bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell‐fusion‐mediated somatic‐cell reprogramming: A mechanism for tissue regeneration
Authors: Lluis Frederic , Cosma Maria Pia
Published: January 2010

Spontaneous cell fusion between two cells of different lineages will originate new hybrid cells that have different features from the original parent cells. It has been shown that injury to a tissue can enhance spontaneous cell–cell fusion events. If one of the parent cells of a cell–cell fusion is highly plastic, such as a stem cell, and the other is a somatic cell, their fusion can be followed by reprogramming events that can generate new hybrid pluripotent cells. These, in turn, have the potential to differentiate and regenerate the damaged tissue. However, if this process is deregulated, this would provide a mechanism for cancer development. J. Cell. Physiol. 223: 6–13, 2010. © 2009 Wiley‐Liss, Inc.
Mitogen‐activated protein kinase‐activated protein kinase 2 (MK2) in skeletal muscle atrophy and hypertrophy
Authors: Norrby Marlene , Tågerud Sven
Published: January 2010

Skeletal muscle is a highly plastic tissue. Overall muscle growth (hypertrophy) or muscle wasting (atrophy) results from alterations in intracellular signaling pathways with important regulatory steps occurring in the nucleus as well as in the cytoplasm. Previous studies have identified components of the Akt/mTor pathway as well as the p38 MAPK pathway as important for skeletal muscle hypertrophy and/or atrophy. The present study tests the hypothesis that MK2, a substrate of p38 which following phosphorylation, can be exported from the nucleus in a complex with p38, may be important for skeletal muscle growth. The expression of MK2 was examined in denervated mouse hind‐limb (atrophic) and hemidiaphragm (transiently hypertrophic) muscles. MK2 mRNA expression decreased after denervation in both atrophic (48% of innervated controls, P < 0.001) and hypertrophic muscle (34% of innervated controls, P < 0.01) but MK2 protein expression decreased only in atrophic muscle (32% of innervated controls, P < 0.01). The level of T205 phosphorylated MK2 increased after denervation in both atrophic (fourfold increase, P < 0.01) and hypertrophic muscles (almost sevenfold increase, P < 0.001) whereas the level of T317 phosphorylated MK2 (necessary for nuclear export) increased after denervation in hypertrophic muscle (nearly threefold increase, P < 0.001) but not in atrophic muscle. Logarithmically transformed relative changes in MK2 phosphorylated at T317 correlated well (r2 = 0.7737) with relative changes in muscle weight. The results suggest a role for MK2 in the regulation of muscle mass, a role which, at least in part, may be related to determining the subcellular localization of p38 in muscle fibers. J. Cell. Physiol. 223: 194–201, 2010. © 2009 Wiley‐Liss, Inc.
EGF and its related growth factors mediate sodium transport in mpkCCDc14 cells via ErbB2 (neu/HER‐2) receptor
Authors: Levchenko Vladislav , Zheleznova Nadezhda N. , Pavlov Tengis S. , Vandewalle Alain , Wilson Patricia D. , Staruschenko Alexander
Published: January 2010

Amiloride‐sensitive sodium entry, via the epithelial sodium channel (ENaC), is the rate‐limiting step for Na+ absorption. Epidermal growth factor (EGF) is involved in the regulation of Na+ transport and ENaC activity. However it is still controversial exactly how EGF regulates ENaC and Na+ absorption. The aim of the present study was to characterize the EGF regulation of Na+ transport in cultured mouse renal collecting duct principal mpkCCDc14 cells, a highly differentiated cell line which retains many characteristics of the cortical collecting duct (CCD). EGF dose dependently regulates basal transepithelial Na+ transport in two phases: an acute phase (<4 h) and a chronic phase (>8 h). Similar effects were observed with TGF‐α, HB‐EGF, and amphiregulin which also belong to the EGF‐related peptide growth factor family. Inhibition of MEK1/2 by PD98059 or U0126 increased acute effects and disrupted chronic effects of EGF on Na+ reabsorption. Inhibition of PI3‐kinase with LY294002 abolished acute effect of EGF. As assessed by Western blotting, ErbB2 is the most predominant member of the ErbB family detected in mpkCCDc14 cells. Immunohistochemistry analysis revealed localization of ErbB2 in the CCD in Sprague–Dawley rat kidneys. Both acute and long‐term effects of EGF were abolished when cells were treated with tyrphostin AG‐825 and ErbB2 inhibitor II, chemically dissimilar selective inhibitors of the ErbB2 receptor. Thus, we conclude that EGF and its related growth factors are important for maintaining transepithelial Na+ transport and that EGF biphasically modulates sodium transport in mpkCCDc14 cells via the ErbB2 receptor. J. Cell. Physiol. 223: 252–259, 2010. © 2009 Wiley‐Liss, Inc.
A versatile synthesis of [2,3,4‐13C3]isoflavones
Authors: Al‐Maharik Nawaf , Botting Nigel P.
Published: January 2010

A flexible synthetic method is presented, which allows all the key isoflavones (daidzein, genistein, glycitein, formononetin and biochanin A) to be prepared in 13C‐labelled form via the same route, involving the thallium(III)‐mediated oxidative rearrangement of a key chalcone intermediate. This method results in the incorporation of 13C atoms at the 2, 3 and 4 positions of the isoflavone skeleton. We also report the first syntheses of 13C‐labelled versions of the daidzein metabolites, equol and ODMA. Copyright © 2009 John Wiley & Sons, Ltd.
Binding site on human immunoglobulin G for the affinity ligand HWRGWV
Authors: Yang Haiou , Gurgel Patrick V. , Williams D. Keith , Bobay Benjamin G. , Cavanagh John , Muddiman David C. , Carbonell Ruben G.
Published: January 2010

