bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of Shp2 tyrosine phosphatase is implicated in leukemogenesis in adult human leukemia
Authors: Xu Rongzhen , Yu Yingzi , Zheng Shu , Zhao Xiaoying , Dong Qinghua , He Zhiwen , Liang Yun , Lu Qinghua , Fang Yongmin , Gan Xiaoxian , Xu Xiaohua , Zhang Suzhan , Dong Qi , Zhang Xiaohong , Feng Gen-Sheng
Published: July 2005

Shp2 tyrosine phosphatase plays a critical role in hematopoiesis, and dominant active mutations have been detected in the human gene PTPN11, encoding Shp2, in child leukemia patients. We report here that although no such mutations were detected in 44 adult leukemia patients screened, Shp2 expression levels were significantly elevated in primary leukemia cells and leukemia cell lines, as compared with normal hematopoietic progenitor cells. The Shp2 protein amounts correlated well with the hyperproliferative capacity but were inversely associated with the differentiation degree of leukemia cells. Suppression of Shp2 expression induced apoptosis and inhibition of leukemic cell clonogenic growth. Notably, the majority of Shp2 was preferentially localized to the plasma membrane and was constitutively phosphorylated on tyrosine in leukemia cells, and also in normal hematopoietic cells following mitogenic stimulation. Based on these results, we propose that aberrantly increased expression of Shp2 may contribute, collaboratively with other factors, to leukemogenesis.
Expression of the inhibitory receptor ILT3 on dendritic cells is dispensable for induction of CD4+Foxp3+ regulatory T cells by 1,25-dihydroxyvitamin D3
Authors: Penna Giuseppe , Roncari Andrea , Amuchastegui Susana , Daniel Kenn C. , Berti Emilio , Colonna Marco , Adorini Luciano
Published: July 2005

1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a secosteroid hormone that renders dendritic cells (DCs) tolerogenic, favoring the induction of regulatory T cells. Induction of DCs with tolerogenic properties by 1,25(OH)2D3 is associated with increased selective expression of immunoglobulin-like transcript 3 (ILT3), suggesting its involvement in the immunoregulatory properties of this hormone. Here we show an in vivo correlate of the increased ILT3 expression on DCs in healing psoriatic lesions following topical treatment with the 1,25(OH)2D3 analog calcipotriol. Analysis of DC subsets reveals a differential regulation of ILT3 expression by 1,25(OH)2D3, with a marked up-regulation in myeloid DCs but no effect on its expression by plasmacytoid DCs. A regulatory role for ILT3 expressed on DCs is indicated by the increased interferon-γ (IFN-γ) secretion promoted by anti-ILT3 addition to cultures of DCs and T cells, but this effect is blunted in 1,25(OH)2D3-treated DCs, suggesting ILT3-independent mechanisms able to regulate T-cell activation. Although ILT3 expression by DCs is required for induction of regulatory T cells, DC pretreatment with 1,25(OH)2D3 leads to induction of CD4+Foxp3+ cells with suppressive activity irrespective of the presence of neutralizing anti-ILT3 monoclonal antibody (mAb), indicating that ILT3 expression is dispensable for the capacity of 1,25(OH)2D3-treated DCs to induce regulatory T cells.
Genetic Services for Familial Cancer Patients: A Follow-Up Survey of National Cancer Institute Cancer Centers
Authors: Epplein Meira , Koon Ksenia P. , Ramsey Scott D. , Potter John D.
Published: July 2005

Purpose

Anecdotal reports suggest that the volume of services offered to individuals concerned with hereditary cancer risk has increased substantially in recent years. As a follow-up to our 1993 survey, we sought to determine how the scope and volume of genetic services has changed between 1993 and 2002.

Methods

We surveyed the 61 National Cancer Institute–designated cancer centers in operation in 2002 using an updated version of the questionnaire from 1993. Analysis included frequencies and summary statistics.

Results

The majority of cancer centers responding (46 of 56 centers; 82.1%) provided some genetic services for evaluation of familial cancer, which is a higher proportion than in 1993 (50%; P < .01). Almost all centers (42 of 46 centers; 91.3%) provided services not only to cancer patients and their families, but also to individuals concerned with risk, which is a change (P = .01) from 1993, when 64.7% of centers offered such services. In addition, increases have been found for most other measures of services rendered for familial genetic services.

Conclusion

As public awareness of cancer susceptibility genes has grown markedly in recent years, the demand has also grown for genetic services to assess familial cancer risk. Major deleterious genetic mutations are rare, and much of the current research in genetic variation focuses on higher prevalence variants that carry lower risks. This may suggest that testing for mutations will move from genetics clinics to primary care and specialty practices. Thus, it is unclear whether the scope and volume of cancer center genetics services will continue to grow as rapidly as they have over the last decade.
Immunohistochemistry Identifies Carriers of Mismatch Repair Gene Defects Causing Hereditary Nonpolyposis Colorectal Cancer
Authors: Stormorken Astrid T. , Bowitz-Lothe Inger Marie , Norèn Tove , Kure Elin , Aase Steinar , Wijnen Juul , Apold Jaran , Heimdal Ketil , Møller Pål
Published: July 2005

Purpose

Hereditary nonpolyposis colorectal cancer (HNPCC) may be caused by mutations in mismatch repair (MMR) genes. The aim of this study was to validate immunohistochemistry and family history as prescreening tools to predict germline mutations in MLH1, MSH2, and MSH6.

Patients and Methods

Pedigrees from 250 families were extended, cancer diagnoses were verified, and families were classified according to the Amsterdam and the Bethesda criteria. Tumor specimens were examined with immunohistochemistry for the presence of MLH1, MSH2, and MSH6 proteins. Mutation analyses were performed in blood samples from the same patients.

