bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactive Oxygen Species Mediated Sustained Activation of Protein Kinase C α and Extracellular Signal-Regulated Kinase for Migration of Human Hepatoma Cell Hepg2
Authors: Wu Wen-Sheng , Tsai Rong Kung , Chang Chung Hsing , Wang Sindy , Wu Jia-Ru , Chang Yu-Xun
Published: October 2006

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) can trigger growth inhibition, epithelial-mesenchymal transition (EMT)–like cell scattering, and migration of hepatoma cells HepG2 in a protein kinase C-α (PKC-α)–dependent manner. Saikosaponin a, an ingredient of antitumorigenic Chinese herb Sho-Saiko-to, inhibited cell growth but did not induce EMT-like cell scattering and cell migration of HepG2. Saikosaponin a and TPA induced transient (for 30 minutes) and sustained (until 6 hours) phosphorylation of extracellular signal-regulated kinase (ERK), respectively. Generation of the reactive oxygen species (ROS) was induced by TPA, but not saikosaponin a, for 3 hours. As expected, scavengers of ROS, such as superoxide dismutase, catalase, and mannitol, and the thiol-containing antioxidant N-acetylcystein dramatically suppressed the TPA-triggered cell migration but not growth inhibition of HepG2. The generation of ROS induced by TPA was PKC, but not ERK, dependent. On the other hand, scavengers of ROS and N-acetylcystein also prevented PKC activation and ERK phosphorylation induced by TPA. On the transcriptional level, TPA can induce gene expression of integrins α5, α6, and β1 and reduce gene expression of E-cahedrin in a PKC- and ROS-dependent manner. In conclusion, ROS play a central role in mediating TPA-triggered sustained PKC and ERK signaling for regulation of gene expression of integrins and E-cahedrin that are responsible for EMT and migration of HepG2. (Mol Cancer Res 2006;4(10):747–58)
Presenilin Function in Caenorhabditis elegans
Authors: Smialowska Agata , Baumeister Ralf
Published: October 2006

The genome of the nematode Caenorhabditis elegans contains homologs of several genes associated with familial Alzheimer’s disease in humans. apl-1 encodes a transmembrane protein belonging to the amyloid precursor protein family, sel-12 and hop-1 are the two somatically expressed presenilin genes that resemble PS1 and PS2 on both a structural and a functional level. Mutations in the sel-12-encoded presenilin gene cause defective Notch/lin-12 signaling and result in reduced egg-laying, caused by cell specification and cell attachment defects. spr-1, spr-3, spr-4 and spr-5 were identified as the suppressors of the egg-laying defect of presenilin/sel-12 loss of function mutants in genetic suppressor screens. The corresponding proteins are C. elegans homologs of human REST, CoREST and LSD1, respectively. REST/NSRF (Re1 silencing transcription factor/neural-restrictive silencing factor) is a transcriptional repressor that blocks the expression of neuronal genes in non-neuronal tissues in vertebrates. CoREST is a conserved histone deacetylase and demethylase-containing co-repressor complex possessing a potential chromatin-modifying activity. It is recruited to the promoter via REST-mediated DNA binding. LSD1 is a flavin-dependent demethylase of histone H3. Mutations in spr-1, spr-3, spr-4 and spr-5 genes suppress the egg-laying phenotype of sel-12 loss of function mutants by derepressing the expression of the second C. elegans presenilin gene, hop-1.
Functional Role of the Low-Density Lipoprotein Receptor-Related Protein in Alzheimer’s Disease
Authors: Waldron Elaine , Jaeger Sebastian , Pietrzik Claus U.
Published: October 2006

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder, characterized by neuronal loss, neurofibrillary tangle formation and the extracellular deposition of amyloid-β (Aβ) plaques. The amyloid precursor protein (APP) and the enzymes responsible for Aβ generation seem to be the base elements triggering the destructive processes. Initially, the low-density lipoprotein receptor-related protein (LRP) was genetically linked to AD and later it emerged to impact on many fundamental events related to this disease. LRP is not only involved in Aβ clearance but is also the major receptor of several AD-associated ligands, e.g. apolipoprotein E and α2-macroglobulin. APP processing is mediated by LRP on many levels. Enhanced APP internalization through LRP decreases cell surface APP levels and thereby reduces APP shedding. As a consequence of increased APP internalization LRP enhances Aβ secretion. These effects could be attributed to the cytoplasmic tails of LRP and APP. The receptors bind via their NPXY motifs to the two PID domains of FE65 and form a tripartite complex. However, it appears that the second NPVY motif of LRP is the one responsible for the observed influence over APP metabolism. A more in-depth knowledge of the mechanisms regulating APP cleavage may offer additional targets for therapeutic intervention.
Amyloid Precursor Protein and BACE Function as Oligomers
Authors: Multhaup Gerd
Published: October 2006

