bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Genesis of the Antibody Conjugate Gemtuzumab Ozogamicin (Mylotarg®) for Acute Myeloid Leukemia
Authors: Hamann Philip R. 
Published: October 2010

Gemtuzumab ozogamicin is an antibody conjugate of calicheamicin that targets the CD33 antigen on differentiating myeloid cells and which is over-expressed on acute myeloid leukemia cells in most patients. It carries a DNA-active calicheamicin derivative selected during preclinical work with various antibodies. The calicheamicin derivative is attached to the hP67.6 antibody via the bifunctional AcBut linker, which allows for hydrolytic release of the calicheamicin in the acidic lysosomes. This conjugate, hP67.6-NAc-gamma calicheamicin DMH AcBut, is potently cytotoxic to most CD33-positive cells in tissue culture with high selectivity versus CD33-negative cells. It is curative of the CD33-expressing HL-60 xenografts and shows selective cytotoxicity in a significant proportion of AML bone marrow samples in a colony-forming assay.
Gemtuzumab ozogamicin has shown significant activity in various clinical trials. In pivotal Phase 2 trials, the remission rate was 26% and the medium recurrence-free survival in a heavily pre-treated patient population was 5.5 months. It was approved by the FDA in May 2000 for use in patients with CD33-positive AML in first relapse who are ≥60 years of age and are not candidates for cytotoxic chemotherapy. In a key on-going study combining it with daunorubicin and cytarabine for first indication, a complete response (CR) rate of 84% with gemtuzumab ozogamicin vs. 55% without has been seen so far with a median duration of CR &gt;6 months. Such studies promise to expand the role of gemtuzumab ozogamicin in the treatment of AML and to give patients more options for the treatment of this commonly fatal disease.
Polymer–Clay Nanocomposites Prepared in Miniemulsion Using the RAFT Process
Authors: Zengeni Eddson , Samakande Austin , Hartmann Patrice C. 
Published: October 2010

This chapter is a review on polymer-clay nanocomposites (PCNs) prepared in miniemulsion using the reversible addition-fragmentation chain transfer (RAFT) process.
One of the most interesting research areas in nanotechnology is the inclusion of nanoparticles in polymers in order to enhance their physical properties e.g. thermal stability, barrier properties and mechanical properties. In the early 1990s the Toyota research group showed that the hydrated cations within the clay layers can be replaced by alkyl ammonium compounds. A reactive clay modifier leads to a strong interfacial adhesion between the clay and the polymer, and subsequently the exceptional mechanical properties during load bearing. The use of tailor-made transfer agents in free-radical polymerisation reactions allows one to achieve control of the polymerisation process. This results in polymers with low polydispersity indices and predictable molar masses. The discovery of the controlled polymerisation techniques, and in particular RAFT agents, was a milestone achievement. RAFT polymerisation now allows the preparation of polymer architectures that were never before envisaged to be possible. Thus, a combination of RAFT technology and clay nanotechnology for the synthesis of PCNs by RAFT-mediated polymerisation can allow the preparation of tailor-made materials with specific properties for niche applications.
Structure of bacterial cellulose synthase subunit D octamer with four inner passageways
Authors: Hu Song-Qing , Gao Yong-Gui , Tajima Kenji , Sunagawa Naoki , Zhou Yong , Kawano Shin , Fujiwara Takaaki , Yoda Takanori , Shimura Daisuke , Satoh Yasuharu , Munekata Masanobu , Tanaka Isao , Yao Min 
Published: October 2010

The cellulose synthesizing terminal complex consisting of subunits A, B, C, and D in
Acetobacter xylinum
spans the outer and inner cell membranes to synthesize and extrude glucan chains, which are assembled into subelementary fibrils and further into a ribbon. We determined the structures of subunit D (AxCeSD/AxBcsD) with both N- and C-terminal His
6
tags, and in complex with cellopentaose. The structure of AxCeSD shows an exquisite cylinder shape (height: ∼65
Å
, outer diameter: ∼90
Å
, and inner diameter: ∼25
Å
) with a right-hand twisted dimer interface on the cylinder wall, formed by octamer as a functional unit. All N termini of the octamer are positioned inside the AxCeSD cylinder and create four passageways. The location of cellopentaoses in the complex structure suggests that four glucan chains are extruded individually through their own passageway along the dimer interface in a twisted manner. The complex structure also shows that the N-terminal loop, especially residue Lys6, seems to be important for cellulose production, as confirmed by in vivo assay using mutant cells with
axcesD
gene disruption and N-terminus truncation. Taking all results together, a model of the bacterial terminal complex is discussed.
Mimicking nature by codelivery of stimulant and inhibitor to create temporally stable and spatially restricted angiogenic zones
Authors: Yuen William W. , Du Nan R. , Chan Chun H. , Silva Eduardo A. , Mooney David J. 
Published: October 2010