Results

Blood samples from affected index persons in 181 families and tumor specimens from 127 of the affected index persons were obtained. Thirty tumors lacked one or more gene products. Sensitivity of immunohistochemistry to detect mutation carriers was 100%, specificity was 82%, and positive predictive value was 85%. Sensitivities, specificities, and positive predictive values for the Amsterdam criteria were 82%, 8%, and 45%, respectively, and for the Bethesda criteria were 100%, 0%, and 48%, respectively. Distribution of mutations was MLH1 = 4, MSH2 = 11, and MSH6 = 4.

Conclusion

Wide clinical criteria to select HNPCC kindreds, followed by immunohistochemistry of tumor material from one affected person in each family, had high sensitivity and specificity to predict MMR mutations.
Significant Effect of Capecitabine on the Pharmacokinetics and Pharmacodynamics of Warfarin in Patients With Cancer
Authors: Camidge Ross , Reigner Bruno , Cassidy Jim , Grange Susan , Abt Markus , Weidekamm Erhard , Jodrell Duncan
Published: July 2005

Purpose

Clinical cases of capecitabine and other fluorouracil-based chemotherapies potentiating the effects of coumarin derivatives have been reported. This study assessed the influence of capecitabine on the pharmacokinetics (PK) and pharmacodynamics (PD) of warfarin.

Patients and Methods

Four patients with advanced/metastatic cancer completed the study, receiving a single oral dose of 20 mg warfarin before the start of standard capecitabine treatment (day 1), and again during the third cycle of capecitabine (day 61). PK parameters of warfarin and capecitabine and PD parameters of warfarin were assessed on days 1 and 61.

Results

During capecitabine treatment, the area under the plasma concentration time curve from 0 to infinity (AUC0-∞) of S-warfarin increased by 57% (90% CI, 32% to 88%) with a 51% prolongation of the elimination half-life (t1/2; 90% CI, 32% to 74%). Exposure to R-warfarin was not significantly affected. Plasma concentrations of capecitabine and its metabolites were not influenced by warfarin. During capecitabine treatment, the effect of warfarin on the baseline corrected AUC of the International Normalized Ratio (INR) increased by 2.8 times (90% CI, 1.33 to 5.70), with the maximum observed INR value almost doubling. Because of the administration of vitamin K to some patients with elevated INRs, these figures are likely to underestimate the true PD effect. Mean baseline factor VII levels dropped while on capecitabine therapy, potentially contributing to the observed PD interaction, though this effect did not reach statistical significance.

Conclusion

There is a significant pharmacokinetic interaction between capecitabine and S-warfarin, resulting in exaggerated anticoagulant activity. Patients receiving warfarin anticoagulant therapy concomitantly with capecitabine should have their INR closely monitored and warfarin doses adjusted accordingly.
Sentinel Lymphadenectomy Does Not Increase the Incidence of In-Transit Metastases in Primary Melanoma
Authors: Kang John C. , Wanek Leslie A. , Essner Richard , Faries Mark B. , Foshag Leland J. , Morton Donald L.
Published: July 2005

Purpose

Recent reports by European investigators suggest that sentinel lymphadenectomy (SLND), a mainstay of melanoma diagnosis and treatment planning, increases the risk of in-transit metastasis (ITM) and should be abandoned. This study compared the incidence of ITM after wide local excision (WLE), WLE plus SLND (SLND), or WLE plus elective lymphadenectomy (ELND) for primary melanoma.

Patients and Methods

Review of our prospective database identified 4,412 patients who underwent WLE (n = 2,771), SLND (n = 1,016), or ELND (n = 625) for stage I/II melanoma (1971 through 2002). The incidence of ITM overall and as a first recurrence was examined before and after computerized prognostic matching of treatment groups. Intergroup statistical comparisons used χ2 analysis and log-rank test.

Results

The incidence of ITM increased with Breslow depth, Clark level, and T stage. Although overall incidence of ITM was significantly higher (P = .0008) after ELND (6.56%) versus WLE (3.36%) or SLND (3.64%), the ELND group had higher risk primaries. Treatment groups matched by T stage (1,875 patients; 625 per group) or by age, sex, Breslow depth, and primary location (1,680 patients; 560 per group), showed no significant differences in ITM overall or as a first recurrence.

Conclusion

There is no relationship between SLND and ITM. Recent reports to the contrary reflect analysis of significantly smaller cohorts not matched for confounding variables such as T stage. The phase III Multicenter Selective Lymphadenectomy Trial will definitively settle the issue; until then, use of SLND, the most accurate staging procedure for early-stage melanoma, should continue.
The Interaction of a New Motor Skill and an Old One: H-Reflex Conditioning and Locomotion in Rats
Authors: Chen Yi , Chen Xiang Yang , Jakeman Lyn B. , Schalk Gerwin , Stokes Bradford T. , Wolpaw Jonathan R.
Published: July 2005

New and old motor skills can interfere with each other or interact in other ways. Because each skill entails a distributed pattern of activity-dependent plasticity, investigation of their interactions is facilitated by simple models. In a well characterized model of simple learning, rats and monkeys gradually change the size of the H-reflex, the electrical analog of the spinal stretch reflex. This study evaluates in normal rats the interactions of this new skill of H-reflex conditioning with the old well established skill of overground locomotion.

In rats in which the soleus H-reflex elicited in the conditioning protocol (i.e., the conditioning H-reflex) had been decreased by down-conditioning, the H-reflexes elicited during the stance and swing phases of locomotion (i.e., the locomotor H-reflexes) were also smaller. Similarly, in rats in which the conditioning H-reflex had been increased by up-conditioning, the locomotor H-reflexes were also larger.

Soleus H-reflex conditioning did not affect the duration, length, or right/left symmetry of the step cycle. However, the conditioned change in the stance H-reflex was positively correlated with change in the amplitude of the soleus locomotor burst, and the correlation was consistent with current estimates of the contribution of primary afferent input to the burst.