Processing of the amyloid precursor protein (APP) by β- and γ-secretases leads to the generation of amyloid-β (Aβ) peptides, which are the toxic agents in the pathogenesis of Alzheimer’s disease. The molecular reasons for the sequential Aβ generation by secretase activities have remained unclear. Our studies support an oligomerization-dependent mechanism for the conversion of APP into Aβ. By different lines of evidence, we showed that APP is capable of forming homodimers and tetramers. Oligomerization of APP occurs in a zipper-like mechanism primarily mediated by two highly conserved sites of the ectodomain. We also found that in human brain tissue β-secretase (BACE) occurred as a dimer, whereas the soluble ectodomain of truncated BACE exclusively occurred in the monomeric form. A mutational analysis of the active sites supports the idea that BACE might have acquired a specific catalytic activity by oligomerization, which is stabilized through the transmembrane and the cytoplasmic domains. Our results predict that APP homodimers are functionally active within the plasma membrane and most likely represent substrates for BACE oligomers. Understanding the molecular tasks of homophilic binding of substrates and secretases will allow to find secretase inhibitors which specifically bind to contact sites of dimers and thus inhibit Aβ formation.
Assembly, Trafficking and Function of γ-Secretase
Authors: Kaether Christoph , Haass Christian , Steiner Harald
Published: October 2006

γ-Secretase catalyzes the final cleavage of the β-amyloid precursor protein to generate amyloid-β peptide, the principal component of amyloid plaques in the brains of patients suffering from Alzheimer’s disease. Here, we review the identification of γ-secretase as a protease complex and its assembly and trafficking to its site(s) of cellular function. In reconstitution experiments, γ-secretase was found to be composed of four integral membrane proteins, presenilin (PS), nicastrin (NCT), PEN-2 and APH-1 that are essential and sufficient for γ-secretase activity. PS, which serves as a catalytic subunit of γ-secretase, was identified as a prototypic member of novel aspartyl proteases of the GxGD type. In human cells, γ-secretase could be further defined as a heterogeneous activity consisting of distinct complexes that are composed of PS1 or PS2 and APH-1a or APH-1b homologues together with NCT and PEN-2. Using green fluorescent protein as a reporter we localized PS and γ-secretase activity at the plasma membrane and endosomes. Investigation of γ-secretase complex assembly in knockdown and knockout cells of the individual subunits allowed us to develop a model of complex assembly in which NCT and APH-1 first stabilize PS before PEN-2 assembles as the last component. Furthermore, we could map domains in PS and PEN-2 that govern assembly and trafficking of the complex. Finally, Rer1 was identified as a PEN-2-binding protein that serves a role as an auxiliary factor for γ-secretase complex assembly.
Regulation of the Human Growth Hormone Gene Family: Possible Role for Pit-1 in Early Stages of Pituitary-Specific Expression and Repression
Authors: Cattini Peter A. , Yang Xiaoyang , Jin Yan , Detillieux Karen A.
Published: October 2006

The somatic cells of a multicellular organism contain an identical complement of genes that need to be expressed specifically and appropriately to allow the normal development and functions associated with an organism. In the eukaryotic cell nucleus, genes are packaged with nucleoprotein histones into chromatin. The human growth hormone (GH)/chorionic somatomammotropin (CS) gene family offers an excellent model to study the relationship between chromatin structure and transcription factor binding in terms of tissue-specific gene expression. The GH/CS gene family consists of five genes (GH-N, GH-V, CS-A, CS-B and CS-L), contained in a single locus on chromosome 17. Although they share approximately 94% sequence similarity, GH-N expression is restricted to pituitary somatotropes while the four placental GH/CS genes are expressed in the villus syncytiotrophoblast. Appropriate expression in vivo is dependent on remote sequences found 14–32 kb upstream of GH-N in the loci of adjacent genes, and these sequences are characterized by five (I–V) nuclease-hypersensitive sites (HS). Pituitary-specific factor Pit-1 binds at HS I/II and plays an essential role in chromatin remodeling and GH-N expression; however, the processes that lead to HS I/II accessibility are unknown. We discuss the possibility that Pit-1-driven remodeling at HS III may precede that at HS I/II in the pituitary. Also, in pituitary chromatin, all five GH/CS genes share similar nuclease sensitivity, suggesting that the conformation of the placental genes is not inhibitory to transcription. Given that the promoters of both GH-N and the placental GH/CS genes contain Pit-1-binding sites, possible mechanisms to restrict placenta GH/CS promoter activity in the pituitary are discussed, including active repression via P sequences located upstream of each of the placental GH/CS genes. Positively or negatively influencing those components known to be important for pituitary transcription may link epigenetic events to key transcription factors in the overall picture of tissue-specific control of gene expression.
Positron Emission Tomography in Acromegaly and Other Pituitary Adenoma Patients
Authors: Muhr Carin
Published: October 2006

Background: Positron emission tomography (PET) is a well-recognized technique used in research, especially for intracranial studies, as well as for clinical practice, and has contributed to the fast development in neuroscience during the last decades. Procedures: We have used PET in pituitary tumors for in vivo characterization with respect to metabolism, 11C-L-methionine and 18F-fluorodeoxyglucose, receptor properties, 11C-N-methylspiperone and 11C-raclopride, and monoamine oxidase B enzyme content, 11C-L-deprenyl; further, for diagnosing and outlining the tumors in differential diagnostic perspectives and in the follow-up of treatment. Observations:11C-raclopride, a specific dopamine antagonist, demonstrated high amounts of dopamine D2 binding in prolactinomas and some growth hormone-secreting adenomas. There was a significant correlation between high amounts of D2 receptors and the positive treatment effect of dopamine agonist therapy. When 11C-L-methionine and 18F-fluorodeoxyglucose were used for metabolic mapping, the highest metabolic activity was found in the prolactinomas, which correlated well with the serum prolactin levels. The growth hormone adenomas also showed high metabolic rates. At treatment follow-up, a considerable decrease in 11C-L-methionine uptake was observed in all tumors that responded positively to the treatment and thus foretold that the medical treatment, both concerning dopamine agonist and somatostatin analogue, was effective. In this respect, PET was valuable to monitor treatment. PET was also shown valuable in differential diagnosing between pituitary adenomas, meningiomas and skull base neuromas. Conclusion: We have found PET to be highly valuable in the research and clinical handling of patients with a pituitary adenoma for in vivo tumor characterization.
Somatostatin and Dopamine-Somatostatin Multiple Ligands Directed towards Somatostatin and Dopamine Receptors in Pituitary Adenomas
Authors: Saveanu Alexandru , Gunz Ginette , Guillen Severine , Dufour Henry , Culler Michael D. , Jaquet Philippe
Published: October 2006

