bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunesurveillance by dendritic cells: potential implication for immunotherapy of endocrine cancers
Authors: Schott Matthias
Published: September 2006

Dendritic cells (DCs) are highly efficient antigen-presenting cells in the immune system with the potential to regulate the system and induce a cytotoxic T-cell response. As a proof of principle, a multitude of animal and human studies has demonstrated that immunization with antigen-loaded DCs may lead to anti-tumour immune responses with tumour regression and rejection of cancer. The identification of tumour antigens that can be recognized by T lymphocytes has facilitated the development of new protocols and enabled immunologists to monitor immune responses. However, to date, long-term clinical effects on larger numbers of cancer patients are missing, and there is no generally accepted DC generation or activation protocol. This review will focus on the most important findings on the role of DCs within the immune system and how to generate and activate these cells in order to induce cytotoxic immunity in non-endocrine and endocrine malignancies. Recently, we and other researchers reported on DC vaccinations in patients with endocrine malignancies mainly in metastasized medullary thyroid carcinoma resulting in tumour-specific immunity and partial clinical responses in some cases. Based on these and other in vitro data, new DC vaccination protocols for the treatment of patients with endocrine tumours have now been conducted.
The role of angiotensin II in the regulation of breast cancer cell adhesion and invasion
Authors: Puddefoot J R , Udeozo U K I , Barker S , Vinson G P
Published: September 2006

As breast cancer remains the most common cause of cancer death in women, there is a continuing need not only to further characterise the processes of cancer progression, but also to improve accuracy of prognostic markers. Breast epithelial cells express components of the renin angiotensin system and studies suggest that these may be altered in disease progression. In addition, altered integrin expression correlates with lymph node metastasis. The aim of this study was to investigate the relationship between angiotensin II (AII) and integrins in breast tissue and, in particular, their role in breast cancer cell metastasis. Using in vitro assays, AII (10−6 M)-treated MCF-7 and T47D breast cancer cells both show reduced adhesion to extracellular matrix proteins collagen-, fibronectin- and laminin-coated wells (P<0.001) and reduced invasion through collagen-, fibronectin- and laminin-coated membranes (P<0.05). This action was inhibited by co-treatment with the angiotensin type 1 receptor (AT1R) antagonist losartan (10−5 M). The addition of the AT2R inhibitor PD123319 (10−5 M) to AII-treated cells had no significant effect. Semi-quantitative reverse transcriptase-PCR and western blotting revealed that cells treated with AII (10−6 M) expressed lower levels of both integrin α3 and β1. Using specific inhibitors, this was shown to occur through protein kinase C signalling. These data suggest that AII reduces cell adhesion and invasion through the type 1 receptor and that this effect may be due to reduced expression of integrins, and in particular α3 and β1.
An in-frame complex germline mutation in the juxtamembrane intracellular domain causing RET activation in familial medullary thyroid carcinoma
Authors: Cordella Daniela , Muzza Marina , Alberti Luisella , Colombo Paolo , Travaglini Pietro , Beck-Peccoz Paolo , Fugazzola Laura , Persani Luca
Published: September 2006

Activating mutations of the RET proto-oncogene are associated with inherited syndromes, multiple endocrine neoplasia (MEN2A/2B) and with familial and sporadic medullary thyroid cancer (MTC). Single base pair missense mutations in the extracellular Cys-rich domain are responsible for most MEN2A and familial MTC (FMTC) cases. Rarely, somatic deletions and germline duplications have been described in sporadic MTC and in FMTC. We report the detection and functional studies of a deletion/insertion in exon 11 (c.2646delGinsTTCT) associated with FMTC. This in-frame complex rearrangement leads to an Asn to Lys change (Lys666Asn) and to a Ser insertion. The mutation was found in the proband, who was diagnosed with metastatic MTC at 41 years, and in her son, who presented diffuse C-cells hyperplasia at 4 years of age. The mutation displayed a transforming activity stronger than Ret wild type (Ret-WT) at the focus formation assay and functional analyses after transient and stable transfection revealed an increased autophosphorylation, indicating the constitutive activation of the receptor. The transforming activity may be favoured by an increased stabilization of the fully mature form of the mutant receptor. Dimerization assay demonstrated that the activation mechanism of the complex mutation is not mediated by stable dimer formation. Computational analysis predicted nonconservative alterations in the mutant protein consistent with a possible modification of the conformation of the receptor. In conclusion, the first molecular studies on a complex germline RET mutation lying in the juxtamembrane region of the receptor are reported. Functional analyses showed that alterations at this level too can lead to a ligand independent Ret activation.
Combination therapy for treating breast cancer using antiestrogen, ERA-923, and the mammalian target of rapamycin inhibitor, temsirolimus
Authors: Sadler T M , Gavriil M , Annable T , Frost P , Greenberger L M , Zhang Y
Published: September 2006

