bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined effects of calcineurin inhibitors or sirolimus with anti-CD40L mAb on alloengraftment under nonmyeloablative conditions
Authors: Taylor Patricia A. , Lees Christopher J. , Wilson Jessica M. , Ehrhardt Michael J. , Campbell Matthew T. , Noelle Randolph J. , Blazar Bruce R. 
Published: October 2002

AbstractThe immunosuppressive drugs, cyclosporine A (CsA), tacrolimus, or sirolimus, were analyzed as single agents and in combination with anti-CD40L monoclonal antibody (mAb) for their effects on alloengraftment in mice conditioned with minimal total body irradiation (TBI). Whereas anti-CD40L mAb facilitated chimerism, neither sirolimus nor CsA resulted in substantial alloengraftment. However, sirolimus was synergistic with anti-CD40L mAb for inducing donor chimerism. Contrary to expectations, CsA, a T-cell receptor (TCR) signaling inhibitor, did not abrogate anti-CD40L mAb-facilitated engraftment but rather increased engraftment in anti-CD40L mAb-treated mice. Although tacrolimus alone or with anti-CD40L mAb resulted in similar levels of donor chimerism, donor T-cell reconstitution was very low in tacrolimus-treated mice. At 1 week after transplantation, CsA decreased thymic numbers more profoundly than sirolimus or tacrolimus in anti-CD40L mAb-treated recipients. In contrast, only sirolimus resulted in a decrease in host splenic T-cell numbers in anti-CD40L mAb-treated recipients. Importantly, sirolimus and anti-CD40L mAb induced profound donor tolerance with 100% acceptance of donor skin grafts placed early after bone marrow transplantation (BMT). In contrast, anti-CD40L mAb alone or in combination with CsA resulted in 12% or less donor skin graft acceptance early (1 month) and 60% or less later (3 months) after BMT. These data have clinical relevance and indicate that immunosuppressive pharmacologic agents enhance anti-CD40L mAb-facilitated alloengraftment and tolerance induction under nonmyeloablative conditioning.
Combined treatment with the checkpoint abrogator UCN-01 and MEK1/2 inhibitors potently induces apoptosis in drug-sensitive and -resistant myeloma cells through an IL-6–independent mechanism
Authors: Dai Yun , Landowski Terry H. , Rosen Steven T. , Dent Paul , Grant Steven 
Published: October 2002

AbstractThe effects of combined exposure to the checkpoint abrogator UCN-01 and pharmacologic MEK1/2 inhibitors were examined in human multiple myeloma (MM) cell lines. Treatment of RPMI8226, NCI-H929, and U266 MM cells with a minimally toxic concentration of UCN-01 (150 nM) for 24 hours resulted in mitogen-activated protein (MAP) kinase activation, an effect that was blocked by coadministration of the MEK1/2 inhibitor PD184352. These events were accompanied by enhanced activation of p34cdc2 and a marked increase in mitochondrial damage (loss of ΔΨm; cytochrome c and Smac/DIABLO (direct IAP binding protein with low pI) release), poly(ADP-ribose) polymerase (PARP) cleavage, and apoptosis. PD184352/UCN-01 also dramatically reduced clonogenic survival in each of the MM cell lines. In contrast to As203, apoptosis induced by PD184352/UCN-01 was not blocked by the free-radical scavenger n-acetyl-l-cysteine. Whereas exogenous interleukin 6 substantially prevented dexamethasone-induced lethality in MM cells, it was unable to protect them from PD184352/UCN-01–induced apoptosis despite enhancing Akt activation. Insulinlike growth factor 1 (IGF-1) also failed to diminish apoptosis induced by this drug regimen. MM cell lines selected for a high degree of resistance to doxorubicin, melphalan, or dexamethasone, or displaying resistance secondary to fibronectin-mediated adherence, remained fully sensitive to PD184352/UCN-01–induced cell death. Finally, primary CD138+ MM cells were also susceptible to UCN-01/MEK inhibitor-mediated apoptosis. Together, these findings suggest that simultaneous disruption of cell cycle and MEK/MAP kinase signaling pathways provides a potent stimulus for mitochondrial damage and apoptosis in MM cells, and also indicate that this strategy bypasses the block to cell death conferred by several other well-described resistance mechanisms.
Locus control regions
Authors: Li Qiliang , Peterson Kenneth R. , Fang Xiangdong , Stamatoyannopoulos George 
Published: October 2002

