bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of 1‐(2′‐deoxy‐2′‐fluoro‐β‐D‐arabinofuranosyl)‐[Methyl‐11C]thymine ([11C]FMAU) via a Stille cross‐coupling reaction with [11C]methyl iodide
Authors: Samuelsson Linda , Långström Bengt
Published: March 2003

1‐(2′‐deoxy‐2′‐fluoro‐β‐D‐arabinofuranosyl)‐[methyl‐11C]thymine ([11C]FMAU) [11C]‐1 was synthesised via a palladium‐mediated Stille coupling reaction of 1‐(2′‐deoxy‐2′‐fluoro‐β‐D‐arabinofuranosyl)‐5‐(trimethylstannyl)uracil 2 with [11C]methyl iodide in a one‐pot procedure. The reaction conditions were optimized by screening various catalysts and solvents, and by altering concentrations and reaction temperatures. The highest yield was obtained using Pd2(dba)3 and P(o‐tolyl)3 in DMF at 130°C for 5 min. Under these conditions the title compound [11C]‐1 was obtained in 28±5% decay‐corrected radiochemical yield calculated from [11C]methyl iodide (number of experiments=7). The radiochemical purity was >99% and the specific radioactivity was 0.1 GBq/μmol at 25 min after end of bombardment. In a typical experiment 700–800 MBq of [11C]FMAU [11C]‐1 was obtained starting from 6–7 GBq of [11C]methyl iodide. A mixed 11C/13C synthesis to yield [11C]‐1/(13C)‐1 followed by 13C‐NMR analysis was used to confirm the labelling position. The labelling procedure was found to be suitable for automation. Copyright © 2002 John Wiley & Sons, Ltd.
Deuterated abscisic acid analogs for mass spectrometry and metabolism studies
Authors: Abrams Suzanne R. , Nelson Ken , Ambrose Stephen J.
Published: March 2003

Four analogs of abscisic acid (ABA) with deuterium atoms at non‐exchangeable positions have been synthesized to be used as standards for quantitation of the plant hormone ABA by mass spectrometry and also to be employed as substrates for metabolism studies. Deuterium atoms were introduced in the side chain of the molecule, at C‐4 and/or C‐5, by deuteride or hydride reduction of a propargylic alcohol, an intermediate in the synthesis. As well, deuterium labels were introduced at the C‐8′ position by conjugate addition of a Grignard reagent containing the label to a cyclohexadienone intermediate, affording specific isotopically labeled ABA molecules with one to five deuterium atoms. Copyright © 2002 John Wiley & Sons, Ltd.
Incorporating diverse traditions into the fundraising practices of nonprofit organizations
Authors: Newman Diana S.
Published: March 2003

Organizations that diversify their internal structures and fundraising practices will be in a better position to serve their increasingly diverse constituents and increase charitable gifts.
The role of segment 32–47 of cholecystokinin receptor type A in CCK8 binding: synthesis, nuclear magnetic resonance, circular dichroism and fluorescence studies
Authors: De Luca Stefania , Ragone Raffaele , Bracco Chiara , Digilio Giuseppe , Tesauro Diego , Saviano Michele , Pedone Carlo , Morelli Giancarlo
Published: March 2003

The segment 32–47 of the N‐terminal extracellular domain of the type A cholecystokinin receptor, CCKA‐R(32–47), was synthesized and structurally characterized in a membrane mimicking environment by CD, NMR and molecular dynamics calculations. The region of CCKA‐R(32–47) encompassing residues 39–46 adopted a well‐defined secondary structure in the presence of DPC micelles, whereas the conformation of the N‐terminal region (segment 32–37) could not be uniquely defined by the NOE derived distance constraints because of local flexibility. The conformation of the binding domain of CCKA‐R(32–47) was different from that found for the intact N‐terminal receptor tail, CCKA‐R(1–47). To assess whether CCKA‐R(32–47) was still able to bind the nonsulfated cholecystokinin C‐terminal octapeptide, CCK8, a series of titrations was carried out in SDS and DPC micelles, and the binding interaction was followed by fluorescence spectroscopy. These titrations gave no evidence for complex formation, whereas a high binding affinity was found between CCKA‐R(1–47) and CCK8. The different affinities for the ligand shown by CCKA‐R(32–47) and CCKA‐R(1–47) were paralleled by different interaction modes between the receptor segments and the micelles. The interaction of CCKA‐R(32–47) with DPC micelles was much weaker than that of CCKA‐R(1–47), because the former receptor segment lacks proper stabilizing contacts with the micelle surface. In the case of SDS micelles CCKA‐R(32–47) was found to form non‐micellar adducts with the detergent that prevented the onset of a functionally significant interaction between the receptor segment and the micelle. It is concluded that tertiary structure interactions brought about by the 1–31 segment play a key role in the stabilization of the membrane bound, biologically active conformation of the N‐terminal extracellular tail of the CCKA receptor. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.
Synthesis and conformational investigation of cyclic dipeptides: 7‐membered rings containing α‐ and β‐amino acids
Authors: Müller‐Hartwieg J. Constanze D. , Akyel Kayhan G. , Zimmermann Jürg
Published: March 2003