Nature frequently utilizes opposing factors to create a stable activator gradient to robustly control pattern formation. This study employs a biomimicry approach, by delivery of both angiogenic and antiangiogenic factors from spatially restricted zones of a synthetic polymer to achieve temporally stable and spatially restricted angiogenic zones in vivo. The simultaneous release of the two spatially separated agents leads to a spatially sharp angiogenic region that is sustained over 3 wk. Further, the contradictory action of the two agents leads to a stable level of proangiogenic stimulation in this region, in spite of significant variations in the individual release rates over time. The resulting spatially restrictive and temporally sustained profiles of active signaling allow the creation of a spatially heterogeneous and functional vasculature.
Structure, function, and folding of phosphoglycerate kinase are strongly perturbed by macromolecular crowding
Authors: Dhar Apratim , Samiotakis Antonios , Ebbinghaus Simon , Nienhaus Lea , Homouz Dirar , Gruebele Martin , Cheung Margaret S. 
Published: October 2010

We combine experiment and computer simulation to show how macromolecular crowding dramatically affects the structure, function, and folding landscape of phosphoglycerate kinase (PGK). Fluorescence labeling shows that compact states of yeast PGK are populated as the amount of crowding agents (Ficoll 70) increases. Coarse-grained molecular simulations reveal three compact ensembles: C (crystal structure), CC (collapsed crystal), and Sph (spherical compact). With an adjustment for viscosity, crowded wild-type PGK and fluorescent PGK are about 15 times or more active in 200 mg/ml Ficoll than in aqueous solution. Our results suggest a previously undescribed solution to the classic problem of how the ADP and diphosphoglycerate binding sites of PGK come together to make ATP: Rather than undergoing a hinge motion, the ADP and substrate sites are already located in proximity under crowded conditions that mimic the in vivo conditions under which the enzyme actually operates. We also examine T-jump unfolding of PGK as a function of crowding experimentally. We uncover a nonmonotonic folding relaxation time vs. Ficoll concentration. Theory and modeling explain why an optimum concentration exists for fastest folding. Below the optimum, folding slows down because the unfolded state is stabilized relative to the transition state. Above the optimum, folding slows down because of increased viscosity.
The Economic Effect of Screening Orthopedic Surgery Patients Preoperatively for Methicillin-ResistantStaphylococcus aureus
Authors: Lee Bruce Y. , Wiringa Ann E. , Bailey Rachel R. , Goyal Vishal , Tsui Becky , Lewis G. Jonathan , Muder Robert R. , Harrison Lee M. 
Published: October 2010

Background and Objective.Patients undergoing orthopedic surgery are susceptible to methicillin-resistantStaphylococcus aureus(MRSA) infections, which can result in increased morbidity, hospital lengths of stay, and medical costs. We sought to estimate the economic value of routine preoperative MRSA screening and decolonization of orthopedic surgery patients.Methods.A stochastic decision-analytic computer simulation model was used to evaluate the economic value of implementing this strategy (compared with no preoperative screening or decolonization) among orthopedic surgery patients from both the third-party payer and hospital perspectives. Sensitivity analyses explored the effects of varying MRSA colonization prevalence, the cost of screening and decolonization, and the probability of decolonization success.Results.Preoperative MRSA screening and decolonization was strongly cost-effective (incremental cost-effectiveness ratio less than $6,000 per quality-adjusted life year) from the third-party payer perspective even when MRSA prevalence was as low as 1%, decolonization success was as low as 25%, and decolonization costs were as high as $300 per patient. In most scenarios this strategy was economically dominant (ie, less costly and more effective than no screening). From the hospital perspective, preoperative MRSA screening and decolonization was the economically dominant strategy for all scenarios explored.Conclusions.Routine preoperative screening and decolonization of orthopedic surgery patients may under many circumstances save hospitals and third-party payers money while providing health benefits.
The Use of Antimicrobial Agents after Diagnosis of Viral Respiratory Tract Infections in Hospitalized Adults: Antibiotics or Anxiolytics?
Authors: Shiley Kevin T. , Lautenbach Ebbing , Lee Ingi 
Published: October 2010