Aim: We report the comparative efficacy of octreotide, cabergoline and multiple ligands directed towards the different somatostatin subtypes (ssts), such as BIM-23A779 and SOM-230, and of chimeric analogs which bind both somatostatin and the dopamine D2 receptors (D2R), such as BIM-23A760 and BIM-23A781, in cell cultures from human growth hormone (GH)-secreting pituitary adenomas. Procedures: RT-PCR analysis of the quantitative expression of the different ssts and D2R mRNAs was performed on tumor fragments of 22 GH-secreting adenomas collected after surgery. Pharmacological studies, using the different ligands, were performed on cell cultures of such tumors. Results: sst2, sst5 and D2R were constantly coexpressed in all tumors, in variable amounts. The levels of expression of sst2 and D2R mRNAs were significantly correlated with the maximal GH suppression by either octreotide or cabergoline (p < 0.001). In each tumor tested, 3 patterns of response, in terms of GH suppression, were observed. GH secretion was preferentially inhibited by the sst2 preferential compound octreotide in 61% of the tumors. In 19% of the tumors, the maximal inhibition of GH release was achieved with the sst5 preferential compound BIM-23268. The dopamine analog cabergoline was the most effective inhibitor of GH secretion in 21% of cases. Among the compounds tested, the most potent inhibitors of GH secretion were the sst2, sst5, D2R chimeric compound BIM-23A760, followed by the sst universal ligand SOM-230. Conclusions: The variable patterns of response to sst2, sst5 and dopamine D2 analogs may explain the greater efficacy of drugs which bind to the 3 receptors in suppressing GH secretion. The biological potency (EC50) and efficacy of the chimeric compound BIM-23A760 on GH secretion can be partly explained by its high affinity for sst2. The effect of multiple receptor activation on the functions of other pituitary tumor types, such as prolactinomas and corticotropinomas, is not presently analyzed, and the efficacy of multireceptor ligands remains to be elucidated.
Is There Still a Role for Radiotherapy in Acromegaly?
Authors: Monson John P.
Published: October 2006

External radiotherapy (ideally 3-field radiotherapy with a daily fractional dose no higher than 1.8 Gy or conformal irradiation) has been used extensively in the treatment of acromegaly, and virtually all studies have documented a predictable but slow reduction in growth hormone (GH) excess, which is at its maximum in the first year after treatment (30–50%) and continues at an average rate of 10–15% thereafter in the long term. Therefore, achievement of ‘safe’ GH concentrations in an acceptable time interval after radiotherapy will be realized only in those patients who have lower GH concentrations prior to irradiation either as a result of mild disease or previous surgery. Recent studies have demonstrated the value of stereotactic radiotherapy (either as multiple arc X-irradiation or as ‘gamma knife’ therapy) in the post-surgical treatment of acromegaly or as salvage therapy for disease persisting after conventional external irradiation. The development of potent medical therapies for acromegaly (somatostatin analogues and the GH receptor antagonist) has called into question the role of radiotherapy in the treatment of this disease. However, even if the concept of primary, open-ended medical therapy for selected patients is accepted, reference to the success rates of surgery and response rates to somatostatin analogues indicates that approximately 10–20% of all patients with acromegaly will require consideration of radiotherapy for hormonal or tumour mass control. For these reasons, radiotherapy (both conventional external and stereotactic irradiation) continues to have a major role in controlling acromegaly in selected patients.
Repeated Intravitreal Injection of Triamcinolone for Exudative Age-Related Macular Degeneration
Authors: Jonas Jost B. , Spandau Ulrich H. , Kamppeter Bernd A. , Vossmerbaeumer Urs , Harder Bjoern
Published: October 2006

Background: Intravitreal triamcinolone acetonide has been discussed as treatment for exudative age-related macular degeneration (AMD). Objectives: To give an updated report on repeated intravitreal injections of triamcinolone acetonide (IVTA) for the treatment of exudative AMD. Methods: The case-series study included 24 patients (24 eyes) with progressive exudative AMD who had shown an increase in, or stabilization of, visual acuity after a first IVTA, and who eventually experienced a deterioration of visual acuity. The 24 (6.5%) eyes were selected out of a total group of 369 eyes who had received IVTA for exudative AMD within the last 5 years. All patients of the study received a second IVTA (approximately 20 mg) 3.7–38.5 months after the first injection. Main outcome measure was visual acuity. Results: After the first injection, best corrected visual acuity improved significantly (p = 0.001) from 0.75 ± 0.34 logMAR to a minimum of 0.58 ± 0.30 logMAR during follow-up, with 10 (42%) eyes improving in visual acuity by two or more Snellen lines. Towards the end of follow-up after the first injection, best corrected visual acuity decreased significantly (p = 0.03) compared with the baseline value. After the second injection, visual acuity did not change markedly from baseline to a mean maximal visual acuity during follow-up. Comparing the last postoperative examination at the end of the follow-up after the second IVTA with the preoperative examination, a significantly (p = 0.001) higher number of eyes lost in visual acuity [19 (79%) eyes] than gained in visual acuity [3 (12%) eyes]. Conclusions: In selected eyes with an increase in visual acuity after a first IVTA (20 mg), repeated IVTA temporarily stabilizes visual acuity with a drop in visual acuity towards the end of follow-up.
Assessment of the Apparent Intra- and Inter-Sample Variability in the Collagen Fibril Diameter in the Posterior Corneal Stroma of Rabbits
Authors: Doughty Michael J. , Bergmanson Jan P.G.
Published: October 2006