The effect of combinations of a mammalian target of rapamycin (mTOR) inhibitor, temsirolimus, and an estrogen receptor-α (ERα) antagonist, ERA-923, on breast carcinoma in culture and in a xenograft model has been studied. Phase III trials are underway using temsirolimus for several cancers. ERA-923 was studied in a phase I trial for tamoxifen refractory metastatic breast cancer and was shown to have good safety profiles. Combination of noninhibitory doses of temsirolimus with suboptimal doses of ERA-923 synergistically inhibited the growth of MCF-7 cells. Synergy was found across a wide range of doses and could also be achieved by combining temsirolimus with other antiestrogens such as raloxifene and 4-hydroxytamoxifen. In vivo combination of temsirolimus and ERA-923 at certain doses and schedules completely inhibited tumor growth, while individual agents were only partially effective. Although the mechanism underlying the synergism remains to be understood, the results were associated with the ability of temsirolimus to block the transcriptional activity mediated by ERα as well as an increase in G1 arrest when it was combined with ERA-923. Results demonstrated for the first time that the combination of temsirolimus and a pure antiestrogen has excellent anticancer activity in preclinical models and, therefore, may have clinical use in treating hormone-dependent tumors.
Concomitant down-regulation of SPRY1 and SPRY2 in prostate carcinoma
Authors: Fritzsche S , Kenzelmann M , Hoffmann M J , Müller M , Engers R , Gröne H-J , Schulz W A
Published: September 2006

Sprouty proteins encoded by the SPRY genes act as modulators and feedback inhibitors of signalling by epidermal growth factor (EGF) and fibroblast growth factor (FGF). Overactivity of EGF and FGF signalling common in prostate cancer might therefore be exacerbated by Sprouty down-regulation. Indeed, down-regulation of SPRY1 and SPRY2 expression has been independently reported. We found both genes modestly down-regulated by microarray expression analysis of microdissected prostate cancers and by quantitative RT-PCR in macrodissected specimens compared with benign tissues. Importantly, the decreases paralleled each other and expression levels of both genes were significantly lower in cancers that recurred within the average follow-up period of 32 months. In contrast to a previous report, no hypermethylation was found to accompany down-regulation of SPRY2 in cancer tissues and cell lines. We additionally investigated the expression of an SPRY1 alternative transcript presumed to be specific for fetal tissues and found its expression moderately well correlated with expression of the standard transcript through diverse tissues and cell lines. The present study confirms and extends previous reports by demonstrating concomitant down-regulation and a significant association with recurrence of SPRY genes.
Gastrointestinal stromal tumors express the orexigen ghrelin
Authors: Ekeblad Sara , Nilsson Bengt , Lejonklou Margareta Halin , Johansson Térèse , Stålberg Peter , Nilsson Ola , Ahlman Håkan , Skogseid Britt
Published: September 2006

Expression of the neuroendocrine marker synaptic vesicle protein 2 (SV2) has been reported in a few cases of gastrointestinal stromal tumors (GISTs). The goal of the present study was to assess the relevance of this finding and identify a possible hormone production in these tumors. We chose to study the orexigen ghrelin and its receptor, since these patients are seldom cachexic, even in advanced disease stages. We investigated ghrelin expression by means of immunohistochemistry on frozen or paraffin-embedded sections from 22 GISTs from a well-characterized patient material. Expression of the growth hormone secretagogue receptor, the ghrelin receptor, was investigated in a subset of lesions. In six tumors, mRNA levels of ghrelin, the ghrelin receptor, and SV2 were analyzed by real-time quantitative PCR. Totally 17 out of 22 tumors showed immunoreactivity for ghrelin. Five out of ten tumors were immunoreactive for the ghrelin receptor, and all of these co-expressed ghrelin. All tumors expressed ghrelin, ghrelin receptor, and SV2 mRNA. GISTs frequently express SV2, ghrelin, and its receptor, indicating the presence of autocrine/paracrine loops.
Angiogenesis and lymphangiogenesis in thyroid proliferative lesions: relationship to type and tumour behaviour
Authors: de la Torre N Garcia , Buley I , Wass J A H , Turner H E
Published: September 2006

The role of angiogenesis and lymphangiogenesis in thyroid cancer pathogenesis has not been elucidated. Patterns for tumour behaviour and metastasic spread vary according to tumour type and whether differences in the angiogenic or lymphangiogenic phenotype influence the route for tumour metastases or determine a more aggressive behaviour has not been fully explored. The angiogenic and lymphangiogenic phenotypes of a large cohort of thyroid proliferative lesions (n=191) were studied. Using immunohistochemistry for CD34, lymphatic vessel endothelial receptor-1 (LYVE-1) (specific markers for vascular and lymphatic endothelium respectively), vascular endothelial growth factor (VEGF-A), VEGF-C and fibroblast growth factor-2 (FGF-2), this study analyses microvascular density (MVD), lymphatic vascular density (LVD), and expression of angiogenic and lymphangiogenic factors in normal thyroid (NT; n=19), multinodular goitre (n=25), toxic multinodular goitre (n=8), Graves’ hyperplasia (n=22), follicular adenoma (n=54), papillary carcinoma (PC; n=27), incidental papillary microcarcinoma (PMC; n=8), follicular carcinoma (FC; n=20) and medullary carcinoma (MC; n=8). MVD was decreased in proliferative lesions, benign and malignant, compared with NT (P<0.0001). In contrast, VEGF-A expression was increased in thyroid carcinomas (PC, FC and MC) when compared with PMC, benign lesions and NT (P<0.0001). LVD was higher in PC and PMC (P=0.001), and VEGF-C expression was increased in PC (P<0.0001). Despite higher LVD and increased expression of VEGF-A and VEGF-C in thyroid cancers, these markers were not related to poor prognosis in terms of tumour size, multifocality and/or presence of lymphatic or distant metastases. In conclusion, angiogenesis is reduced in thyroid proliferative lesions compared with NT tissue. However, VEGF-A expression is upregulated in thyroid cancers. Lymphangiogenesis and VEGF-C expression are increased in thyroid tumours prone to lymphatic metastases. This may be an important mechanism underlying the differences in metastatic behaviour between papillary and follicular thyroid cancer.
Role of carbonic anhydrase IX expression in prediction of the efficacy and outcome of primary epirubicin/tamoxifen therapy for breast cancer
Authors: Generali Daniele , Fox Stephen B , Berruti Alfredo , Brizzi Maria P , Campo Leticia , Bonardi Simone , Wigfield Simon M , Bruzzi Paolo , Bersiga Alessandra , Allevi Giovanni , Milani Manuela , Aguggini Sergio , Dogliotti Luigi , Bottini Alberto , Harris Adrian L
Published: September 2006