Objective.Because extensive antibiotic use by inpatients has been associated with the development of multidrug-resistant organisms, we aimed to determine which variables were associated with the use of antibiotics after viral respiratory tract infection diagnosis among adult patients admitted to the hospital with respiratory symptoms.Methods.A retrospective cohort study was conducted at 2 affiliated urban hospitals in Pennsylvania. We identified all adult patients admitted to the hospital during the period from November 1, 2005, through August 1, 2007, with a viral assay positive for influenza A or B, parainfluenza, adenovirus, or respiratory syncytial virus. Among these patients, we identified those who received antibiotics after the diagnosis of viral RTL Data on demographics; comorbidities; and physical examination, laboratory, and radiographic findings were ascertained to identify risk factors for antimicrobial use among these patients.Results.A total of 196 hospitalized patients with positive viral assay results were included; 125 of 131 patients administered antibiotics continued to receive them after viral RTI diagnosis. Among 52 patients with an abnormal chest radiograph, 46 continued antibiotic therapy. An abnormal chest radiograph was independently associated with continued antibiotic use (adjusted odds ratio, 4.28 [95% confidence interval, 1.71-10.77]; P = .002). However, the majority of patients (79 of 125 [63%]) who continued antibiotic therapy had normal chest imaging findings. Eight patients (6%) who continued antibiotic therapy and no patients who stopped developed C. difficile infection (95% CI, 1.5-00; p = .05), but there was no significant difference in length of stay or mortality.Conclusions.Antibiotics are commonly used to treat hospitalized patients with known acute viral RTIs. Continued use is strongly associated with abnormal radiograph findings at admission. However, the reasons for continuation of antibiotics in the treatment of the majority of patients with normal radiographs are unclear and may represent inappropriate use.
The Arabidopsis Botrytis Susceptible1 Interactor Defines a Subclass of RING E3 Ligases That Regulate Pathogen and Stress Responses
Authors: Luo Hongli , Laluk Kristin , Lai Zhibing , Veronese Paola , Song Fengming , Mengiste Tesfaye 
Published: October 2010

Abstract
We studied the function of Arabidopsis (Arabidopsis thaliana) Botrytis Susceptible1 Interactor (BOI) in plant responses to pathogen infection and abiotic stress. BOI physically interacts with and ubiquitinates Arabidopsis BOS1, an R2R3MYB transcription factor previously implicated in stress and pathogen responses. In transgenic plants expressing the BOS1-β-glucuronidase transgene, β-glucuronidase activity could be detected only after inhibition of the proteosome, suggesting that BOS1 is a target of ubiquitin-mediated degradation by the proteosome. Plants with reduced BOI transcript levels generated through RNA interference (BOI RNAi) were more susceptible to the necrotrophic fungus Botrytis cinerea and less tolerant to salt stress. In addition, BOI RNAi plants exhibited increased cell death induced by the phytotoxin α-picolinic acid and by a virulent strain of the bacterial pathogen Pseudomonas syringae, coincident with peak disease symptoms. However, the hypersensitive cell death associated with different race-specific resistance genes was unaffected by changes in the level of BOI transcript. BOI expression was enhanced by B. cinerea and salt stress but repressed by the plant hormone gibberellin, indicating a complex regulation of BOI gene expression. Interestingly, BOI RNAi plants exhibit reduced growth responsiveness to gibberellin. We also present data revealing the function of three Arabidopsis BOI-RELATED GENES (BRGs), which contribute to B. cinerea resistance and the suppression of disease-associated cell death. In sum, BOI and BRGs represent a subclass of RING E3 ligases that contribute to plant disease resistance and abiotic stress tolerance through the suppression of pathogen-induced as well as stress-induced cell death.
A prospective study into the aetiology of lymphocytic duodenosis
Authors: Aziz I. , Evans K. E. , Hopper A. D. , Smillie D. M. , Sanders D. S. 
Published: October 2010

