bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA editing complex interactions with a site for full-round U deletion in Trypanosoma brucei
Authors: Sacharidou Anastasia , Cifuentes-Rojas Catherine , Halbig Kari , Hernandez Alfredo , Dangott Lawrence J. , De Nova-Ocampo Monica , Cruz-Reyes Jorge
Published: May 2006

Trypanosome U insertion and U deletion RNA editing of mitochondrial pre-mRNAs is catalyzed by multisubunit editing complexes as directed by partially complementary guide RNAs. The basic enzymatic activities and protein composition of these high-molecular mass complexes have been under intense study, but their specific protein interactions with functional pre-mRNA/gRNA substrates remains unknown. We show that editing complexes purified through extensive ion-exchange chromatography and immunoprecipitation make specific cross-linking interactions with A6 pre-mRNA containing a single 32P and photoreactive 4-thioU at the scissile bond of a functional site for full-round U deletion. At least four direct protein–RNA contacts are detected at this site by cross-linking. All four interactions are stimulated by unpaired residues just 5′ of the pre-mRNA/gRNA anchor duplex, but strongly inhibited by pairing of the editing site region. Furthermore, competition analysis with homologous and heterologous transcripts suggests preferential contacts of the editing complex with the mRNA/gRNA duplex substrate. This apparent structural selectivity suggests that the RNA–protein interactions we observe may be involved in recognition of editing sites and/or catalysis in assembled complexes.
RBP16 stimulates trypanosome RNA editing in vitro at an early step in the editing reaction
Authors: Miller Melissa M. , Halbig Kari , Cruz-Reyes Jorge , Read Laurie K.
Published: May 2006

RBP16 is an abundant RNA binding protein from Trypanosoma brucei mitochondria that affects both RNA editing and stability. We report here experiments aimed at elucidating the mechanism of RBP16 function in RNA editing. In in vitro RNA editing assays, recombinant RBP16 is able to significantly stimulate insertion editing of both CYb and A6 pre-mRNAs. Enhancement of in vitro editing activity occurs at, or prior to, the step of pre-mRNA cleavage, as evidenced by increased accumulation of pre-mRNA 3′ cleavage products in the presence of RBP16. Mutated RBP16 that is severely compromised in cold shock domain (CSD)-mediated RNA binding was able to enhance editing to levels comparable to the wild-type protein in some assays at the highest RBP16 levels tested. However, at low RBP16 concentrations or in assays with native, oligo(U)-tail-bearing gRNAs, editing stimulation by mutant RBP16 was somewhat compromised. Together, these results indicate that both the N-terminal CSD and C-terminal RGG RNA binding domains of RBP16 are required for maximal editing stimulation. Finally, the relaxed specificity of RBP16 for stimulation of both CYb and A6 editing in vitro implicates additional specificity factors that account for the strict CYb specificity of RBP16 action in editing in vivo. Our results constitute the first report of any putative RNA editing accessory factor eliciting an effect on editing in vitro. Overall, these results support a novel accessory role for RBP16 in U insertion editing.
Observation of Two 4-Coordinated Al Sites in Montmorillonite using High Magnetic Field Strength 27Al MQMAS NMR
Authors: Ohkubo Takahiro , Kanehashi Koji , Saito Koji , Ikeda Yasuhisa
Published: May 2006

Analyses of the layer structure of Na-montmorillonite have been performed using 27Al MAS and 27Al MQMAS NMR techniques. Results of 27Al MAS NMR measurements at higher magnetic field strength (16.4 T) suggest that the 4-coordinated Al site in Na-montmorillonite has two different structures. This was confirmed by the fact that two peaks corresponding to 4-coordinated Al are observed in the 27Al MQMAS NMR at high magnetic field strength. The ratio of two 4-coordinated Al sites was found to be affected by water in the interlayer space because the area ratio of cross peaks corresponding to two 4-coordinated Al sites changes with the water content.
Soil Mineralogy Evolution in the INRA 42 Plots Experiment (Versailles, France)
Authors: Pernes-Debuyser A. , Pernes M. , Velde B. , Tessier D.
Published: May 2006

Natural soils change by long-term pedogenetic mechanisms, but tillage effects can also strongly affect the evolution of soils, mainly their physicochemical properties. The present paper describes the impact of fertilizers and amendments on soil mineralogy in experimental plots, without plant interaction.

The soils of the 42 plots experiment at the INRA experimental station in Versailles (France) have been managed with fertilizers without plant growth since 1929. Strong changes in pH were observed and cation exchange capacities doubled between low and high pH (from 3.6 to 8.2). Strong acidification caused more evolution in the clay particle distribution without selective action on the clay composition.

While the clay content varied only slightly, the organic matter content changed considerably, decreasing with non-organic treatment and increasing in the plot with manure treatment. The major clay minerals in the experimental plots are two disordered illite-smectite mixed-layer minerals, with minor amounts of illite/mica and kaolinite. Most treatments effected only minor changes in clay mineralogy. However the illite (non-expandable mineral) content increased in plots with K addition either as KCl treatment or in manure amendments by increasing the illite content and the illite (non-expandable layer) content of the I-S minerals. Manure changed the I-S mineral to a greater extent.
Behavior of Smectite in Strong Salt Brines under Conditions Relevant to the Disposal of Low- to Medium-Grade Nuclear Waste
Authors: Hofmann Heiko , Bauer Andreas , Warr Laurence N.
Published: May 2006