The purpose of this study is to investigate the role of carbonic anhydrase IX (CAIX) expression in predicting the response to epirubicin and disease-free survival (DFS) in breast cancer patients enrolled in a single institution trial of primary anthracycline and tamoxifen therapy. CAIX expression was assessed in 183 patients with T2–4 N0–1 breast cancer enrolled in a randomized trial comparing four cycles of single agent epirubicin versus epirubicin + tamoxifen as primary systemic treatment. All patients received postoperatively four cycles of the four weekly i.v. cyclophosphamide, methotrexate, 5-fluorouracil regimen. Patients with estrogen receptor (ER)-positive primary tumors received 5 years of adjuvant tamoxifen. Pretreatment, p53 (P = 0.007), c-erbB2 (P < 0.01), and Ki67 (P = 0.02) were directly associated with CAIX expression, while bcl2 (P < 0.000) and ER (P = 0.000) and progesterone receptor (PgR; P < 0.01) were inversely correlated. In multivariate analysis, only high p53 and low bcl2 were independently associated with CAIX positivity. CAIX immunostaining was significantly associated with poor outcome for DFS (P < 0.002) and overall survival (P = 0.001). In multivariate analysis, a significant interaction was found between CAIX and markers of hormone sensitivity, bcl2 (P = 0.01), ER (P = 0.02), PgR (P = 0.02), and lymph node involvement (P = 0.04), in predicting DFS. Presently, there are few clinical markers of resistance to tamoxifen treatment in ER-positive tumors. CAIX expression in breast cancer patients shows a negative predictive role of treatment efficacy in ER-positive patients on the adjuvant tamoxifen after primary chemo-endocrine therapy. Studies investigating the effects of pH on tamoxifen uptake and the effects of therapy with CA inhibitors are planned.
Vascular endothelial growth factor induces proliferation of breast cancer cells and inhibits the anti-proliferative activity of anti-hormones
Authors: Liang Yayun , Brekken Rolf A , Hyder Salman M
Published: September 2006

Increased levels of vascular endothelial growth factor (VEGF) are associated with a poor response of breast cancer to anti-hormone treatment. Although VEGF is regarded as an endothelial-specific growth factor, recent reports have shown that VEGF can promote proliferation of other cell types, including breast tumor cells. We have characterized the proliferative effects of VEGF in breast cancer cell lines that are commonly used for understanding the role of estrogens, progestins, and anti-hormones on tumor growth. Since steroid hormones can increase the level of VEGF in certain breast cancer cells, we evaluated the effects of exogenous VEGF on the growth-suppressive effects of anti-estrogen (ICI 182,780) and RU-486 (anti-progestin mifepristone) in human breast cancer cells. VEGF165 and VEGF121 increased the proliferation of tumor cell lines that expressed VEGFR-2 (VEGF receptor 2) (flk/kdr) via the extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/MAPK) pathway. Furthermore, VEGF induced the expression of the anti-apoptotic protein Bcl-2 and blocked down-regulation of Bcl-2 by ICI 182,780 and induced Bcl-2 in BT-474 and T47-D cells even in the presence of RU-486. Increased Bcl-2 levels in response to VEGF were associated with increased proliferation and survival of tumor cells even in the presence of anti-hormones. These results suggest that VEGF stimulates proliferation of VEGFR2-positive tumor cells, promotes survival via the expression and activity of Bcl-2 and overrides the growth-suppressive effects of anti-hormones. This represents a potential explanation for anti-hormone resistance and tumor progression in clinical samples. Thus, it may be useful to use combined modality treatment involving anti-hormones and anti-angiogenic agents to treat breast cancers that express elevated levels of VEGF.
Novel concepts for the chemoprevention of breast cancer through aromatase inhibition
Authors: Kendall Anne , Dowsett Mitch
Published: September 2006

Aromatase inhibitors (AIs) have a proven role in the treatment of early and metastatic breast cancer. The success of tamoxifen in reducing the relative risk of developing hormone-sensitive breast cancer in chemoprevention trials has been hampered by their long-term toxicity profile. AIs have the potential to further reduce rates of breast cancer in high-risk postmenopausal women. This article reviews the evidence to support the potential efficacy of AIs in the chemoprevention setting. It particularly focuses on a discussion of novel concepts of utilising AIs, so that they reduce breast cancer risk while minimising systemic toxicity, and highlights the importance of accurately developing risk prediction algorithms.
Factors influencing household willingness to pay (WTP) for drinking water in peri-urban areas: a case study in the Indian context
Authors: Venkatachalam L.
Published: September 2006

One of the major issues confronted by the agencies formulating polices for water supply projects in developing countries is how to achieve efficiency, equity and sustainability. Achieving these objectives warrants an understanding of the determinants of household behaviour towards various aspects of water supply projects, such as improved water supply services and the associated willingness to pay value for specified services. Since these determinants are site-specific in nature, it is imperative that the water supply authorities identify and accommodate these factors appropriately in water supply policies. This paper discusses the results of a case study that looked into identification of such determinants of household behavior in relation to improved water supply services in a peri-urban context in Tamil Nadu, India.
Urban Stormwater Tracing with the Naturally Occurring Deuterium Isotope
Authors: Sidle W.C. , Lee P.Y.
Published: September 2006