Affinity ligand HWRGWV has demonstrated the ability to isolate human immunoglobulin G (hIgG) from mammalian cell culture media. The ligand specifically binds hIgG through its Fc portion. This work shows that deglycosylation of hIgG has no influence on its binding to the HWRGWV ligand and the ligand does not compete with Protein A or Protein G in binding hIgG. It is suggested by the mass spectrometry (MS) data and docking simulation that HWRGWV binds to the pFc portion of hIgG and interacts with the amino acids in the loop Ser383–Asn389 (SNGQPEN) located in the CH3 domain. Subsequent modeling has suggested a possible three‐dimensional minimized solution structure for the interaction of hIgG and the HWRGWV ligand. The results support the fact that a peptide as small as a hexamer can have specific interactions with large proteins such as hIgG. Copyright © 2009 John Wiley & Sons, Ltd.
Regioisomer characterization of triacylglycerols by non‐aqueous reversed‐phase liquid chromatography/electrospray ionization mass spectrometry using silver nitrate as a postcolumn reagent
Authors: Lévêque Nathalie L. , Héron Sylvie , Tchapla Alain
Published: January 2010

Triacylglycerols (TAGs) provide a challenge for mass spectrometry (MS) analysis because of their complexity. In particular, for dietary, nutritional and metabolic purposes, the positional placement of fatty acids on the glycerol backbone of TAGs is a crucial aspect. To solve this problem, we have investigated the TAGs' fragmentation patterns using an ion trap mass spectrometer. A series of pure regioisomeric pairs of TAGs (POP/PPO, POO/OPO and OSO/SOO) were cationized by Ag+ after their separation by non‐aqueous reversed‐phase liquid chromatography (NARP‐LC) before MS to improve MS sensitivity. Electrospray ionization–MS (ESI‐MS) conditions were optimized in order to produce characteristic [M + Ag + AgNO3]+ ions from each TAG, which were then fragmented to produce MS/MS spectra and then fragmented further to produce up to MS5 spectra. The observation of ions produced by LC‐MS5 of on‐line Ag+‐cationized TAG provided unambiguous information on the fatty acid distribution on the glycerol backbone. These strategies of MS to MS5 experiments were applied to identify components and to determine the regiospecificity of TAG within a complex mixture of lipids in natural oils. Copyright © 2010 John Wiley & Sons, Ltd.
Analysis and cloudiness influence on UV total irradiation
Authors: Santos Julia Bilbao , Villán David Mateos , Castrillo Argimiro de Miguel
Published: January 2010

Ultraviolet (UV) total solar irradiation, 290–385 nm (UVT), at ground level in Valladolid, Spain (lat. 41°40′N, long. 4°50′W and 840 m a.s.l.), has been recorded from February 2001 to June 2008. The temporal evolution of the UVT irradiation follows a sinusoidal pattern with maximums in summer and minimums in winter. A complete statistical study of hourly and daily values of UVT solar irradiation has been carried out. The results show that the stability is greater in the summer months and it can be concluded that the maximum values can be considered as representative of UVT irradiation. During an average year, the accumulated UVT solar irradiation is 244.5 MJ m−2. The relationships between UVT and global solar irradiation have been analysed finding a relationship of 4.2% between them. A potential relationship between both also provides good results. The dependence of UVT solar radiation with solar elevation and cloudiness has been studied. It can be concluded that solar elevation is the main factor to take into account for modelling the UV solar radiation. The dependence of UV/G ratio with cloudiness has been shown introducing the clearness index or global hemispherical transmittance (kt). This ratio has an increasing trend with the cloud cover and hence, it can be deduced that the presence of clouds reduces the global radiation more strongly than the UV component does. UV hemispherical transmittance (ktuv) has been evaluated. It has been found that ktuv values represent almost 70% of the global hemispherical transmittance in Valladolid city. With a potential relationship between both transmittances coefficient of determination values higher than 0.9 are also achieved. Copyright © 2010 Royal Meteorological Society
Response to the comments on ‘time trends of daily maximum and minimum temperatures in Catalonia (NE Spain) for the period 1975–2004’
Authors: Martínez M. D. , Serra C. , Burgueño A. , Lana X.
Published: January 2010

Some comments published recently on a study of time trends of daily maximum and minimum temperatures, Tmax and Tmin, have generated certain controversy with respect to a specific property of the Standard Normal Homogeneity Test (SNHT) and the applicability of the absolute and relative versions of this test. New insights to both questions are introduced in the present response. Copyright © 2010 Royal Meteorological Society
Why Pulse Duration Matters in Photovoltaics
Authors: Patel Rajesh S. , Bovatsek Jim , Tamhankar Ashwini
Published: January 2010

In the manufacture of thin‐film photovoltaic (TFPV) solar panels, Q‐switched diode‐pumped solid‐state (DPSS) lasers are routinely used for “laser scribing” – the selective removal of thin‐film materials. These lasers are available at various wavelengths (266–1064nm), output powers (0.5–34W), repetition rates (up to 500KHz) and pulse durations (<10 to greater than 100ns).

Developing the ideal laser scribe process – that is, one that removes only the desired material leaving the adjacent material unaffected – can be a challenge. In a non‐ideal scribe process, not only can there be leftover material, but also high ridges can form along the scribe line. Additionally, the supportive glass substrate can develop micro‐cracks that can then cause lift‐off of the thin‐film material. Because these unwanted ridges and burrs interfere with subsequent thin‐film layers, these non‐uniformities can lead to electrical shorts that reduce TFPV efficiencies and yields.