Two industrial bentonites, IBECO SEAL-80 and TIXOTON TE, have been proposed as potential backfill material in the German Asse salt dome, a test field for the disposal of low- to medium-grade active nuclear waste. Considering the unlikely but possible case of a barrier breakdown with infiltration of a highly concentrated salt brine, the physicochemical stability and material behavior of these bentonites in a saturated salt brine (predominantly MgCl2) at 25°C were studied over the time period of 150 days. The results show that no mineral transformations occurred throughout the duration of the experiments and minor dissolution was only active during the first days. Some chemical properties, namely sorption capability and swelling, were reduced during contact with the salt brine, but could be reversed by removing the salt after treatment. Despite restriction of the CEC in the presence of salt solution, interlayer cation exchange reactions are still active in this environment. The long-term chemical stability of smectite in salt brine is predicted under these low-temperature conditions, but the increased permeability during aggregate formation could lead to physical breakdown of the backfill component.
Mass Changes during Adsorption of Metal Bipyridyl Complexes by Clay Films Monitored with an Electrochemical Quartz Crystal Microbalance
Authors: Sun Laisheng , Villemure Gilles
Published: May 2006

The adsorption of [M(bpy)3]2+ ions (M = Ru or Os) by clay films immersed in pure water and in electrolyte solutions was investigated by electrochemical quartz crystal microbalance (EQCM), UV-visible spectroscopy and powder X-ray diffraction. In water, the adsorption of the cations resulted in a decrease in the mass of the films. This decrease in mass is attributed to the expulsion of some 50 water molecules from the clay interlayer spaces for each cation adsorbed. Water is lost to make room for the large metal complex cations in the interlayer spaces, and because of decreases in the volume of the interlayer spaces during adsorption of the cations. In 0.05 M NaCl or 0.05 M Na2SO4, UV-visible measurements show a rapid initial adsorption of the cations by ion exchange, followed by a slower additional adsorption of the cations above the clay’s CEC, presumably as ion pairs with the electrolyte counter ions. The EQCM show initial reductions in the mass of the films that were two to three times larger in pure water. These initial mass decreases were followed by smaller mass ‘re-increases’ at longer times that were not observed in water. The larger initial mass losses are attributed to the loss of more water from the clay interlayer spaces. In 0.5 M Na2SO4 or 1.0 M NaCl, adsorption of the cations never exceeded the clay’s CEC. The initial decreases in mass upon addition of the cations all but disappeared, leaving only the smaller positive mass changes at longer times.
Insight into the Binding of Divalent Cations to Sepia Eumelanin from IR Absorption Spectroscopy
Authors: Hong Lian , Simon John D.
Published: May 2006

IR absorption spectroscopy is used to examine the binding of the divalent cations Mg(II), Za(II), Zn(II) and Cu(II) to melanin granules isolated from the ink sacs of Sepia officinalis. The functional groups of the melanin granules interacting with the bound metal ions are deduced by examining the effect of metal concentration on transition frequencies associated with the COOH, NH and OH moieties of the pigment. The coordinating groups vary with metal ion and with concentration. For the experimental conditions used (initial solution pH of 4, ionic strength of 100 mM and a melanin concentration of 1 mg mL−1) Mg(II), Ca(II) and Zn(II) bind to carboxylate groups and Cu(II) binds predominantly to phenolic (catechol) groups However, at a concentration of 10 mM Cu(II) also shows evidence of binding to carboxylate and amine groups, reflecting a secondary binding site that becomes populated as the catechol sites are depleted.
Adverse pregnancy outcomes in offspring of fathers working in biomedical research laboratories
Authors: Magnusson Linda L. , Bodin Lennart , Wennborg Helena
Published: May 2006

Background

Laboratory work may constitute a possible health hazard for workers as well as for their offspring, and involves a wide range of exposures, such as organic solvents, carcinogenic agents, ionizing radiation, and/or microbiological agents. Adverse pregnancy outcomes in the offspring of male employees in biomedical research laboratories are examined.

Methods

Offspring to males employed 1970–1989 at four Swedish universities were identified via the Medical Birth Register (MBR), along with other pregnancy parameters. Offspring of fathers with laboratory work (n = 2,281) is considered exposed, and of non‐laboratory employees unexposed (n = 1,909). Exposure data were obtained by questionnaires to research group leaders. Logistic regression analysis estimated odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Paternal laboratory work in general showed no statistically significant increased ORs concerning birth weight and/or gestational age, but work specifically with radioactive isotopes gave OR 1.8 (CI 1.0–3.2) for high birth weight and a relative risk of 1.2 (CI 1.0–1.4) for sex ratio (male/female).

Conclusions

There was no clear association between periconceptional paternal laboratory work and adverse reproductive outcomes, but use of radioactive isotopes showed increased OR for high birth weight in offspring. Am. J. Ind. Med. 49:468–473, 2006. © 2006 Wiley‐Liss, Inc.
A new case of Grange syndrome without cardiac findings
Authors: Wallerstein Robert , Augustyn Ann Marie , Wallerstein Donna , Elton Leslie , Tejeiro Beatriz , Johnson Valerie , Lieberman Kenneth
Published: May 2006

Grange syndrome comprises arterial stenoses with hypertension, brachysyndactyly, bone fragility, learning disability, and cardiac defects. To date, we know of two reported families with five affected individuals. We report on one of the youngest cases, in a third family, a 3‐year‐old girl with brachysyndactyly, renal artery stenosis with hypertension, and bone fragility. She does not have apparent cardiac disease, suggesting cardiac anomalies may not be an obligatory finding in this syndrome. © 2006 Wiley‐Liss, Inc.
Metaphyseal dysplasia of Braun–Tinschert type: Report of a Japanese girl
Authors: Takata Shinjiro , Nishimura Gen , Ikegawa Shiro , Kuroda Yasuhiro , Nishino Mizuho , Matsui Yoshito , Yasui Natsuo
Published: May 2006