Measurements of naturally occurring deuterium isotope (δD) assist in tracing water components during wet weather flows in an urban watershed. A transect of installations in the vadose and saturated zones was completed in the vicinity of a small stream and storm sewer. High‐resolution deuterium mass spectrometry discriminated between storm sewer leaks and other water sources such as direct runoff, bank seepage, and groundwater flow to a stream channel. Isotope hydrograph separation indicates that groundwater or vadose water predominantly contributed to the volume of stream water compared to direct surface runoff during a storm event. Significant differences in δD in the subsurface suggest that multiple flow components exist beyond the time period of a storm event. Deuterium measurements are helpful for modeling leaks and seepage and refining mass balances of flows in urban watersheds.
Treatment of Acid Mine Drainage with Anaerobic Solid‐Substrate Reactors
Authors: Drury William J.
Published: September 2006

Anaerobic solid‐substrate reactors were used in a laboratory study of acid mine drainage treatment. Parallel systems were run continuously for 23 months, both containing a solid substrate of 2:1 (weight) cow manure and sawdust. One system had cheese whey added with the mine drainage to provide an additional electron donor source to stimulate sulfate‐reducing bacteria activity. Effluent pH from the reactor with whey addition was relatively constant at 6.5. Effluent pH from the reactor without whey addition dropped over time from 6.7 to approximately 5.5. Whey addition increased effluent alkalinity [550 to 700 mg/L as calcium carbonate (CaCD3) versus 50 to 300 mg/L as CaCD3] and sulfate removal (98 to 80% versus 60 to 40%). Sulfate removal rate with whey addition decreased over time from 250 to 120 mmol/m3·d, whereas it decreased from 250 to 40 mmol/m3·d without whey addition. Whey addition increased removal of dissolved iron (84 versus <0%), dissolved manganese (40 versus 2%), and dissolved zinc (99.7 versus 96.0%) in the second part of the experiment. Copper and cadmium removals were greater than 99%, and arsenic removal was 84% without whey addition and 89% with whey addition. Effluent sulfide concentrations were approximately I order of magnitude greater with whey addition. A 63‐day period of excessive loading permanently decreased treatment efficiency without whey addition.
A Critical Analysis of Classical Design Equations for Waste Stabilization Lagoons and Other Wastewater Treatment Systems
Authors: von Sperling Marcos
Published: September 2006

This paper analyzes the applicability of classical equations to the design of waste stabilization lagoons and to other wastewater treatment processes based on the structure removed BOD load = a × applied BOD load + b, where BOD is biochemical oxygen demand. Although the emphasis is on waste stabilization lagoons, this type of equation is presented by several researchers describing wastewater treatment processes, used worldwide, and cited in virtually all textbooks in the field of wastewater treatment. However, the equation has a problem of bias in its structure because the so‐called independent variable (applied load) is not actually independent; it is implicitly present in the dependent variable (removed load, which is equal to applied load minus effluent load). By definition, the equation can achieve high correlation coefficients because it is a good predictor of removed load. However, the more important variables effluent load and removal efficiency are not well estimated by this equation, undermining its intended applicability. This conclusion is supported by results obtained in a simplified didactic example with a small data set and a Monte Carlo simulation with a large data set (500 values).
Potential Water‐Quality Effects from Iron Cyanide Anticaking Agents in Road Salt
Authors: Paschka Michael G. , Ghosh Rajat S. , Dzombak David A.
Published: September 2006

Water‐soluble iron cyanide compounds are widely used as anticaking agents in road salt, which creates potential contamination of surface and groundwater with these compounds when the salt dissolves and is washed off roads in runoff. This paper presents a summary of available information on iron cyanide use in road salt and its potential effects on water quality. Also, estimates of total cyanide concentrations in snow‐melt runoff from roadways are presented as simple mass‐balance calculations. Although available infoffilation does not indicate a widespread problem, it also is clear that the water‐quality effects of cyanide in road salt have not been examined much. Considering the large, and increasing, volume of road salt used for deicing, studies are needed to determine levels of total and free cyanide in surface and groundwater adjacent to salt storage facilities and along roads with open drainage ditches. Results could be combined with current knowledge of the fate and transport of cyanide to assess water‐quality effects of iron cyanide anticaking agents used in road salt.
Factors Influencing Ultraviolet Disinfection Performance Part II: Association of Coliform Bacteria with Wastewater Particles
Authors: Emerick Robert W. , Loge Frank J. , Thompson Don , Darby Jeannie L.
Published: September 2006

A technique is described for quantifying the number of particles with embedded coliform bacteria in wastewater samples. This technique was applied to eight different wastewater samples collected from cight significantly different treatment processes (five variations of the activated‐sludge process, a trickling filter, an aerated lagoon, and a facultative lagoon). For all treatment process types that did not usc chemical coagulants, total number of particles with embedded coliform bacteria correlated linearly with number of residual coliform bacteria following high doses of UV light. Lagoon treatment processes led to the formation of fewer bacteria‐associated particles than either the activated‐sludge or trickling‐filter processes. Chemical coagulants showed a potential to significantly reduce the inactivation fraction of coliform bacteria associated with particles.
Metal Distributions in Complexes with Chiarella vulgaris in Seawater and Wastewater
Authors: Pascucci Peter R. , Kowalak Albert D.
Published: September 2006