Aliment Pharmacol Ther 2010; 32: 1392–1397SummaryBackground  Lymphocytic duodenosis is defined by normal villous architecture and intraepithelial lymphocytes (IELs) >25 per 100 enterocytes. Such patients should not be diagnosed with coeliac disease, solely by histology, as previous retrospective studies have suggested other associations with lymphocytic duodenosis.Aim  To study prospectively the aetiology of lymphocytic duodenosis.Methods  One hundred patients with lymphocytic duodenosis were investigated rigorously for coeliac disease and other known associations for lymphocytic duodenosis by initial investigations of coeliac serology, and exclusion of infection. Of 34 with no explanation for lymphocytic duodenosis, 29 underwent repeat duodenal biopsies following a gluten challenge.Results  Coeliac disease was present in 16% of patients with lymphocytic duodenosis. In the absence of a positive coeliac diagnosis, lymphocytic duodenosis was most commonly associated with drugs (21%), infection (19%), immune dysregulation (4%), inflammatory bowel disease (2%), microscopic colitis (2%), sarcoidosis (1%) and IgA deficiency (1%). Of 34 with no known associations, 18 had symptoms of irritable bowel syndrome (IBS), and in 29 patients investigated with repeat duodenal biopsies, the IEL count returned to normal in 22.Conclusions  In 66% of cases of lymphocytic duodenosis, a known association can be found by further investigations; importantly, 16% will have coeliac disease. In those with no apparent cause, there may be an association with IBS and the IEL count becomes normal on repeat biopsy in 76%.
Association of functional polymorphisms related to the transcriptional level of FOXP3 with prognosis of autoimmune thyroid diseases
Authors: Inoue N , Watanabe M , Morita M , Tomizawa R , Akamizu T , Tatsumi K , Hidaka Y , Iwatani Y 
Published: October 2010

Summary
The severity of Hashimoto's disease (HD) and intractability (or inducibility to remission) of Graves' disease (GD) varies among patients. Forkhead box P3 (FoxP3) is a crucial regulatory factor for the development and function of regulatory T (Treg) cells, and deficiency of the FoxP3 gene (FOXP3) suppresses the regulatory function of Treg cells. To clarify the association of the functional polymorphisms of the FOXP3 with the prognosis of GD and HD, we genotyped −3499A/G, −3279C/A and −2383C/T polymorphisms in FOXP3 gene obtained from 38 patients with severe HD, 40 patients with mild HD, 65 patients with intractable GD, in whom remission was difficult to induce, 44 patients with GD in remission and 71 healthy volunteers. The −3279CA genotype was more frequent in patients with GD in remission than in patients with intractable GD, and the −3279AA genotype, which correlates to defective transcription of FOXP3, was absent in patients with GD in remission. The −2383CC genotype was more frequent in patients with severe HD than in those with mild HD. In conclusion, the −3279A/C polymorphism is related to the development and intractability of GD and the −2383CC genotype to the severity of HD.
The value of detectable thyroglobulin in patients with differentiated thyroid cancer after initial 131I therapy
Authors: van Dijk D. , Plukker J. T. M. , van der Horst‐Schrivers A. N. A. , Jansen L. , Brouwers A. H. , Muller‐Kobold A. , Sluiter W. J. , Links T. P. 
Published: October 2010

SummaryObjective  To assess the prognostic value of detectable thyroglobulin (Tg) after initial surgery and radioactive iodine (131I) therapy by comparing patients with a negative post‐therapeutic whole body scan (WBS) with either detectable or undetectable Tg.Background  Differentiated thyroid cancer has a good prognosis. However, recurrences can occur up to 30 years after initial treatment. Because life‐long follow‐up is necessary, it is important to explore possible risk factors associated with recurrence and mortality.Design, patients and measurements  We studied 539 patients who were treated between 1980 and 2007. After the last therapeutic dosage of 5550 MBq 131I, 72 patients had negative post‐therapeutic WBS and positive Tg levels (Tg+ group) and 399 patients had negative post‐therapeutic WBS and negative Tg (Tg‐ group). The 68 remaining patients had proven residual macroscopic disease. We investigated recurrences and overall mortality in the Tg+ and Tg‐ group compared with the Dutch population.Results  In the Tg+ group, detectable recurrences occurred significantly earlier and more frequently than in the Tg‐ group (19%vs 13%, P = 0·024). Survival between these groups was comparable, but shorter than the general Dutch population [Standardised Mortality Rate (SMR) 1·38 (95% CI 1·12;1·63) (P = 0·003)]. Disease‐free survival in the Tg groups was comparable and not significantly different from the Dutch population [SMR = 1·09 (95% CI 0·81;1·34) (P = 0·569)].Conclusion  Patients with detectable Tg during the last 131I treatment and a negative post‐therapeutic WBS have significant earlier and more recurrences than patients without detectable Tg. Survival in both groups is comparable. After initial therapy, the combination of a negative high dose post‐therapeutic WBS with detectable Tg is a valuable predictor for earlier and more recurrences, but is not associated with survival.
Elevated anti‐Müllerian hormone (AMH) and inhibin B levels in prepubertal girls with type 1 diabetes mellitus
Authors: Codner Ethel , Iñiguez Germán , Hernández Isabel M. , Lopez Patricia , Rhumie Hana K. , Villarroel Claudio , Rey Rodolfo A. 
Published: October 2010