We report on a 7‐year‐old Japanese girl with metaphyseal dysplasia (MD) of Braun–Tinschert type, a recently recognized, autosomal dominant sclerosing bone dysplasia. All individuals with the disorder from four families in the literature originated from a small town in Bohemia or its vicinity. The occurrence of the disorder in a Japanese girl indicates that it is not restricted to Germans. The radiographic hallmarks of the disorder include metaphyseal undermodeling (Erlenmeyer‐flask deformity); osteosclerosis of the chondroosseous junctions, metaphyseal cortices, and epiphyseal margins; and exostosis‐like bone excrescences at the metaphyseal‐diaphyseal junctions. In the girl we described, the latter two findings were conspicuous at age 4 years, but became less prominent with increasing age. The metaphyseal trabeculae were somewhat coarse. The humeri exhibited varus deformity, and the ulnae and fibulae mild bowing. The mean bone mineral density of the lumbar spine was lower than that of age‐matched controls. The patient exhibited premature loss of primary teeth, likely to be a sign of increased periodontal bone resorption. Markers of bone formation and resorption were both increased, an indication of a high rate of bone turnover. © 2006 Wiley‐Liss, Inc.
Nablus mask‐like facial syndrome is caused by a microdeletion of 8q detected by array‐based comparative genomic hybridization
Authors: Shieh Joseph T.C. , Aradhya Swaroop , Novelli Antonio , Manning Melanie A. , Cherry Athena M. , Brumblay Janet , Salpietro Carmelo D. , Bernardini Laura , Dallapiccola Bruno , Hoyme H. Eugene
Published: May 2006

In 2000, Teebi reported on a 4‐year‐old boy with a distinctive pattern of malformation, which he termed the “Nablus mask‐like facial syndrome” (OMIM# 608156). Characterization of this syndrome has been difficult because of the paucity of patients described in the medical literature and its unknown etiology and pathogenesis. We present two patients with Nablus mask‐like facial syndrome who both display a microdeletion in the 8q21‐8q22 region detected by array‐based comparative genomic hybridization. Patient 1, a boy, has a distinct facial appearance characterized by severe blepharophimosis, tight‐appearing glistening facial skin, sparse and unruly hair, a flat and broad nose, and distinctive ears that are triangular in shape with prominent antihelices. He also demonstrates camptodactyly, contractures, unusual dentition, cryptorchidism, mild developmental delay, and a happy demeanor. Patient 2, a girl with a strikingly similar phenotype, was previously described in a report by Salpietro et al. 2003. She has distinctive ears, dental anomalies, and developmental delay. The etiology of her pattern of malformation was not identified at that time. Although high‐resolution chromosome and subtelomeric FISH analyses were normal, array‐based comparative genomic hybridization revealed an approximately 4 Mb deletion involving the 8q21.3‐8q22.1 region in both patients. This region encompasses a number of genes that may contribute to this unique phenotype. These results demonstrate a chromosomal microdeletion as the etiology of Nablus mask‐like facial syndrome and emphasize the diagnostic utility of array‐based comparative genomic hybridization in the evaluation of multiple malformation syndromes of previously unrecognized causation. © 2006 Wiley‐Liss, Inc.
Pattern of p63 mutations and their phenotypes—update
Authors: Rinne Tuula , Hamel Ben , Bokhoven Hans van , Brunner Han G.
Published: May 2006

Heterozygous mutations in the transcription factor gene p63 cause at least six different syndromes with various combinations of ectodermal dysplasia, orofacial clefting and limb malformations. Here we will present an update of mutations in the p63 gene together with a comprehensive overview of the associated clinical features in 227 patients. These data confirm the previously recognized genotype–phenotype associations. Moreover, we report that there is a large degree of clinical variability in each of the p63‐associated disorders. This is illustrated by the different phenotypes that are seen for the five‐hotspot mutations that explain almost 90% of all EEC syndrome patients. © 2006 Wiley‐Liss, Inc.
Overgrowth with severe developmental delay following IVF/ICSI: A newly recognized syndrome?
Authors: Shah Prakesh S. , Weksberg Rosanna , Chitayat David
Published: May 2006

We report on a child with postnatal overgrowth, noted from 3 months of age, associated with severe developmental delay and refractory seizures. The patient was conceived using in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). The patient's features do not resemble any reported overgrowth syndromes reported so far. We propose that this is a previously unrecognized disorder. The potential role of ICSI/IVF in the pathogenesis of this condition is unknown. No imprinting defect at chromosome 11p15 was identified. © 2006 Wiley‐Liss, Inc.
PHOX2B analysis in non‐syndromic neuroblastoma cases shows novel mutations and genotype–phenotype associations
Authors: McConville Carmel , Reid Sarah , Baskcomb Linda , Douglas Jenny , Rahman Nazneen
Published: May 2006