The synthesis of heterocyclic compounds containing the 7‐membered ring system [1,4]diazepane‐2,5‐dione is described. The aim of this study was to elaborate the solid phase and solution synthesis of eight representatives of the cyclic scaffold and to investigate their chemical stability and their conformational properties. The solid phase synthesis was performed on aminomethyl polystyrene resin using 5‐(4‐formyl‐3,5‐dimethoxyphenoxy)valeric acid as a backbone linker system (BAL‐linker). After attachment of the α‐ and β‐amino acid and deprotection of the amino function, the dipeptide ester was obtained. The molecule was cyclized on the solid support by treatment with NaOMe in MeOH/NMP. The product was cleaved from the resin by TFA. For the solution pathway the linear dipeptides were synthesized by coupling of the BOC‐protected L‐α‐amino acid with the β2‐amino acid ester (EDC/HOBT). After N‐ and C‐terminal deprotection of the dipeptide, the linear species was cyclized with EDC/HOBT at a concentration of 3 mM in DMF. The products showed high chemical stability after storage in DMSO at room temperature for weeks. The x‐ray and two dimensional NMR investigations were performed to investigate the conformation of the molecules. Three types of configuration could be distinguished by NMR, depending on the substitution pattern of the cyclic compounds. The x‐ray results confirmed the NMR observations. In general the 7‐membered rings showed rigidity, thus they could represent optimal scaffolds for new receptor ligands. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.
Inhibition of ascorbic acid‐induced modifications in lens proteins by peptides
Authors: Argirova Mariana , Argirov Ognyan
Published: March 2003

The effects of three dipeptides L‐phenylalanyl‐glycine, glycyl‐L‐phenylalanine, and aspartame (L‐aspartyl‐L‐phenylalanine, methyl ester) as inhibitors of the ascorbic acid‐induced modifications in lens proteins were studied. Their efficiency was compared to that of two known inhibitors—aminoguanidine and carnosine. The tested dipeptides diminished protein carbonyl content by 32–58% and most moderated the formation of chromophores, as measured by the absorbency at 325 nm of the glycated proteins. The appearance of non‐tryptophan fluorescence (excitation 340 nm/emission 410 nm) was observed for proteins glycated with ascorbic acid. All of the dipeptides examined, as well as aminoguanidine, decreased this glycation‐related fluorescence. The potential inhibitors prevented the intensive formation of very high molecular weight aggregates. A competitive mechanism of their inhibitory effect was proposed, based on the reactivity of individual substances toward ascorbic acid. These findings indicate that they have a potential for use as alternatives for aminoguanidine as an anti‐glycation agent. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.
On the Dispersion and Small‐Amplitude Oscillation Measurements of High Amylopectin Potato Starch
Authors: Ortega‐Ojeda Fernando E. , Larsson Helena , Eliasson Ann‐Charlotte
Published: March 2003

Differential scanning calorimetry (DSC), optical microscopy and turbidity measurements were used to define experimental conditions (time, temperature and shearing) for dissolving high amylopectin potato starch (HAPP) granules. A simple, less time consuming and non‐chemical method for preparing starch samples was established. Small‐amplitude oscillation measurements were used to characterise the behaviour of the resulting solutions. The DSC, microscopy and turbidity experiments showed that preparing the samples at 140 °C was necessary to dissolve HAPP, with no further detectable granule structures. Rheological measurements showed that the storage (G') and loss (G'') moduli increased with concentration. At a HAPP concentration of 2 % G'' > G' and the system behaved like a diluted solution. The frequency dependence also decreased with increasing concentration. At 14 % HAPP, the system showed more gel‐like properties with G' more or less independent of frequency.
Kinetics of Starch Gelatinisation and Mass Transfer During Cooking of Taro (Colocasia esculenta L. Schott) Slices
Authors: Njintang Yanou Nicolas , Mbofung Carl M. F.
Published: March 2003

Taro slices of different thickness (5, 10 and 15 mm) were cooked for varying periods of time (5, 10, 20 and 40 min) and dried at different temperatures (70, 80 and 90 °C). Flours obtained from the slices were evaluated for their degree of gelatinisation, their content of sugars and phenolic compounds. The results showed that starch gelatinisation as well as the diffusion of sugars and phenolic compounds during cooking each followed a first‐order reaction of the general form ln(1‐α) = ‐k·t. The gelatinisation rate constant, kG , and the rate constants for the diffusion of sugars and phenolic compounds, kL, increased with temperature and decreased with slice thickness.
Parametric analysis of analytical solutions to one‐ and two‐dimensional problems in couple‐stress theory of elasticity
Authors: Kulesh M.A. , Matveenko V.P. , Shardakov I.N.
Published: March 2003

In this paper the fundamentals of the asymmetric elasticity theory are used to consider one‐ and two‐dimensional boundary‐value problems: shear deformation of elastic infinite plane layer(plate); torsion of a ring rigidly fixed at the external contour due to rotation of the inner one; deformation of a plane washer caused by a rigid displacement of the internal contour relative to the external one; the Kirsch problem on unilateral extension of a plate loosened by a circular hole.

The solution of each problem is compared with the corresponding solution obtained in the framework of the classical theory of elasticity. The comparison is made in terms of macro‐parameters introduced to characterize the degree of difference between these solutions. The analysis of the obtained results show that for each problem under consideration this difference is not essential. It is worthy of note that the macro‐parameters used for comparison can be constructively measured by experiment. The obtained results can be used to outline a key diagram of experiments enabling one to detect the effects of “couple” response of the examined medium.
Comparison of Surgical Treatments of Gallstone Ileus: Preliminary Report
Authors: Doko Marko , Zovak Mario , Kopljar Mario , Glavan Elizabet , Ljubicic Neven , Hochstädter Hrvoje
Published: March 2003