This article addresses the various ways in which pulse duration affects the laser scribe process – specifically thin‐film removal thresholds, scribe quality and substrate quality. It is shown that laser systems with shorter pulse durations will generally result in a laser scribe process that has lower material removal thresholds, cleaner scribes and minimal damage to glass substrates, ultimately leading to higher yields and lower overall manufacturing costs of TFPV panels.
Increasing the Photovoltaic Efficiency
Authors: Oesterlin Peter , Purath Andreas
Published: January 2010

Driven by falling prices and competitive pressure manufacturers of photovoltaic cells are seeking for new methods and cell concepts to reduce production costs and increase cell efficiency. Developments which have been of more academic interest over the past years are close to find their way into volume production. While laser applications are already standard for structuring of thin film PV glass panels, they are not yet widely established in the silicon‐wafer‐based cell manufacturing, which still represents more than 80% of the photovoltaic market. However, without adding too much complexity to the process flow most of the new cell concepts are only feasible by introduction of laser processes.
Ready to Work: Solid State Slab Laser
Authors: Du Keming
Published: January 2010

Through an optimal combination of crystal shape, cooling and resonator design, solid state slab lasers may possess special features: short pulse duration and high peak output power, high pulse repetition rate, high beam quality at high average power and flexibility in beam profile, from circular beam profile, through line shaped one dimensional top‐hat, to two dimensional top‐hat with rectangular cross section. Those open for slab lasers a variety of unique applications with added value, such glass processing, scribing, and particle imaging velocimetry and pumping of dye lasers.
Observe the Beam at the Center of Interest
Authors: Schwede Harald
Published: January 2010

For many laser applications it is essential to focus the beam. The characteristics of the focused beam determine fundamentally the result of the laser process. The key parameters for characterizing a laser beam are: the laser power, the beam width, the beam position, the beam propagation ratio M2, the polarization etc. Measurements at the focus of high power laser are a very demanding task. This article will start with a short review on the techniques to focus a beam. Then we are going to concentrate on different concepts how to realize a practical focus diagnostics. Finally, we discuss some typical results and analyze the relation between cause and effect.
Keeping the Customer Promise
Authors: Edmund Robert
Published: January 2010

Since 1942 Edmund Optics serves as one of the world wide leading suppliers of optics and optical components to industry. Laser Technik Journal spoke to Robert Edmund, President and CEO of Edmund Optics, about the slow recovery from recession, security and imaging market driving the optics industry in Europe and new opportunities.
Modified retrograde‐flow medial plantar island flap for reconstruction of distal dorsal forefoot defects—Two case reports
Authors: Tsai Johnlong , Liao Han‐Tsung , Ulusal Betul Gozel , Chen Chien‐Tzung , Lin Chih‐Hung
Published: January 2010

Soft tissue reconstruction of the distal forefoot and toes poses a difficult problem. Skin grafts are not suitable when deep structures are exposed. Local flaps are not available, particularly for defects of the toes. Free flaps are spared for larger defects. Medial plantar flap has been widely used for plantar defects, especially weight‐bearing surface of the heel. Distally based retrograde‐flow design of this flap allows the transfer of the pedicled flap distally and provides coverage of soft tissue over the metatarsal heads. In this report, we further modified the retrograde‐flow medial plantar island flap to extend its use for distal dorsal forefoot defects. The technique and outcomes of two patients are presented. © 2010 Wiley‐Liss, Inc. Microsurgery, 2010.
Anterolateral thigh adipofascial flap for the restoration of facial contour deformities
Authors: Jin Xiaolei , Teng Li , Xu Jiajie , Lu Jianjian , Zhang Chao , Zhang Bo , Zhao Zhenmin
Published: January 2010

From January 2000 to May 2008, 50 patients with facial contour deformities underwent soft tissue augmentation with 51 anterolateral thigh (ALT) adipofascial flaps. Fifty flaps survived with no complications; partial fat necrosis occurred in one flap. Mean follow‐up was 16 months. Flaps ranged from 10 × 6 cm to 20 × 12 cm. Perforators were found in 50 flaps, 43 musculocutaneous perforators (84.3%) and 7 septocutaneous perforators (13.7%), with a mean of 2.5 perforators per flap. In one flap (2.0%), no perforator was found. In this case, we used an anteromedial thigh adipofascial flap using the medial branch of the descending branch of lateral circumflex femoral artery as the vascular pedicle. Relatively symmetric facial contour was achieved in 20 cases. In 30 cases, adjunctive procedures including flap debulking, fat injection, and resuspension were necessary, and 23 patients achieved satisfactory outcomes. We conclude that the ALT adipofascial flap can be successfully elevated and transplanted for the correction of soft tissue facial defects. This flap can provide tissue to fill large defects, and posses the qualities of pliability, an excellent blood supply, ease of suspension and fixation, and minimal morbidity at the donor site. © 2010 Wiley‐Liss, Inc. Microsurgery 30:368–375, 2010.
Continuous local intraarterial infusion of anticoagulants for microvascular free tissue transfer in primary reconstruction of the lower limb following resection of sarcoma
Authors: Saito Akira , Sawaizumi Masayuki , Imai Tomohiro , Matsumoto Seiichi
Published: January 2010

