bluuebunny/crossref_metadata_2025 huggingface dataset:
New lead-copper minerals from the Mendip Hills (Somerset)
Authors: Spencer L. J.
Published: February 2007

Although mining operations have been carried on in the Mendip Hills for a period of about 2000 years—probably since pre-Roman times, very little is known respecting the minerals that occur in the district. The reason for this is that most of the mines were exhausted previous to the development of mineralogy as an exact science; and furthermore only few specimens have been preserved in collections. During the nineteenth century operations were mainly confined to re-working the vast accumulations of refuse left by the earlier miners. This work was continued at the St. Cuthbert's Lead Works (1 mile ESE. of Priddy) up to the year 1908, since when all work has ceased on the Hill. The latest mining was for iron and manganese ores at Higher Pitts farm (1 mile SSE. of Priddy); here work ceased in 1893.
Late-onset central hypoventilation syndrome: a family genetic study
Authors: Doherty L. S. , Kiely J. L. , Deegan P. C. , Nolan G. , McCabe S. , Green A. J. , Ennis S. , McNicholas W. T.
Published: February 2007

Congenital central hypoventilation syndrome is a rare disorder characterised by chronic alveolar hypoventilation, which becomes more pronounced during sleep and may be associated with neurocristopathies, such as Hirchsprung's disease. A mutation in thePHOX2Bgene has recently been identified.

In a family of both parents and five offspring, detailed clinical assessment, pulmonary function testing, overnight sleep studies and ventilatory responsiveness to progressive hypercapnia (V′R,CO2) were performed, in addition to analysis of known genetic loci for this condition.

The father and four of the offspring demonstrated features of central hypoventilation with nonapnoeic oxygen desaturation during sleep and diminishedV′R,CO2, despite normal pulmonary function. The lowest sleep saturation was median (range) 79% (67–83%) andV′R,CO2was 2.1 (0.03–4.3) L·min-1·kPa-1. The normal values for the authors’ centre (St Vincent's University Hospital, Dublin, Ireland) are 15–40 L·min-1·kPa-1. An in-frame five amino acid polyalanine expansion of thePHOX2Bgene was found in all affected subjects, while the mother and fifth child, who did not have features of central hypoventilation, had a normalPHOX2Bgene. Magnetic resonance imaging of the brainstem in one severely affected child was normal.

The present study of a unique family confirms that transmission of late-onset congenital central hypoventilation syndrome is autosomal dominant in nature.
Molecular mechanisms involved in interleukin-4-induced human neutrophils: expression and regulation of suppressor of cytokine signaling
Authors: Ratthé Claude , Pelletier Martin , Chiasson Sonia , Girard Denis
Published: February 2007

Interleukin-4 (IL-4) is a CD132-dependent cytokine known to activate the Jak-STAT pathway in different cells and cell lines. Although IL-4 has been demonstrated previously to be an agonist in human neutrophils, its capacity to activate different cell signaling pathways in these cells has never been investigated. Two types of IL-4 receptor (IL-4R) exist: the Type I (CD132/IL-4R1 heterodimer) and the Type II (IL-4Rα/IL-13Rα1 heterodimer). In a previous study, we demonstrated that neutrophils express the Type I receptor. Herein, using flow cytometry, we demonstrated that neutrophils, unlike U-937 cells, do not express IL-13Rα1 and IL-13Rα2 and confirmed the expression of CD132 and IL-4Rα on their surface. We also demonstrated that IL-4 induced phosphorylation of Syk, p38, Erk-1/2, JNK, Jak-1, Jak-2, STAT6, and STAT1 and that treatment of cells with the inhibitors piceatannol, SB203580, PD98059, or AG490 reversed the ability of IL-4 to delay neutrophil apoptosis. Using RT-PCR, we demonstrated for the first time that neutrophils express mRNA for all suppressor of cytokine signaling (SOCS) members, namely SOCS1–7 and cytokine-inducible Src homology 2 protein. It is interesting that IL-4 increased expression of SOCS3 at the mRNA and protein levels. The effect of IL-4 on SOCS3 protein expression was increased markedly when the proteasome inhibitor MG132 was added to the cultures, but this was inhibited by cycloheximide, suggesting that SOCS3 is de novo-synthesized in response to IL-4. We conclude that neutrophils express only the Type I IL-4R on their surface and that IL-4 signals via different cell signaling pathways, including the Jak/STAT/SOCS pathway.
Potent inhibition of store-operated Ca2+ influx and superoxide production in HL60 cells and polymorphonuclear neutrophils by the pyrazole derivative BTP2
Authors: Steinckwich Natacha , Frippiat Jean-Pol , Stasia Marie-José , Erard Marie , Boxio Rachel , Tankosic Christiane , Doignon Isabelle , Nüße Oliver
Published: February 2007