Abstract

Gallstone ileus is an uncommon cause of small bowel obstruction, accounting for only 1% to 4% of all intestinal obstructions. In the group of patients over 65 years of age, gallstones cause about 25% of all non‐strangulated obstructions of the small bowel. Gallstone ileus is burdened with high mortality rate, ranging from 12% to 18%, and most patients are of advanced age, with many other concomitant diseases that may increase the operative risk. The purpose of this study was to compare the two investigated surgical procedures: treatment of intestinal obstruction alone or combined with urgent cholecystectomy and fistula repair. Analysis of 30 patients undergoing operation for gallstone ileus at the Clinical Hospital “Sestre milosrdnice” between 1985 and 2001 is presented. Patients were treated either for ileus alone (group 1, 11 patients) or as one‐stage procedure with urgent fistula closure (group 2, 19 patients). Operating time was significantly longer for the one‐stage procedure. Complications occurred in 3 of 11 patients (27.3%) from group 1 and in 11 of 18 patients (61.1%) from group 2 (one tailed, p = 0.043). One patient in group 1 died and two patients in group 2 died. Urgent fistula repair was significantly associated with the occurrence of complications (odds ratio [OR] 12.1, 95% confidence internal [95% CI] 1.2–121.5). Simple enterotomy should be the procedure of choice for patients with gallstone ileus. The one‐stage procedure including urgent fistula repair should be reserved only for highly selected patients with absolute indications.
Phosphatase activity of non‐heme chloroperoxidase from the bacterium Serratia marcescens
Authors: Preobrazhenskaya Yuliya V , Voskoboev Alexander I , Burd Vasilii N
Published: March 2003

Haloperoxidases are enzymes capable of formation of carbon–halogen bonds in the presence of hydrogen peroxide and halide ions. A mechanism of halogenation catalyzed by heme‐ and metal‐independent bacterial haloperoxidases differs from other representatives of this group of enzymes. Here we report for the first time that bacterial non‐heme haloperoxidases possess a phosphatase activity. Chloroperoxidase from Serratia marcescens W 250 purified up to homogeneity is shown to catalyze p‐nitrophenylphosphate hydrolysis (Km value, 1.8±0.1 mM at pH 5.7). The reaction is activated by Mg2+ and F−, and is inhibited by WO4
2−, tartrate, acetate and phosphate anions. The irreversible inhibition by phenylmethanesulfonyl fluoride, modificator of serine residue in active site, decreases in the presence of phosphate ions. A mechanism of phosphoesters hydrolysis by non‐heme haloperoxidases is proposed.
Impaired voltage‐gated K+ channel expression in brain during experimental cancer cachexia
Authors: Coma Mireia , Vicente Rubén , Busquets Silvia , Carbó Neus , Tamkun Michael M , López-Soriano Francisco J , Argilés Josep M , Felipe Antonio
Published: March 2003

Cancer‐induced cachexia affects most advanced cancer patients. It is characterized by anorexia, profound metabolic dysfunctions, and severe neurological disorders. Here we show that voltage‐gated potassium channel (Kv) expression is impaired in the brain of tumor‐bearing animals. Expression of both delayed rectifier (Kv1.1, Kv1.2, Kv1.3, Kv1.5, Kv1.6, Kv2.1, Kv3.1, Kv4.2) and A‐type potassium channels (Kv1.4, Kv3.3, Kv3.4) was greatly down‐regulated in brain from animals bearing a Yoshida AH‐130 ascites hepatoma. The possible compensatory mechanisms (Kv1.4/Kv4.2), expression of redundant genes (Kv3.1/Kv3.3) and heteromultimeric channel formation (Kv2.1/Kv9.3) were also affected. The high circulating levels of TNFα and the reduced expression of the anti‐apoptotic protein Bcl‐XL found in the brain of tumor‐bearing animals indicate that this response could be mediated by an increase in brain cell death due to apoptosis. The results suggest that brain function is impaired during cancer cachexia, and may account for the cancer‐induced anorectic response and other neurological alterations.
Unexpected catalytic site variation in phosphoprotein phosphatase homologues of cofactor‐dependent phosphoglycerate mutase
Authors: Rigden Daniel J.
Published: March 2003

The cofactor‐dependent phosphoglycerate mutase (dPGM) superfamily contains, besides mutases, a variety of phosphatases, both broadly and narrowly substrate‐specific. Distant dPGM homologues, conspicuously abundant in microbial genomes, represent a challenge for functional annotation based on sequence comparison alone. Here we carry out sequence analysis and molecular modelling of two families of bacterial dPGM homologues, one the SixA phosphoprotein phosphatases, the other containing various proteins of no known molecular function. The models show how SixA proteins have adapted to phosphoprotein substrate and suggest that the second family may also encode phosphoprotein phosphatases. Unexpected variation in catalytic and substrate‐binding residues is observed in the models.
H9c2 cardiac myoblasts undergo apoptosis in a model of ischemia consisting of serum deprivation and hypoxia: inhibition by PMA
Authors: Bonavita Francesca , Stefanelli Claudio , Giordano Emanuele , Columbaro Marta , Facchini Annalisa , Bonafè Francesca , Caldarera Claudio Marcello , Guarnieri Carlo
Published: March 2003

Cardiac myocytes undergo apoptosis under condition of ischemia. Little is known, however, about the molecular pathways that mediate this response. We show that serum deprivation and hypoxia, components of ischemia in vivo, resulted in apoptosis of rat ventricular myoblast cells H9c2. Hypoxia alone did not induce significant apoptosis for at least 48 h, but largely increased the proapoptotic action of serum deprivation. H9c2 cells apoptosis is evidenced by an increase in terminal (TdT)‐mediated dUTP nick end‐labeling‐positive nuclei and by activation of caspases 3, 6, 7 and 9, and loss of mitochondrial functions. In this model of simulated ischemia, represented by serum deprivation plus hypoxia, cardiomyoblasts apoptosis was associated with a p53‐independent Bax accumulation and with a down‐regulation of Bcl‐xL, whereas the levels of cIAP‐1, cIAP‐2 and X‐IAP proteins did not change. Phorbol‐12‐myristate‐13‐acetate significantly reduced the induction of apoptosis, inhibiting caspase 3 cleavage, Bax accumulation, Bcl‐xL down‐regulation as well as restoring cell viability.
Identification of genes possibly related to storage root induction in sweetpotato
Authors: You Min Kyoung , Hur Cheol Goo , Ahn Young Sup , Suh Mi Chung , Jeong Byeong Choon , Shin Jeong Sheop , Bae Jung Myung
Published: March 2003