In free tissue transfers, preventing microvascular thrombosis is the first priority to achieve a successful result. Numerous protocols exist for preventing thrombosis postoperatively. We performed continuous local intraarterial infusion of anticoagulants in 11 patients undergoing wide resection of malignant soft tissue tumors, followed by primary microvascular reconstruction in the lower limb. A catheter designed for epidural anesthesia was inserted into the femoral artery and connected to a syringe pump. A daily dose of 100 ml comprising 2,000 U of heparin and 40 μg of prostaglandin E1 was administered by means of continuous infusion for seven consecutive days as a standard regime. There were no cases of thrombosis during the continuous local intraarterial infusion of anticoagulants. There were no serious systemic complications. Although we have described limited cases and supporting data are lacking, we feel that this procedure might be useful for microsurgical reconstruction of the lower limb. © 2010 Wiley‐Liss, Inc. Microsurgery 30:376–379, 2010.
Development of techniques for gastrojejunal bypass surgery in obese mice
Authors: Lan Zhu , Zassoko Roman , Liu Weihua , Garcia Bertha , Sun Hongtao , Wang Rennian , Wang Hao
Published: January 2010

We have previously described a duodenojejunal bypass (DJB) surgical model in healthy C57BL/6 mice. However, our pilot study showed that the same surgical technique caused a high mortality rate in obese mice. In this study, to significantly improve animal survival rate following bariatric surgery and thereby providing a stable surgical model for the study of glucose homeostasis in obese mice, we have used modified techniques and developed the end‐to‐side gastrojejunal bypass (GJB) surgery in obese C57BL/6 with impaired glucose tolerance. The modification consisted of using the distal part of the jejunum for biliopancreatic diversion including: 1) ligation of the distal stomach at the level of the pylorus; 2) connection the jejunum to the anterior wall of stomach in an end‐to‐side fashion; and 3) diverting the biliopancreatic secretions through the blind limb into the distal jejunum through an end‐to‐side anastomosis. We found that by modifying the proximal end‐to‐end duodenojejunal anastomosis, described in our original model, to an end‐to‐side gastrojejunal anastomosis in these obese mice, we were able to significantly improve the postoperative mortality in this study. We have also demonstrated that performing the GJB surgery in obese mice resulted in significant weight loss, normalized blood glucose levels, and prevented acute pancreatitis. This newly developed GJB surgery in the obese mice offers a unique advantage to study the mechanisms of gastrointestinal surgery as treatment for type 2 diabetes. © 2010 Wiley‐Liss, Inc. Microsurgery, 2010.
NMR characterization of 1,1′‐binaphthyl‐2,2′‐diyl hydrogen phosphate binding to chiral molecular micelles
Authors: Kingsbury Stephanie A. , Ducommun Curtis J. , Zahakaylo Bryan M. , Dickinson Elizabeth H. , Morris Kevin F.
Published: January 2010

NMR spectroscopy was used to characterize the binding of the chiral compound 1,1′‐binaphthyl‐2,2′‐diyl hydrogen phosphate (BNP) to five molecular micelles with chiral dipeptide headgroups. Molecular micelles have covalent linkages between the surfactant monomers and are used as chiral mobile phase modifiers in electrokinetic chromatography. Nuclear overhauser enhancement spectroscopy (NOESY) analyses of (S)‐BNP:molecular micelle mixtures showed that in each solution the (S)‐BNP interacted predominately with the N‐terminal amino acid of the molecular micelle's dipeptide headgroup. NOESY spectra were also used to generate group binding maps for (S)‐BNP:molecular micelle mixtures. In these maps, percentages are assigned to the (S)‐BNP protons to represent the relative strengths of their interactions with a specified molecular micelle proton. All maps showed that (S)‐BNP inserted into a previously reported chiral groove formed between the molecular micelle's dipeptide headgroup and hydrocarbon chain. In the resulting intermolecular complexes, the (S)‐BNP protons nearest to the analyte phosphate group were found to point toward the N‐terminal Hα proton of the molecular micelle headgroup. Finally, pulsed field gradient NMR diffusion experiments were used to measure association constants for (R) and (S)‐BNP binding to each molecular micelle. These K values were then used to calculate the differences in the enantiomers' free energies of binding, Δ(ΔG). The NMR‐derived Δ(ΔG) values were found to scale linearly with electrokinetic chromatography (EKC) chiral selectivities from the literature. Copyright © 2010 John Wiley & Sons, Ltd.
Monitoring youth exposure to advertising on television: the devil is in the details
Authors: Jernigan David H. , Ross Craig
Published: January 2010

In the wake of increasing evidence that youth exposure to alcohol marketing is a risk factor in underage drinking, public health researchers are trying a variety of methods to measure that exposure. Based on lessons learned from more than 20 reports on exposure produced by the Center on Alcohol Marketing and Youth, best practices in data sources, definitions of terms and specific measurement issues such as census versus sampling, identifying the at‐risk population and performing basic calculations of gross rating points (GRPs) and GRP ratios are reviewed, using examples from work of the Center and other public health researchers. Specific recommendations for best practices in calculating and reporting exposure metrics are provided, including how to measure and report trends, differentiating between audit and planning perspectives and the importance of measuring exposure at both the category and the brand level. These recommendations are relevant not only to the monitoring of youth exposure to alcohol marketing, but also exposure to marketing for other potentially harmful products such as foods of low nutritional value, tobacco and pharmaceutical drugs.

Copyright © 2009 John Wiley & Sons, Ltd.
Peripheral blood stem cell support for multiple cycles of dose intensive induction therapy is feasible with little risk of tumor contamination in advanced stage neuroblastoma: A report from the Childrens Oncology Group
Authors: Bensimhon Pamela , Villablanca Judith G. , Sender Leonard S. , Matthay Katherine K. , Park Julie R. , Seeger Robert , London Wendy B. , Yap John Stephen F. , Kreissman Susan G.
Published: January 2010

Background

Poor outcome in Stage 4 neuroblastoma may be improved with increased dose intensity of therapy. We investigated the feasibility of sequential collection and infusion of peripheral blood stem cells (PBSCs) as hematopoietic support for non‐myeloablative dose intensive induction chemotherapy given every 21–28 days.