Although H-reflex conditioning and locomotion did not interfere with each other, H-reflex conditioning did affect how locomotion was produced: it changed soleus burst amplitude and may have induced compensatory changes in the activity of other muscles. These results illustrate and clarify the subtlety and complexity of skill interactions. They also suggest that H-reflex conditioning might be used to improve the abnormal locomotion produced by spinal cord injury or other disorders of supraspinal control.
Swelling behavior of semi‐interpenetrating polymer network hydrogels composed of poly(vinyl alcohol) and poly(acrylamide‐co‐sodium methacrylate)
Authors: Mohan Y. Murali , Murthy P. S. Keshava , Sreeramulu J. , Raju K. Mohana
Published: July 2005

Interpenetrating polymer network (IPN) hydrogels based on poly(vinyl alcohol) (PVA) and poly(acrylamide‐co‐sodium methacrylate) poly(AAm‐co‐SMA) were prepared by the semi IPN method. These IPN hydrogels were prepared by polymerizing aqueous solution of acrylamide and sodium methacrylate, using ammonium persulphate/N,N,N1,N1‐tetramethylethylenediamine (APS/TMEDA) initiating system and N,N1‐methylene‐bisacrylamide (MBA) as a crosslinker in the presence of a host polymer, poly(vinyl alcohol). The influence of reaction conditions, such as the concentration of PVA, sodium methacrylate, crosslinker, initiator, and reaction temperature, on the swelling behavior of these IPNs was investigated in detail. The results showed that the IPN hydrogels exhibited different swelling behavior as the reaction conditions varied. To verify the structural difference in the IPN hydrogels, scanning electron microscopy (SEM) was used to identify the morphological changes in the IPN as the concentration of crosslinker varied. In addition to MBA, two other crosslinkers were also employed in the preparation of IPNs to illustrate the difference in their swelling phenomena. The swelling kinetics, equilibrium water content, and water transport mechanism of all the IPN hydrogels were investigated. IPN hydrogels being ionic in nature, the swelling behavior was significantly affected by environmental conditions, such as temperature, ionic strength, and pH of the swelling medium. Further, their swelling behavior was also examined in different physiological bio‐fluids. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 302–314, 2005
A new composite from cellulose industrial waste and elastomeric polyurethane
Authors: Silva M. C. , Silva G. G.
Published: July 2005

Cellulose fiber waste from the white cellulose pulp purification process produced by the company Nipo Cellulose‐Brazil (CENIBRA) was used in the preparation of composites with polyurethane. An elastomeric polyurethane based on polyether poly(tetramethylene glycol) and 4,4‐diphenylmethane diisocyanate was used as polymeric matrix. Structural, thermal, and morphological characterization of the composites was carried out by infrared spectroscopy, thermogravimetry, differential scanning calorimetry, and scanning electron microscopy. The results indicate that interfacial interaction between the cellulose fiber residue and the polyurethane matrix occurs and that cellulose waste is a promising reinforcement for polyurethane composites. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 336–340, 2005
Synthesis and characterization of side‐chain liquid‐crystalline elastomers containing cholesterol
Authors: He Xiao‐Zhi , Xiao Ling‐Jiu , Zhang Bao‐Yan , Xiao Wen‐Qiang
Published: July 2005

A series of new smectic and cholesteric liquid‐crystalline elastomers were prepared by graft polymerization of mesogenic monomer with the chiral and nonmesogenic crosslinking agent using polymethylhydrosiloxane as backbone. The chemical structures of the monomers and polymers obtained were confirmed by Fourier transform infrared and proton nuclear magnetic resonance spectra. The mesomorphic properties were investigated by differential scanning calorimetry, polarizing optical microscopy, and X‐ray diffraction measurements. M1 showed cholesteric phase during the heating and the cooling cycle. Polymer P1, elastomers P2 and P3 exhibited smectic phase, elastomers P4P6 showed chiral smectic C phase, P7 showed cholesteric phase, and P8 displayed stress‐induced birefringence. The elastomers containing less than 15 mol % M2 displayed elasticity and reversible phase transition with wide mesophase temperature ranges. Experimental results demonstrated that the glass transition temperatures, the isotropization temperatures, and the mesophase temperature ranges decreased with increasing content of the crosslinking unit. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 383–390, 2005
Anatomy that must be taught to a medical undergraduate: An interview‐based survey in an Indian medical school
Authors: Nayak Satheesha , Ramnarayan K. , Somayaji S.N.
Published: July 2005

Confusion still exists about the anatomy to be taught to the medical undergraduate. We did an interview‐based survey at the Melaka Manipal Medical College in Manipal, India, to try to evaluate the quantum of anatomy that should be taught to the medical undergraduate. The results suggest that excluding trivia and making anatomy more clinically oriented would be advantageous. A hybrid approach to anatomy including both problem‐based learning and discipline‐based curricula would be a better option than the regional or systemic approaches. Anat Rec (Part B: New Anat) 285B:16–18, 2005. © 2005 Wiley‐Liss, Inc.
DNA methylation in mammalian development and disease
Authors: Dean Wendy , Lucifero Diana , Santos Fátima
Published: July 2005

Epigenetic modification of the cytosine base of DNA by its methylation introduced the possibility that beyond the inherent information contained within the nucleotide sequence there was an additional layer of information added to the underlying genetic code. DNA methylation has been implicated in a wide range of biological functions, including an essential developmental role in the reprogramming of germ cells and early embryos, the repression of endogenous retrotransposons, and a generalized role in gene expression. Special functions of DNA methylation include the marking of one of the parental alleles of many imprinted genes, a group of genes essential for growth and development in mammals with a unique parent‐of‐origin expression pattern, a role in stabilizing X‐chromosome inactivation, and centromere function. In this regard, it is not surprising that errors in establishing or maintaining patterns of methylation are associated with a diverse group of human diseases and syndromes. Birth Defects Research (Part C) 75:98–111, 2005. © Wiley‐Liss, Inc.
Epigenetic deregulation of genomic imprinting in human disorders and following assisted reproduction
Authors: Arnaud Philippe , Feil Robert
Published: July 2005