To identify genes related to initiation of storage root development in sweetpotato, a cDNA library was constructed with early stage storage roots (0.3–1 cm in diameter). Single‐pass sequences of the 5′ ends of 2859 sweetpotato cDNA clones were assembled into 483 clusters and 442 singletons. Comparison of sweetpotato expressed sequence tags (ESTs) to nodulation/tumorigenesis‐related sequence databases (nodule‐, tumor‐, potato tuber‐ and development‐related sequences) revealed that homologs of 39 sweetpotato EST sequences potentially involved in gene regulation, signal transduction and development were present in at least one of the nodulation/tumorigenesis‐related sequence databases. Northern blot analyses of these 39 sequences identified 22 differentially expressed genes in early stage storage root and fibrous root. These differentially expressed genes will be potential candidates for research to elucidate the molecular processes related to sweetpotato storage root induction.
Structure–function analysis of the A20‐binding inhibitor of NF‐κB activation, ABIN‐1
Authors: Heyninck Karen , Kreike Marja M , Beyaert Rudi
Published: March 2003

Nuclear factor κB (NF‐κB)‐dependent gene expression plays an important role in numerous cellular processes including stress responses, inflammation and cell proliferation. Therefore, the activity of this transcription factor needs to be tightly regulated. Among others, the NF‐κB‐dependent zinc finger protein A20 is involved in the negative feedback regulation of NF‐κB activation in response to tumor necrosis factor (TNF). We previously demonstrated that A20 can interact with A20‐binding inhibitors of NF‐κB activation (ABINs), which have the potential to inhibit TNF‐induced activation of NF‐κB upon overexpression. The ABIN proteins were therefore proposed to mediate the NF‐κB inhibiting function of A20. Here we demonstrate the presence of a short homologous region in ABINs and IκB kinase γ, the regulatory subunit of the IκB kinase complex. Site‐specific mutagenesis of this region abolished the NF‐κB inhibiting function of ABIN‐1, without affecting the interaction with A20. Furthermore, coexpression of these ABIN‐1 mutants interfered in a dominant negative manner with the NF‐κB inhibiting function of ABIN‐1, whereas the A20‐mediated inhibition was unaffected. These results suggest that A20 and ABIN‐1 probably act independently of their mutual interaction.
Calcium regulates the PI3K‐Akt pathway in stretched osteoblasts
Authors: Danciu Theodora E , Adam Rosalyn M , Naruse Keiji , Freeman Michael R , Hauschka Peter V
Published: March 2003

Mechanical loading plays a vital role in maintaining bone architecture. The process by which osteoblasts convert mechanical signals into biochemical responses leading to bone remodeling is not fully understood. The earliest cellular response detected in mechanically stimulated osteoblasts is an increase in intracellular calcium concentration ([Ca2+]i). In this study, we used the clonal mouse osteoblast cell line MC3T3‐E1 to show that uniaxial cyclic stretch induces: (1) an immediate increase in [Ca2+]i, and (2) the phosphorylation of critical osteoblast proteins that are implicated in cell proliferation, gene regulation, and cell survival. Our data suggest that cyclic stretch activates the phosphoinositide 3‐kinase (PI3K) pathway including: PI3K, Akt, FKHR, and AFX. Moreover, cyclic stretch also causes the phosphorylation of stress‐activated protein kinase/c‐Jun N‐terminal kinase. Attenuation in the level of phosphorylation of these proteins was observed by stretching cells in Ca2+‐free medium, using intra‐ (BAPTA‐AM) and extracellular (BAPTA) calcium chelators, or gadolinium, suggesting that influx of extracellular calcium plays a significant role in the early response of osteoblasts to mechanical stimuli.
Regulation of telomerase activity and anti‐apoptotic function by protein–protein interaction and phosphorylation
Authors: Haendeler Judith , Hoffmann Jörg , Rahman Sandy , Zeiher Andreas M , Dimmeler Stefanie
Published: March 2003

The enzyme telomerase is necessary for the synthesis and maintenance of telomere length. The catalytic subunit, telomerase reverse transcriptase (TERT), is regulated by interaction with the 90 kDa heat shock protein (HSP90) and by Akt‐dependent phosphorylation. Here, we demonstrate that HSP90 and Akt physically interact with TERT. Treatment of cells with novobiocin, which blocks C‐terminal interaction of HSP90, disrupted HSP90 binding to Akt, induced Akt dephosphorylation and significantly reduced telomerase activity. The reduction of TERT activity by novobiocin was associated with an increase in apoptosis. Likewise, the induction of Akt dephosphorylation by protein phosphatase 2A (PP2A) reduced telomerase activity. HSP90 is known to prevent PP2A‐mediated dephosphorylation of Akt. To investigate whether the effect of novobiocin is due to the reduction of Akt or TERT phosphorylation, we overexpressed a phospho‐mimetic, active Akt (T308D/S473D). Akt (T308D/S473D) prevented novobiocin‐induced reduction of telomerase activity and the stimulation of apoptosis. Moreover, overexpression of a dominant negative PP2A construct (PP2A(L199P)) as well as incubation with the PP2A inhibitor okadaic acid blocked the inhibition of telomerase activity by novobiocin. These data suggest that the association between HSP90, Akt and TERT in concert with the phosphorylation of TERT is necessary for maintaining telomerase activity and inhibition of apoptosis.
Involvement of cholesterol in the inhibitory effect of dimethyl‐β‐cyclodextrin on P‐glycoprotein and MRP2 function in Caco‐2 cells
Authors: Yunomae Kiyokazu , Arima Hidetoshi , Hirayama Fumitoshi , Uekama Kaneto
Published: March 2003