AbstractLocus control regions (LCRs) are operationally defined by their ability to enhance the expression of linked genes to physiological levels in a tissue-specific and copy number–dependent manner at ectopic chromatin sites. Although their composition and locations relative to their cognate genes are different, LCRs have been described in a broad spectrum of mammalian gene systems, suggesting that they play an important role in the control of eukaryotic gene expression. The discovery of the LCR in the β-globin locus and the characterization of LCRs in other loci reinforces the concept that developmental and cell lineage–specific regulation of gene expression relies not on gene-proximal elements such as promoters, enhancers, and silencers exclusively, but also on long-range interactions of variouscis regulatory elements and dynamic chromatin alterations.
Echo-planar magnetic resonance imaging of Gaviscon alginate rafts in-vivo
Authors: Marciani Luca , Little Sarah L , Snee Janice , Coleman Nicholas S , Tyler Damian J , Sykes John , Jolliffe Ian G , Dettmar Peter W , Spiller Robin C , Gowland Penny A 
Published: October 2002

Abstract
Liquid Gaviscon and Gaviscon Advance are established reflux suppressant formulations. This study describes the use of echo-planar magnetic resonance imaging (EPI) to visualise non-invasively intragastric alginate rafts of Liquid Gaviscon and Gaviscon Advance in healthy subjects. Secondly, the feasibility of using relaxation rate (T2−1) measurements to monitor changes in the physicochemical properties of the rafts in-vivo is evaluated. Six subjects ingested 500 mL of a liquid meal and received a single dose of 20 mL Liquid Gaviscon or 10 mL Gaviscon Advance on 2 separate visits each and were imaged every 15 min. An alginate raft was observed in the stomach for all subjects and both treatments. The raft was observed to consist of a few large fragments on the majority of the scans for both products. At t = 60 min a raft was still present in all cases. Three-dimensional volume reconstructions showed, for the first time, the spatial distribution of the rafts within the gastric lumen. The T2−1 data showed potential for assessment of dynamic changes in the physicochemical properties of the alginate rafts in-vivo. We conclude that EPI shows great potential in assessing alginate rafts formation in-vivo.
In-vivo and in-vitro anti-inflammatory effect of Echinacea purpurea and Hypericum perforatum
Authors: Raso Giuseppina Mattace , Pacilio Maria , Di Carlo Giulia , Esposito Emanuela , Pinto Luisa , Meli Rosaria 
Published: October 2002

Abstract
Echinacea purpurea (L.) Moench and Hypericum perforatum (L.) were evaluated for their anti-inflammatory activity against carrageenan-induced paw oedema in mice. Each drug was administered orally to mice at 30 and 100 mg kg−1, twice daily. Only the higher dose significantly inhibited, time dependently, the formation of oedema, evaluated as area under the curve (echinacea P &lt; 0.01; hypericum P &lt; 0.05). Western blot analysis showed that in-vivo treatment with these extracts could modulate lipopolysaccharide (LPS) and interferon-γ induced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in peritoneal macrophages. In particular, treatment with 100 mg kg−1 hypericum inhibited both iNOS and COX-2 expression, whereas treatment with 100 mg kg−1 echinacea down-regulated only COX-2 expression. The present study suggests that the anti-inflammatory effect of these extracts could be in part related to their modulation of COX-2 expression.
Amitriptyline has a dual effect on the conductive properties of the epithelial Na channel
Authors: Pena Florentina , Neaga Emil , Amuzescu Bogdan , Nitu Alina , Flonta Maria-Luisa 
Published: October 2002