Imprinted genes play important roles in the regulation of growth and development, and several have been shown to influence behavior. Their allele‐specific expression depends on inheritance from either the mother or the father, and is regulated by “imprinting control regions” (ICRs). ICRs are controlled by DNA methylation, which is present on one of the two parental alleles only. These allelic methylation marks are established in either the female or the male germline, following the erasure of preexisting DNA methylation in the primordial germ cells. After fertilization, the allelic DNA methylation at ICRs is maintained in all somatic cells of the developing embryo. This epigenetic “life cycle” of imprinting (germline erasure, germline establishment, and somatic maintenance) can be disrupted in several human diseases, including Beckwith‐Wiedemann syndrome (BWS), Prader‐Willi syndrome (PWS), Angelman syndrome and Hydatidiform mole. In the neurodevelopmental Rett syndrome, the way the ICR mediates imprinted expression is perturbed. Recent studies indicate that assisted reproduction technologies (ART) can sometimes affect the epigenetic cycle of imprinting as well, and that this gives rise to imprinting disease syndromes. This finding warrants careful monitoring of the epigenetic effects, and absolute risks, of currently used and novel reproduction technologies. Birth Defects Research (Part C) 75: 81–97, 2005. © 2005 Wiley‐Liss, Inc.
Mechanisms and consequences of paternally‐transmitted chromosomal abnormalities
Authors: Marchetti Francesco , Wyrobek Andrew J.
Published: July 2005

Paternally‐transmitted chromosomal damage has been associated with pregnancy loss, developmental and morphological defects, infant mortality, infertility, and genetic diseases in the offspring, including cancer. There is epidemiological evidence linking paternal exposure to occupational or environmental agents with an increased risk of abnormal reproductive outcomes. There is also a large body of literature on germ cell mutagenesis in rodents showing that treatment of male germ cells with mutagens has dramatic consequences on reproduction, producing effects such as those observed in human epidemiological studies. However, we know very little about the etiology, transmission, and early embryonic consequences of paternally‐derived chromosomal abnormalities. The available evidence suggests that: 1) there are distinct patterns of germ cell–stage differences in the sensitivity of induction of transmissible genetic damage, with male postmeiotic cells being the most sensitive; 2) cytogenetic abnormalities at first metaphase after fertilization are critical intermediates between paternal exposure and abnormal reproductive outcomes; and 3) there are maternal susceptibility factors that may have profound effects on the amount of sperm DNA damage that is converted into chromosomal aberrations in the zygote and that directly affect the risk for abnormal reproductive outcomes. Birth Defects Research (Part C) 75:112–129, 2005. © 2005 Wiley‐Liss, Inc.
Randomized clinical trial of the anabolic effect of hypocaloric parenteral nutrition after abdominal surgery
Authors: Schricker T , Wykes L , Eberhart L , Carli F , Meterissian S
Published: July 2005

Background

The observed failure of hypocaloric nutrition to establish an anabolic state after surgery may reflect inadequate control for the type and quality of analgesia in the studies performed. This study was designed to test the hypothesis that hypocaloric nutrition induces anabolism in patients who receive effective segmental pain relief using perioperative epidural analgesia.

Methods

Sixteen patients who underwent colorectal surgery and received epidural analgesia were randomly assigned to receive intravenous glucose either without (glucose only) or with amino acids (nutrition). Feeding was administered over 48 h from surgical skin incision until the second day after operation. Glucose provided 50 per cent of the patient's resting energy expenditure (REE). Amino acids were infused at rates that provided 20 per cent of REE. Leucine rate of appearance (Ra), leucine oxidation and non-oxidative leucine disposal (NOLD) were assessed by measuring l-[1-13C]leucine kinetics. A positive leucine balance, that is the difference between NOLD and leucine Ra, indicated anabolism.

Results

After surgery, leucine Ra in the nutrition group was lower than that in the glucose only group (mean(s.d.) 88(25) versus 131(22) µmol per kg per h). The leucine balance remained negative in the glucose only group, whereas it became positive in the nutrition group (mean(s.d.) −24(3) versus 38(12) µmol per kg per h; P < 0·001).

Conclusion

Patients who receive hypocaloric parenteral nutrition can be rendered anabolic after colorectal surgery in the presence of epidural analgesia.
Randomized clinical trial of the effect of a saline-linked radiofrequency coagulator on blood loss during hepatic resection
Authors: Arita J , Hasegawa K , Kokudo N , Sano K , Sugawara Y , Makuuchi M
Published: July 2005

Background

Use of a saline-linked radiofrequency coagulator (dissecting sealer) has been suggested to reduce blood loss during hepatic resection. A randomized clinical trial was conducted to assess the effects of using the device on the amount of blood loss.

Methods

Patients scheduled to undergo hepatic resection were randomly assigned to either use of the dissecting sealer or the clamp crushing method. The primary outcome measure was blood loss during liver parenchymal division. Multivariate analysis was also performed.

Results

Ninety-four consecutive patients underwent hepatic resection and 40 patients were assigned to each group. There were no significant differences between the dissecting sealer and clamp crushing groups in blood loss during liver parenchymal division (median 373 versus 535 ml; P = 0·252) or total intraoperative blood loss (665 versus 733 ml; P = 0·450). Multivariate analysis revealed that use of the dissecting sealer offered no protection against blood loss compared with the clamp crushing method (odds ratio 1·17 (95 per cent confidence interval 0·39 to 3·53); P = 0·777), whereas number of resections, thoracotomy and type of resection had a significant effect.