Divalent cadmium (Cd), copper (Cu), iron (Fe), nickel (Ni), lead (Pb), and zinc (Zn) simultaneous complexes with an algal biomass Chiarella vulgaris were studied for bioremediation purposes in various aqueous media: distilled‐deionized water (DDIW), seawater, nuclear‐reactor pool water, and process wastewater. Reactions were monitored using various dry masses of algae (2 to 12 mg) at constant temperature (20 to 22 °C) and constant metal concentrations for reaction times ranging from 0 to 150 minutes. Complexes occurred within 30 minutes and reached a steady state after 80 to 120 minutes. Distribution constants (K'd) were calculated for the complexes and relative orders of K'd were reported. The K'd are used to evaluate relative efficiency of metal remediation from waters. Lead, Cu, and Ni complexes had the greatest K'd values and those metals were most efficiently removed from these waters. Zinc and Fe formed the most labile complexes. The order of Kd values for complexes in DDIW was Pb > Cu > Cd > Zn, then Cu > Cd > Zn in seawater, Cd > Cu > Zn in reactor pool water, and Ni > Cd > Cu > Zn > Fe in wastewater. C. vulgaris biomass may potentially be used as an alternative to traditional water treatment methods for simultaneous extraction of metals from seawater, process wastewater, or drinking water.
Anaerobic Biotransformation of Chlorinated Aliphatic Hydrocarbons: Ugly Duckling to Beautiful Swan
Authors: Parkin Gene F.
Published: September 2006

For many years anaerobic biological processes were reputed to be more sensitive than aerobic processes to toxic substances such as chlorinated aliphatic hydrocarbons (CAH) and thus a poor choice for treating water containing these compounds. This was especially true for water containing perchloroethylene (PCE) or trichloroethylene (TCE) because vinyl chloride, a human carcinogen, is produced when these two compounds are degraded anaerobically. Aerobic treatment with organisms containing oxygenase enzyme systems, which could fortuitously degrade a wide variety of chlorinated aliphatics (but not PCE), was favored. Recently, however, several enrichments and organisms have been isolated that will convert PCE and TCE into ethene and ethane, as shown by field data. Because of this evidence, anaerobic processes are now considered a significant alternative treatment for CAH contamination.  Recent work at the University of Iowa, Iowa City, has focused on the effect of mixtures of CAHs on biotransformation of individual organic compounds and the potential for a combined methanogen‐iron (Fe(0)) system to improve CAH bioremediation. At the concentration ranges tested, the presence of a mixture of CAHs seems to decrease rate of transformation of individual organics. However, there are important exceptions; in some cases a mixture of CAHs seems to facilitate transformation of an individual organic compound. Combination of an active methanogenic population with Fe(0) increases the rate and extent of transformation of carbon tetrachloride and chloroform. Results with PCE and 1, 1, 1‐trichloroethane are less clear.
The Effect of Anaerobic Selectors on Nocardioform Organism Growth in Activated Sludge
Authors: Fainsod Abraham , Pagilla Krishna R. , Jenkins David , Pitt Paul A. , Mamais Daniel
Published: September 2006

Laboratory‐ and full‐scale experiments were conducted to investigate the use of anaerobic selectors for control of nocardioform organisms in activated sludge. The laboratory‐scale, anaerobic‐selector, activated‐sludge system, which exhibited enhanced biological phosphorus removal (EBPR) at a 2.4‐day total mean cell retention time (MCRT) with a pH of 6.3, a temperature of 20 °C, and an anaerobic selector hydraulic retention time (HRT) of 50 minutes, controlled nocardioforms to below detectable levels whereas nocardioforms were present in a completely mixed control. The full‐scale, anaerobic‐selector, activated‐sludge system performing EBPR at a 3.5‐day average MCRT, average temperature of 20 °C, and anaerobic selector HRT of 17 to 24 minutes reduced nocardioform organism levels below those achieved when the full‐scale plant was operated at conditions that did not permit EBPR (i.e., MCRT of 1.7 days and anaerobic selector HRT of less than 19 minutes). In the full‐scale plant, the lowest nocardioform organism levels and effluent dissolved orthophosphate concentrations were associated with the highest MCRT tested (4.6 days).
Evaluation of the Capacity of Phosphorus‐Accumulating Organisms To Use Nitrate and Oxygen as Final Electron Acceptors: A Theoretical Study on Population Dynamics
Authors: Filipe Carlos D.M. , Daigger Glen T.
Published: September 2006

Ability of phosphorus‐accumulating organisms (PAGs) capable of using both nitrate and oxygen as temlinal electron acceptors to compete successfully in biological excess phosphorus removal (BEPR) systems was assessed relative to purely aerobic PAGs. The anoxic‐aerobic population has a significant competitive disadvantage when competing with PAGs that can only use oxygen because of a lower thermodynamic efficiency of anoxic growth compared to aerobic growth. This causes less efficient use of stored poly‐β‐hydroxy‐butyrate under anoxic conditions, leading to the washout of the anoxic‐aerobic population from the system. This analysis provides a potential explanation of why growth of denitrifying PAGs (DPAGs) has not been observed in some BEPR systems. This work also suggests that introduction of even a small aerobic zones in a BEPR system will strongly affect accumulation of DPAGs. In addition, a hypothetical model to describe acetate uptake under anoxic conditions was developed, and simulations performed with it produced results that agree with experimental observations published in the literature.
Calcifying Fibrous Pseudotumor of the Myocardium
Authors: Kirby Patricia A. , Sato Yutaka , Tannous Raymond , Dehner Louis P.
Published: September 2006