Purpose: To assess the natural variability in the diameter of small collagen fibrils in the lamellae of corneal stroma of healthy young rabbits. Materials and Methods: The corneas of 6 young adult female New Zealand White rabbits (2.1 kg) were prepared for transmission electron microscopy (TEM) by fixation with a cacodylate-buffered 2% glutaraldehyde (pH 7.2–7.4, 320–340 mosm/kg). The corneas were embedded in Epon-Araldite, thin sections prepared from the central region of the posterior corneal stroma and stained with acidic uranyl acetate followed by acidic lead citrate. High magnification (×33,000) micrographs were taken, and fibril diameters (FDs) measured at a final magnification of ×275,000 to a resolution of 2 nm. Results: Assessment of sampling-related errors indicated that the average diameter of the fibrils within any particular micrograph could be estimated to within 1% or better by measures of 100 fibrils. Assessments of the intra-sample variance (6 micrographs taken from the same cornea) indicated a group mean FD of 32.4 ± 3.6 nm, whilst the inter-sample variance (6 micrographs taken from 6 different corneas) yielded an average of 33.1 ± 4.5 nm (n = 100 fibrils/micrograph, ±SD). However, group-averaged data sets of FDs, while unimodal, were not normally distributed, and cumulative averaging indicated a fixed range of FDs across the data sets. Conclusions: Intra- and inter-sample variability in collagen FDs is very similar, but the analysis indicates that the collagen fibrils are not homogeneous and that closely adjacent lamellae can have subtle differences in average FD.
UV Absorption in Human Oral Mucosal Epithelial Sheets for Ocular Surface Reconstruction
Authors: Yokoo Seiichi , Yamagami Satoru , Mimura Tatsuya , Amano Shiro , Saijo Hideto , Mori Yoshiyuki , Takato Tsuyoshi
Published: October 2006

Background: Ocular surface reconstruction with autologous oral mucosal epithelium has attracted attention as a novel treatment strategy that avoids allograft rejection. Objectives: To evaluate the absorption of ultraviolet (UV) A or B irradiation by human oral mucosal epithelium cultured on human amniotic membrane. Methods: Human oral mucosal and limbal epithelial cells were co-cultured on amniotic membrane with inactivated 3T3 fibroblasts. The cell sheets were also subjected to UV-A (365 nm) or UV-B (302 nm) irradiation at energy levels ranging from 50 to 800 µW/cm2, and the UV absorption rate was measured with a UV irradiation meter. Results: Cultured oral mucosal epithelium had a structure with 3–5 layers of cells, consistent with the histological features of cultured corneal limbal epithelium after 4 weeks. The decrease in UV-A absorption of cultivated oral mucosal epithelium ranged from 25 to 36% of that for cultured corneal epithelium. The increase in UV-B absorption by cultured oral mucosal epithelium between 200 and 800 µW/cm2 was approximately 145% of that for cultured corneal limbal epithelium. Conclusion: Our data demonstrated that cultured oral mucosal epithelium has low UV-A and high UV-B absorption capacity as compared with those of cultured corneal epithelium, suggesting that oral mucosal epithelium can compensate for UV absorption of corneal epithelium.
Genipin Suppresses Subconjunctival Fibroblast Migration, Proliferation and Myofibroblast Transdifferentiation
Authors: Kitano Ai , Saika Shizuya , Yamanaka Osamu , Ikeda Kazuo , Reinach Peter S. , Nakajima Yuji , Okada Yuka , Shirai Kumi , Ohnishi Yoshitaka
Published: October 2006

Purpose: Inchin-ko-to is a herbal medicine which has therapeutic effects in ameliorating liver fibrosis or cholestatic liver diseases. Its main bioactive component is genipin, which is an intestinal bacterial metabolite of this medication. Accordingly, we determined whether or not Inchin-ko-to suppresses in a wound healing model subconjunctival fibroblast (SCF) migration proliferation and myofibroblast transdifferentiation since an inhibitory effect could be of value in improving trabeculotomy outcome. Methods: Effects of genipin on SCF cell migration were examined subsequent to wounding confluent monolayer cultures. Alamar blue staining evaluated the effects of genipin (0–50 µg/ml) on fibroblast cell proliferation. Immunostaining determined α-smooth muscle actin (αSMA) expression. Western blotting evaluated (αSMA) expression and phospho-Smad2 formation. Real-time RT-PCR evaluated TGFβ1 and collagen Iα2 mRNA expression. Enzyme-immunoassay determined culture medium collagen I content. Results: Genipin suppressed wound-induced cell migration and proliferation. It also decreased collagen type I TGFβ1 and αSMA mRNA and protein expression. Smad2 signaling was inhibited by genipin in a dose-dependent manner. Conclusion: Genipin suppresses injury-induced fibrogenic responses in SCFs. This result suggests that the herbal medicine Inchin-ko-to might have therapeutic value following trabeculotomy.
Triple-Layer Duct-to-Mucosa Pancreaticojejunostomy after Pancreaticoduodenectomy
Authors: Ibrahim Salleh , Tay Khoon Hean , Launois Bernard , Tan Ngian Chye
Published: October 2006