Abstract
This study was undertaken with the aim of testing the action of amitriptyline on the epithelial Na channel (ENaC), which belongs to the same family (Deg/ENaC) as ASICs (acid-sensing ion channels) and many other putative members in the brain. We assumed that, having a common protein structure, characterization of the amitriptyline-ENaC interaction could help to elucidate the analgesic mechanism of this tricyclic antidepressant. Na-channel characteristics were derived from the analysis of blocker-induced lorentzian noise produced by amiloride. The effect of amitriptyline, present in the mucosal bathing solution, on the transepithelial short-circuit current (1sc) and conductance (Gt), and on the blocker-induced noise of apical Na channels, was studied on isolated ventral skin of the frog Rana ridibunda. Amitriptyline exerted a dual effect on the macroscopic short-circuit current and conductance of the epithelia, increasing these two parameters in the concentration range 0.1–50 μM, while at higher concentrations (100–1000 μM) it showed an inhibitory action. The decrease in the association rate (k01) of amiloride to the apical Na channels from 15.6 ± 4.2 μM−1 S−1 in control Cl-Ringer to 7.4 ± 1.7 μM−1 S−1 at 200 μM amitriptyline in a concentration-dependent manner suggests a competitive binding of amitriptyline to the pyrazine ring binding site for amiloride.
Evodia rutaecarpa protects against circulation failure and organ dysfunction in endotoxaemic rats through modulating nitric oxide release
Authors: Chiou Wen Fei , Ko Han Chieh , Chen Chieh Fu , Chou Cheng Jen 
Published: October 2002

Abstract
Using a rat model of septic shock we studied the effects of Evodia rutaecarpa, a Chinese herbal medicine with antimicrobial and anti-inflammatory activity, on haemodynamic parameters, biochemical markers of organ function and nitric oxide (NO) production. Anaesthetized rats challenged with a high dosage of endotoxin (Escherichia coli lipopolysaccharide; LPS; 50 mg kg−1, i.v.) for 6 h showed a severe decrease in mean arterial pressure. This was accompanied by delayed bradycardia, vascular hyporeactivity to phenylephrine and increase in plasma levels of lactate dehydrogenase, aspartate aminotransferase, bilirubin and creatinine, as well as NOx (NO−2 plus NO−3). Pretreatment with ethanol extract of E. rutaecarpa (25,50 and 100 mg kg−1, i.v.), 1 h before LPS, dose-dependently prevented the circulation failure, vascular hyporeactivity to phenylephrine, prevented liver dysfunction and reduced the NOx over-production in plasma in endotoxaemic rats. A selective inducible NO-synthase (iNOS) inhibitor, aminoguanidine (15 mg kg−1, i.v.), also effectively ameliorated the above pathophysiological phenomenon associated with endotoxaemia so that the normal condition was approached. Endotoxaemia for 6 h resulted in a significant increase in iNOS activity in the liver homogenate, which was attenuated significantly by E. rutaecarpa pretreatment. In summary, E. rutaecarpa, at the dosages used, exerted these beneficial effects probably through inhibition of iNOS activity and subsequent modulation of the release of NO. These significant results may offer E. rutaecarpa as a candidate for the treatment of this model of endotoxaemia.
Synthesis and Evaluation of Cationic Lipids Bearing Cholesteryl Groups for Gene Delivery In Vitro
Authors: Zhu Man-Zhou , Wu Qi-Hua , Zhang Guisheng , Ren Tan , Liu Dexi , Guo Qing-Xiang 
Published: October 2002