Calcifying fibrous pseudotumor is an uncommon tumor first described in 1988 as a childhood fibrous tumor with psammoma bodies. The typical pathological findings are those of a densely collagenized fibrous tumor with psammomatous and dystrophic calcification accompanied by a lymphoplasmacytic infiltrate. To date these tumors are reported in subcutaneous and deep soft tissues of the extremities and trunk, groin, scrotum, pleura, mediastinum, paratracheal region, peritoneum, neck, mesentery, omentum, serosa, lung, bone, and gallbladder. We describe a 17-year-old girl with a myocardial calcifying fibrous tumor, and we review the English literature.
Bronchial Atresia is Common to Extralobar Sequestration, Intralobar Sequestration, Congenital Cystic Adenomatoid Malformation, and Lobar Emphysema
Authors: Riedlinger Wolfram F.J. , Vargas Sara O. , Jennings Russell W. , Estroff Judy A. , Barnewolt Carol E. , Lillehei Craig W. , Wilson Jay M. , Colin Andrew A. , Reid Lynne M. , Kozakewich Harry P. W.
Published: September 2006

Congenital cystic adenomatoid malformation (CCAM), intralobar sequestration (ILS), extralobar sequestration (ELS), and lobar emphysema (LE) are well-accepted entities; however, certain findings are common to all, particularly the parenchymal maldevelopment characterizing CCAM. Isolated reports have described bronchial atresia (BA) in some specimens in all 4 entities, but this finding has not been evaluated in a prospective manner. With the aid of a dissecting microscope, we prospectively examined 47 lung specimens resected during the past 4 years and submitted with the clinical impression of ELS ( n = 11), ILS ( n = 11), CCAM ( n = 20), LE ( n = 4), and airway-esophageal communication ( n = 1). Most lesions were detected by prenatal ultrasound and were resected during infancy. The clinical impression and pathologic findings were compared. Pathologic examination revealed atresia of a lobar, segmental, or subsegmental bronchus in 100% of ELS, 82% of ILS, 70% of CCAM, and 50% of LE (those clinically recognized to have BA or minor CCAM) cases. Parenchymal maldevelopment that characterizes CCAM was present in 100% of CCAM cases (as expected by definition) as well as in 91% of ELS, 91% of ILS, and 50% of LE (those with BA) cases. Bronchial atresia is present in all ELS, most ILS and CCAM, and some LE cases, and its detection is greatly enhanced with the dissecting microscope. Bronchial atresia and CCAM nearly always coexist. It may be that both have the same etiopathogenesis with anatomic differences accounted for by aberrant genetic programs or other insults, perhaps modified by time of onset or duration.
Syringocystadenoma Papilliferum: A Rare Breast Tumor in a Young Boy
Authors: Vaos George , Pierrakou Paraskevi
Published: September 2006

Syringocystadenoma papilliferum of the breast is extremely rare in children. However, some occasional cases have been diagnosed in females. This report documents a case of syringocystadenoma papilliferum occurring in a healthy 4-year-old male. Histopathologically, this tumor, located deep in the dermis, was characterized by the presence of papillary projections extending into the lumen of epithelial cystic invaginations in a background of dense fibrous tissue. The papillary projections and the duct-like structures were lined by an inner columnar epithelium, which demonstrated luminal apical decapitation secretion, and had an outer layer of smaller cuboidal cells. These findings support apocrine differentiation in this case. A fairly dense mononuclear infiltrate in the stroma of the tumor, especially in the papillary projections, was also present. Although syringocystadenoma papilliferum is rare in children, it should not be summarily ruled out during examinations of masses found in the pediatric male breast. It is important to recognize this unusual location of the tumor so that a prompt diagnosis, based on histopathology and surgical excision, can be proposed.
Chorion Nodosum: A Placental Feature of the Severe Early Amnion Rupture Sequence
Authors: Stanek Jerzy , Adeniran Adebowale
Published: September 2006

A lesion of placental membranes and/or chorionic disc mesenchyme found in 4 of 13 cases of the limb-body wall complex (LBWC) and in 1 case of term extraamniotic pregnancy, named chorion nodosum (ChN), is described. All five ChN cases were associated with amniotic bands. Although grossly inapparent and histologically superficially similar to amnion nodosum, ChN is a distinct flat lesion located in the chorion denuded of amnion, occurring in different clinical settings, and most probably having a different pathogenesis, because it has bimodal gestational age distribution and occurs earlier in pregnancy when associated with LBWC, and only in the LBWC cases associated with amniotic bands. Therefore, not only oligohydramnios but also other factors involved in etiopathogenesis of LBWC are most probably operative in ChN, such as early vascular disruption, direct contact of the chorion denuded of amnion with fetal body, or a metabolic defect of fetal epidermis and amnionic epithelium. Prolonged severe oligohydramnios most probably plays main role in the pathogenesis of ChN in term extraamniotic pregnancy.
Mixing simulation of a viscous Newtonian liquid in a twin sigma blade mixer
Authors: Connelly Robin K. , Kokini Jozef L.
Published: September 2006