We compared the inhibitory effect of various cyclodextrins (CyDs) on P‐glycoprotein (P‐gp) and multidrug resistance‐associated protein 2 (MRP2) function and examined the contribution of cholesterol to the inhibitory effect of 2,6‐di‐O‐methyl‐β‐cyclodextrin (DM‐β‐CyD) on the efflux activity of the function in Caco‐2 cell monolayers. Of various CyDs, DM‐β‐CyD significantly impaired the efflux activity of P‐gp and MRP2. DM‐β‐CyD released P‐gp and MRP2 from the monolayers in the apical side's transport buffer and decreased the extent of cholesterol as well as P‐gp and MRP2 in caveolae of Caco‐2 cell monolayers, but not caveolin and flotillin‐1. On the other hand, DM‐β‐CyD did not change MDR1 and MRP2 mRNA levels. Therefore, these results suggest that the inhibitory effect of DM‐β‐CyD on P‐gp and MRP2 function, at least in part, could be attributed to the release of these transporters from the apical membranes into the medium as secondary effects through cholesterol‐depletion in caveolae after treatment of Caco‐2 cell monolayers with DM‐β‐CyD.
Mechanical factors influence the expression of endostatin—an inhibitor of angiogenesis—in tendons
Authors: Pufe Thomas , Petersen Wolf , Kurz Bodo , Tsokos Michael , Tillmann Bernhard , Mentlein Rolf
Published: March 2003

Avascular zones of tendons are predisposed for degenerative changes and spontaneous rupture. Therefore, we analyzed the expression of the endogenous angiogenesis inhibiting factor endostatin in human fetal and adult tendons by immunohistochemical and biochemical methods. Moreover, to elucidate factors involved in the regulation of vascularity, we exposed primary cultures of rat tendon cells to intermittent hydrostatic pressure (0.2 MPa, 0.1 Hz for 24 h), and measured the endostatin content by ELISA and the effect of the conditioned medium to the proliferation of human umbilical vein endothelial cells (HUVEC).

In fetal tendons high endostatin levels could be quantified by ELISA whereas low levels were found in adult tissue. In fetal tendons endostatin could also be immunostained in endothelial cells but mainly in fibroblasts. In adult Achilles tendons endostatin immunostaining was restricted to endothelial cells. In the tibialis posterior tendon—as an example for “wrap around”—endostatin immunostaining remained positive in the fibrocartilage adjacent to the medial malleolus. Fibrochondrocytes of the type II collagen positive fibrocartilage were intensively stained with the endostatin antibody. Factor VIII immunostaining showed that this region was largely avascular. Monolayer cultures of tendon cells released measurable amounts of endostatin into their culture supernatants. Application of intermittent hydrostatic pressure increased endostatin expression significantly. The conditioned media of tendon fibroblasts cultivated under intermittent hydrostatic pressure inhibited the proliferation of HUVEC in a dose dependent way.

The spatial expression of endostatin in adult gliding tendons suggests that mechanical factors are involved in the regulation of this anti‐angiogenic factor. In accordance, tendon cells exposed to intermittent hydrostatic pressure inhibit endothelial cell proliferation via humoral factors and produce endostatin. These findings support the view that the development and maintenance of avascular zones in tendons might be caused by a mechanically induced upregulation of anti‐angiogenic factors. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Glucose‐mediated in vitro glycation modulates biomechanical integrity of the soft tissues but not hard tissues
Authors: Reddy G. Kesava
Published: March 2003

Glycation induced crosslinking of connective tissue collagen is thought to be involved in the pathogenesis of various disorders associated with diabetes and aging. Although the formation of the glycation related collagen crosslinks appears to be universal for all tissues, currently it is unknown whether differences exist between soft and hard tissue biomechanics in response to glucose‐mediated in vitro glycation. In this study, the impact of non‐enzymatic glycation was investigated on tendons and bones, using them as models for soft and hard tissue respectively. Achilles tendons from rabbits, and femur and tibia from rats, were subjected to in vitro glycation with glucose. Sixty days following glycation, the matrix integrity of the tendons and bones was evaluated and compared with the respective non‐glycated tissue (n = 10 in each group). The results revealed that the impact of glycation was significant on the tendon but not on the bone. Measurements of the biomechanical stability of glycated tendons indicated a significant increase in maximum load (21%), Young's modulus of elasticity (72%), energy to yield (35%) and toughness (68%) compared to the non‐glycated tendons. No significant differences were found in breaking strength, bending stiffness, energy to yield and toughness between glycated and non‐glycated femurs or tibias. The deformation of both soft and hard tissue was unaffected by the glycation. Measurements at ultimate tissue failure (break point) revealed that glycated tendons bore significantly higher load and energy absorption than non‐glycated tendons. In contrast, the deformation of the glycated tendons at break point was considerably reduced as compared to control tendons. However, glycation had no significant effects on the hard tissue biomechanical properties at break point. The results of this study demonstrate that in vitro glycation influences the biomechanical properties of soft tissue but not hard tissue. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Long‐term intermittent shear deformation improves the quality of cartilaginous tissue formed in vitro
Authors: Waldman Stephen D. , Spiteri Caroline G. , Grynpas Marc D. , Pilliar Robert M. , Kandel Rita A.
Published: March 2003

