bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoantibodies against granulocyte colony‐stimulating factor in Felty's syndrome and neutropenic systemic lupus erythematosus
Authors: Hellmich Bernhard , Csernok Elena , Schatz Helmut , Gross Wolfgang L. , Schnabel Armin 
Published: October 2002

AbstractObjectiveCytokines and growth factors can be a target of autoantibodies in systemic inflammatory diseases. We examined whether patients with neutropenia and either Felty's syndrome (FS) or systemic lupus erythematosus (SLE) have autoantibodies against granulocyte colony‐stimulating factor (G‐CSF) and whether these autoantibodies are functionally relevant.MethodsFifteen patients with neutropenia due to FS were matched for age, sex, and disease activity with 16 normocytic rheumatoid arthritis (RA) control patients. Sixteen patients with SLE and neutropenia were matched with 16 normocytic SLE control patients. Antibodies against G‐CSF were measured by enzyme‐linked immunosorbent assay and Western blotting. Antibody specificity was verified by competitive inhibition using recombinant human G‐CSF. The effect of anti–G‐CSF antibodies on the functional activity of their target molecule was measured in a bioassay using G‐CSF–sensitive murine 32D cells.ResultsIgG anti–G‐CSF was found in 11 FS patients, 6 SLE patients with neutropenia, 6 SLE control patients, and none of the RA control patients. IgM anti–G‐CSF was found in 6 neutropenic and 3 normocytic SLE patients. Anti–G‐CSF antibodies were associated with an exaggerated serum level of G‐CSF and a low neutrophil count. A neutralizing effect of anti–G‐CSF antibodies on its target molecule was found in 3 of the 9 patients tested. Irrespective of the presence or absence of anti–G‐CSF antibodies, neutropenic patients with FS and SLE had exaggerated serum levels of G‐CSF.ConclusionAnti–G‐CSF autoantibodies are common in neutropenia due to FS and SLE. In individual patients, these autoantibodies have a neutralizing capacity. In patients without neutralizing antibodies, hyposensitivity of the myeloid cells to G‐CSF appears to be central to the pathogenesis of the neutropenia in FS and SLE.
Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis
Authors: Aganna Ebun , Martinon Fabio , Hawkins Philip N. , Ross John B. , Swan Daniel C. , Booth David R. , Lachmann Helen J. , Gaudet Roxanne , Woo Patricia , Feighery Conleth , Cotter Finbarr E. , Thome Margot , Hitman Graham A. , Tschopp Jürg , McDermott Michael F. 
Published: October 2002

AbstractObjectiveFamilial cold urticaria (FCU) and Muckle‐Wells syndrome (MWS) are dominantly inherited autoinflammatory disorders that cause rashes, fever, arthralgia, and in some subjects, AA amyloidosis, and have been mapped to chromosome 1q44. Sensorineural deafness in MWS, and provocation of symptoms by cold in FCU, are distinctive features. This study was undertaken to characterize the genetic basis of FCU, MWS, and an overlapping disorder in French Canadian, British, and Indian families, respectively.MethodsMutations in the candidate gene NALP3, which has also been named CIAS1 and PYPAF1, were sought in the study families, in a British/Spanish patient with apparent sporadic MWS, and in matched population controls. Identified variants were sought in 50 European subjects with uncharacterized, apparently sporadic periodic fever syndromes, 48 subjects with rheumatoid arthritis (RA), and 19 subjects with juvenile idiopathic arthritis (JIA).ResultsPoint mutations, encoding putative protein variants R262W and L307P, were present in all affected members of the Indian and French Canadian families, respectively, but not in controls. The R262W variant was also present in the subject with sporadic MWS. The V200M variant was present in all affected members of the British family with MWS, in 2 of the 50 subjects with uncharacterized periodic fevers, and in 1 of 130 Caucasian and 2 of 48 Indian healthy controls. No mutations were identified among the subjects with RA or JIA.ConclusionThese findings confirm that mutations in the NALP3/CIAS1/PYPAF1 gene are associated with FCU and MWS, and that disease severity and clinical features may differ substantially within and between families. Analysis of this gene will improve classification of patients with inherited or apparently sporadic periodic fever syndromes.
Pharmacological and pharmacokinetic evaluation of celecoxib prodrugs in rats
Authors: Mamidi Rao N.V.S. , Mullangi Ramesh , Kota Jagannath , Bhamidipati Ravikanth , Khan Ansar A. , Katneni Kasiram , Datla Srinivasaraju , Singh Sunil K. , Rao Koteswar Y. , Seshagiri Rao C. , Srinivas Nuggehally R. , Rajagopalan Ramanujam 
Published: October 2002