Abstract
A series of cationic lipids were designed and synthesized as vectors for gene delivery. The lipids contain a ketal moiety as a linker and a cholesteryl group as a hydrophobic tail. The framework of cholesteryl derivatives could increase the stability of liposomes by stabilizing the bilayers and their complexes with DNA to improve the transfection efficiency. The ketal bonds in lipids should easily degrade in an acidic environment in a cell (pH = 2–5) after transfection, resulting in little toxicity; in the neutral environment outside of cells (pH = 7), they should be stable as gene carriers. Gene transfer experiments in vitro with BL-6, 3LL, 293, 3T3, and Hela cells were performed. The results show that the gene transfection activity of three lipids is quite high, with least toxicity to cells under the experimental conditions.
SH-Group Introduction to the N-terminal of Subtilisin and Preparation of Immobilized and Dimeric Enzymes
Authors: Tada Tomoko , Mano Kazuhito , Yoshida Eri , Tanaka Naoki , Kunugi Shigeru 
Published: October 2002

Abstract
An SH group was introduced at the N-terminal of subtilisin Carlsberg by reacting with 2-iminothiolane·HCl (Traut reagent) in weakly basic media. The obtained subtilisin-SH was coupled with maleimide connected to an amine polymer (poly(allylamine); PAA), both in soluble and insoluble forms, or connected to the N-terminal of another subtilisin molecule. The immobilized subtilisins and subtilisin dimer thus obtained showed higher specificity towards proteineous substrates, although they had lower activities towards a tetrapeptide substrate. Subtilisins immobilized (conjugated) to PAA were more stable against autolytic and thermal disactivation than the intact enzyme.
Effect of Substitution on the Electrical Conductivity of LiMxMn2−xO4 (M = Cu, Mg, Zn)
Authors: Tomita Yasumasa , Yonekura Hiroshi , Kobayashi Kenkichiro 
Published: October 2002

Abstract
LiMxMn2−xO4 (M = Cu, Mg and Zn; x ≤ 0.5) was synthesized and the variance of the crystal structure and the electrical conductivity due to the substitution were studied. The crystal structure was changed by substitution, and the lattice constants decreased with x in LiZnxMn2−xO4. Both Zn and Li ions occupied tetrahedral sites. The Li–O bond became longer and Mn–O became shorter with increasing the content. The electrical conductivity for Mg and Zn compounds decreased from 10−4 S cm−1 to 10−7 S cm−1 with an increase in the Mg and Zn content. In the Cu compound, the conductivity was not changed very much. The infrared spectra for the Mg and Zn compounds shifted with x, indicating that the Mn–O bond became shorter and the Li–O bond longer with an increase in x. An XPS study showed a conversion of Mn3+ to Mn4+ with increasing the Mg, Zn or Cu content in these compounds.
Selective Transport of Heavy Metal Ions across a Cation-Exchange Membrane with a Chelating Agent in the Receiving Phase
Authors: Igawa Manabu , Narita Yohei , Okochi Hiroshi 
Published: October 2002

Abstract
Heavy metal ions can be selectively transported under the concentration gradient across a cation-exchange membrane with a chelating agent in the receiving phase. The selectivity depends on the complex formation constants of the ions with the agent. Metal ions are adsorbed into a cation-exchange membrane via the ion-exchange reaction and diffuse across the membrane. The desorption process is facilitated by the complexation in the receiving phase, which causes a large transport rate across the membrane. A transport equation was established and the theoretical values estimated by the equation and the permeation characteristics values obtained experimentally agreed well with the measured ion flux. The selectivity of the metal ions in the mixed solution is increased in the adequate concentration of the chelating agent in the receiving phase, when the chelate formation reaction may occur competitively between the ions with the agent in the receiving phase. The metal ions in the complex solution can be stripped as free ions across a cation-exchange membrane via the ion-exchange reaction with protons under a concentration gradient of acid.
Self-Assembly of Hexakis(4-pyridylmethoxy)cyclotriphosphazene and 1,4-Anthracenedicarboxylic Acid: Structure and Inclusion Behavior
Authors: Itaya Tomoyuki , Azuma Nagao , Inoue Kenzo 
Published: October 2002