Conclusion

Use of a dissecting sealer offered no substantial benefit over the clamp crushing method in reducing blood loss during hepatic resection.
Therapeutic cell fusion
Authors: Willenbring H
Published: July 2005

This article continues the Journal's 2005 series of leaders highlighting areas where laboratory science meets clinical practice. In it Dr Holger Willenbring of the Oregon Stem Cell Center discusses the promise of therapeutic cell fusion and the difficulties that remain in bringing this technique into clinical practice.
Cost-effectiveness of endovascular abdominal aortic aneurysm repair
Authors: Michaels J A , Drury D , Thomas S M
Published: July 2005

Background

The rapid introduction of endovascular abdominal aortic aneurysm repair (EVAR) has considerable implications for the management of abdominal aortic aneurysm (AAA). This study was undertaken to determine an optimal strategy for the use of EVAR based on the best currently available evidence.

Methods

Economic modelling and probabilistic sensitivity analysis considered reference cases representing a fit 70-year-old with a 5·5-cm diameter AAA (RC1) and an 80-year-old with a 6·5-cm AAA unfit for open surgery (RC2). Results were assessed as incremental cost-effectiveness ratio (ICER) compared with open repair (RC1) or conservative management (RC2).

Results

In RC1 EVAR produced a gain of 0·10 quality-adjusted life years (QALYs) for an estimated cost of £11 449, giving an ICER of £110 000 per QALY. EVAR consistently had an ICER above £30 000 per QALY over a range of sensitivity analyses and alternative scenarios. In RC2 EVAR produced an estimated benefit of 1·64 QALYs for an incremental cost of £14 077 giving an incremental cost per QALY of £8579.

Conclusion

It is unlikely that EVAR for fit patients suitable for open repair is within the commonly accepted range of cost-effectiveness for a new technology. For those unfit for conventional open repair it is likely to be a cost-effective alternative to non-operative management. Sensitivity analysis suggests that research efforts should concentrate on determining accurate rates for late complications and reintervention, particularly in patients with high operative risks.
Randomized clinical trial of mechanical bowel preparation versus no preparation before elective left-sided colorectal surgery (Br J Surg 2004; 92: 409-414)
Authors: Goldstone A R , Kennedy N , Metcalfe M
Published: July 2005

The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses can be sent electronically via the BJS website (www.bjs.co.uk) or by post. All letters will be reviewed and, if approved, appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length. Letters submitted by post should be typed on A4-sized paper in double spacing and should be accompanied by a disk.
A rapid and simple HPLC‐UV method for the determination of inhibition characteristics of farnesyl transferase inhibitors
Authors: Appels Natalie M. G. M. , Tung Kien‐On , Rosing Hilde , Schellens Jan H. M. , Beijnen Jos H.
Published: July 2005

Ras proteins play an important role in the development of cancer. Farnesyl transferase inhibitors (FTIs) block the first obligatory post‐translational step for activation, prenylation, of Ras proteins. To find new potent FTIs, rapid enzyme activity assays are required to reduce FTI development time. Most assays to date are based on radioactive labelled substrates. We developed a new, in vitro, farnesyl transferase assay based on gradient chromatography coupled to UV detection. Unfarnesylated and farnesylated H‐Ras proteins were resolved on a C18 wide‐pore HPLC column and their concentrations were determined with use of a calibration curve of unfarnesylated H‐Ras. The assay was used to investigate inhibition characteristics of FTIs. The IC50 values of the FTIs L778,123 and SCH66336 were 4.2 nm and 78 µm, respectively. This assay could support the screening and development of FTIs to obtain rapid insights into their inhibitory properties. Copyright © 2005 John Wiley & Sons, Ltd.
A Combined ESI‐ and MALDI‐MS(/MS) Study of Peripherally Persulfonylated Dendrimers: False Negative Results by MALDI‐MS and Analysis of Defects
Authors: Felder Thorsten , Schalley Christoph A. , Fakhrnabavi Hassan , Lukin Oleg
Published: July 2005

Mass spectrometry, in particular MALDI‐MS, has often been used as a valuable means to characterize dendritic molecules with respect to their molecular masses. Also, it is a valuable tool for analyzing potential defects in their structure which result from incomplete synthetic steps. This article presents a comparison of ESI and MALDI mass spectrometric experiments on dendrimers persulfonylated at their periphery. While the ESI mass spectra easily permit impurities and defects to be identified and thus provide evidence for sample purity, reactions with acidic matrices occur during the MALDI process. The resulting defects are identical to those expected from incomplete substitution. Thus, in these cases, MALDI‐MS yields false negative results. With mass‐selected, ESI‐generated ions, collision experiments were performed in an FT‐ICR mass spectrometer cell to provide detailed insight into the fragmentation patterns of the various dendrimers. Different fragmentation patterns are observed depending on the exact structure of the dendrimer. Also, the nature of the charge is important. The fragmentation reactions for protonated species differ much from those binding a sodium or potassium ion. These differences can be traced back to different sites for binding H+ versus Na+ or K+. Tandem MS experiments on mass‐selected dendrimer ions with defects can be used to distinguish different types of defects. A concise structural assignment can thus be made on the basis of these experiments. Even mixtures of two isobaric defect variants with the same elemental composition can be identified.
Pd–Cu Bimetallic Catalyzed Domino Cyclization of α‐Allenols Followed by a Coupling Reaction: New Sequence Leading to Functionalized Spirolactams
Authors: Alcaide Benito , Almendros Pedro , Rodríguez‐Acebes Raquel
Published: July 2005