Background: Pancreaticoduodenectomy is associated with a high degree of morbidity; the main cause is failure of the pancreatic anastomosis. It is imperative that this is performed safely and is secure. Pancreatic leaks will lead to serious morbidity and even mortality. Here we describe the use of a new surgical triple-layer pancreaticojejunostomy in a group of patients with minimal morbidity. Methods: This is a retrospective review from a prospective database. Fifty-one consecutive patients underwent a pancreaticoduodenectomy (either pylorus-preserving (PPPD) or classical Whipple’s) from May 1999 to December 2005 and had the pancreaticojejunostomy reconstructed as described below. Results: The mean age of the 51 patients was 56.71 ± 9.0 years; 32 (62.7%) were female and 19 (37.3%) were males. The mean operating time was 368.55 ± 57.94 min; the average blood loss was 396 ± 236 ml with 15 patients (29.4%) requiring postoperative blood transfusions. The mean pancreatic duct size was 4.94 ± 2.6 mm. In terms of pancreatic texture, there were 33 (64.7%) hard pancreas and 18 (35.3%) soft pancreas. PPPD was performed on 28 (54.9%) and the classical Whipple’s procedure on 23 (45.1%). Twelve patients had postoperative complications; only 1 patient had a pancreatic fistula which was treated conservatively. Conclusion: This method is safe and reliable. It can be used for a myriad of pancreas remnants with a wide range of pancreatic duct sizes.
Alterations in the Lipid Metabolism of Rat Aorta: Effects of Vitamin A Deficiency
Authors: Gatica Laura V. , Vega Verónica A. , Zirulnik Fanny , Oliveros Liliana B. , Gimenez María S.
Published: October 2006

Antioxidants are known to reduce cardiovascular disease by reducing the concentration of free radicals in the vessel wall and by preventing the oxidative modification of low-density lipoproteins. The prooxidative effect of a vitamin-A-deficient diet on the aorta has previously been demonstrated by us. In this study, the lipid metabolism in the aorta of rats fed on a vitamin-A-deficient diet was evaluated. Vitamin A deficiency induced a hypolipidemic effect (lower serum triglyceride and cholesterol levels) and a decreased serum paraoxonase 1/arylesterase activity. The concentrations of triglycerides, total cholesterol, free and esterified cholesterol, and phospholipids were increased in the aorta of vitamin-A-deficient rats. The phospholipid compositions showed an increase in phosphatidylcholine (PC), phosphatidylinositol plus phosphatidylserine and phosphatidylethanolamine, a decrease in sphingomyelin, and no change in phosphatidylglycerol. In the aorta, the increase in triglycerides was associated with an increased fatty acid synthesis and mRNA expression of diacylglycerol acyltransferase 1. The increased PC content was attributed to an increased synthesis, as measured by [methyl-14C]choline incorporation into PC and high CTP:phosphocholine cytidylyltransferase-α mRNA expression. The cholesterol synthesis, evaluated by [1-14C]acetate incorporated into cholesterol and mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase, did not change. The lipoprotein lipase and lectin-like oxidized low-density lipoprotein receptor 1 mRNA expression levels increased in the aorta of vitamin-A-deficient animals. The incorporation of vitamin A into the diet of vitamin-A-deficient rats reverted all the changes observed. These results indicate that a vitamin-A-deficient diet,in addition to having a prooxidative effect, alters the aorta lipid metabolism.
Oxaliplatin as First-Line Treatment in Inoperable Biliary Tract Carcinoma
Authors: Androulakis Nikolaos , Aravantinos Gerasimos , Syrigos Kostas , Polyzos Aris , Ziras Nikolaos , Tselepatiotis Evangelos , Samonis George , Kentepozidis Nikolaos , Giassas Stylianos , Vamvakas Lambros , Georgoulias Vassilis
Published: October 2006

Background: A multicenter phase II study was conducted in order to evaluate the efficacy and safety of oxaliplatin as first-line treatment of patients with locally advanced or metastatic carcinoma of the biliary tract. Patients and Methods: Twenty-nine chemo-naïve patients with locally advanced or metastatic biliary tract carcinoma received oxaliplatin 130 mg/m2 i.v. every 21 days. Patients were treated until tumor progression or unacceptable toxicity. Results: An objective response (3 complete responses, 3 partial responses) was achieved in 6 patients (20.6%, 95% CI 5.95–35.4). Disease control (complete response, partial response and stable disease) was observed in 14 patients (48.2%). The median time to tumor progression was 3 months (range 0.7–39) and the median overall survival was 7 months (range 1–39). The 1-year survival rate was 32%. Toxicity was mild. Conclusion: Oxaliplatin is an active agent against biliary tract carcinoma and therefore should be further investigated in combination with other cytotoxic drugs.
Capecitabine and Mitomycin C Is an Effective Combination for Anthracycline- and Taxane-Resistant Metastatic Breast Cancer
Authors: Massacesi Cristian , La Cesa Annalisa , Marcucci Fabiana , Pilone Alberta , Rocchi Marco B.L. , Zepponi Laura , Santini Daniele , Tonini Giuseppe , Burattini Luciano
Published: October 2006