Store-operated calcium entry (SOCE) is a key regulator in the activation of leukocytes. 3,5-Bistrifluoromethyl pyrazole (BTP) derivatives have been identified recently as inhibitors of T lymphocyte activation. The inhibitory effect of one of these compounds, N-(4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl)-4-methyl-1,2,3-thiadiazole-5-carboxamide (BTP2), appears to be a result of inhibition of SOC influx. Polymorphonuclear neutrophils provide effective protection against bacterial infection, but they are also involved in tissue damage during chronic inflammation. As for T lymphocytes, their activation relies on SOCE. We therefore investigated the effect of BTP2 on calcium homeostasis and functional responses of human neutrophils. BTP2 significantly inhibited the calcium influx after stimulation with thapsigargin or fMLF. This inhibition was seen after 5 min of incubation with 10 μM BTP2 and after 24 h with lower concentrations. With 24 h incubation, the effect appeared irreversible, as the removal of BTP2 3 h before the experiment did not reduce this inhibition in granulocyte-differentiated HL60 cells. In human neutrophils, BTP2 reduced superoxide anion production by 82% after 24 h of incubation. On the contrary, phagocytosis, intraphagosomal radical production, and bacterial killing by neutrophils were not reduced significantly, even after 24 h treatment with 10 μM BTP2. This work suggests that BTP2 could become an important tool to characterize calcium signaling in neutrophils. Furthermore, BTP2 or related compounds could constitute a new approach to the down-regulation of neutrophils in chronic inflammatory disease without compromising antibacterial host defense.
Peptidoglycan and mannose-based molecular patterns trigger the arachidonic acid cascade in human polymorphonuclear leukocytes
Authors: Valera Isela , Vigo Ana González , Alonso Sara , Barbolla Luz , Crespo Mariano Sánchez , Fernández Nieves
Published: February 2007

The release of arachidonic acid (AA) in response to microorganism-derived products acting on pattern recognition receptors (PRR) was assayed in human polymorphonuclear leukocytes (PMN). Peptidoglycan (PGN) and mannan were found to be strong inducers of AA metabolism, as they produced the release of AA at a similar extent to that produced by agonists of pathophysiological relevance such as complement-coated zymosan particles and IgG immune complexes. In sharp contrast, lipoteichoic acid, LPS, muramyldipeptide, and the bacterial lipoprotein mimic palmitoyl-3-cysteine-serine-lysine-4 failed to do so. Leukotriene B4 and PGE2 were synthesized in response to mannan and PGN, thus suggesting that the lipoxygenase and the cyclooxygenase routes are operative in human PMN in response to pathogen-associated molecular patterns (PAMP). Analysis of the lipid extracts of supernatants and cell pellets as well as pharmacological studies with the calpain inhibitor calpeptin and the cytosolic phospholipase A2 (PLA2) inhibitor pyrrolidine-1 showed the dependence of AA release on cytosolic PLA2-catalyzed reactions. The effect of PGN was not inhibited by previous treatment with anti-TLR2 mAb, thus suggesting a nonarchetypal involvement of the TLR2 signaling route and/or participation of other receptors. Because of the abundance of mannose-based and PGN-containing PAMP in fungi and bacteria and the wide array of PRR in human PMN, these finding disclose a role of prime importance for PAMP and PRR in AA metabolism in the inflammatory response mediated by PMN.
Estrogens and Antiestrogens as Etiological Factors and Therapeutics for Prostate Cancer
Authors: HO SHUK‐MEI , LEUNG YUET‐KIN , CHUNG IRVING
Published: February 2007

Abstract:  Mounting evidence supports a key role played by estrogen or estrogen in synergy with an androgen, in the pathogenesis of prostate cancer (PCa). New experimental data suggest that this process could begin as early as prenatal life. During adulthood, estrogen carcinogenicity is believed to be mediated by the combined effects of hormone‐induced, unscheduled cell proliferation and bioactivation of estrogens to genotoxic carcinogens. Increased bioavailability of estrogen through age‐dependent increases in conversion from androgen could also be a contributing factor. Individual variations and race‐/ethnic‐based differences in circulating or locally formed estrogens or in tissue estrogen responsiveness may explain differential PCa risk among individuals or different populations. Estrogen receptor (ER)‐α and ER‐β are the main mediators of estrogen action in the prostate. However, ER‐β is the first ER subtype expressed in the fetal prostate. During cancer development, ER‐β expression is first lost as tumors progress into high grade in the primary site. Yet, its reexpression occurs in all metastatic cases of PCa. A change in cytosine methylation in a regulatory CpG island located in the proximal promoter of ER‐β may constitute an “on/off” switch for reversible regulation of ER‐β expression. A variety of estrogenic/antiestrogenic/selective estrogen receptor modulator (SERM)‐like compounds have been shown to use non‐ERE pathways, such as tethering of ER‐β to NF‐κB binding proteins, Sp2, or Ap1 for gene transactivation. These findings open new avenues for drug design that now focuses on developing a new generation of estrogen‐based PCa therapies with maximal proapoptotic action but few or no side effects.
Hormonal Treatment of Human Hepatocellular Carcinoma
Authors: DI MAIO MASSIMO , DE MAIO ERMELINDA , MORABITO ALESSANDRO , D'ANIELLO ROBERTA , DE FEO GIANFRANCO , GALLO CIRO , PERRONE FRANCESCO
Published: February 2007