Methods

Twenty‐two children with Stage 4 neuroblastoma (≥1 year of age) received two cycles of high‐dose cyclophosphamide (4 g/m2), doxorubicin (75 mg/m2), and vincristine (2 mg/m2) followed by three cycles of interpatient dose escalating carboplatin (Dose Level 0 = 800 mg/m2; Dose Level 1 = 1,000 mg/m2), high‐dose cyclophosphamide (4 g/m2), and etoposide (600 mg/m2). PBSC were harvested following cycle 2, 3, and 4 in Cohort 1 and infused after each subsequent cycle. In Cohort 2, PBSC were harvested after cycle 2 and split into three aliquots for infusion. Dose limiting toxicity (DLT) and ability to administer cycles within 28 days was assessed.

Results

Sufficient PBSC (≥2 × 106 CD34 cells/kg per infusion) were collected from 17/21 eligible patients with minimal toxicity and no detectable neuroblastoma cells by immunocytology. Carboplatin at 1000 mg/m2 resulted in DLT of delayed platelet recovery >28 days in 4/8 patients. Despite de‐escalation to 800 mg/m2, platelet DLT occurred in 4/7 Cohort 1 and 3/7 Cohort 2 patients.

Conclusion

As defined in this protocol, doses of carboplatin were not tolerable with the PBSC dose administered. However, it was feasible to collect sufficient PBSC from small neuroblastoma patients to use as hematopoietic support with minimal risk of tumor contamination and toxicity. Pediatr Blood Cancer 2010;54:596–602. © 2009 Wiley‐Liss, Inc.
Inpatient use of laxatives during opioid administration in children with sickle cell disease
Authors: O'Brien Sarah H. , Fan Ling , Kelleher Kelly J.
Published: January 2010

Background

Constipation is a frequent adverse drug event seen with opioids, the first‐line therapy for sickle cell pain crises. Proactive use of laxatives and stool softeners is recommended when opioids are prescribed. Our objective was to generate national estimates of the inpatient use of laxatives during opioid administration in children with sickle cell disease (SCD) and identify associations between individual and hospital‐level factors and laxative prescription.

Procedure

We analyzed data from 29 children's hospitals in the Pediatric Health Information System, extracting patients 0–18 years of age with SCD hospitalized between 7/1/2007 and 6/30/2008. Our main outcome measure was the percentage of opioid‐receiving patients who also received a laxative or stool softener.

Results

Six thousand ninety‐three total SCD admissions received opioids. Two‐thirds (66%) of patients received at least one laxative, and 31% received more than one. The most commonly prescribed constipation medication was polyethylene glycol‐electrolyte solution (42.0%), followed by docusate (31.4%) and senna (13.6%). Logistic regression revealed that increasing age was associated with increased use of laxatives, as were length of stay >1 day (OR = 3.12), medical as compared to surgical admissions (OR = 4.16), and discharge diagnosis of constipation (OR = 18.6). Patients were somewhat less likely to receive laxatives in small and large volume hospitals as compared to medium hospitals.

Conclusions

A substantial number of hospitalized patients with SCD receiving opioids do not receive laxatives and there is unexpected variability in the use of these medications. Increased attention needs to be paid to constipation prophylaxis in patients with SCD, particularly in younger patients and post‐surgical patients. Pediatr Blood Cancer 2010;54:559–562. © 2009 Wiley‐Liss, Inc.
A prospective study of a long‐term follow‐up of an observation program for neuroblastoma detected by mass screening
Authors: Tanaka Mio , Kigasawa Hisato , Kato Keisuke , Ijiri Rieko , Nishihira Hirokazu , Aida Noriko , Ohama Youkatsu , Tanaka Yukichi
Published: January 2010

Background

A nationwide mass screening for neuroblastoma (NBL) in 6‐month‐old infants (MS6M) was performed in Japan from 1985 to 2003. Favorable biological features were identified for most of the detected tumors; consequently, we began an observation program for selected screened patients in 1993. Here, we report the clinicopathological findings and present status of patients enrolled in our observation program, with the goal of evaluating its usefulness.

Procedure

Between 1993 and 2003, 53 of 101 patients with NBL detected by MS6M were enrolled. The patients were divided into four groups according to changes in urinary VMA and HVA levels and tumor size.

Results

Urinary VMA and HVA levels decreased in 39 of 53 patients. In 17 of these 39 patients, the tumor became undetectable (Group A); in 22 patients the tumor was detectable (Group B). In seven patients, tumor marker levels varied, and tumor volume gradually increased (Group C). In six patients, tumor marker levels and tumor volume increased in the short term (Group D). One patient had multiple tumors (1M according to International Neuroblastoma Staging System). All tumors in Groups C and D, four tumors in Group B, and one tumor in the 1M patient were removed. No unfavorable biologic factors were noted in any excised tumor.

Conclusions

The observation program of the present study, one of the largest series for MS6M, confirmed that over 70% of patients who fulfilled the criteria could be observed without surgery. Pediatr Blood Cancer 2010;54:573–578. © 2009 Wiley‐Liss, Inc.
Resolving a genetic paradox throughout preimplantation genetic diagnosis for autosomal dominant severe congenital neutropenia
Authors: Malcov Mira , Reches Adi , Ben‐Yosef Dalit , Cohen Tania , Amit Ami , Dgany Orly , Tamary Hannah , Yaron Yuval
Published: January 2010

Objective

Severe congenital neutropenia is an inherited disease characterized by low peripheral blood neutrophils, amenable to bone marrow transplantation. Genetic analysis in the family here described detected a ELA2 splice‐site mutation in the affected child and also in his asymptomatic father. The parents requested preimplantation genetic diagnosis (PGD), coupled with HLA matching, to obtain a suitable bone marrow donor for the affected child.