Capecitabine is converted to 5-fluorouracil by thymidine phosphorylase, and mitomycin C is capable of upregulating the expression of thymidine phosphorylase suggesting a synergistic effect. Fifty-three patients (median age 62 years) with anthracycline- and taxane-resistant, metastatic breast cancer received mitomycin C 6 mg/m2 on day 1, and capecitabine (Xeloda) 2,000 mg/m2/day from day 1 to day 14 with cycles repeated every 4 weeks. Overall, 77.4% had visceral metastases and 33 were pretreated with ≧3 chemotherapy lines. A median of 6 cycles were given (range 1–19) with a complete response observed in 2 patients (3.9%), partial response in 17 (33.3%) and stable disease in 19 (37.2%). Overall response rate was 37.2% (95% CI, 24.0–50.5%), with a median duration of 10.4 months. Median time to progression was 8.1 months and median survival was 17.4 months (1- and 2-year survival rates of 60 and 28%, respectively). Toxicity was mild. The most frequent grade 3/4 events were neutropenia (5.7% of patients), diarrhea (3.8%), and deep venous thrombosis (3.8%). Capecitabine plus mitomycin C may represent an effective and manageable treatment option for advanced breast cancer patients resistant to anthracyclines and taxanes. This approach provides an alternative for pretreated patients with advanced breast cancer.
A Phase I Study of the Optimized Cryptic Peptide TERT572Y in Patients with Advanced Malignancies
Authors: Mavroudis D. , Bolonakis I. , Cornet S. , Myllaki G. , Kanellou P. , Kotsakis A. , Galanis A. , Nikoloudi I. , Spyropoulou M. , Menez J. , Miconnet I. , Niniraki M. , Cordopatis P. , Kosmatopoulos K. , Georgoulias V.
Published: October 2006

Objective: It was the aim of this study to evaluate the safety of the optimized cryptic peptide TERT572Y in pretreated patients with advanced cancer. Methods: Nineteen patients with progressive and chemotherapy-refractory tumors received escalated doses (2–6 mg) of 2 subcutaneous injections of the optimized TERT572Y peptide followed by 4 subcutaneous injections of the native TERT572 peptide every 3 weeks. Both TERT peptides were coinjected with adjuvant Montanide ISA51. Toxicity was evaluated every 3 weeks and peptide-specific CD8+ cells were detected by flow cytometry using TERT572Y tetramers. Results: Fourteen out of 19 patients completed the vaccination program. No grade III/IV toxicity was observed. Grade I anemia was observed in 4 patients and local skin reaction at the injection site in 11 patients. Other nonhematologic toxicities were mild, and no late toxicity was observed after a median postvaccination follow-up period of 10.7 months. There was no dose-limiting toxicity. Peripheral blood TERT572Y-specific CD8+ lymphocytes were detected in 13 out of 14 evaluable patients after 2 injections with the optimized TERT572Y peptide. There was no complete or partial response, but 4 patients (21%) with persistent TERT572Y-specific CD8+ experienced stable disease for a median of 10.5 months. Conclusion: TERT572Y peptide vaccine is well tolerated and effective in eliciting specific TERT572Y CD8+ lymphocytes in pretreated cancer patients, demonstrating that cryptic peptides could be used in cancer immunotherapy.
Bolstering the Proliferation Security Initiative at Sea: A Comparative Analysis of Ship-boarding as a Bilateral and Multilateral Implementing Mechanism
Authors: Spadi Fabio
Published: October 2006

The political significance of the PSI – and the implementation thereof – cannot reap its maximum potential if it is not supported by an adequate legal framework to regulate, inter alia, the interdiction of suspect vessels. The US Administration, very much the leading actor behind the Initiative, has been at the forefront of the efforts to develop an accompanying and effective international legal system, both at bilateral and multilateral levels, following the blueprint of what has already been accomplished in the area of counter-narcotics interdiction. However, the consent of the States involved remains paramount even within the context of the bilateral and multilateral agreements elaborated so far. These agreements, which are examined and compared in the article, in many ways do not attain the same sophistication as that of the counter-narcotics agreements. This is probably unavoidable, in light of the largely discretionary nature of the key concepts of the PSI, such as the definition of what are States or non-State actors of proliferation concern.
Personal Influence and the Effects of the National Youth Anti-Drug Media Campaign
Authors: Hornik Robert
Published: October 2006

Personal Influence (Katz and Lazarsfeld 1955/2006) put forward and tested a variety of hypotheses about how social contexts constrain media effects. Five such hypotheses are described: three about interactions of media exposure with social context (Stability, Conformity, and Instrumental) and two about two-step flow effects (Relay and Message Interpretation). Each is tested here with data from the evaluation of the National Youth Anti-Drug Media Campaign. The evaluation of the campaign has suggested boomerang outcomes—more exposure to the campaign led to more interest in marijuana use. This article examined whether those effects were magnified through interactions with siblings. In general, no evidence showed that older siblings' beliefs or behavior interacted with younger siblings' exposure to campaign messages in producing effects. However, evidence showed that the two-step flow did operate: older siblings were themselves affected by their own exposure to the campaign and, in turn, affected the beliefs and behaviors of their younger brothers and sisters.
The Influence of Personal Influence on the Study of Audiences
Authors: Livingstone Sonia
Published: October 2006