Abstract
2,2,4,4,6,6-Hexakis(4-pyridylmethoxy)-2λ5,4λ5,6λ5,-cyclotriphosphazene (PyPN) and 1,4-anthracenedicarboxylic acid (DCA) formed polymeric supramolecules through hydrogen bonding between carboxyl and pyridyl groups. Two supramolecular self-assemblies were obtained: crystals 1 composed of PyPN/DCA = 1 : 2 from DMSO solution, and crystals 2 composed of PyPN/DCA = 1 : 3 from DMF solution. The former is monoclinic, space group P21/n with a = 12.419 Å, b = 24.10 Å, c = 20.794 Å, β = 93.53°, V = 6212 Å3, Z = 4. The X-ray analysis showed that the complementary hydrogen bonding occurs with two DCA molecules, one on each side of the phosphazene ring of PyPN, to give a novel assembly with polymeric structure. The self-assembly obtained from DMF solution seems to take a cylindrical structure composed of an alternating sequence of one PyPN and three DCA molecules and to be packed into a hexagonal arrangement, as suggested by X-ray diffraction data. These results and the inclusion behaviors of the solvent molecules into 1 and 2 are described.
The Crystal Structure and Tribology of a Novel Organic Crystalline Powder: the Mechanism of Lubricity
Authors: Nonomura Yoshimune , Kurita Kenkou , Kashimoto Akio , Hotta Hajime , Suzuki Toshiyuki , Kaneko Yohei , Iitaka Kazuhiro 
Published: October 2002

Abstract
A novel lubricant material, calcium N-lauroyl taurate (C11H23CONH(CH2)2SO3·0.5Ca, CaLT), has been synthesized and characterized. The powder of CaLT is a plate-shaped crystal with a lamellar structure. CaLT shows superior lubricity as a result of its unique internal and aggregate structure. When the CaLT powder is applied to an artificial skin, the frictional coefficient is favorably lower than that of other solid lubricants of similar type. The frictional coefficient of CaLT decreases rapidly at initial passage and becomes constant when CaLT is repeatedly rubbed onto an artificial skin. The high lubricity may result from disintegration of the powder aggregates, cleavage of the lamellar layers and deformation of the powder particles. This novel lubricant material, CaLT, will be a powerful ingredient of some cosmetic and/or personal-care products in the near future.
Hyperproinsulinaemia in elderly subjects: evidence for age-related pancreatic β-cell dysfunction
Authors: Gama R , Medina-Layachi N , Ranganath L , Hampton S , Morgan L , Marks V 
Published: October 2002

SUMMARY. We investigated whether pancreatic pathogenesis of glucose intolerance in the elderly by comparing plasma glucose, immunoreactive insulin, C-peptide and proinsulin concentrations during a 100-g oral glucose load in six healthy older male volunteers [aged 69 (65·9-74·9) years; median (95% confidence limits)] and seven young male controls [aged 24·0 (21·9-26·3) years]. Fasting and integrated concentrations of glucose and C-peptide were similar in the elderly and young. Although fasting, insulin and proinsulin levels were similar, integrated insulin ( P=0·05) and proinsulin ( P< 0·05) concentrations were higher in the elderly than in controls. Insulin resistance, measured as homeostasis model assessment, was greater ( P< 0·05) in the elderly than in controls. Elderly men had greater molar ratios of integrated insulin:C-peptide ( P< 0·05) and proinsulin:Cpeptide ( P< 0·01) but their respective fasting molar ratios were similar when compared with controls. Pancreatic β-cell secretion in older subjects, as assessed by C-peptide concentrations, was inappropriately low in the presence of insulin resistance. Their post-prandial 'hyperinsulinaemia' is probably due to a combination of hyperproinsulinaemia and reduced metabolic clearance of insulin. Older subjects had disproportionately high proinsulin to C-peptide levels, suggesting pancreatic β-cell dysfunction. These results are consistent with the notion that decreased insulin sensitivity and pancreatic β-cell dysfunction may predispose the elderly to glucose intolerance.
Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies
Authors: Sonntag O , Scholer A 
Published: October 2002