Abstract:  Animal models of experimental liver carcinogenesis and epidemiological studies in humans suggest a relationship between sex hormones and hepatocellular carcinoma (HCC). In 1997, a systematic review of the existing, small randomized trials evaluating the antiestrogen tamoxifen yielded a positive result, but the large randomized CLIP‐1 trial showed no survival advantage from the addition of tamoxifen to best supportive care. A possible explanation for the negative results is the lack of patient selection, but the expression of estrogen (ER) and progesterone (PgR) receptors in HCC does not clearly affect the survival outcome of the patients treated with tamoxifen. In the last years, it has been proposed that negative results might be due to the fact that tamoxifen in HCC could act via an ER‐independent pathway, which requires much higher doses than those usually administered, but a double‐blind Asian randomized trial conducted to assess possible dose‐response effect showed no efficacy for tamoxifen, with an inversely negative impact with increasing dose. According to the results of large trials and of the Cochrane systematic review, neither further trials are warranted with tamoxifen in HCC, nor should any use in clinical practice be considered. Interesting results have been obtained when the type of hormonal treatment (tamoxifen or megestrol) has been chosen according to the presence of wild‐type or variant ER, but these results should be confirmed in large randomized trials. Negative results have been obtained with antiandrogen therapy. In conclusion, hormonal treatment should not be a part of the current management of HCC patients.
The Role of Estrogens in Normal and Abnormal Development of the Prostate Gland
Authors: PRINS GAIL S. , HUANG LIWEI , BIRCH LYNN , PU YONGBING
Published: February 2007

Abstract:  Estrogens play a physiologic role during prostate development with regard to programming stromal cells and directing early morphogenic events. However, if estrogenic exposures are abnormally high during the critical developmental period, permanent alterations in prostate branching morphogenesis and cellular differentiation will result, a process referred to as neonatal imprinting or developmental estrogenization. These perturbations are associated with an increased incidence of prostatic lesions with aging, which include hyperplasia, inflammation, and dysplasia. To understand how early estrogenic exposures can permanently alter the prostate and predispose it to neoplasia, we examined the effects of estrogens on prostatic steroid receptors and key developmental genes. Transient and permanent alterations in prostatic AR, ERα, ERβ, and RARs are observed. We propose that estrogen‐induced alterations in these critical transcription factors play a fundamental role in initiating prostatic growth and differentiation defects by shifting the prostate from an androgen‐dominated gland to one whose development is regulated by estrogens and retinoids. This in turn leads to specific disruptions in the expression patterns of key prostatic developmental genes that normally dictate morphogenesis and differentiation. Specifically, we find transient reductions in Nkx3.1 and permanent reductions in Hoxb‐13, which lead to differentiation defects particularly within the ventral lobe. Prolonged developmental expression of Bmp‐4 contributes to hypomorphic growth throughout the prostatic complex. Reduced expression of Fgf10 and Shh and their cognate receptors in the dorsolateral lobes leads to branching defects in those specific regions in response to neonatal estrogens. We hypothesize that these molecular changes initiated early in life predispose the prostate to the neoplastic state upon aging.
Red Wine Extract Prevents Neuronal Apoptosis in Vitro and Reduces Mortality of Transgenic Mice
Authors: AMODIO ROSALBA , ESPOSITO ENNIO , DE RUVO CATERINA , BELLAVIA VINCENZO , AMODIO EMANUELE , CARRUBA GIUSEPPE
Published: February 2007

Abstract:  In this work, we have investigated the effects of nutritional antioxidants as antidegenerative agents on glutamate‐induced apoptosis in primary cultures of cerebellar granule neurons (CGNs). Glutamate‐induced apoptosis is also associated with intracellular [Ca2+]i overload, generation of reactive oxygen species (ROS), depression of cell energy metabolism, cytochrome c release, and increase in caspase‐3 activity. Pretreatment (3 h) with red wine extract (5 μg/mL) and ascorbic acid (30 μM) blocks glutamate‐induced apoptosis in CGNs. In vivo experiments carried out on transgenic mice expressing the human mutated Cu, Zn superoxide dismutase (SOD1) G93A (mSOD1G93A) show that mice fed with lyophilized red wine have significantly increased survival as compared to control, untreated animals.
Estrogens and Mechanisms of Prostate Cancer Progression
Authors: CARRUBA GIUSEPPE
Published: February 2007

Abstract:  Prostate cancer is a major health issue in westernized countries, being considered a prototypical age‐related, androgen‐dependent tumor. However, data on the association between circulating androgens and prostate cancer have been inconsistent and mostly not compatible with the androgen hypothesis. In addition, plasma androgen‐to‐estrogen ratio appears to decrease with age, suggesting that estrogens may also have a role. Results from our own and others' studies suggest that circulating steroids cannot be considered representative of their actual intraprostatic levels. This is a consequence of the expression and/or activity of steroid enzymes, including 17β‐hydroxysteroid dehydrogenase (17β‐HSD), 5α‐reductase, 3α/3β‐HSD, and aromatase, which may eventually lead to a differential tissue accumulation of steroid derivatives having distinct biological activities. Interestingly, many of the genes encoding for steroid enzymes are highly polymorphic in nature, although only a few studies have investigated their relation with prostate cancer and the data presently available are inconclusive. Locally produced or metabolically transformed estrogens may differently affect proliferative activity of prostate cancer cells. In our studies, estrogen may either stimulate or decrease prostate cancer cell growth, also depending on the receptor status. In particular, an imbalance of ERα and ERβ expression may be critical to determine the ultimate estrogen effects on prostate cancer cell growth. Furthermore, evidence is accumulating that estrogens regulate gene transcription through an array of estrogen‐response elements (EREs) and non‐EREs, either ligand‐dependent or ‐independent. This is further complicated by the presence of receptor isoforms, distinct cofactor interaction, and potential heterodimerization. Based on this combined evidence, a hypothetical model of prostate cancer progression is presented.
Metabolic Profiles of Androgens in Malignant Human Liver Cell Lines
Authors: GRANATA ORAZIA M. , COCCIADIFERRO LETIZIA , MICELI VITALE , POLITO LUCIA M. , CAMPISI ILDEGARDA , CARRUBA GIUSEPPE
Published: February 2007