The flow of a viscous Newtonian fluid in a twin sigma blade mixer over the course of a blade cycle is simulated using FEM with mesh superposition, and the resulting velocity profiles are used to calculate the paths of material points in order to do an analysis of the distributive mixing and overall efficiency of the mixer over time. Visual inspection of the material‐point distribution, as well as mixing measures that include the cluster distribution index, scale of segregation and mean length of stretch showed the overall mixing effectiveness of this mixer, although there was some positions that had better distributive and stretch capability than others. The mean time‐averaged efficiency was related to the specific blade positions and found to remain above zero, while its standard deviation was reducing over time, indicating that the majority of the material points were experiencing equivalent levels of stretching over time. © 2006 American Institute of Chemical Engineers AIChE J, 2006
Retinoblastoma‐related geneRb2/p130 are rarely mutated in Burkitt's lymphoma from Brazil
Authors: Klumb C.E. , Magluta E.P.S. , Rezende L.M.M. , Apa A.G. , Alonso J.F.S. , Maia R.C.
Published: September 2006

It has been suggested that alterations of cell cycle genes probably contribute to the pathogenesis of endemic Burkitt's lymphoma (BL) in addition to c‐MYC translocation. Mutations disrupting the normal nuclear localization signal of the retinoblastoma‐related gene Rb2/p130 have been documented in BL cell lines and primary tumors from endemic areas. The aim of this study was to investigate the involvement of Rb2/p130 gene in the pathogenesis of sporadic BL in Brazil. DNA samples from 26 pediatric BL tumors and two healthy blood donors were screened by PCR amplification followed by single strand conformation polymorphism analysis of exons 19 and 20 (B domain) and exons 21 and 22 (C‐terminus), where most of the point mutations in the Rb2/p130 gene were identified. No abnormal band shifts were present in the samples analyzed. We concluded that mutations in exons 19–22 of the Rb2/p130 are unlikely to be involved directly in the pathogenesis of sporadic Brazilian BL. Am. J. Hematol., 2007. © 2006 Wiley‐Liss, Inc.
Molecular basis of human dentin diseases
Authors: MacDougall Mary , Dong Juan , Acevedo Ana Carolina
Published: September 2006

In recent years, substantial progress has been made regarding the molecular etiology of human structural tooth diseases that alter dentin matrix formation. These diseases have been classified into two major groups with subtypes: dentin dysplasia (DD) types I and II and dentinogenesis imperfecta (DGI) types I–III. Genetic linkage studies have identified the critical loci for DD‐II, DGI‐II, and DGI‐II to human chromosome 4q21. Located within the common disease loci for these diseases is cluster of dentin/bone genes that includes osteopontin (OPN), bone sialoprotein (BSP), matrix extracellular phosphoglycoprotein (MEPE), dentin matrix protein 1 (DMP1), and dentin sialophosphoprotein (DSPP). To date, only mutations within dentin sialophosphoprotein have been associated with the pathogenesis of dentin diseases including DGI types‐II and ‐III and DD‐II. In this article, we overview the recent literature related to these dentin genetic diseases, their clinical features, and molecular pathogenesis. © 2006 Wiley‐Liss, Inc.
Variants in mitochondrial tRNAGlu, tRNAArg, and tRNAThr may influence the phenotypic manifestation of deafness‐associated 12S rRNA A1555G mutation in three Han Chinese families with hearing loss
Authors: Young Wie‐Yen , Zhao Lidong , Qian Yaping , Li Ronghua , Chen Jing , Yuan Huijun , Dai Pu , Zhai Suoqiang , Han Dongyi , Guan Min‐Xin
Published: September 2006

We report here on the clinical, genetic, and molecular characterization of three Han Chinese pedigrees with aminoglycoside‐induced and nonsyndromic hearing loss. Clinical evaluation revealed the variable phenotype of hearing loss including severity, age‐at‐onset, audiometric configuration in these subjects. Penetrances of hearing loss in BJ107, BJ108, and BJ109 pedigrees are 35%, 63%, and 67%, respectively. Mutational analysis of the complete mitochondrial genomes in these pedigrees showed the identical homoplasmic A1555G mutation and distinct sets of mitochondrial DNA (mtDNA) variants belonging to haplogroups N, F, and M, respectively. Of these variants, the A14693G mutation in the tRNAGlu, the T15908C mutation in the tRNAThr, and the T10454C mutation in the tRNAArg are of special interest as these mutations occur at positions which are highly evolutionarily conserved nucleotides of corresponding tRNAs. These homoplasmic mtDNA mutations were absent among 156 unrelated Chinese controls. The A14693G and T10454C mutations occur at the highly conserved bases of the TψC‐loop of tRNAGlu and tRNAArg, respectively. Furthermore, the T15908C mutation in the tRNAThr disrupts a highly conserved A‐U base‐pairing at the D‐stem of this tRNA. The alteration of structure of these tRNAs by these mtDNA mutations may lead to a failure in tRNA metabolism, thereby causing impairment of mitochondrial translation. Thus, mitochondrial dysfunctions, caused by the A1555G mutation, would be worsened by these mtDNA mutations. Therefore, these mtDNA mutations may have a potential modifier role in increasing the penetrance and expressivity of the deafness‐associated 12S rRNA A1555G mutation in those Chinese pedigrees. © 2006 Wiley‐Liss, Inc.
Novel mitochondrial DNA mutations associated with myopathy, cardiomyopathy, renal failure, and deafness
Authors: Feigenbaum Annette , Bai Ren‐Kui , Doherty Emily S. , Kwon Haeyoung , Tan Duanjun , Sloane Avril , Cutz Ernest , Robinson Brian H. , Wong Lee‐Jun C.
Published: September 2006