The formation of cartilaginous tissue in vitro is a promising alternative to repair damaged articular cartilage. However, recent attempts to tissue‐engineer articular cartilage that has similar properties to the native tissue have proven to be difficult. The in vitro‐formed cartilaginous tissue typically has a similar proteoglycan content to native cartilage, but has a reduced collagen content and only a fraction of the mechanical properties. In this study, we investigated whether the intermittent application of cyclic shearing forces during tissue formation would improve the tissue quality. Chondrocyte cultures were stimulated at a 2% shear strain amplitude at a frequency of 1 Hz for 400 cycles every 2nd day. At one week, both collagen and proteoglycan synthesis increased (23 ± 6% and 20 ± 6%, respectively) over the unstimulated, static controls. At four weeks, an increased amount of tissue formed (stimulated: 1.85 ± 0.08, unstimulated: 1.58 ± 0.07 mg dry wt.). This tissue contained approximately 40% more collagen (stimulated: 511 ± 23, unstimulated: 367 ± 24 μg/construct) and 35% more proteoglycans (stimulated: 376 ± 21, unstimulated: 279 ± 26 μg/construct). Tissues that formed in the presence of shearing forces also displayed a 3‐fold increase in compressive load‐bearing capacity (stimulated: 16 ± 5, unstimulated: 5 ± 1 kPa max. equilibrium stress) and a 6‐fold increase in stiffness (stimulated: 112 ± 36, unstimulated: 20 ± 6 kPa max. equilibrium modulus) compared to the static controls. These results demonstrate that intermittent application of dynamic shearing forces over a four‐week period improves the quality of cartilaginous tissue formed in vitro. Interestingly, low amplitudes of shear stimulation for short periods of time (6 min of stimulation applied every 2nd day) produced these changes. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Spermine prevents cytochrome c release in glucocorticoid‐induced apoptosis in mouse thymocytes
Authors: Hegardt Cecilia , Andersson Gunnar , Oredsson Stina M
Published: March 2003

Apoptosis can be induced in primary cultures of mouse thymocytes using the glucocorticoid dexamethasone. Addition of the polyamine spermine simultaneously with dexamethasone reduces the induction of apoptosis compared to treatment with dexamethasone alone. We investigated the signal transduction pathway at the mitochondrial level in order to elucidate spermine's protective effect. Mitochondrial involvement is evident due to the loss of mitochondrial transmembrane potential, release of cytochrome c into the cytosol and activation of caspase‐9 in dexamethasone‐treated thymocytes. The addition of spermine inhibited the release of cytochrome c from the mitochondria into the cytosol, and also the activation of caspase‐9. When the mitogen concanavalin A (Con A) was added to dexamethasone‐ plus spermine‐treated thymocytes, the number of apoptotic cells in the pre‐G1peak was reduced compared to thymocytes treated with only dexamethasone plus spermine. Comparing concanavalin A added to dexamethasone‐treated or to dexamethasone plus spermine‐treated thymocytes, showed a markedly reduced pre‐G1peak in the latter. Thus, the spermine‐induced inhibition of cytochrome c release confers a survival advantage on thymocytes.
Anti‐oxidative properties of beta‐blockers and angiotensin‐converting enzyme inhibitors in congestive heart failure
Authors: Chin Bernard S.P. , Langford Nigel J. , Nuttall Sarah L. , Gibbs Christopher R. , Blann Andrew D. , Lip Gregory Y.H.
Published: March 2003

Background:

Chronic elevation of plasma catecholamines and sympathetic stimulation in chronic heart failure (CHF) leads to increased production of free radicals, and so possibly to endothelial damage/dysfunction and atheroma formation. Abnormal oxidative stress may therefore be related to some of the high mortality and morbidity in CHF. The objective of the present prospective open study was to compare the effects of β‐blockers and ACE inhibitors in relation to oxidative stress and endothelial damage in CHF.

Methods:

We studied 66 outpatients with CHF: 46 patients were established on an ACE inhibitor and were then started on a β‐blocker, and 20 patients not previously on ACE‐inhibitors were started on lisinopril. Baseline levels of the measured parameters were compared to 22 healthy control subjects. Serum lipid hydroperoxides (LHP) and total antioxidant capacity (TAC) were determined as indices of oxidative damage and antioxidant defence, and plasma von Willebrand factor (vWf) as an index of endothelial damage/dysfunction.

Results:

Baseline indices for the measures of oxidative damage and endothelial function in the 66 CHF patients were significantly higher than healthy control subjects [median LHP 7.5 (5.9–12.6) vs. 4.8 μmol/l, P=0.0022; TAC 428 (365–567) vs. 336 Trollox Eq. Units, P=0.0005; mean vWf 134±27 vs. 89±23 IU/dl, P<0.0001]. Following 3 months of maintenance therapy with β‐blockers, there was significant reduction in LHP levels, but not TAC or vWf. ACE inhibitor therapy also significantly reduced vWf levels, but failed to have any statistically significant effects on LHP or TAC.

Conclusion:

This pilot study suggests that oxidative stress in CHF may be due to increased free radical production or inefficient free radical clearance by scavengers. β‐Blockers, but not ACE inhibitors, reduced lipid peroxidation in patients with CHF. No relation was demonstrated between a reduction in oxidative damage and endothelial damage/dysfunction.
Affektiver Halo in Mitarbeiterbefragungen
Authors: Borg Ingwer
Published: March 2003

Zusammenfassung. Mitarbeiterbefragungen enthalten immer zahlreiche Items zur Zufriedenheit der Mitarbeiter mit verschiedenen Dimensionen ihrer Arbeit wie z. B. den Arbeitsplatzbedingungen, der Tätigkeit, der Bezahlung oder dem Vorgesetzten. Die Antworten auf diese Items sind meist systematisch “zu positiv“ in dem Sinn, dass sie positiver ausfallen als die Urteile zu den Teilaspekten der jeweiligen Dimension. Zudem sind die Items oft so hoch positiv interkorreliert, dass sich statistisch praktisch nur ein Faktor zeigt. Für die Praxis ergibt sich hieraus der Eindruck hochgradiger Redundanz. Diese Phänomene werden hier durch das “Sandwich-Modell“ erklärt. Es besagt, dass sich die Zufriedenheit mit einer Dimension der Arbeit ergibt als Kompromiss der Einstellungen zu den einzelnen Komponenten dieser Dimensionen und der allgemeinen Arbeitszufriedenheit, die als affektiver Halo alle Zufriedenheitsurteile überstrahlt. Eine statistische Korrektur der Items in Bezug auf diesen Halo führt zu Indikatoren, die die gleiche Struktur besitzen wie die Originaldaten, aber nicht redundant und damit für Führungsinstrumente informativer sind.
Belastungs- und Beanspruchungsmomente bei der Teleheimarbeit
Authors: Treier Michael
Published: March 2003