This article looks back at the publication of Personal Influence (Katz and Lazarsfeld 1955) to bring into focus the multistranded history of discussion and debate over the mass media audience during the twentieth century. In contrast with the heroic narrative, constructed retrospectively, that prioritizes cultural studies' approaches to audiences, the author suggests that this rich and interdisciplinary history offers many fruitful ways forward as the agenda shifts from mass media to new media audiences. Although audience research has long been characterized by struggles between critical and administrative schools of communication, and between opposed perspectives on the relation of the individual to society, Katz and Lazarsfeld's work, and subsequent work by Katz and his collaborators, suggests possibilities for convergence, or at least productive dialogue, across hitherto polarized perspectives as researchers collectively seek to understand how, in their everyday lives, people can, and could, engage with media to further democratic participation in the public sphere.
Public Connection through Media Consumption: Between Oversocialization and De-Socialization?
Authors: Couldry Nick , Markham Tim
Published: October 2006

This article reviews the ongoing contribution of Personal Influence to our understanding of media' social consequences from the perspective of recent research (the London School of Economics “Public Connection” project, 2003-2006, conducted by the authors and Sonia Livingstone) into the extent to which shared habits of media consumption help sustain, or not, U.K. citizens' orientation to a public world. As well as reviewing specific findings of the Public Connection project that intersect with themes of Personal Influence(particularly on citizens' networks of social interaction and the available discursive contexts in which they can put their mediated knowledge of the public world to use), the article reviews the methodological similarities and differences between this recent project and that of Katz and Lazarsfeld. The result, the authors conclude, is to confirm the continued salience of the questions about the social embeddedness of media influences that Katz and Lazarsfeld posed.
Personal Influence and the Bracketing of Women's History
Authors: Douglas Susan J.
Published: October 2006

This article reviews both what Personal Influence revealed about the two-step flow within women's inter-personal networks and what it failed to capture about women's experiences during the tumultuous changes in gender roles between 1945, when the data were collected, and 1955, when the study was published. One of the central contradictions of the Decatur Study is that it simultaneously disguises that it is women who are being studied here yet universalizes them as representative of the general population. But the article also argues that despite the blind spots and ahistoricity of Personal Influence, it was a crucial reminder that women, despite being individual targets of much media fare, were also embedded in social networks through which they influenced other women and were, in turn, influenced by them.
Fifteen Pages that Shook the Field: Personal Influence, Edward Shils, and the Remembered History of Mass Communication Research
Authors: Pooley Jefferson
Published: October 2006

Personal Influence's fifteen-page account of the development of mass communication research has had more influence on the field's historical self-understanding than anything published before or since. According to Elihu Katz and Paul Lazarsfeld's well-written, two-stage narrative, a loose and undisciplined body of prewar thought had concluded naively that media are powerful—a myth punctured by the rigorous studies of Lazarsfeld and others, which showed time and again that media impact is in fact limited. This “powerful-tolimited-effects” story line remains textbook boilerplate and literature review dogma fifty years later. This article traces the emergence of the Personal Influence synopsis, with special attention to (1) Lazarsfeld's audience-dependent framing of key media research findings and (2) the surprisingly prominent role of Edward Shils in supplying key elements of the narrative.
Personal Influence and the End of the Masses
Authors: Scannell Paddy
Published: October 2006

This article offers an exogenous historical analysis of Personal Influence, arguing that it offers an engaged response to a fundamental change taking place at that time in the world economy as it moved from scarcity to abundance. The ten year delay in the publication of the book after the original field work was done in Decatur, Illinois, in 1945 suggests that the sociology of mass communication had difficulty in making sense of the data that work produced. It needed the new sociology of interpersonal communication to interpret it. In accounting for the fusion of these two different sociologies in the work that was finally published, this article indicates the passing of the time of the masses and the coming of the time of everyday life.
Personal Influence: A Radical Theory of Action
Authors: Kadushin Charles
Published: October 2006

Katz and Lazarsfeld's Personal Influence presents a “theory of action” that privileges interpersonal influence. In contrast, classic theories of action from Hobbes, Kant, Freud, and Parsons ignored the impact of personal influence in their theories of human action. Once scholars recognized the importance of adding interpersonal influence to the action scheme, they saw that influences naturally radiated from the immediate inter personal environment to the larger social network. Both the interpersonal environment and further social network connections have been loosely termed “social capital.” Long before the term “social capital” entered the social science lexicon, Personal Influence explored the consequences of a network of advice-giving others. Ahead of its time, the book lacked some currently available technical and conceptual resources to fully meet its ambitious goal of locating the relative impact of personal influence on individual decision making. Nonetheless, current students of social capital and decision making have more to learn from this book than they may realize.
Personal Influence and the New Paradigm: Some Inadvertent Consequences
Authors: Lang Kurt , Lang Gladys Engel
Published: October 2006

An examination of the reception given Personal Influence when first published points to highly selective interpretations of the findings. The claims reviewers made for the influence of interpersonal communication relative to the mass media, especially in the political process, went even beyond those advanced by the authors. They overlooked not only the very restricted conceptualization of “effects” that guided the Decatur research but also previously accumulated evidence on multiple kinds of media influence. This article argues that the new conventional wisdom pitting personal versus mass media effects associated with this and previous studies in the Columbia tradition discouraged, however inadvertently, a coming generation of sociologists from researching the effects—particularly long-range effects—of mass communication. As a consequence, academic sociology came to cede much of the high ground it once occupied in media studies to political science and to more professionally oriented departments or schools of communication.
A Cross-Cultural Study of Environmental Motive Concerns and Their Implications for Proenvironmental Behavior
Authors: Milfont Taciano L. , Duckitt John , Cameron Linda D.
Published: October 2006