Patients with mitochondrial disease usually manifest multisystemic dysfunction with a broad clinical spectrum. When the tests for common mitochondrial DNA (mtDNA) point mutations are negative and the mtDNA defects are still hypothesized, it is necessary to screen the entire mitochondrial genome for unknown mutations in order to confirm the diagnosis. We report an 8‐year‐old girl who had a long history of ragged‐red fiber myopathy, short stature, and deafness, who ultimately developed renal failure and fatal cardiac dysfunction. Respiratory chain enzyme analysis on muscle biopsy revealed deficiency in complexes I, II/III, and IV. Whole mitochondrial genome sequencing analysis was performed. Three novel changes: homoplasmic 15458T > C and 15519T > C in cytochrome b, and a near homoplasmic 5783G > A in tRNAcys, were found in the proband in various tissues. Her mother and asymptomatic sibling also carry the two homoplasmic mutations and the heteroplasmic 5783G > A mutation in blood, hair follicles, and buccal cells, at lower percentage. The 5783G > A mutation occurs at the T arm of tRNAcys, resulting in the disruption of the stem structure, which may reduce the stability of the tRNA. 15458T > C changes an amino acid serine to proline at a conserved α‐helix, which may force the helix to bend. These two mutations may have pathogenic significance. This case emphasizes the importance of pursuing more extensive mutational analysis of mtDNA in the absence of common mtDNA point mutations or large deletions, when there is a high suspicion of a mitochondrial disorder. © 2006 Wiley‐Liss, Inc.
Die supramolekulare Chemie organisch‐anorganischer Hybrid‐Nanomaterialien
Authors: Descalzo Ana B. , Martínez‐Máñez Ramón , Sancenón Félix , Hoffmann Katrin , Rurack Knut
Published: September 2006

Die Entwicklung von Hybridmaterialien mit stark verbesserten Funktionen gelingt durch die Kombination geeigneter Nanomaterialien als Träger mit Motiven aus der supramolekularen Chemie. Diese “hetero‐supramolekularen” Konzepte bieten vielfältige Möglichkeiten, die Lücken zwischen der Molekülchemie, Materialwissenschaften und Nanotechnologie zu schließen. Im Hinblick auf funktionelle Aspekte wurden in jüngster Zeit wichtige Fortschritte erzielt, z. B. verbesserte Erkennungs‐ und Sensoreigenschaften durch die Anordnung von Molekülen auf vororganisierten Oberflächen, der reversible Aufbau von nanometergroßen Netzwerken und dreidimensionalen Strukturen oder biomimetische und gesteuerte chemische Prozesse in Hybrid‐Nanomaterialien, die als Grundlage für hoch spezialisierte Protokolle in dreidimensionalen Gerüststrukturen dienen können. Diese Ansätze ermöglichen eine Feinabstimmung der Eigenschaften von Nanomaterialien und eröffnen neue Perspektiven für die Anwendung supramolekularer Konzepte.
Photo‐induced iron‐catalyzed allylic amination of unfunctionalized olefins with nitroarenes
Authors: Srivastava Radhey S.
Published: September 2006

Photochemical reactions between unfuctionalized olefins and nitroarenes under CO pressure, catalyzed by [Cp*Fe(CO)2]2, form the corresponding allyl amines. The use of mechanistic probes containing 2‐nitrobiphenyl, 2,3‐dimethylbutadiene and pentafluoronitrobenzene suggest that neither aryl nitrene nor nitrosoarene is the active aminating agent in these transformations. Copyright © 2006 John Wiley & Sons, Ltd.
NMR Spectroscopic Observation of a Metal‐Free Acetylide Anion
Authors: Tanaka Yoshiyuki , Arakawa Makoto , Yamaguchi Yohei , Hori Chieko , Ueno Masahiro , Tanaka Takeyuki , Imahori Tatsushi , Kondo Yoshinori
Published: September 2006

A metal‐free acetylide was observed by using NMR spectroscopy. Metal‐free acetylides are closely related to reactive intermediates (carbanions) in solution; therefore, they have been regarded as unobservable species. However, we generated this highly reactive and unstable species through the deprotonation of phenylacetylene by using the strong nonmetallic phosphazene base tBu‐P4. In the presence of tBu‐P4, the J coupling between the ethynyl carbon and hydrogen nuclei (1JC,H) of phenylacetylene disappeared; this indicates the deprotonation of the alkyne terminal. Furthermore, a large low‐field shift (approximately 90 ppm) of the alkyne carbon resonance was observed. We concluded that we have observed a metal‐free carbanion with a formal charge on an sp‐hybridized carbon atom for the first time.
Microwave‐Assisted Synthesis of a Superparamagnetic Surface‐Functionalized Porous Fe3O4/C Nanocomposite
Authors: Hu Xianluo , Yu Jimmy C.
Published: September 2006

An Fe3O4/C nanocomposite was synthesized in a microwave‐assisted hydrothermal reaction. This green wet‐chemical approach is simple, low‐cost, and ideal for large‐scale production. The resulting composite material was characterized by transmission electron microscopy, powder X‐ray diffraction, energy‐dispersive X‐ray spectroscopy, Brunauer–Emmett–Teller analysis, X‐ray photoelectron spectroscopy, vibrating sample magnetometry, and UV/Vis spectroscopy. The product possesses porous structures and exhibits superparamagnetic behavior. Interestingly, its functional groups were inherited from the starting materials. This hydrophilic and biocompatible nanocomposite may find applications in catalysis, separation, adsorption, and bionanotechnology.