Methods

A PGD protocol was developed, based on multiplex nested PCR for direct analysis of the ELA2 mutation, flanking polymorphic markers and HLA typing.

Results

The amplification efficiency of the mutation was > 90% in single leukocytes from the affected child but only 67% in the father. Analysis of single haploid sperm cells from the father demonstrated three different sperm‐cell populations: (1) sperm cells harboring the ELA2 mutation on the ‘affected’ haplotype, (2) sperm cells without the ELA2 mutation on the ‘normal’ haplotype, and (3) sperm cells without the ELA2 mutation on the ‘affected’ haplotype.

Conclusion

These data demonstrate that the ELA2 mutation in the father occurred de novo during his embryonic development, resulting in somatic as well as germ‐line mosaicism. This conclusion was also taken into consideration when PGD was performed. Copyright © 2010 John Wiley & Sons, Ltd.
Changes in US antidepressant and antipsychotic prescription patterns during a period of FDA actions
Authors: Pamer Carol A. , Hammad Tarek A. , Wu Yu‐te , Kaplan Sigal , Rochester George , Governale Laura , Mosholder Andrew D.
Published: January 2010

Purpose

To determine if paroxetine versus non‐paroxetine selective serotonin reuptake inhibitors (SSRIs) prescribing changed after the June 2003 FDA Paroxetine Public Health Advisory (PPHA) and if antidepressant and antipsychotic prescribing changed after the February 2004 FDA Advisory Committee Meeting (FDACM).

Methods

Ecologic analysis using estimates of patients dispensed antidepressants and antipsychotics, census data, and promotional spending data. Data sources were SDI: Vector One®, US Census, and IMS Health®. Measures were monthly use levels (number of patients dispensed antidepressants, antipsychotics, paroxetine, and non‐paroxetine SSRIs prescriptions by age group per population count). Percent changes pre‐ to post‐PPHA were used to assess changes in paroxetine versus non‐paroxetine SSRIs prescribing. Interrupted time series (ITS) analysis was performed to examine use level changes post‐FDACM by drug groups (all antidepressants and all antipsychotics).

Results

Post‐PPHA mean paroxetine use levels decreased for all age groups (range: 5.5–34.1%). Mean non‐paroxetine SSRIs use levels increased (range: 4.6–17.1%). Post‐PPHA changes were greatest for 6–12 and 13–17 year olds. Decreased mean antidepressant drug use levels from pre‐ to post‐FDACM were observed in all groups under 25 years old. A statistically significant decrease in the slopes from pre‐ to post‐FDACM was observed for persons aged 13–17 and 18–24 years. The difference between the forecasted mean use level and the observed mean use level (in 12‐month intervals) was statistically significant for all ages combined (−107.26; 95% CI: −166.32, −48.20) and 1–5 (−3.1; 95% CI: −4.62, −1.58), 6–12 (−36.02; 95% CI: −62.92, −9.12) and 25 years, and older groups (−83.17; 95% CI: −153.95, −12.39). For all age groups, decreases in the slopes of antipsychotic drugs use from pre‐ to post‐FDACM were observed, although these slope changes were not statistically significant. The difference between the forecasted mean antipsychotic drugs use level and the observed mean use level (in 12‐month intervals) was statistically significantly lower for all age groups.

Conclusions

Antidepressant use changed post‐PPHA and ‐FDACM, with a differential pattern by age. There was no evidence of increased antipsychotic use post‐FDACM. Ecologic data cannot determine if changes were due to depression not treated with medications or the prescribing of fewer antidepressants for other conditions. Published in 2009 by John Wiley & Sons, Ltd.
Potential bias caused by control selection in secondary data analysis: Nonaspirin nonsteroidal anti‐inflammatory drugs and hemorrhagic stroke
Authors: Choi Nam‐Kyong , Hahn Seokyung , Yoon Byung‐Woo , Park Byung‐Joo
Published: January 2010

Background

This study investigated the potential for bias introduction when selecting controls for secondary analysis of case‐control study data.

Methods

We used a data set previously collected for an acute brain bleeding analysis (ABBA) study, which was designed to investigate the risk of hemorrhagic stroke (HS) resulting from the use of phenylpropanolamine in Korea. Cases in that study had experienced an HS. Each HS case was matched with age‐ and gender‐based hospital and community controls. Information was obtained on drug exposures including nonaspirin nonsteroidal anti‐inflammatory drugs (NANSAIDs). Odds ratios (OR) for, and 95% confidence intervals (CI) of, experiencing an HS were calculated using conditional logistic regressions for each control group.

Results

A total of 940 patients were matched with 1880 controls. The OR of HS occurring in NANSAID users was 1.18 (95%CI, 0.80–1.73) in community controls and 0.67 (95%CI, 0.45–0.98) in hospital controls. The majority of the hospital controls were selected from patients who had visited neurology, neurosurgery, or orthopedic departments.