Abstract:  In this study we have investigated androgen (testosterone and androstenedione) metabolism in malignant HepG2, Huh‐7, and HA22T human liver cell lines. Following 72‐h incubation with testosterone or androstenedione, estrogen formation through aromatase activity was consistently higher in HepG2 cells (being nearly 100%) and moderate in Huh7 cells (34%), while it was undetectable in HA22T cells. The produced estrogens are completely conjugated by estrogen sulpho‐transferase (EST) in HepG2 cells, while nearly 25% remains in the free form in Huh‐7 cells. The HA22T and Huh‐7 cells show a markedly different balance of 5α‐ versus 5β‐reduced androgens (65.7% vs. 2.5% and 2.6% vs. 22.2%, respectively), while no detectable 5α/5β‐reduced androgen is formed in HepG2 cells. These divergent metabolic profiles, coupling aromatase to EST, and to 5α/5β‐reductase, hint at a differential regulation of androgen metabolic pathways that may ultimately lead to a distinct impact of biologically active metabolites on growth and function of human liver cancer cells.
Monocyte–Macrophage System as a Target for Estrogen and Selective Estrogen Receptor Modulators
Authors: HÄRKÖNEN PIRKKO L. , VÄÄNÄNEN H. KALERVO
Published: February 2007

Abstract:  Postmenopausal decline of estrogen production is associated with development of several degenerative disorders such as osteoporosis, neuroinflammatory diseases and vascular wall degeneration. These are associated with the activation of the cells of the monocyte–macrophage system in a context‐dependent manner. Estrogen regulates differentiation, maturation and function of many cell types in this system directly or indirectly via other cells by autocrine/paracrine mechanisms. Estrogen effects on the monocyte–macrophage system are primarily repressive. Most of these effects are mediated by repression of expression of genes for cytokines or modulation of other inflammatory mediators by the estrogen receptor (ER)‐dependent or nongenomic pathways. The ER‐dependent mechanisms mostly involve modulation of the nuclear factor kappa B (NF‐kappaB) pathway for transcriptional regulation of cytokine or other mediator genes. In the context of hormone‐regulated cancer, estrogen can influence production of cytokines or other inflammatory mediators by both tumor cells and tumor‐invading macrophages. The interactions of breast and prostate cancer cells with tumor‐associated macrophages (TAMs) may play an important role in tumor progression and even in the development of resistance to hormonal treatment. Regulation of the monocyte–macrophage system by estrogen and cross‐talk between the ER and cytokine‐mediated pathways provides multiple novel targets for development of selective ER modulator (SERM) molecules for prevention and treatment of postmenopausal degenerative and neoplastic diseases.
Quality of Life in Operable Colon Cancer Patients Receiving Oral Compared With Intravenous Chemotherapy: Results From National Surgical Adjuvant Breast and Bowel Project Trial C-06
Authors: Kopec Jacek A. , Yothers Greg , Ganz Patricia A. , Land Stephanie R. , Cecchini Reena S. , Wieand H. Samuel , Lembersky Barry C. , Wolmark Norman
Published: February 2007

Purpose

We compared health-related quality of life (HRQL), symptoms, and convenience of care (COC) in patients with stage II/III carcinoma of the colon who received either oral uracil/ftorafur (UFT) plus leucovorin (LV) or standard intravenous (IV) fluorouracil (FU) plus LV as adjuvant chemotherapy.

Patients and Methods

We measured HRQL with the Functional Assessment of Cancer Therapy–Colorectal (FACT-C) questionnaire, Short Form-36 Vitality Scale (SF-36), and a Quality of Life Rating Scale (QLRS) at baseline, once during chemotherapy, and at 1 year. We used the Symptom Distress Scale (SDS) and treatment-specific Symptom Checklist (SCL) to assess symptoms and a modified Burden of Care form to assess COC at baseline, on day 1 of each treatment cycle, and at 1 year. Repeated measures analyses controlling for demographic variables and baseline scores were used for statistical comparisons.

Results

The study accrued 1,608 patients, 803 to the FU arm and 805 to the UFT arm. There were no differences between the arms in overall FACT-C scores, FACT-C scores within the subscales of colon-specific, physical, emotional, social, and functional health, or QLRS scores. Patients taking UFT reported substantially higher COC. Statistically significant but small differences were observed for SF-36, favoring FU, and for SDS and SCL, both favoring UFT.

Conclusion

Patients perceive adjuvant treatment with UFT + LV as more convenient than standard IV treatment with FU + LV. Both regimens are well tolerated and do not differ in their impact on HRQL.
Long-Term Clinical Outcome After Postchemotherapy Retroperitoneal Lymph Node Dissection in Men With Residual Teratoma
Authors: Carver Brett S. , Shayegan Bobby , Serio Angel , Motzer Robert J. , Bosl George J. , Sheinfeld Joel
Published: February 2007

Purpose

The histologic finding of teratoma occurs in approximately 40% of all postchemotherapy retroperitoneal lymph node dissections (PC-RPLND). We evaluated patients at our institution undergoing initial PC-RPLND for teratoma to determine their clinical outcome.