Neuroblastoma (NB) is an embryonal tumor originating from neural crest cells and is one of the most common solid tumors of childhood. Recently, constitutional mutations in PHOX2B have been shown to confer an increased risk of NB. To date, mutations predisposing to neural crest tumors have been reported in 20 individuals from 16 families. These families included additional clinical features such as Hirschsprung (HSCR) disease or congenital central hypoventilation syndrome, either in the index case or relatives. The contribution of PHOX2B mutations to NB cases without additional features is unclear. To address this we sequenced PHOX2B in constitutional DNA from 86 individuals with non‐syndromic NB (4 cases had a family history of NB). We identified two mutations, 600delC, a frameshift mutation in an individual with isolated, unifocal NB and G197D, a missense mutation that was present in a family with multiple individuals with NB but no evidence of autonomic dysfunction. These data demonstrate that PHOX2B mutations are a rare cause of non‐syndromic NB. The mutations we identified are outside the domains typically mutated in PHOX2B syndromes. This provides further evidence that the underlying PHOX2B mutational mechanism influences tumor risk and suggests that the position of missense mutations may influence the resulting phenotype. © 2006 Wiley‐Liss, Inc.
Autosomal dominant syndrome resembling Coffin–Siris syndrome
Authors: Flynn Maureen A. , Milunsky Jeff M.
Published: May 2006

Coffin–Siris syndrome is a multiple congenital anomaly/mental retardation syndrome with phenotypic variability [OMIM 135900]. The diagnosis is based solely on clinical findings, as there is currently no molecular, biochemical, or cytogenetic analysis available to confirm a diagnosis. Although typically described as an autosomal recessive disorder, autosomal dominant inheritance has also been infrequently reported. We describe a mother and her two daughters who all have features that resemble Coffin–Siris syndrome. However, this is not a completely convincing diagnosis given that hypertelorism is not a feature of Coffin–Siris syndrome and the family is relatively mildly affected. Yet, this family provides further evidence of an autosomal dominant mode of inheritance for a likely variant of Coffin–Siris syndrome (at least in some families). In addition, Sibling 1 had premature thelarche. She is the second reported individual within the spectrum of Coffin–Siris syndrome to have premature thelarche, indicating that it may be a rare clinical feature. © 2006 Wiley‐Liss, Inc.
Comprehensive screening of multiple epiphyseal dysplasia mutations in Japanese population
Authors: Itoh Taichi , Shirahama Shuya , Nakashima Eiji , Maeda Koichi , Haga Nobuhiko , Kitoh Hiroshi , Kosaki Rika , Ohashi Hirofumi , Nishimura Gen , Ikegawa Shiro
Published: May 2006

Multiple epiphyseal dysplasia (MED) is among the most genetically heterogeneous skeletal dysplasias. Six genes involved in MED, COMP, MATN3, COL9A1, COL9A2, COL9A3, and DTDST have been identified; however, the presence of additional disease genes has been reported, and the detection rate for mutations in known genes accounts for no more than 50% of patients with MED in Western populations. Here, we screened the six known disease genes in 35 consecutive Japanese MED patients. We analyzed the entire coding region of each gene, along with flanking intron–exon junctions, by direct sequencing. A total of 19 mutations were identified in COMP, MATN3, COL9A2, COL9A3, and DTDST. The detection rate for known mutations was higher in this study than in previous reports, and we identified a substantially different spectrum of mutations. Mutations in MATN3 were more prevalent among these Japanese patients, whereas no DTDST mutations were detected. Most of the mutations were localized within specific regions of each gene: COMP mutations were found in the calmodulin‐like repeat domains; MATN3 mutations in the von Willebrand factor type A domain; and type IX collagen gene mutations occurred in the third collagenous domains. Based on the integration of clinical and genetic information, we propose an algorithm for detecting mutations in Japanese MED patients. Our study further supports the existence of additional MED gene(s). © 2006 Wiley‐Liss, Inc.
Influence of polymerization conditions on the structure and properties of polyethylene/polypropylene in‐reactor alloy synthesized in the gas phase with a spherical Ziegler–Natta catalyst
Authors: Fu Zhisheng , Dong Qi , Li Na , Fan Zhiqiang , Xu Junting
Published: May 2006

A spherical TiCl4/MgCl2‐based catalyst was used in the synthesis of in‐reactor polyethylene/polypropylene alloys by polyethylene homopolymerization and subsequent homopolymerization of propylene in the gas phase. Different conditions in the ethylene homopolymerization stage, such as monomer pressure and polymerization temperature, were investigated, and their influences on the structure and properties of in‐reactor alloys were studied. Raising the polymerization temperature is the most effective way of speeding up polymerization and regulating the ethylene content of polyethylene (PE)/polypropylene (PP) alloys, but it will cause a greater increase in the PE‐b‐PP block copolymer fraction (named fraction D) than in the fraction of PP‐block‐PE in which the PP segments have low or medium isotacticity (named fraction A). Although changing ethylene monomer pressure could influence the ethylene content of PE/PP alloys slightly, it is an effective way of regulating the structural distribution. Reducing the monomer pressure will evidently increase fractions A and D. The mechanical properties of the alloys, including impact strength and flexural modulus, can be regulated in a broad range with changes in polymerization conditions. These properties are highly dependent on the amount, distribution, and chain structure of fractions A and D. The impact strength is affected by both fraction A and fraction D in a complicated way, whereas the flexural modulus is mainly determined by the amount of fraction A. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2136–2143, 2006
Information systems citation patterns from International Conference on Information Systems articles
Authors: Chuan Chan Hock , Kim Hee‐Woong , Tan Weai Chee
Published: May 2006

Research patterns could enhance understanding of the Information Systems (IS) field. Citation analysis is the methodology commonly used to determine such research patterns. In this study, the citation methodology is applied to one of the top‐ranked Information Systems conferences—International Conference on Information Systems (ICIS). Information is extracted from papers in the proceedings of ICIS 2000 to 2002. A total of 145 base articles and 4,226 citations are used. Research patterns are obtained using total citations, citations per journal or conference, and overlapping citations. We then provide the citation ranking of journals and conferences. We also examine the difference between the citation ranking in this study and the ranking of IS journals and IS conferences in other studies. Based on the comparison, we confirm that IS research is a multidisciplinary research area. We also identify the most cited papers and authors in the IS research area, and the organizations most active in producing papers in the top‐rated IS conference. We discuss the findings and implications of the study.
The dual nature of neurotrophins
Authors: Schweigreiter Rüdiger
Published: May 2006