SummaryObjective  Elevated anti‐Müllerian hormone (AMH) and adrenal androgen levels have been observed during childhood in girls at risk of developing polycystic ovarian syndrome (PCOS). The aim of this study was to evaluate ovarian function and adrenal steroid levels in prepubertal girls with type 1 diabetes mellitus (T1D).Design  Cross‐sectional study.Patients/Measurements  We evaluated hormonal and ultrasonographic characteristics in girls with T1D (N = 73) and compared them to characteristics found in a control group of healthy girls (N = 86). Data are reported as geometric means (95% CI).Results  Prepubertal girls with T1D had higher levels of AMH (29·1 pmol/l (23·2–36·3) vs 20·9 pmol/l (16·6–26·1), P = 0·038), inhibin B (arithmetic mean: 16·7 pg/ml (11·6–21·7) vs 11·7 pg/ml (10·0–13·5), P = 0·044) and dehydroepiandrosterone sulphate (DHEAS) (0·3 nmol/l (0·2–0·6) vs 0·2 nmol/l (0·1–0·3)) than controls (P = 0·045). During puberty, decreasing AMH levels were observed in girls with T1D only (P < 0·0001). Girls with T1D in Tanner stages 4–5 had lower AMH levels than their paired healthy controls (10·1 pmol/l (7·4–13·9) vs 15·7 pmol/l (11·6–21·3), respectively, P = 0·047).Conclusions  Our observations indicate that prepubertal girls with T1D may exhibit similar endocrine findings to those of other girls at risk of developing PCOS. The elevated levels of AMH and inhibin B suggest that higher numbers of follicles are present in the ovary during childhood in these patients and that insulin treatment may act as a local growth factor. In addition, AMH levels differed in prepubertal and pubertal girls, suggesting that the effect of T1D on ovarian folliculogenesis changes once gonadotrophin levels rise during puberty.
Phenological responses to extreme droughts in a Mediterranean forest
Authors: MISSON LAURENT , DEGUELDRE DAVID , COLLIN CHRISTIAN , RODRIGUEZ RAQUEL , ROCHETEAU ALAIN , OURCIVAL JEAN‐MARC , RAMBAL SERGE 
Published: October 2010

AbstractMediterranean regions are projected to experience more frequent, prolonged and severe drought as a consequence of climate change. We used a retractable rainfall shelter, to investigate the impact of extreme droughts on the development of Quercus ilex leaves, flowers and fruit. In 2008, 97% of rainfall was excluded from a forest plot during the autumn, representing 50% of the 1127 mm of rain that fell during the year. In 2009, 87% of rainfall was excluded during the spring, representing 58% of the 749 mm that fell during the year. The rainfall shelter did not impact neither incident radiation nor air temperature. Autumn rainfall exclusion did not significantly affect leaf, flowers or fruit development. Spring rainfall exclusion resulted in larger and more sustained depression of leaf water potential during the key phases of foliar and floral development. Consequently, only half of the sampled trees (6) reached the shoot lengthening stage which leads to functionally mature leaves (phenophase 4), with one abandoning leaf development at budburst (phenophase 3) and the other two at the bud swelling stage (phenophase 2). All trees of the control plot passed phenophase 4, with most reaching complete leaf development. The impact of extreme droughts on flower development differed between the sexes. The spring exclusion had no effect on male flower, but only one of six trees completed female fruit maturation, compared with four in the control plot. The difference between the male and female drought impacts is likely attributable to the occurrence of male floral development before the period of lowest leaf water potential, and to the lower resource allocation requirements of male flowers. The information provided by our experimental approach may constitute a crucial step to evaluate the impact of increasing drought due to climate change on the most dominant Mediterranean tree species and to help drawing a full picture of the ecological consequences of the decline in water resource on forest dynamics under changing conditions.