Patients and Methods

We identified 210 patients from 1989 to 2003 with nonseminomatous germ cell tumors (NSGCT) who underwent initial PC-RPLND and were found to have only teratoma in the retroperitoneum. Clinical and pathologic information was obtained from our prospective surgical database, and clinical outcome was reported.

Results

Of the 210 patients in our series, 192 (92%) received only induction chemotherapy, and 18 (9%) required additional chemotherapy regimens. PC-RPLND pathology revealed mature teratoma in 178 patients (85%), immature teratoma in 15 patients (7%), and teratoma with malignant transformation in 17 patients (8%). With a median follow-up time for survivors of 37 months, disease recurred in 30 patients. The probability of remaining free of disease recurrence at 5 and 10 years was 83% and 80%, respectively. Of the 30 patients with disease recurrence, 10 (33%) had recurrence with teratoma, five (17%) had recurrence with teratoma with malignant transformation, and 15 (50%) had recurrence with viable germ cell tumor. On multivariable analysis, residual mass size and International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification were predictors of disease recurrence (P < .0005 and = .001, respectively).

Conclusion

PC-RPLND remains critical in the management of patients with NSGCT. Patients found to have teratoma at PC-RPLND have a 10-year probability of freedom from recurrence of 80%. The size of the residual mass and IGCCCG risk classification were significant predictors of disease recurrence.
Health-Related Quality of Life During and After Intraperitoneal Versus Intravenous Chemotherapy for Optimally Debulked Ovarian Cancer: A Gynecologic Oncology Group Study
Authors: Wenzel Lari B. , Huang Helen Q. , Armstrong Deborah K. , Walker Joan L. , Cella David
Published: February 2007

Purpose

A Gynecologic Oncology Group (GOG) randomized phase III trial (GOG 172) in optimal stage III epithelial ovarian cancer showed that intravenous (IV) paclitaxel plus intraperitoneal (IP) cisplatin and paclitaxel significantly lengthened progression-free survival and overall survival compared with IV paclitaxel and cisplatin. The purpose of this report is to comprehensively evaluate the patient-reported outcomes associated with IP versus IV therapy.

Patients and Methods

Four hundred fifteen eligible women were enrolled onto GOG 172 at member institutions. The Functional Assessment of Cancer Therapy–Trial Outcome Index (FACT-TOI; which includes physical, functional, and ovarian subscales) and neurotoxicity (Ntx) and abdominal discomfort (AD) subscales were used to assess patient-reported outcomes. Assessments were completed before random assignment, before cycle 4, and 3 to 6 weeks and 12 months after treatment.

Results

Physical and functional well-being and ovarian cancer symptoms were significantly worse in the IP arm before cycle 4 (P < .001) and 3 to 6 weeks after treatment (P = .001 for FACT-TOI). Patients in the IP arm also reported significantly worse AD before cycle 4 (P < .001) and significantly worse Ntx 3 to 6 weeks (P = .001) and 12 months (P = .003) after completing IP treatment. In general, however, the quality of life of both groups improved over time.

Conclusion

During active treatment, patients on the IP arm experienced more health-related quality-of-life disruption, AD, and Ntx compared with patients receiving conventional IV therapy. However, only Ntx remained significantly greater for IP patients 12 months after treatment. This trade-off should be included when discussing treatment options with patients. Future studies to mitigate the added burden associated with IP therapy are planned.
Phase III Trial of Concurrent or Sequential Adjuvant Chemoradiotherapy After Conservative Surgery for Early-Stage Breast Cancer: Final Results of the ARCOSEIN Trial
Authors: Toledano Alain , Azria David , Garaud Pascal , Fourquet Alain , Serin Daniel , Bosset Jean-François , Miny-Buffet Joelle , Favre Anne , Le Floch Olivier , Calais Gilles
Published: February 2007

Purpose

In 1996, we initiated the French multicenter phase III randomized trial to compare the effect on disease-free survival (DFS) of concurrent versus sequential chemotherapy (CT) and radiotherapy (RT) after breast-conserving surgery for stages I and II breast cancer. This report presents the clinical results with a median follow-up of 60 months.

Patients and Methods

Between February 1996 and April 2000, 716 patients were entered onto this trial. Adjuvant treatment began within 6 weeks after surgery. Sequential treatment of CT administered first followed by RT was compared with concurrent treatment of CT administered with RT. The CT regimen consisted of mitoxantrone (12 mg/m2), fluorouracil (500 mg/m2), and cyclophosphamide (500 mg/m2) on day 1, and it was repeated every 21 days for six courses. RT was delivered to the breast and, when indicated, to the regional lymphatics.

Results

There was no statistically significant difference in treatment in the 5-year DFS (80% in both groups; P = .83), locoregional recurrence-free survival (LRFS; 92% in sequential v 95% in concurrent; P = .76), metastasis-free survival (87% in sequential v 84% in concurrent; P = .55), or overall survival (90% in sequential v 91% in concurrent; P = .76). Nevertheless, in the node-positive subgroup, the 5-year LRFS was statistically better in the concurrent arm (97% in concurrent v 91% in sequential; P = .02), corresponding to a risk of locoregional recurrence decreased by 39% (hazard ratio, 0.61; 95% CI, 0.38 to 0.93).