Neurotrophins are a small family of dimeric secretory proteins in vertebrate neurons with a broad spectrum of functions. They are generated as pro‐proteins with a functionality that is distinct from the proteolytically processed form. The cellular responses of neurotrophins are mediated by three different types of receptor proteins, the receptor tyrosine kinases of the Trk family, the neurotrophin receptor p75NTR, which is a member of the tumor necrosis factor receptor (TNFR) superfamily, and sortilin, previously characterized as neurotensin receptor. Recent studies have revealed an intriguing pattern: neurotrophins can elicit opposing signals utilising their variable configuration and different receptor types. BioEssays 28: 583–594, 2006. © 2006 Wiley Periodicals, Inc.
Primary bone lymphoma: Treatment results and prognostic factors with long‐term follow‐up of 82 patients
Authors: Beal Kathryn , Allen Laura , Yahalom Joachim
Published: May 2006

BACKGROUND

To the authors' knowledge, there is limited information on the preferred treatment and long‐term prognosis of primary bone lymphomas (PBLs). All PBL cases treated at the study center between 1963 and 2003 were analyzed to determine patient, disease, and treatment factors that could affect outcome measured by overall survival (OS), cause‐specific survival (CSS), and freedom‐from‐treatment failure (FFTF).

METHODS

A total of 101 patients with PBL diagnosed at the study institution were identified. Nineteen patients were excluded because they transferred their treatment or follow‐up to another center. Disease control, survival, and prognostic factors were analyzed for all 82 remaining patients.

RESULTS

The median age of the patients was 48 years (range, 11–83 years). Approximately 80% presented with diffuse large‐cell lymphoma (DLCL), and 81% presented with Ann Arbor Stage I or II disease. Approximately 57% were treated with combined modality therapy, 14% were treated with radiation therapy alone, and 30% were treated with chemotherapy alone. The median follow‐up was 67 months (range, 2–280 months). The 5‐year OS, CSS, and FFTF were 88%, 96%, and 81%, respectively. The 5‐year OS for patients treated with combined modality versus single‐modality therapy was 95% versus 78% (P = .013), and the 5‐year FFTF for patients treated with combined modality versus single‐modality therapy was 90% versus 67% (P = .025). The 5‐year CSS for patients treated with combined modality versus single‐modality therapy was 95% versus 83% (P = .065). Using a Cox regression for multivariate analysis, age <40 years and use of combined modality therapy were found to be favorable prognostic factors for OS, CSS, and FFTF.

CONCLUSIONS

To the authors' knowledge, the current study is the largest series of patients with PBL treated with modern curative modalities. The data demonstrate that primary lymphoma involving the bone has an excellent prognosis. Patients with PBL treated with combined modality versus single modality therapy were found to have a superior outcome, with a significantly better survival. Cancer 2006. © 2006 American Cancer Society.
Outcomes in patients with splenic marginal zone lymphoma and marginal zone lymphoma treated with rituximab with or without chemotherapy or chemotherapy alone
Authors: Tsimberidou Apostolia M. , Catovsky Daniel , Schlette Ellen , O'Brien Susan , Wierda William G. , Kantarjian Hagop , Garcia‐Manero Guillermo , Wen Sijin , Do Kim‐Anh , Lerner Susan , Keating Michael J.
Published: May 2006

BACKGROUND

The optimal management of patients with splenic marginal zone lymphoma/marginal zone lymphoma (SMZL) is controversial. The objective of this retrospective study was to compare the outcomes of patients with SMZL who received treatment with rituximab, rituximab plus chemotherapy, or chemotherapy alone.

METHODS

The Leukemia Service database was searched for patients with splenic lymphoma who were registered between May 1995 and October 2004. The indications for treatment were the same as those used for patients with chronic lymphocytic leukemia.

RESULTS

SMZL was confirmed in 70 patients. The median age was 64 years. The median number of CD20 molecules per cell was 69 × 103. Forty‐three patients required systemic therapy; rituximab in 26 patients, chemotherapy plus rituximab in 6 patients, and chemotherapy alone in 11 patients. Ten additional patients underwent splenectomy, and 17 patients were in the observation group. The overall response rates were 88% with rituximab, 83% with rituximab plus chemotherapy, and 55% with chemotherapy alone; the 3‐year survival rates were 95%, 100%, and 55%, respectively. The 3‐year failure‐free survival (FFS) rates were 86%, 100%, and 45% in the rituximab, rituximab plus chemotherapy, and chemotherapy alone groups, respectively. Rituximab treatments resulted in longer survival and FFS compared with chemotherapy. Rituximab alone resulted in disappearance of splenomegaly in 92% of patients and normalization of absolute lymphocyte counts. In univariate analysis, younger age and rituximab‐based therapy were predictive of longer FFS.

CONCLUSIONS

Rituximab with or without chemotherapy was found to have major activity in patients with SMZL. These results may be associated with high levels of cellular CD20 antigen sites. Rituximab should be the treatment of choice, at least in older patients with SMZL who have comorbid diseases. Cancer 2006. © 2006 American Cancer Society.
Dedifferentiated central chondrosarcoma
Authors: Staals Eric L. , Bacchini Patrizia , Bertoni Franco
Published: May 2006

BACKGROUND

The prognosis for patients who develop dedifferentiation of central chondrosarcoma traditionally has been poor. Because not much has been reported about this rare lesion, many uncertainties remain about prognostic factors.