Zusammenfassung. Diese Studie folgt nicht den Untersuchungen zur Telearbeit, die den Leser überwiegend mit den Potenzialen und Erwartungen zur Telearbeit im Zusammenhang mit der Informatisierung der Arbeitswelt konfrontieren, sondern beschäftigt sich mit den Belastungs- und Beanspruchungsmomenten bei der Teleheimarbeit. Im Rahmen dieser Darstellung wird der Fokus auf die Arbeits- und Beanspruchungsanalyse bei Teleheimarbeitsplätzen gelegt.
“Mitarbeiterorientierung“ als Bestandteil eines Controlling-Systems in einer großen Landesverwaltung
Authors: Neubach Barbara , Schmidt Klaus-Helmut , Hollmann Sven , Heuer Herbert
Published: March 2003

Zusammenfassung. Im vorliegenden Beitrag wird über die Entwicklung und Einführung eines Controlling-Systems in der Finanzverwaltung von Nordrhein-Westfalen berichtet, das neben leistungsbezogenen Zielen auch das strategische Ziel der “Mitarbeiterorientierung“ mit entsprechenden Kenngrößen abbildet. Der Messansatz wird vorgestellt, und es wird ein Verfahren zum Aufbau eines Wissensmanagement beschrieben, das - als Teil des Controlling-Systems - die einzelnen Dienststellen bei der mitarbeiterorientierten Arbeits- und Organisationsgestaltung unterstützen soll. Das Verfahren besteht in einer Abfolge aufeinander aufbauender Workshops, in denen Beschäftigte aus Dienststellen mit divergierenden Kenngrößenausprägungen Faktoren identifizieren, die aus ihrer Sicht Einfluss auf die Mitarbeiterorientierung nehmen. Die Ergebnisse dieser vergleichenden Analysen wurden in einem Handbuch dokumentiert und allen Dienststellen zur Nutzung verfügbar gemacht.
Rezension des “Teamklima-Inventar (TKI)“ von F. C. Brodbeck, N. Anderson und M. West 1
Authors: Antoni Conny
Published: March 2003

Zusammenfassung. Das Teamklima-Inventar (TKI, Brodbeck, Anderson & West, 2000) ist ein Fragebogen zur Messung der Arbeitsatmosphäre für Innovation und Effektivität in Teams. Es ist eine psychometrisch validierte deutsche Übersetzung des Team Climate Inventory ( Anderson & West, 1994 , 1996 , 1998) . Das Verfahren ist als Diagnoseinstrument zur Teamentwicklung konzipiert und kann zum internen Benchmarking von Teams, zur Gestaltung und Evaluation von Interventionen bezüglich ihrer Auswirkungen auf das Teamklima eingesetzt werden. Für diese Zwecke kann das TKI als ein gut dokumentiertes, reliables und vergleichsweise valides Verfahren zur Erfassung des Innovationsklimas in Arbeitsgruppen angesehen werden. Die prädiktive und insbesondere die Konstruktvalidität des TKI bedürfen noch einer weiteren Überprüfung.
Small-diameter portacaval h-graft shunt: A paradigm shift back to surgical shunting in the management of variceal bleeding in patients with preserved liver function
Authors: Hillebrand Donald J. , Kojouri Kourosh , Cao Sean , Runyon Bruce A. , Ojogho Okechukwu , Concepcion Waldo
Published: March 2003

Small-diameter portacaval H-graft (SDPHG) shunts are partial portosystemic shunts that control variceal bleeding while preserving nutrient blood flow to the liver, minimizing postoperative encephalopathy and liver failure. Since July 1, 1997, we placed SDPHG shunts in 18 patients (age, 52.1 ± 2.6 years; range, 35 to 72 years) with cirrhosis (Child’s class A, B, and C in 6, 10, and 2 patients, respectively) and refractory variceal bleeding who were not candidates for transplantation. Ten procedures (55.6%) were urgent or emergent. SDPHG shunts effectively reduced the portacaval pressure gradient (18 ± 3 v 5 ± 2 mm Hg; P < .05). Surgical times (210 ± 11 minutes), estimated blood losses (358.3 ± 107.8 mL), transfusion requirements (0 transfusions in 10 patients; 55.6% mean, 0.9 ± 0.3 units), and postoperative hospitalization (7.7 ± 1.0 days) were excellent. Surgical mortality (30 days) was 0%. During 14.0 ± 1.9 months (range, 1.1 to 29.1 months) of follow-up, 4 patients (22.2%) died, including both patients with Child’s class C cirrhosis. The cumulative 1-year survival rate was 82.1% (Child’s class A, B, and C, 83.3%, 90%, and 0%, respectively). Long-term survivors had significantly lower preoperative Child-Pugh scores compared with nonsurvivors (7.8 ± 0.3 v 9.5 ± 1.0; P < .05). Postoperative encephalopathy developed in 3 survivors (20%). Fifteen patients (83.3%) have not experienced rebleeding; shunt failure led to rebleeding in only 1 patient (5.6%). SDPHG shunt placement can be performed with low morbidity and surgical mortality. Nontransplantation candidates with Child’s class A and B cirrhosis have excellent long-term survival with this safe, effective, and definitive treatment for refractory variceal bleeding.
Gastrointestinal transplantation: An update
Authors: Kumar Nagappan , Grant David
Published: March 2003

Gastrointestinal transplantation is a life-saving option for patients who have chronic intestinal failure and cannot tolerate total parenteral nutrition (TPN). Early referral is important because of the scarcity of donors and the increased risk of complications in debilitated recipients. One-year patient survival rates range from 50% to 70%. Despite the use of intense immune suppression, most patients experience at least 1 episode of graft rejection. More than 80% of the survivors are able to stop TPN and resume an unrestricted oral diet. Patients with functioning grafts have a good quality of life.
Multiple-spin effects in fast magic angle spinning Lee–Goldburg cross-polarization experiments in uniformly labeled compounds
Authors: Ladizhansky V. , Vinogradov E. , van Rossum B.-J. , de Groot H. J. M. , Vega S.
Published: March 2003