Conclusion

This treatment protocol remains an appealing clinical option for many women with operable breast cancer at a high risk of recurrence. Combination treatments with new drugs for breast cancer are warranted.
Tumor Origin of Endothelial Cells in Human Neuroblastoma
Authors: Pezzolo Annalisa , Parodi Federica , Corrias Maria Valeria , Cinti Roberta , Gambini Claudio , Pistoia Vito
Published: February 2007

Purpose

Malignant cells are genetically unstable and prone to develop chemotherapy resistance, whereas tumor vasculature is usually of host origin and genetically stable. Tumor endothelial microvessels attract interest as therapeutic targets, but their genetic instability would curtail such approach. Here, we have investigated the tumor origin of endothelial microvessels in human neuroblastoma (NB).

Materials and Methods

Paraffin-embedded tissue sections from 10 MYCN-amplified tumors (six stage 4, three stage 3, and one stage 1) were studied. Endothelial cells (ECs) were detected by immunofluorescent staining for CD31 or CD105, and MYCN amplification was detected using fluorescence in situ hybridization (FISH). In xenografts of the HTLA-230 human NB cell line, human ECs were detected by CD31 staining, mouse ECs were detected by CD34 staining, and MYCN amplification and murine DNA were detected using FISH.

Results

MYCN-amplified ECs formed approximately 70% of tumor endothelial microvessels in two stage 4 tumors and 20% in one stage 3 tumor. Similar results were obtained after EC labeling with CD31 or CD105. Staining for alpha-smooth muscle actin in combination with MYCN FISH demonstrated that tumor-derived ECs were coated with pericytes. These vessels were functional because they contained RBCs. Approximately 70% of endothelial vessels from HTLA-230 xenografts stained for human CD31, but not murine CD34, and displayed MYCN amplification, thus proving their tumor origin.

Conclusion

NB-associated endothelial microvessels can originate from tumor cells, and this finding challenges the tenet that tumor vasculature is genetically stable. The possibility that NB-derived ECs are chemotherapy resistant warrants further investigation.
IL-13 mediates the recruitment of reserve cells for fusion during IGF-1-induced hypertrophy of human myotubes
Authors: Jacquemin Virginie , Butler-Browne Gillian Sandra , Furling Denis , Mouly Vincent
Published: February 2007

Insulin-like growth factor-1 (IGF-1) has been shown to induce skeletal muscle hypertrophy, to prevent the loss of muscle mass with ageing and to improve the muscle phenotype of dystrophic mice. We previously developed a model of IGF-1-induced hypertrophy of human myotubes, in which hypertrophy was not only characterized by an increase in myotube size and myosin content but also by an increased recruitment of reserve cells for fusion. Here, we describe a new mechanism of IGF-1-induced hypertrophy by demonstrating that IGF-1 signals exclusively to myotubes but not to reserve cells, leading, under the control of the transcription factor NFATc2, to the secretion of IL-13 that will secondly recruit reserve cells for differentiation and fusion. In addition, we show that IGF-1 also signals to myotubes to stimulate protein metabolism via Akt by (1) activating the mTOR-p70S6K-S6 pathway and inhibiting GSK-3β, both involved in the control of protein translation, and (2) inhibiting the Foxo1–atrogin-1 protein degradation pathway.
IQGAP1 regulates cell motility by linking growth factor signaling to actin assembly
Authors: Benseñor Lorena B. , Kan Ho-Man , Wang Ningning , Wallrabe Horst , Davidson Lance A. , Cai Ying , Schafer Dorothy A. , Bloom George S.
Published: February 2007

IQGAP1 has been implicated as a regulator of cell motility because its overexpression or underexpression stimulates or inhibits cell migration, respectively, but the underlying mechanisms are not well understood. Here, we present evidence that IQGAP1 stimulates branched actin filament assembly, which provides the force for lamellipodial protrusion, and that this function of IQGAP1 is regulated by binding of type 2 fibroblast growth factor (FGF2) to a cognate receptor, FGFR1. Stimulation of serum-starved MDBK cells with FGF2 promoted IQGAP1-dependent lamellipodial protrusion and cell migration, and intracellular associations of IQGAP1 with FGFR1 – and two other factors – the Arp2/3 complex and its activator N-WASP, that coordinately promote nucleation of branched actin filament networks. FGF2 also induced recruitment of IQGAP1, FGFR1, N-WASP and Arp2/3 complex to lamellipodia. N-WASP was also required for FGF2-stimulated migration of MDBK cells. In vitro, IQGAP1 bound directly to the cytoplasmic tail of FGFR1 and to N-WASP, and stimulated branched actin filament nucleation in the presence of N-WASP and the Arp2/3 complex. Based on these observations, we conclude that IQGAP1 links FGF2 signaling to Arp2/3 complex-dependent actin assembly by serving as a binding partner for FGFR1 and as an activator of N-WASP.
Robotic control in knee joint replacement surgery
Authors: Davies B L , Rodriguez y Baena F M , Barrett A R W , Gomes M P S F , Harris S J , Jakopec M , Cobb J P
Published: February 2007