METHODS

In this retrospective study, the clinical, radiographic, and histologic features and the treatments in 123 patients from the Rizzoli Institute were reviewed in an attempt to define which factors may be related to outcome in patients with dedifferentiated central chondrosarcoma.

RESULTS

Among 123 patients who were included in this study, 109 patients were treated at the Rizzoli Institute, and 14 patients were seen in consultation. There were 66 males and 57 females, and their average age was 59 years. The femur (62 patients), pelvis (28 patients), and humerus (20 patients) were the most common locations. Radiographically, a soft tissue mass was present in 87% of patients, and a bimorphic pattern was appreciated in 53% of patients. Histologically, the cartilaginous component was considered Grade 1 in 63% of patients and Grade 2 in 37% of patients. In most patients, the dedifferentiated component showed the features of an osteosarcoma (92 patients), followed by fibrosarcoma (19 patients), and malignant fibrous histiocytoma (9 patients). For 101 patients, surgery was a component of their definitive management. In 25 patients, surgery was combined with chemotherapy. The 2‐year and 5‐year survival rates were 34% and 24%, respectively. The median survival was 13 months (95% confidence interval, 9‐17 months).

CONCLUSIONS

Metastatic disease at diagnosis, malignant fibrous histiocytoma dedifferentiation, and a high percentage of dedifferentiated component were related to poorer outcomes. There was no statistical evidence of any beneficial effect from adjuvant chemotherapy. Cancer 2006. © 2006 American Cancer Society.
Influence of local recurrence on survival in patients with extremity osteosarcoma treated with neoadjuvant chemotherapy
Authors: Bacci Gaetano , Longhi Alessandra , Cesari Marilena , Versari Michela , Bertoni Franco
Published: May 2006

BACKGROUND

Risk factors for local recurrence (LR) after osteosarcoma, such as surgical margins and histologic response to preoperative treatment, have been well documented, whereas the outcome for patients who locally recur has not been well established yet.

METHODS

Retrospective analysis of the management and outcome of 44 patients who developed LR after treatment of osteosarcoma of the extremities with neoadjuvant chemotherapy was performed in a single institution between 1983 and 1999.

RESULTS

In 24 patients (54.5%), LR was the first sign of recurrence; in 8 patients (18.2%) LR followed systemic recurrence and in 12 patients (27.3%), the 2 events, local and systemic recurrence, were concurrent. Of the 44 patients, 26 with local recurrences were free of disease, but only 5 were long‐term event‐free survivors, and 39 patients developed further recurrences: 37 died of the tumor and 2 were alive with uncontrolled disease at the time of last follow‐up. The 5‐year disease‐free survival rate after the last recurrence was 15.9%; it was 25.9% for patients who achieved remission and 0% for the others. The only prognostic factor identified for post‐LR disease‐free survival was the presence of systemic recurrence at the time of diagnosis of LR or before (5‐year postrecurrence event‐free survival rate of 29.1% for patients without metastases at the time of local recurrence vs. 0% for those with metastases; P = .02).

CONCLUSIONS

These results confirm that patients with osteosarcoma of the extremities who develop LR are at a very significantly high risk of developing metastatic disease and dying of the tumor. Cancer 2006. © 2006 American Cancer Society.
Supraclavicular radiation for breast cancer does not increase the 10‐year risk of stroke
Authors: Woodward Wendy A. , Giordano Sharon H. , Duan Zhigang , Hortobagyi Gabriel N. , Buchholz Thomas A.
Published: May 2006

BACKGROUND

Modern radiation techniques, which limit the radiation dose to the heart during treatment for breast cancer, have greatly reduced the risk of radiation‐induced cardiac injury. However, the risk of radiation damage to the carotid artery, which is often incidentally included in the supraclavicular radiation field for breast cancer treatment, is not routinely examined, and the technique used to treat this field has not changed significantly from early radiation trials. The purpose of the current study was to compare the incidence of hospitalization for stroke among women with breast cancer treated with supraclavicular radiation with those who received radiation therapy to the breast but not the supraclavicular fossa.

METHODS

Data from the Surveillance, Epidemiology, and End Results (SEER)‐Medicare database for 5752 women who were diagnosed with American Joint Committee on Cancer (AJCC) Stage I‐III nonmetastatic breast cancer between 1988 and 1997 were analyzed. Women included were age ≥66 years, had known lymph node (LN) status, had tumors measuring ≤5 cm, underwent breast surgery, and received adjuvant radiation therapy (with or without supraclavicular irradiation). Patients with <5 years of follow‐up were excluded because events in the first 5 years after radiation were unlikely to be radiation induced. A Cox proportional hazards model was used to compare patients with 0 positive LNs (surrogate group for no supraclavicular radiation, n = 5281) with patients with >4 positive LNs (surrogate for supraclavicular radiation group, n = 471) for the endpoint of hospitalization for stroke. Time‐to‐event curves were calculated using the conditional Kaplan–Meier method.