A group of international experts prepared two lists of drugs with their serum/plasma and urine concentrations, which should be used when evaluating the performance of a new laboratory method. The two lists were verified by running in vitro interference studies in three European laboratories on Hitachi instruments. The study identified the following new interferants: acid phosphatase in serum by ibuprofen and theophylline; non-prostatic acid phosphatase in serum by cefoxitin and doxycycline; creatine kinase MB in serum by doxycycline; total bilirubin in serum (Jendrassik-Grof method) by rifampicin and intralipid; total bilirubin in serum (DPD method) by intralipid; creatinine in serum (Jaffe method) by cefoxitin; fructosamine in serum by levodopa and methyldopa; uric acid in serum by levodopa, methyldopa and tetracycline; carbamazepine in serum by doxycycline, levodopa, methyldopa and metronidazole; digitoxin in serum by rifampcin; phenytoin in serum by doxycycline, ibuprofen, metronidazole and theophylline; theophylline in serum by acetaminophen, cefoxitin, doxycycline, levodopa, phenylbutazone and rifampicin; tobramycin in serum by cefoxitin, doxycycline, levodopa, rifampicin and phenylbutazone; valproic acid in serum by phenylbutazone; C3 in serum by intralipid; C4 in serum by doxycycline; rheumatoid factor in serum by ibuprofen and metronidazole; pancreatic amylase and total amylase in urine by acetylcysteine, ascorbic acid, cefoxitin, gentamicin, levodopa, methyldopa and ofloxacin; magnesium in urine by acetylcysteine, gentamicin and methyldopa; β2-microglobulin in urine by ascorbic acid; total protein in urine by ascorbic acid, Ca-dobesilate and phenylbutazone. Interference in acid phosphatase, creatine kinase MB and bilirubin methods was observed at very low analyte concentrations, and therefore it may not be evident at higher concentrations. The study confirmed the usefulness of the recommendation.
Comparison of intact and 'whole molecule' parathyroid hormone assays in patients with histologically confirmed post-renal transplant osteodystrophy
Authors: Godber Ian M , Parker Cornelle R , Lawson Nigel , Hitch Tony , Porter Christine J , Roe Simon D , Cassidy Michael JD , Hosking David J 
Published: October 2002

Background Fragments of parathyroid hormone (PTH) have been identified (amino acids 7-84) which may interfere with commercially available 'intact molecule' PTH assays. Novel assays which employ an antibody directed to the first seven amino acids of the N-terminus of PTH are thought to be free from cross-reactivity with the 7-84 fragments, and therefore measure true 'whole molecule' PTH. Transplant recipients (as well as those in end-stage renal failure) have been reported to have elevated levels of 'intact' in comparison with 'whole molecule' PTH. Methods PTH concentrations were assessed in serum samples obtained from female renal transplant recipients previously classified as either having hyperparathyroid ( n = 14) or adynamic bone disease ( n = 14) by transiliac crest bone biopsy. PTH was measured as 'whole molecule' (Scantibodies 'whole molecule' PTH) and 'intact' (DPC Immulite 2000 intact PTH and Scantibodies total PTH). Results Scantibodies 'whole molecule' PTH (all-subject mean 48·7 ng/L, ± 53·0) were significantly lower than DPC intact (83·5 ng/L, ± 88·1; P ≤0001) and Scantibodies total PTH (80·5 ng/L, ≤ 92·4; P ≤ 0·0001). However, the differences between the 'whole molecule' and 'intact' measurements were similar across the two patient groups, and reflected the lower reference range employed by the 'whole molecule' assay. Conclusion The 'whole molecule' PTH assay was unable to discriminate between the two patient populations and provided very little additional clinical information to that obtained from the intact PTH assays.