A brief history of robotic systems in knee arthroplasty is provided. The place of autonomous robots is then discussed and compared to more recent ‘hands-on’ robotic systems that can be more cost effective. The case is made for robotic systems to have a clear justification, with improved benefits compared to those from cheaper navigation systems. A number of more recent, smaller, robot systems for knee arthroplasty are also described. A specific example is given of an active constraint medical robot, the ACROBOT system, used in a prospective randomized controlled trial of unicondylar robotic knee arthroplasty in which the robot was compared to conventional surgery. The results of the trial are presented together with a discussion of the need for measures of accuracy to be introduced so that the efficacy of the robotic surgery can be immediately identified, rather than have to wait for a number of years before long-term clinical improvements can be demonstrated.
Minimizing Information Loss and Preserving Privacy
Authors: Menon Syam , Sarkar Sumit
Published: February 2007

The need to hide sensitive information before sharing databases has long been recognized. In the context of data mining, sensitive information often takes the form of itemsets that need to be suppressed before the data is released. This paper considers the problem of minimizing the number of nonsensitive itemsets lost while concealing sensitive ones. It is shown to be an intractably large version of an NP-hard problem. Consequently, a two-phased procedure that involves the solution of two smaller NP-hard problems is proposed as a practical and effective alternative. In the first phase, a procedure to solve a sanitization problem identifies how the support for sensitive itemsets could be eliminated from a specific transaction by removing the fewest number of items from it. This leads to a modified frequent itemset hiding problem, where transactions to be sanitized are selected such that the number of nonsensitive itemsets lost, while concealing sensitive ones, is minimized. Heuristic procedures are developed for these problems using intuition derived from their integer programming formulations. Results from computational experiments conducted on a publicly available retail data set and three large data sets generated using IBM’s synthetic data generator indicate that these approaches are very effective, solving problems involving up to 10 million transactions in a short period of time. The results also show that the process of sanitization has considerable bearing on the quality of solutions obtained.
Optimal Advertising and Promotion Budgets in Dynamic Markets with Brand Equity as a Mediating Variable
Authors: Sriram S. , Kalwani Manohar U.
Published: February 2007

We study the optimal levels of advertising and promotion budgets in dynamic markets with brand equity as a mediating variable. To this end, we develop and estimate a state-space model based on the Kalman filter that captures the dynamics of brand equity as influenced by its drivers, such as the brand’s advertising and sales promotion expenditures. By integrating the Kalman filter with the random coefficients logit demand model, our estimation allows us to capture the dynamics of brand equity as well as to model consumer heterogeneity using store-level data. Using these demand model estimates, we determine the Markov perfect equilibrium advertising and promotion strategies. Our empirical analysis is based on store-level scanner data in the orange juice category, which comprises two major brands—Tropicana and Minute Maid. As expected, we find that sales promotions have a significant positive effect on consumers’ utility and induce consumers to switch to the promoted brand. However, there is also a negative effect of promotions on brand equity that carries over from period to period. Overall, we find that while sales promotions have a net positive impact both in the short term and in the long term, the implied total profit elasticity including the long-term effect is smaller than the short-term profit elasticity. Correspondingly, we expect myopic decision makers to allocate higher than optimal expenditures to sales promotions. Our results from the supply-side analysis reveal that the actual promotion levels for both brands are indeed higher than the optimal budgets for the forward-looking (long-term orientation) as well as the two-year planning horizon scenarios. Hence, it may be profitable for both brands to reduce their promotion levels. Further, we find that although the forward-looking promotional spending levels are higher for the smaller brand, Minute Maid, it is market leader Tropicana that spends more on sales promotions. Turning to optimal advertising budgets, we find that the equilibrium forward-looking advertising levels are higher for Tropicana, the brand that has higher brand equity and a higher responsiveness to advertising. Further, as expected, the optimal forward-looking advertising levels are higher than the myopic levels and the two-year planning horizon levels for both brands. However, the forward-looking advertising levels are lower than the actual advertising expenditures for both brands. This implies that even when we consider the long-term effects of advertising, the brands are overspending on advertising.
Effects of Logging Second‐Growth Forests on Headwater Populations of Coastal Cutthroat Trout: A 6‐Year, Multistream, Before‐and‐After Field Experiment
Authors: De Groot Jennifer D. , Hinch Scott G. , Richardson John S.
Published: February 2007

To understand how logging of second‐growth forests affects populations of coastal cutthroat trout Oncorhynchus clarkii clarkii, we examined trout relative abundance, body condition (mass relative to length), and physical and thermal habitat in the summer and winter in four headwater streams (two treatment streams and two nonlogged control streams) over a 6‐year period (2 years prelogging [1997–1998] and 4 years postlogging [1999–2002]). This is one of the first efforts to conduct a multiyear, replicated stream, before‐and‐after experiment on this scale to assess the effects of logging on fish and habitat. In the treatment streams, 21% of the watershed area was logged by clear‐cutting (no scarification or slash‐burning). Careful logging approaches were employed to remove most of the riparian overstory (i.e., no machines were used within 5 m of stream, logs were felled and yarded away from riparian zones, all shrubs were left behind, and large wood was left in streams). Because a cooler summer climate occurred coincidentally with our postlogging period (the mean daily average summer air temperature was 1–2°C cooler than the temperature during the prelogging period), the mean average and mean maximum daily stream temperatures declined after the logging period in the control streams and remained the same in the treatment streams. After accounting for the effects of climate, logging had warmed treatment streams by about 1°C. We could not detect any logging treatment effects on summer or winter relative abundance or condition, nor were any changes evident to instream physical habitat associated with the logging treatment. These results were probably attributable to the careful logging approaches employed and the cooler climate that occurred during the postlogging period.
Highly conductive SnO2 thin films for flat‐panel displays
Authors: Isono Takamitsu , Fukuda Takeshi , Nakagawa Kouji , Usui Reo , Satoh Ryohei , Morinaga Eiji , Mihara Yu
Published: February 2007