RESULTS

The median follow‐up for the 0 and 4+ LN cohorts were 92 months and 90 months, respectively (minimum of 60 months). The 10‐year and 15‐year actuarial freedom from hospitalization for stroke was 91% (0 LN) versus 89.5% (4+ LN) and 79% (0 LN) versus 81.6% (4+ LN), respectively (P = .28). Estrogen receptor status was balanced between the 2 cohorts. As expected, the 4+ cohort had more advanced tumors, higher stage, larger tumor size, and higher grade (P<.0001). In multivariate analysis including LN group, year of diagnosis, age, race, type of surgery, stage, tumor size, grade, estrogen receptor status, and Charlson comorbidity score, only increased age (hazard ratio [HR] for ages 70‐74 years, 1.6; HR for ages 75‐79 years, 2.1; and HR for age 80+ years, 2.7) and increasing comorbidity score were predictive of an increased risk of hospitalization for stroke.

CONCLUSIONS

Although patients with nonbreast malignancies treated with higher doses to the carotid arteries have been shown to have an increased risk of carotid injury, no evidence was found that radiation to the carotid delivered during supraclavicular irradiation for breast cancer increases the risk of hospitalization for stroke. Cancer 2006. © 2006 American Cancer Society.
Expression of estrogen receptors‐α and ‐β in bladder cancer cell lines and human bladder tumor tissue
Authors: Shen Steven S. , Smith Carolyn L. , Hsieh Jer‐Tsong , Yu Jiang , Kim Isaac Y. , Jian Weiguo , Sonpavde Guru , Ayala Gustavo E. , Younes Mamoun , Lerner Seth P.
Published: May 2006

BACKGROUND

Estrogen receptors (ERs) are known to mediate important physiologic responses as well as the growth of some tumors in response to estradiol stimulation. In a previous study the selective ER modulator raloxifene was shown to induce apoptosis in an ERβ‐positive bladder cancer cell line. However, the expression of ERβ in human bladder cancer has not been thoroughly investigated.

METHODS

ERα and ERβ expression in 224 bladder tumor samples was evaluated using tissue microarray and immunohistochemistry. Levels of ERα and ERβ protein and mRNA expression were determined in several bladder cancer cell lines using quantitative reverse‐transcriptase polymerase chain reaction (RT‐PCR) and Western blot analysis. The effect of estradiol and antiestrogen treatments on RT4 bladder cancer cell growth was determined by cell proliferation assays.

RESULTS

Analyses revealed that only 2 human bladder cancers weakly expressed ERα. In contrast, the expression of ERβ was detected in 141 tumors (63%). ERβ was expressed in 58% of WHO Grade 1 and 2 tumors, whereas 70% of Grade 3 tumors demonstrated expression (P=.085). Importantly, although only 53% and 55% of Ta and T1 tumors demonstrated ERβ expression, 80% of T2, 81% of T3, and 75% of T4 tumors showed ERβ expression. The differences in ERβ expression between Ta/T1 and T2/T3/T4 tumors were found to be highly significant (P<.001). Metastatic transitional cell carcinomas had ERβ expression (80%) comparable to that of muscle invasive bladder cancers. Western blot analysis detected ERβ protein expression in each of the 5 bladder cancer cell lines tested, whereas no or very low levels of ERα were found. Quantitative RT‐PCR revealed that higher levels of ERβ than ERα mRNA were present in 5637, T‐24, TSU‐Pr1, and TCC‐Sup bladder cancer cells, whereas ER‐α mRNA levels were greater than ERβ in RT4 cells. Treatment with 17β‐estradiol modestly increased RT4 cell growth, whereas the antiestrogens, 4‐hydroxtamoxifen, raloxifene, or ICI 182,780 inhibited the growth of RT4 cells.

CONCLUSIONS

ERβ is the dominant receptor expressed in bladder cancer cell lines and in the majority of human bladder tumors. Moreover, the degree of ERβ expression increases with increasing stage and grade of differentiation. Antiestrogens have an inhibitory effect on the growth of bladder cancer cells in vitro. Cancer 2006. © 2006 American Cancer Society.
Polymersomes as viral capsid mimics
Authors: Ahmed Fariyal , Photos Peter J. , Discher Dennis E.
Published: May 2006

Polymersomes are self‐assembled polymer shells composed of block copolymer amphiphiles. These synthetic amphiphiles have a similar amphiphilicity to lipids, but they have much larger molecular weights and so for this reason, plus many others reviewed here, comparisons of polymersomes to viral capsids composed of large polypeptide chains seem increasingly more appropriate. The wide range of polymers being used to make polymersomes is summarized together with descriptions of physical properties such as stability and permeability. Emerging studies of in vivo stealthiness and programmed disassembly for controlled release are also elaborated here together with a summary of targeting in vitro. Comparisons of polymersomes to viral capsids are shown to encompass many aspects of current designs. Drug Dev. Res. 67:4–14, 2006. © 2006 Wiley‐Liss, Inc.
Magnetic nanoparticles for drug delivery
Authors: Dobson Jon
Published: May 2006

Targeting specific sites in vivo for the delivery of therapeutic compounds presents a major obstacle to the treatment of many diseases. One targeted delivery technique that has gained prominence in recent years is the use of magnetic nanoparticles. In these systems, therapeutic compounds are attached to biocompatible magnetic nanoparticles and magnetic fields generated outside the body are focused on specific targets in vivo. The fields capture the particle complex resulting in enhanced delivery to the target site. This review will focus on technical aspects of magnetic targeting as well as nanoparticle design and animal and clinical trials. Drug Dev. Res. 67:55–60, 2006. © 2006 Wiley‐Liss, Inc.
Mouse coat color mutations: From fancy mice to functional genomics
Authors: Steingrímsson Eiríkur , Copeland Neal G. , Jenkins Nancy A.
Published: May 2006