The proton–carbon polarization exchange in Lee–Goldburg cross-polarization magic angle spinning (LG-CP MAS) nuclear magnetic resonance experiments on uniformly C13-labeled compounds at high spinning frequency is studied. It is shown that the multiple carbon labels in the samples greatly influence the spin dynamics during the LG-CP mixing times. The zeroth order effective LG-CP MAS spin Hamiltonian is a sum of zero quantum dipolar interaction terms. These pairwise dipolar terms generally do not commute with each other, making it impossible to factorize the evolution operator. Consequently, the frequencies of the dipolar oscillations as well as the polarization transfer amplitudes become strongly dependent on the configuration of the spins involved in the multiple heteronuclear couplings. The strong carbon–proton couplings usually attenuate polarization transfers between weakly coupled spins. In practice, this implies that except for strongly coupled or isolated heteronuclear C13–H1 spin pairs, it is difficult to unambiguously extract structural constraints from experimental data. To better understand the complexity of the LG-CP processes, experiments on simple three- and four-spin systems are simulated and analyzed. More specifically, it is shown that in CH13–CH13 and CH213–C13 spin systems, a significant amount of the proton polarization can be transferred to both carbons, despite the fact that the individual proton–carbon heteronuclear couplings between each proton and the carbon spins are very different. The dependence of the polarization transfer on the position of the proton carrier frequency is analyzed and it is shown that by an appropriate choice of this frequency, specific polarization transfer pathways can be selected. Experimental results from [U–13C] tyrosine.HCl and [U–13C, N15] histidine.HCl.H2O samples are in satisfactory agreement with simulations.
Optimal Hamiltonian identification: The synthesis of quantum optimal control and quantum inversion
Authors: Geremia J. M. , Rabitz H.
Published: March 2003

We introduce optimal identification (OI), a collaborative laboratory/computational algorithm for extracting quantum Hamiltonians from experimental data specifically sought to minimize the inversion error. OI incorporates the components of quantum control and inversion by combining ultrafast pulse shaping technology and high throughput experiments with global inversion techniques to actively identify quantum Hamiltonians from tailored observations. The OI concept rests on the general notion that optimal data can be measured under the influence of suitable controls to minimize uncertainty in the extracted Hamiltonian despite data limitations such as finite resolution and noise. As an illustration of the operating principles of OI, the transition dipole moments of a multilevel quantum Hamiltonian are extracted from simulated population transfer experiments. The OI algorithm revealed a simple optimal experiment that determined the Hamiltonian matrix elements to an accuracy two orders of magnitude better than obtained from inverting 500 random data sets. The optimal and nonlinear nature of the algorithm were shown to be capable of reliably identifying the Hamiltonian even when there were more variables than observations. Furthermore, the optimal experiment acted as a tailored filter to prevent the laboratory noise from significantly propagating into the extracted Hamiltonian.
Interaction energy surfaces of small hydrocarbon molecules
Authors: Jalkanen Jukka-Pekka , Pakkanen Tapani A. , Yang Yan , Rowley Richard L.
Published: March 2003

Nonbonding interactions of small alkane molecules were studied with ab initio methods. Previously reported energy data for ethane and propane dimers were supplemented with 1747 new configurations of dimers involving slightly larger hydrocarbons. The completed work provides interaction energy surfaces for all combinations of dimer pairs involving ethane, propane, isobutane, and neopentane and thus contains information of all chemical groups found in acyclic alkanes. The strongest attraction of the studied molecule pairs was encountered in isobutane C2h dimer, where an energy minimum of −1.784 kcal mol−1 at 4.28 Å separation of centermost carbon atoms was observed. The composite data set was fitted with a modified Morse pair potential energy function representing each interatomic C–C, C–H, and H–H interaction for easy transfer to molecular dynamics simulation programs. The new generic parameter set was shown to describe the ab initio data for these small alkane molecules with good accuracy. Qualitative comparisons with previously reported potential models were also made, and the relative capability of the models to reproduce quantum-chemical potential energy surfaces was investigated.
Photodissociation of Mg(CH2=CHCN)n+: Excited electronic states of n=1 and 2 and intracluster electron transfer for n=3 and 4
Authors: Furuya Ari , Ohshimo Keijiro , Tsunoyama Hironori , Misaizu Fuminori , Ohno Koichi , Watanabe Hidekazu
Published: March 2003

Photodissociation spectra of mass-selected Mg(CH2=CHCN)n+ cluster ions were investigated in the wavelength region from 415 to 225 nm and 495 to 225 nm for n=1 and 2, respectively, by monitoring the total yield of fragment ions. The absorption bands exhibit large shifts from the P2–S2 resonance line of Mg+. In the spectrum of n=1, there are two bands at 26 400 and 40 800 cm−1. On the other hand, three absorption bands at 22 600, 28 800, and 37 500 cm−1 appear in the spectrum of n=2. The most stable structures in the ground state for n=1 and 2 were obtained by DFT(B3LYP/6-31+G*) calculations, and transition energies from these structures were obtained by using configuration interaction singles approach with the same basis set. The calculated excitation energies show good agreement with the experimental results. In addition, fragment ions of Mg(CH2=CHCN)m+ with m=4 and 5 are found to have high intensities from the parent ions of n=6–10 at a dissociation wavelength of 355 nm. From the result of theoretical calculations for n=3 and 4, a valence electron of Mg+ is found to transfer to the solvating acrylonitrile molecules in these sizes, although this process does not cause an anionic polymerization reaction that observed in alkali metal atom-acrylonitrile neutral clusters.