A novel regioselective metal‐catalyzed spirocyclization of α‐allenols–cross coupling (Heck, Sonogashira, and Suzuki) reaction sequence, leading to potentially bioactive spirocyclic lactam derivatives has been developed. Precursors for the tandem spirocyclization–coupling reaction, α‐allenols2 a–dwere obtained starting from α‐oxolactams1 a–cvia indium‐mediated Barbier‐type carbonyl‐allenylation reaction in aqueous media by using our previously described methodologies.
Direct Organocatalytic Asymmetric α‐Sulfenylation of Activated CH Bonds in Lactones, Lactams, and β‐Dicarbonyl Compounds
Authors: Sobhani Sara , Fielenbach Doris , Marigo Mauro , Wabnitz Tobias C. , Jørgensen Karl Anker
Published: July 2005

The application of cinchona alkaloid derivatives as catalysts for enantioselective α‐sulfenylation of activated CH bonds in lactones, lactams, and β‐dicarbonyl compounds by different electrophilic sulfur reagents is presented. Optically active products are obtained in good to excellent yields and up to 91 % ee. Furthermore, the diastereoselective reduction of α‐sulfenylated β‐keto esters to give optically active α‐sulfenylated β‐hydroxy esters has been studied. A model for the intermediate is presented, in which the protonated cinchona alkaloid interacts with the substrate leading to face‐shielding in accordance with the enantioselective α‐sulfenylation step.
[W(CO)5]‐Catalyzed endo‐ or exo‐Cycloisomerization Reactions of 1,1‐Disubstituted 4‐Pentyn‐1‐ols: Experimental and Theoretical Studies
Authors: Barluenga José , Diéguez Alejandro , Rodríguez Félix , Fañanás Francisco J. , Sordo Tomás , Campomanes Pablo
Published: July 2005

The [W(CO)5]‐catalyzed cycloisomerization reaction of 1,1‐disubstituted 4‐pentyn‐1‐ol derivatives has been studied from both, an experimental and theoretical point of view. Three different catalytic systems have been evaluated {preformed [(thf)W(CO)5], [W(CO)6]/excess Et3N, and [W(CO)6]/2 mol % Et3N]. We have found that the reaction proceeds to give the formal endo‐ or exo‐cycloisomerization products depending on the amount of Et3N used and on the substitution along the alkyl chain of the starting alkynol. The theoretical study allowed us to find the mechanisms of the reactions which explain the formation of the formal endo‐ or exo‐cycloisomerization products.
CO Oxidation on Pt‐Modified Rh(111) Electrodes
Authors: Housmans T. H. M. , Feliu J. M. , Gómez R. , Koper M. T. M.
Published: July 2005

The CO electro‐oxidation reaction was studied on platinum‐modified Rh(111) electrodes in 0.5 M H2SO4 using cyclic voltammetry and chronoamperometry. The Pt–Rh(111) electrodes were generated during voltammetric cycles at 50 mV s−1 in a 30 μM H2PtCl6 and 0.5 M H2SO4 solution. Surfaces generated by n deposition cycles were investigated (Ptn–Rh(111) with n=2, 4, 6, 8, 10, and 16). The blank cyclic voltammograms of these surfaces are characterized by a pronounced sharpening of the hydrogen/(bi)sulfate adsorption/desorption peaks, typical for Rh(111), and the appearance of contributions between 0.1 and 0.4 V, which were ascribed to hydrogen/(bi)sulfate adsorption/desorption on the deposited platinum. At higher potentials, the surface oxidation of Rh(111) is enhanced by the presence of platinum. The structure of the Pt‐modified electrodes was investigated by STM imaging. At low Pt coverages (Pt2–Rh(111)), monoatomically high islands are formed, which grow three dimensionally as the number of deposition cycles increases. After eight cycles, the monolayer islands have grown in diameter and range from mono‐ to multiatomic height. At even higher Pt coverage (Pt16–Rh(111)), the islands grow to particles of approx. 10 nm in diameter, which are 5–6 atoms high. The CO stripping voltammetry on these surfaces is characterized by two peaks: A low‐potential, structure‐insensitive peak, ascribed to CO reacting at the platinum monolayer islands, whose onset is shifted 150, 250, and 100 mV negatively with respect to pure Rh(111), Pt(111), and polycrystalline Pt, respectively, indicating the enhanced CO electro‐oxidation properties of the Pt overlayer system. A peak at higher potentials displays strong structure sensitivity (particle‐size effect) and was ascribed to CO reacting on the islands of multiatomic height. Current–time transients recorded on the surface with the highest amount of monolayer islands (Pt4–Rh(111)) also indicate enhanced CO‐oxidation kinetics. Comparison of the Pt4–Rh(111) current–time transients recorded at 0.635, 0.675, and 0.750 V versus RHE (reversible hydrogen electrode) with those of pure Rh(111) and Pt(111) shows greatly reduced reaction times. A Cottrellian decay at long times indicates surface‐diffusion‐limited CO oxidation on the bare Rh(111) surface, while the peak visible at short times is indicative of CO reacting at the monolayer platinum islands. The results presented here show that, as indicated by density functional theory (DFT) calculations, the CO‐adlayer oxidation for this system is enhanced compared to both pure Rh and Pt.
Experimental and Theoretical Investigation of the Room‐Temperature Photoluminescence of Amorphized Pb(Zr,Ti)O3
Authors: Orhan Emmanuelle , Pontes Fenelon M. , Leite Edson R. , Pizani Paulo S. , Varela José A. , Longo Elson
Published: July 2005

Ultrafine PbZr0.20Ti0.80O3 was amorphized through high‐energy mechanical milling. The structural evolution through the amorphization process was accompanied by various characterization techniques, such as X‐ray diffraction, Fourier‐transformed IR spectroscopy (FTIR), high‐resolution transmission electron microscopy (HR‐TEM), and Raman spectroscopy. A strong photoluminescence was measured at room temperature for amorphized PbZr0.20Ti0.80O3, and interpreted by means of high‐level quantum mechanical calculations in the density functional theory framework. Three periodic models were used to represent the crystalline and amorphized PbZr0.20Ti0.80O3, and they allowed the calculation of electronic properties that are consistent with the experimental data and that explain the appearance of photoluminescence.
fMRI study of language lateralization in children and adults
Authors: Szaflarski Jerzy P. , Holland Scott K. , Schmithorst Vincent J. , Byars Anna W.
Published: July 2005