Mouse coat color mutations have a long history in biomedical research. The viable and visible phenotype of most coat color mutations has made the pigment cell, the melanocyte, an ideal system for genetic, molecular, and cellular analysis. Molecular cloning and analysis of many of the different coat color mutations have revealed the roles of a diverse range of genes, and today we know more about the pathways and proteins that regulate the development and function of pigment cells than we know about most other cell types in mammalian organisms. Coat color mutations have also provided novel insights into stem cell biology and human diseases, including melanoma. In the future, it will be important to build on this history and knowledge by taking advantage of the extensive repertoire of recently developed genome‐wide methodologies, available genomic information, and the powerful methods that have been developed for modifying the mouse genome to systematically dissect the development and function of this important cell type. The usefulness of coat color mutations has just begun to emerge. Developmental Dynamics 235:2401–2411, 2006. © 2006 Wiley‐Liss, Inc.
The Synthesis of Substituted Benzo[c]chromen‐6‐ones by a Suzuki Coupling and Lactonization Sequence Using Ionic Liquids – from Laboratory Scale to Multi‐Kilogram Synthesis
Authors: Kemperman Gerardus J. , Ter Horst B. , Van de Goor D. , Roeters T. , Bergwerff J. , Van der Eem R. , Basten J.
Published: May 2006

A series of benzo[c]chromen‐6‐ones are prepared by a Suzuki coupling and lactonization sequence starting with 2‐methoxyphenylboronic acids and methyl 2‐bromobenzoate derivatives. The use of ionic liquids in this synthesis has been explored. It was found that the Suzuki coupling proceeds much faster when a catalytic amount of the ionic liquid [BMIM][PF6] is used. By using the Lewis acidic ionic liquids [BMIM][Al2Cl7] or [TMAH][Al2Cl7] the methyl 2‐(2‐methoxyphenyl)benzoate product obtained from the Suzuki coupling can be converted to benzo[c]chromen‐6‐ones in one step, while the conventional route involves three steps. The use of ionic liquids is demonstrated in the synthesis of a variety of benzo[c]chromen‐6‐ones. It is also shown that the application of ionic liquids is not limited to laboratory scale experiments, as a process was developed and performed on a multi‐kilogram scale. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
The essential oil composition of Phlomis cretica C. Presl
Authors: Basta Andriani , Tzakou Olga , Couladis Maria
Published: May 2006

The essential oils from the verticillasters and leaves of Phlomis cretica were analyzed by GC and GC‐MS. The main constituents of the verticillasters essential oil were germacrene D (34.0%) and germacrene B (11.0%). The leaf oil contained germacrene D (47.9%) and α‐pinene (11.2%) as major constituents. Copyright © 2006 John Wiley & Sons, Ltd.
Composition of essential oils of Helichrysum italicum (Roth) G. Don fil subsp. italicum from Tuscan archipelago islands
Authors: Paolini Julien , Desjobert Jean‐Marie , Costa Jean , Bernardini Antoine‐François , Castellini Cinzia Buti , Cioni Pier‐Luigi , Flamini Guido , Morelli Ivano
Published: May 2006

The essential oils obtained by water distillation from the aerial parts of Helichrysum italicum subsp. italicum growing on Tuscan Archipelago Islands were analyzed by CG‐RI and CG‐MS. These oils were characterized by the predominance of oxygenated compounds and by a qualitatively homogeneous composition. However, according to the amounts of β‐diketones and neryl acetate, two chemical compositions were distinguished. Copyright © 2006 John Wiley & Sons, Ltd.
The Jahn–Teller and pseudo‐Jahn–Teller effects in the anion photoelectron spectroscopy of B3 cluster
Authors: Venkatesan T. S. , Deepika K. , Mahapatra S.
Published: May 2006

The photodetachment spectroscopy of B anion is theoretically studied with the aid of a quantum dynamical approach. The theoretical results are compared with the available experimental photoelectron spectra of B. Both B and B3 possess D3h symmetry at the equilibrium configuration of their electronic ground state. Distortion of B3 along its degenerate vibrational mode ν2 splits the degeneracy of its excited
$\widetilde{C}^2E^{\prime}$
electronic manifold and exhibits (E ⊗ e)‐Jahn–Teller (JT) activity. The components of the JT split potential energy surface form conical intersections, and they can also undergo pseudo‐Jahn–Teller (PJT) crossings with the $\widetilde{X}^2A_1^{\prime}$
electronic ground state of B3 via the degenerate ν2 vibrational mode. The impact of the JT and PJT interactions on the nuclear dynamics of B3 in its $\widetilde{X}^2A_1^{\prime}-\widetilde{C}^2E^{\prime}$
electronic states is examined here by establishing a diabatic model Hamiltonian. The parameters of the electronic part of this Hamiltonian are calculated by performing electronic structure calculations and the nuclear dynamics on it is simulated by solving quantum eigenvalue equation. The theoretical results are in good accord with the experimental data. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1093–1100, 2006
Resilience in the face of potential trauma: Clinical practices and illustrations
Authors: Mancini Anthony D. , Bonanno George A.
Published: May 2006

Many persons exposed to loss or potentially traumatic events manage the stresses of these experiences with minimal to no impact on their daily functioning. The prevalence of this resilient capacity has surprised researchers and clinicians alike and refocused clinical practice. We review three key points about resilience: resilience is different from the process of recovery; resilience in the face of loss or potential trauma is common; and there are multiple and sometimes unexpected pathways to resilience. We then present six clinical practices informed by the study of resilience, illustrating key points with clinical vignettes. © 2006 Wiley Periodicals, Inc. J Clin Psychol: In Session 62: 971–985, 2006.