Bang 
Published: May 2004

AbstractThe polymerization of ϵ‐caprolactone (ϵ‐CL) was initiated by the terminal alcohol of methoxy poly(ethylene glycol) (MPEG) as an initiator via activated ring‐opening polymerization in the presence of HCl · Et2O as a monomer activator. The molecular weights of the poly(ϵ‐caprolactone) (PCL) in MPEG–PCL diblock copolymers controlled with the feed ratio of ϵ‐CL to MPEG. The polymerization was preceded by living fashion with no termination or chain transfer. This polymerization procedure offered MPEG–PCL diblock copolymers with well‐defined structures. The gel‐to‐sol transitions of MPEG–PCL diblock copolymer solutions were also examined. The diblock copolymers synthesized with various MPEG and PCL lengths were dissolved in water at 80°C in various concentrations. The polymer solutions formed gel at room temperature. The formed gel became fluids again by increasing the temperature. The gel‐to‐sol transition showed strong dependence on the length of the MPEG and PCL diblock segments. When the polymer solution was injected into rat, it became a gel at body temperature. The formed gel maintained for 1 month. We confirmed that MPEG–PCL diblock copolymers with well‐defined structures served as new thermo‐sensitive biomaterials. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 154–158, 2004