Conclusion

The difference between OR values estimated from hospital and community controls could be the result of selection bias. The study data were originally obtained for a different purpose than this study, and NANSAID use was not considered when the hospital controls were selected. When performing secondary analyses, extra care is needed to note whether the results are consistent across control groups and whether there are indications of bias related to the selection of those controls. Copyright © 2010 John Wiley & Sons, Ltd.
Application of free‐flow IEF to identify protein candidates changing under microgravity conditions
Authors: Pietsch Jessica , Kussian Richard , Sickmann Albert , Bauer Johann , Weber Gerhard , Nissum Mikkel , Westphal Kriss , Egli Marcel , Grosse Jirka , Schönberger Johann , Wildgruber Robert , Infanger Manfred , Grimm Daniela
Published: January 2010

Using antibody‐related methods, we recently found that human thyroid cells express various proteins differently depending on whether they are cultured under normal gravity (1g) or simulated microgravity (s‐μg). In this study, we performed proteome analysis in order to identify more gravity‐sensitive thyroid proteins. Cells cultured under 1g or s‐μg conditions were sonicated. Proteins released into the supernatant and those remaining in the cell fragments were fractionated by free‐flow IEF. The fractions obtained were further separated by SDS‐gel electrophoresis. Selected gel pieces were excised and their proteins were determined by MS. A total of 235 different proteins were found. Out of 235 proteins, 37 appeared to be first identifications in human thyroid cells. Comparing SDS gel lanes of equally numbered free‐flow IEF fractions revealed similar patterns with a number of identical bands if proteins of a distinct cell line had been applied, irrespective of whether the cells had been cultured under 1g or s‐μg. Most of the identical band pairs contained identical proteins. However, the concentrations of some types of proteins were different within the two pieces of gel. Proteins that concentrated differently in such pieces of gel are considered as candidates for further investigations of gravitational sensitivity.
Unrestrictive identification of non‐phosphorylation PTMs in yeast kinases by MS and PTMap
Authors: Zhang Kai , Chen Yue , Zhang Zhihong , Tao Shengce , Zhu Heng , Zhao Yingming
Published: January 2010

A few protein PTMs, such as phosphorylation and ubiquitination, are known to be critical in regulation of protein kinase activities. However, the roles of other PTMs have not been extensively studied in kinases. Development of a comprehensive description of all types of PTMs and discovering novel in vivo PTMs in low abundance represent major analytical challenges. Toward this goal, we have developed a strategy for systematic and accurate identification of the full‐spectrum of PTMs in yeast protein kinases. Our strategy involves isolation of GST‐fused kinase proteins, MS analysis, and unrestrictive PTM identification by PTMap algorithm. Among the 30 purified yeast kinases, we identified 27 different types of PTMs, and 53 PTM sites, among which are 13 novel mass shifts that have not been previously reported, likely representing novel PTMs. These results represent a significant expansion of our current understanding of PTMs in kinases and suggest highly complex regulation of kinase function.
Global phosphoproteomic effects of natural tyrosine kinase inhibitor, genistein, on signaling pathways
Authors: Yan Guang‐Rong , Xiao Chuan‐Le , He Gui‐Wei , Yin Xing‐Feng , Chen Nan‐Peng , Cao Ya , He Qing‐Yu
Published: January 2010

Genistein is a natural protein tyrosine kinase inhibitor that exerts anti‐cancer effect by inducing G2/M arrest and apoptosis. However, the phosphotyrosine signaling pathways mediated by genistein are largely unknown. In this study, we combined tyrosine phosphoprotein enrichment with MS‐based quantitative proteomics technology to globally identify genistein‐regulated tyrosine phosphoproteins aiming to depict genistein‐inhibited phosphotyrosine cascades. Our experiments resulted in the identification of 213 phosphotyrosine sites on 181 genistein‐regulated proteins. Many identified phosphoproteins, including nine protein kinases, eight receptors, five protein phosphatases, seven transcriptical regulators and four signal adaptors, were novel inhibitory effectors with no previously known function in the anti‐cancer mechanism of genistein. Functional analysis suggested that genistein‐regulated protein tyrosine phosphorylation mainly by inhibiting the activity of tyrosine kinase EGFR, PDGFR, insulin receptor, Abl, Fgr, Itk, Fyn and Src. Core signaling molecules inhibited by genistein can be functionally categorized into the canonial Receptor‐MAPK or Receptor‐PI3K/AKT cascades. The method used here may be suitable for the identification of inhibitory effectors and tyrosine kinases regulated by anti‐cancer drugs.
Functionalized surfactant mediated reactions of carboxylate, phosphate and sulphonate esters
Authors: Tiwari Shuchi , Ghosh Kallol K. , Marek Jan , Kuca Kamil
Published: January 2010

Nucleophilic reactivity of some functionalized surfactants, i.e. quaternary pyridinium aldoximes towards the hydrolysis of p‐nitrophenyl acetate (PNPA), p‐nitrophenyl benzoate (PNPB), p‐nitrophenyldiphenyl phosphate (PNPDPP) and p‐nitrophenyl p‐toluene sulphonate (PNPTS) has been studied at pH 7.1 and 27 °C. Addition of functionalized surfactant to reaction medium causes progressive increase in the rate of hydrolysis and reaches a maximum and then decreases due to further addition of surfactant. An increase in the alkyl chain length of functionalized surfactants resulted in an increase in the first‐order rate constant. The apparent pKa and CMC of functionalized surfactants have also been determined by spectrophotometric and conductometric methods, respectively. Copyright © 2009 John Wiley & Sons, Ltd.
How to observe the oxidation of magnesia‐supported Pd clusters by scanning tunnelling microscopy
Authors: Walter Michael , Moseler Michael
Published: January 2010

The structure of adsorbed bare and oxidised Pd9 clusters on a MgO(001) bilayer supported by an Ag(001) surface are studied by density functional theory (DFT). Results for the bare cluster are compared with corresponding calculations of Pd9 on a free‐standing MgO(001) trilayer – a system that already reproduces the adsorption properties of thick MgO films. A 3D double trigonal antiprism is compared to a 2D fragment of a Pd(111) plane. In contrast to the findings for gold clusters, the Pd9 3D ground state on a thick MgO film is still energetically favourable on a thin metal supported MgO film – despite the substantial charge transfer from the metal support to the 2D cluster. Simulated scanning tunnelling microscopy images predict that the oxide formation should be easily detectable for negative bias voltages, since the highest occupied molecular orbitals of both the pristine as well as the oxidised clusters possess a strong Pd(d) contribution localised on the Pd atoms. At positive bias, the nodal structure of delocalised unoccupied orbitals sometimes masks the nuclear positions.