Language lateralization in the brain is dependent on family history of handedness, personal handedness, pathology, and other factors. The influence of age on language lateralization is not completely understood. Increasing left lateralization of language with age has been observed in children, while the reverse has been noted in healthy young adults. It is not known whether the trend of decreasing language lateralization with age continues in the late decades of life and at what age the inflection in language lateralization trend as a function of age occurs. In this study, we examined the effect of age on language lateralization in 170 healthy right‐handed children and adults ages 5–67 using functional MRI (fMRI) and a verb generation task. Our findings indicate that language lateralization to the dominant hemisphere increases between the ages 5 and 20 years, plateaus between 20 and 25 years, and slowly decreases between 25 and 70 years. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Multicomponent Strecker Reaction under High Pressure
Authors: Matsumoto Kiyoshi , Kim Jong Chul , Iida Hirokazu , Hamana Hiroshi , Kumamoto Koji , Kotsuki Hiyoshizo , Jenner Gérard
Published: July 2005

For the first time, uncatalyzed, high‐pressure (0.6 GPa) reactions with ketones have proven to be a powerful way to perform the three‐component Strecker synthesis of α‐amino nitriles in high yields. Two types of double Strecker reactions were achieved, but attempts to perform triple Strecker reactions were unsuccessful.
Process‐Scale Total Synthesis of Nature‐Identical (−)‐(S,S)‐7‐Hydroxycalamenal in High Enantiomeric Purity through Catalytic Enantioselective Hydrogenation
Authors: Benincori Tiziana , Bruno Silvana , Celentano Giuseppe , Pilati Tullio , Ponti Alessandro , Rizzo Simona , Sada Mara , Sannicolò Francesco
Published: July 2005

A process‐scale stereoselective synthesis of nature‐identical (−)‐(S,S)‐7‐hydroxycalamenal (=(−)‐(5S,8S)‐5,6,7,8‐tetrahydro‐3‐hydroxy‐5‐methyl‐8‐(1‐methylethyl)naphthalene‐2‐carbaldehyde; (−)‐1a) in 96% enantiomeric excess (ee) with the aid of chiral Ru complexes has been developed. The key step was the enantioselective hydrogenation of easily accessible 2‐(4‐methoxyphenyl)‐3‐methylbut‐2‐enoic acid (10) to (+)‐11 in a 86% ee (Scheme 5 and Table 1). A substantial increase in optical purity (96% ee) was achieved by induced crystallization of the intermediate (+)‐3,4‐dihydro‐4‐(1‐methylethyl)‐7‐methoxy‐2H‐naphthalen‐1‐one ((+)‐3). Computational conformation analysis carried out on the analog (−)‐9 rationalized the high diastereoselectivity achieved in the catalytic hydrogenation of the CC bond.
Basicity of Phenyl‐ and Methyl‐Substituted 1,2,4‐Oxadiazoles
Authors: Trifonov Rostislav E. , Volovodenko Anna P. , Vergizov Sergei N. , Shirinbekov Nabi I. , Gindin Vladimir A. , Koren Andrei O. , Ostrovskii Vladimir A.
Published: July 2005

The basicity of a series of 3,5‐disubstituted 1,2,4‐oxadiazoles in aqueous H2SO4 was examined by means of UV and 1H‐NMR spectroscopy. The experimental data were analyzed by the modified Yates–McClelland method to yield the following pK values: 3,5‐dimethyl‐1,2,4‐oxadiazole, −1.66±0.06; 3‐methyl‐5‐phenyl‐1,2,4‐oxadiazole, −2.61±0.02; 3‐phenyl‐5‐methyl‐1,2,4‐oxadiazole, −2.95±0.01; 3,5‐diphenyl‐1,2,4‐oxadiazole, −3.55±0.06. A pK value of ca. −3.7 was estimated for the parent unsubstituted 1,2,4‐oxadiazole based on substituents' additivity increments. Possible protonation sites of the compounds were discussed in terms of both experimental data and theoretical calculations (HF/6‐31G**). Generally, protonation is most likely to occur at N(4) of the 1,2,4‐oxadiazole ring. However, concurrent formation of both N(4)‐ and N(2)‐protonated species in comparable amounts is possible in the case of 3‐phenyl‐1,2,4‐oxadiazoles.
Functionalised Bicyclic exo‐Glycals by Alkynol Cycloisomerisation of Hydroxy 1,3‐Diynes and Hydroxy Haloalkynes
Authors: Miao Zhiwei , Xu Ming , Hoffmann Barbara , Bernet Bruno , Vasella Andrea
Published: July 2005