Abstract— SnO2 is considered to be a promising alternative material for indium tin oxide (ITO), which is used for thin‐film transparent electrodes in flat‐panel displays (FPDs) and is facing a serious indium depletion problem. However, annealing processes in the manufacture of plasma‐display panels (PDPs), which are major FPDs, cause high resistivity in SnO2 films. To obtain lower resistivity after the annealing processes, the relationship between deposition conditions and resistivity and the influences of annealing on resistivity, both theoretically and experimentally, were investigated. As a solution, a method involving the formation of a coating of SiO2 on SnO2 is proposed, and a SnO2 resistivity as low as 6.60 × 10−5 Ω‐m was obtained after annealing.
Anisotropic Crosshole Resistivity Tomography for Ground Safety Analysis of a High-Storied Building Over an Abandoned Mine
Authors: Kim Jung-Ho , Yi Myeong-Jong , Cho Seong-Jun , Son Jeong-Sul , Song Won-Kyong
Published: February 2007

Crosshole resistivity tomography was performed to image the subsurface structures and mine cavities beneath a 25 story apartment building constructed at an abandoned mining site, and to provide the underground model for the safety analysis of the building. Strong electrical anisotropy was observed in the measured data, which has proven to be mainly due to geology. In order to deal with the anisotropy effect and to reconstruct the subsurface images reflecting the underground status precisely, we developed anisotropy inversion codes for resistivity tomography. The algorithm is based on finite element approximations for the forward modeling; the ACB (Active Constraint Balancing) method was adopted in the program in order to enhance the resolving power of the smoothness constraint least-squares inversion. All the acquired data were inverted by the developed inversion code so as to reconstruct the subsurface images, which match quite well with the geological mapping result. In particular, the locations of cavities were delineated more precisely owing to the anisotropic characteristics of the basement rock. Based on the subsurface model established by the resistivity tomography, rock engineering numerical analysis was further carried out. The result obtained from this analysis showed that the high-storied building is safe, even though three abandoned tunnels of the old mine are located beneath the building.
Toward a Definition of Moving-Picture Dance
Authors: Carroll Noël
Published: February 2007

Almost since the inception of moving pictures, those pictures have often featured dance. The obvious reason for this is that the natural subject of moving pictures is movement. And dances—along with hurtling locomotives, car chases, cattle stampedes, tennis matches, intergalactic dog-fights, and the like—move. Thus, a significant portion of the history of moving pictures involves dance movement. Many moving-picture makers have devoted admirable amounts of effort and imagination to portraying dance in or through media as diverse as film, video, and computer animation. The purpose of this essay is to attempt to offer a philosophical characterization of this field of activity; that is, I will try to define moving-picture dance.

Many readers, learning of my intention, are apt to groan “labeling again, how boring.” To a certain extent I can sympathize with that sentiment. It is far more interesting to talk about work than it is to set about classifying it. The concrete achievements of the field are more important than abstractions about it. Nevertheless, despite my ready acknowledgment of this, I will persist for several reasons.

First, whenever festivals of this sort of work are held, it is very likely that at one time or another almost everyone present will be tempted to say of some work that it doesn't really belong on the program. Everyone complains about labeling, but sooner or later most people feel compelled to invoke some favorite definition of their own. For human beings, categorizations are unavoidable, even if we like to pretend indifference to them. And most of us can feign indifference only for so long; most of us have a breaking point. Thus, it seems to me a good idea to get this issue out in the open and to discuss it abstractly—to compare and contrast the various categorizations in play and to develop dialectically from them a comprehensive framework that makes sense of our practices and that resonates with our intuitions about its compass.
The Social-Emotional Side of Learning Disabilities
Authors: Elksnin Linda K. , Elksnin Nick
Published: February 2007

This article provides a context for this special issue devoted to the social-emotional side of learning disabilities (LD). The impact LD definitions have on policy and practice, the prevalence of social-emotional deficits among youth with LD, relevant social-emotional terms, and the rationale for teaching social-emotional skills are discussed. Finally, the articles comprising this special issue are introduced.
Temperament and Learning Disability
Authors: Teglasi Hedwig , Cohn andrea , Meshbesher Nicole
Published: February 2007

The link between learning problems and social-emotional difficulties is well documented and both are associated with temperamental risk factors. Whereas temperament refers to individual differences in biologically based dispositions for responding to and engaging with one's surroundings, developmental outcomes are the products of experiences as influenced by temperament in concert with other variables and the opportunities, challenges, and supports of the child's various contexts. A review of the research supports pathways between temperament and outcomes that are direct, indirect, bidirectional, and hierarchical. Interventions that are informed by temperament may address the various pathways through which temperament influences outcomes.
The Social-Emotional Side of Learning Disabilities: A Science-Based Presentation of the State of the Art
Authors: Bryan Tanis , Burstein Karen , Ergul Cevriye
Published: February 2007

For over 30 years, researchers have studied the social-emotional side of learning disabilities (LD). This article highlights the science-based research on three domains of social skills of children with LD: characteristics, interventions, and the impact of policy. The article concludes with concerns regarding the translation of research on social-emotional factors into practice and the likelihood that social-emotional problems are being adequately addressed in public schools.