Environmental concern can be driven by biospheric, egoistic or altruistic motives. Few studies, however, have compared these three environmental motive concerns across cultural groups. This study investigated differences between European New Zealanders and Asian New Zealanders in environmental motive concerns and their implications for proenvironmental behaviors. The results demonstrated that the tripartite model of environmental concerns provided good fit in both samples. They also indicated that Asian New Zealanders were significantly higher than European New Zealanders on egoistic concern, whereas European New Zealanders were significantly higher on biospheric concern. For European New Zealanders, biospheric concern predicted proenvironmental behavior positively, whereas egoistic concern predicted it negatively. For Asian New Zealanders, in contrast, both biospheric and altruistic concerns predicted proenvironmental behavior positively. The implications of these findings for environmental education campaigns are discussed.
DTGR: Disruption-Tolerant Geographic Routing for Wireless Ad Hoc Networks
Authors: Li Yingjie , Lai Ten H. , Liu Ming T. , Sun Min-Te , Yang Junmo
Published: October 2006

In wireless ad hoc networks, temporary link disruptions can frequently occur due to the presence of obstacles, node mobility, and so on. These disruptions can result in a node’s incorrect perception of its neighbor set when the neighbor set is constructed via beacon sampling (e.g., beacon collisions may result in the removal of a node j from the neighbor set of a node i, although j is within the transmission range of i). Such a behavior can adversely affect the performance of position-based routing algorithms as it may lead to inefficient routing or packet dropping. To address this, the authors propose a scheme that allows node i to associate each of its neighbor j with a reachability value that is a measure of the stability of the link between i and j. They then apply their scheme to greedy perimeter stateless routing (GPSR) and design two new routing algorithms: disruption-tolerant geographic routing—simple forwarding (DTGR-SF) and disruption-tolerant geographic routing—waiting before forwarding (DTGR-WF), in which nodes use reachability values to make forwarding decisions. The authors compare the performances of DTGR-SF and DTGR-WF with that of GPSR in various simulation settings. Their simulation results show that proposed algorithms perform better in settings where disruptions are present. In networks with few occurrences of disruptions, their schemes achieve the same high performance as that of GPSR.
Algorithms and Trade-Offs in Multicast Service Overlay Design
Authors: Lao Li , Cui Jun-Hong , Gerla Mario
Published: October 2006

The Multicast Service Overlay Network (MSON) has been recently introduced to address some of the deployment and maintenance problems of IP multicast and application-level multicast. An MSON is essentially a backbone service overlay provisioned by an MSON provider and designed to “multiplex” multiple-user overlays. It consists of service nodes or proxies deployed by the provider. The proxies are strategically deployed to form a backbone overlay and provide multicasting functionalities for supporting many user groups simultaneously. The MSON provider designs the backbone overlay for a large user population and can therefore enjoy large-scale economies and benefits. Since the deployment of an MSON is a capital-intensive investment, it is very imperative to carefully design the MSON so that the provider can make the best revenue out of this investment. In this article, the authors formulate the MSON design problem by taking into account operational costs of the MSON provider. They then explore three subproblems: overlay proxy placement, overlay link selection, and bandwidth dimensioning. For each of these subproblems, the authors present several algorithms and discuss their design trade-offs. By simulations, they investigate the effectiveness of different overlay design algorithms, analyze their impact on multicast performance, and suggest some practical solutions for MSON design.
Pharmacokinetics of a Newly Identified Active Metabolite of Buspirone After Administration of Buspirone Over Its Therapeutic Dose Range
Authors: Dockens Randy C. , Salazar Daniel E. , Fulmor I. Edgar , Wehling Michele , Arnold Mark E. , Croop Robert
Published: October 2006

The objective of this study was to assess the pharmacokinetics of a newly identified active metabolite of buspirone, 6‐hydroxybuspirone (6OHB), over the therapeutic dose range of buspirone. A 26‐day, open‐label, nonrandomized, single‐sequence, dose‐escalation study in normal healthy volunteers was conducted (N = 13). Subjects received escalating doses of buspirone with each dose administered for 5 days starting at a dose of 5 mg twice daily and increasing up to 30 mg twice daily. Plasma concentrations of 6OHB were approximately 40‐fold greater than those of buspirone. 6OHB was rapidly formed following buspirone administration, and exposure increased proportionally with buspirone dose. Further research regarding the safety and efficacy of 6OHB itself is warranted.
Paul’s Stoicizing Politics in Romans 12-13: The Role of 13.1-10 in the Argument
Authors: Engberg-Pedersen Troels
Published: October 2006

This article argues for the intrinsic coherence of Rom. 12-13 by considering the meaning of the transitions between the various sections of the text. In this light, the article proposes an understanding of Paul’s politics that draws on Stoic ideas in two important places: 13.1-7 (compared with Seneca, De Clementia 1.1-4) and the transition between 13.7 and 13.8 (drawing on the Stoic and Pauline idea of (see pdf for character), ‘as if not’). As a formula for Paul’s Stoicizing politics in Rom. 12-13, the note suggests the following: engagement in this world and disengagement from it but total engagement elsewhere.