Functionalised bicyclic exo‐glycals are readily obtained by base‐catalysed (typically MeONa in MeOH) alkynol cycloisomerisation of ethynylated cyclic saccharides. Thus, base treatment of the phenylethynyl‐ and halogenoethynylated 1‐O‐acetyl‐ribofuranoses 22–24 and the 4‐ethynylated 1‐thioglucopyranosides 30–33 gave – after deacetylation – selectively the (Z)‐configured exocyclic enol ethers 26–28 (84–91%) and 34–37 (63–76%), respectively, resulting from a trans‐5‐exo‐dig cyclisation. The ring closure to the trans‐dioxahexahydroindans 34–37 is favoured by a concerted intramolecular protonation of the intermediate vinyl anion by the neighbouring HOC(3). Cycloisomerisation of the 6‐O‐acetyl‐4‐(phenylethynyl)‐1‐thio‐α‐D‐glucopyranoside 39 occurred via the corresponding phenylethynylated allenes to provide the galacto‐configured (Z)‐ and (E)‐cis‐dioxahexahydroindans 40 (30%) and 41 (51%). Surprisingly, the HOC(4) unprotected α‐d‐galactopyranosyl‐buta‐1,3‐diyne 15 and the β‐D‐glucopyranosyl‐buta‐1,3‐diyne 51 (and its 2‐bromoethynyl analogue) undergo a 6‐exo‐dig ring closure to the 2,5‐dioxabicyclo[2.2.2]octanes 16–19 and 52/53, respectively, the ring closure requiring a boat conformation (B1,4 for 15, 1,4B for 51). Ring strain (anti‐reflex effect) prevents an alkynol cycloisomerisation of 4‐(phenylbuta‐1,3‐diynyl, bromoethynyl, or iodoethynyl)levoglucosan 56–59, and 56 reacted by elimination to the hex‐1‐ene‐3,5‐diyne 59 (82%), while isomerisation of 57 and 58 led to epimeric mixtures of the haloallenes 60 (82%) and 61 (68%).
Solid‐State NMR Study of the Tautomerism of Acetylacetone Included in a Host Matrix
Authors: Claramunt Rosa M. , López Concepción , Lott Susanne , Santa María M. Dolores , Alkorta Ibon , Elguero José
Published: July 2005

The tautomerism of the enol form of acetylacetone (=pentane‐2,4‐dione; 1) inside a host cavity has been studied by means of solid‐state 13C‐NMR spectroscopy (SSNMR) using the variable‐temperature CPMAS technique. It appears that the enol form, 4‐hydroxypent‐3‐en‐2‐one (1a), exists in an equilibrium with an identical tautomer (1c) trough OH ⋅⋅⋅O proton transfer. The experimental results (energy barrier and chemical shifts) were rationalized by means of MP2 and GIAO calculations.
NMR‐Solution Structures in Methanol of an α‐Heptapeptide, of a β3/β2‐Nonapeptide, and of an all‐β3‐Icosapeptide Carrying the 20 Proteinogenic Side Chains
Authors: Seebach Dieter , Mathad Raveendra I. , Kimmerlin Thierry , Mahajan Yogesh R. , Bindschädler Pascal , Rueping Magnus , Jaun Bernhard , Hilty Christian , Etezady‐Esfarjani Touraj
Published: July 2005

The NMR‐solution structure of an α‐heptapeptide with a central Aib residue was investigated in order to verify that, in contrast to β‐peptides, short α‐peptides do not form a helical structures in MeOH. Although the central Aib residue was found to induce a bend in the experimentally determined structure, no secondary structure typical for longer α‐peptides or proteins was found. A β2/β3‐nonapeptide with polar, positively charged side chains was subjected to NMR analysis in MeOH and H2O. Whereas, in MeOH, it folds into a 10/12‐helix very similar to the structure determined for a corresponding β2/β3‐nonapeptide with only aliphatic side chains, no dominant conformation could be determined in H2O. Finally, the NMR analysis of a β3‐icosapeptide containing the side chains of all 20 proteinogenic amino acids in MeOH is described. It revealed that this 20mer folds into a 314‐helix over its whole length forming six full turns, the longest 314‐helix found so far. Together, our findings confirm that, in contrast to α‐peptides, β‐peptides not only form helices with just six residues, but also form helices that are longer than helical sections usually observed in proteins or natural peptides. The higher helix‐forming propensity of long β‐peptides is attributed to the conformation‐stabilizing effect of the staggered ethane sections in β‐peptides which outweighs the detrimental effect of the increasing macrodipole.
Cycloaddition Reactions of 7‐Benzylidenecycloocta‐1,3,5‐triene with Ethenetetracarbonitrile and 4‐Phenyl‐3H‐1,2,4‐triazole‐3,5(4H)‐dione
Authors: Clements Philip , Gream George E. , Kirkbride Paul K. , Pyke Simon M.
Published: July 2005

An (E)/(Z) mixture (3 : 2) of 7‐benzylidenecycloocta‐1,3,5‐triene (5) is obtained when 1‐benzylcycloocta‐1,3,5,7‐tetraene (7), prepared by an improved procedure, is treated with t‐BuOK in THF. Alternatively, a ca. 9 : 1 mixture (E)/(Z)‐5 can be prepared in a Wittig reaction involving benzaldehyde and cycloocta‐2,4,6‐trien‐1‐ylidenetriphenylphoshorane (9). Treatment of (E)/(Z)‐5 88 : 12 with ethenetetracarbonitrile (TCNE) gave a complex mixture of products, from which seven mono‐adducts and two bis‐adducts were isolated (Sect. 2.2.1). Of the mono‐adducts, four are π4+π2 adducts: two ((E)‐ and (Z)‐isomers) are derived from valence tautomers of the two isomers of (E)/(Z)‐5, while it is tentatively suggested that the other two (again (E)‐ and (Z)‐isomers) are formed from the intermediacy of a pentadienyl zwitterion (Sect. 2.3). The remaining three mono‐adducts, two of which are epimers, are π8+π2 adducts. It is suggested that they are derived from the intermediacy of homotropylium zwitterions (Sect. 2.3). For the two bis‐adducts, it is postulated that they are derived from an initial π2+π2 cycloaddition involving the homotropylium zwitterions followed by π4+π2 cycloaddition to the valence tautomer of each of the π2+π2 cycloadducts. With 4‐phenyl‐3H‐1,2,4‐triazole‐3,5(4H)‐dione (6), (E)/(Z)‐5 91 : 9 yielded two π4+π2 cycloadducts ((E)‐ and (Z)‐isomers) as well as two epimeric π8+π2 cycloadducts (Sect. 2.2.2). The intermediacy of pentadienyl (tentative suggestion) and homotropylium zwitterions accounts for the formation of the products (Sect. 2.3).