magnified image

Simulated STM images for (a,d) Pd9@MgO(001)@Ag(001), (b,e) Pd9O2@MgO(001)@Ag(001) and (c,f) Pd9O4@MgO (001)@Ag(001).
Fragmentation of plumeran indole alkaloids from Aspidosperma spruceanum by electrospray ionization tandem mass spectrometry
Authors: Aguiar Gabriela P. , Wakabayashi Kamila A. L. , Luz Guilherme F. , Oliveira Vilma B. , Mathias Leda , Vieira Ivo J. C. , Braz‐Filho Raimundo , Crotti Antonio E. M.
Published: January 2010

The fragmentation of six plumeran indole alkaloids (PIAs) previously isolated from Aspidosperma spruceanum has been investigated by electrospray ionization tandem mass spectrometry (ESI‐MS/MS) in the positive ion mode. The fragmentation pathways have been established on the basis of MS/MS experiments using fragment ions generated in‐source and deuterium‐labeled alkaloids as precursor ions and on the basis of accurate mass measurements. Our results demonstrated that the fragmentation routes observed for the protonated PIAs are essentially derived from a pericyclic reaction and from the opening of rings D and E, followed by 1,4‐hydrogen rearrangements. Product ions resulting from radical eliminations were also observed, contrary to the ‘even‐electron rule’. Our data reveals that some product ions from protonated PIAs provide crucial information for the characterization of the acyl substituent at N‐1, the methoxyl and hydroxyl groups at the aromatic moiety, and give evidence of an ether bridge between C‐18 and C‐21. The data reported here were used for the dereplication of these compounds in a stem bark methanolic extract of Aspidosperma spruceanum. Copyright © 2010 John Wiley & Sons, Ltd.
A microfluidic reactor for rapid, low‐pressure proteolysis with on‐chip electrospray ionization
Authors: Liuni Peter , Rob Tamanna , Wilson Derek J.
Published: January 2010

A microfluidic reactor that enables rapid digestion of proteins prior to on‐line analysis by electrospray ionization mass spectrometry (ESI‐MS) is introduced. The device incorporates a wide (1.5 cm), shallow (10 µm) reactor ‘well’ that is functionalized with pepsin‐agarose, a design that facilitates low‐pressure operation and high clogging resistance. Electrospray ionization is carried out directly from a short metal capillary integrated into the chip outlet. Fabrication, involving laser ablation of polymethyl methacrylate (PMMA), is exceedingly straightforward and inexpensive. High sequence coverage spectra of myoglobin (Mb), ubiquitin (Ub) and bovine serum albumin (BSA) digests were obtained after <4 s of residence time in the reactor. Stress testing showed little loss of performance over ∼2 h continuous use at high flow rates (30 µL/min). The device provides a convenient platform for a range of applications in proteomics and structural biology, i.e. to enable high‐throughput workflows or to limit back‐exchange in spatially resolved hydrogen/deuterium exchange (HDX) experiments. Copyright © 2010 John Wiley & Sons, Ltd.
Investigation of collision‐induced dissociations involving odd‐electron ion formation under positive electrospray ionization conditions using accurate mass
Authors: Xu Guifen , Huang Tom , Zhang Jennifer , Huang Jennifer K. , Carlson Timothy , Miao Shichang
Published: January 2010

Collision induced dissociation (CID) has been extensively used for structure elucidation. CID in the electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) modes has been found to generate mostly even‐electron fragment ions while it has been occasionally reported to form odd‐electron free radical ions. However, the structural requirements and the fragmentation mechanisms for free‐radical CIDs have not been well characterized in the literature. For this purpose, we studied a series of aromatic and non‐aromatic compounds such as sulfonamides, N‐aryl amides, tert‐butyl‐substituted aromatic compounds, aryl alkyl ethers, and O‐alkyl aryl oximes using the LTQ™ and LTQ Orbitrap™ linear ion trap mass spectrometers. The accurate measurement of the fragment ion masses established the unambiguous assignment of the fragment structures resulting from the test compounds. Our results showed that free radical fragmentation is structure dependent and is to a large extent correlated with the neighboring groups in the structures that stabilize the newly formed free radical ions. Copyright © 2010 John Wiley & Sons, Ltd.
Determination and imaging of metabolites from Vitis vinifera leaves by laser desorption/ionisation time‐of‐flight mass spectrometry
Authors: Hamm Gregory , Carré Vincent , Poutaraud Anne , Maunit Benoît , Frache Gilles , Merdinoglu Didier , Muller Jean‐François
Published: January 2010

Analysis of grapevine phytoalexins at the surface of Vitis vinifera leaves has been achieved by laser desorption/ionisation time‐of‐flight mass spectrometry (LDI‐ToFMS) without matrix deposition. This simple and rapid sampling method was successfully applied to map small organic compounds at the surface of grapevine leaves. It was also demonstrated that the laser wavelength is a highly critical parameter. Both 266 and 337 nm laser wavelengths were used but the 266 nm wavelength gave increased spatial resolution and better sensitivity for the detection of the targeted metabolites (resveratrol and linked stilbene compounds). Mass spectrometry imaging of grapevine Cabernet Sauvignon leaves revealed specific locations with respect to Plasmopara viticola pathogen infection or light illumination. Copyright © 2010 John Wiley & Sons, Ltd.