AbstractThis study demonstrates the utility of an in vitro – in vivo correlative approach in the selection and optimization of a prodrug candidate of celecoxib (CBX), a COX2 inhibitor. As an initial screening step, a comparative single oral dose pharmacokinetic study was conducted in rats for CBX and its three aliphatic acyl water‐soluble prodrugs viz., CBX‐acetyl (CBX‐AC), CBX‐propionyl (CBX‐PR) and CBX‐butyryl (CBX‐BU) at high equimolar dose, 100 mg/kg. Only CBX‐BU and CBX‐PR converted rapidly to CBX and yielded approximately five‐fold greater systemic exposure of CBX than CBX alone or CBX‐AC. Rank order of systemic exposure of prodrugs in its intact form was CBX‐AC >CBX‐PR >CBX‐BU. Further in vitro hydrolysis studies of CBX prodrugs in intestinal mucosal suspensions and liver homogenates indicated that CBX‐BU is rapidly and completely converted to CBX, whereas CBX‐PR and CBX‐AC require longer incubation period for complete conversion to CBX. There was a very good correlation of the in vitro and in vivo data supporting CBX‐BU as the prodrug of choice. Further in vitro pharmacological studies showed that COX2 selective inhibition is improved for CBX‐BU as compared to CBX‐AC and CBX‐PR. Dose proportionality in pharmacokinetic studies of CBX‐BU and CBX at equimolar oral doses confirmed that relative oral bioavailability of CBX was improved following CBX‐BU administration and there was linearity in pharmacokinetics of CBX over a wide dose range (10–100 mg/kg), whereas CBX in its conventional form showed poor bioavailability and lack of dose linearity in pharmacokinetics. The oral bioavailability of CBX from CBX‐BU was dose independent and was in the range 78–96%. At a 50% reduced molar dose, CBX‐BU showed an equivalent efficacy to that of CBX in the in vivo carrageenan model. Based on the study, water‐soluble CBX‐BU prodrug can be considered for clinical development in view of its potential advantages.Copyright © 2002 John Wiley & Sons, Ltd.
Pharmacokinetics and tissue distribution of intravenous pefloxacin for antibiotic prophylaxis in biliary surgery
Authors: Gascón A.R. , Campo E. , Olea E. , Hernández R.M. , Calvo B. , Errasti J. , Pedraz J.L. 
Published: October 2002

AbstractThe plasma levels and tissue penetration of pefloxacin were studied after prophylactic administration to patients undergoing elective biliary surgery. Pefloxacin was administered as a single dose of 800 mg given intravenously as an infusion 1 h before surgery. Over a period of two years, cultures of bile and stone were performed after cholecystectomy in order to find the main pathogens present in the geographical area of the hospital of Txagorritxu (Vitoria, Spain), as well as to test the antimicrobial susceptibility of these bacteria to pefloxacin. Thirty seven per cent of the bile and stone cultures were positive, and 75 different species were isolated. E. coli was the predominant microorganism (25%). Other frequent microorganisms were E. faecium (9.3%), S. epidermidis (6.6%) and Cl. perfringens (6.6%). Most species isolated were susceptible to pefloxacin, with MIC90 values of 0.125 μg/ml for E. coli, 0.5 μg/ml for S. epidermidis and 1 μg/ml for Cl. perfringens. E. faecium was resistant, with a MIC90 value of 8 μg/ml but a MIC50 of 4 μg/ml (intermediate). After pefloxacin infusion, adequate drug plasma levels (>MIC90) for the most frequent pathogens were found throughout the procedure. Elimination half‐life was estimated as 22.03±6.91 h; the area under the concentration–time curve from zero to infinite had a value of 275.07±130.02 mg h/l and the values for volume of distribution at steady‐state and plasma clearance were 96.48±28.65 L and 3.60±1.83 l/h, respectively. Bile pefloxacin concentrations generally exceeded the minimum inhibitory concentrations for most relevant pathogens. Drug levels in gallbladder and subcutaneous tissues were also above the MIC90 for extended periods. Patients were observed daily throughout their hospital stay. This included examination of the surgical wound and recording of body temperature. No cases of anaerobic infection were noted in the study patients. Other constants such as hospitalization stay and time of recuperation were normal for this type of surgery. According to these results, pefloxacin presents many features that make it suitable for use as a therapeutic prophylactic agent, such as its broad spectrum of antimicrobial activity and favorable pharmacokinetic properties. Copyright © 2002 John Wiley & Sons, Ltd.
Disposition of acamprosate in the rat: Influence of probenecid
Authors: Zornoza Teodoro , Guerri Consuelo , Polache Ana , Granero Luis 
Published: October 2002

AbstractThe purpose of the present study was to investigate the disposition of acamprosate (calcium bis acetyl‐homotaurine) in the rat. Initially, we studied the linearity of acamprosate disposition and the fraction of acamprosate excreted unchanged in the urine of the animals. Rats received 9.3, 36.6 or 73.3 mg/kg of the drug as an intravenous bolus. The statistical analysis of the pharmacokinetic parameters did not reveal any significant difference, indicating that acamprosate disposition was linear within the range of the doses assayed. On average, 95% of the administered dose was excreted unchanged in the urine of the animals in the 0–6 h post‐administration period indicating that renal excretion is the main elimination route for this drug. Acamprosate was also administered by the intravenous route at three different constant infusion rates (2.65, 132.5 and 530 μg/min) in order to quantify total (Clt) and renal (Clr) plasma clearances at steady‐state conditions. The mean Clr values were, respectively, 4.60±0.42, 4.28±0.52 and 4.08±0.67 ml/min, practically equivalent to the Clt values (4.78±0.38, 4.51±0.36 and 4.21±0.56 ml/min), confirming that the drug is mainly eliminated via renal excretion. Moreover, Clr values were clearly higher than the glomerular filtration rate (2.61±0.26 ml/min), suggesting the existence of a highly efficient tubular secretion mechanism in the renal excretion of the drug. To confirm this hypothesis, two groups of rats were intravenously treated with probenecid (33.3 or 66.6 mg/kg) prior to acamprosate administration (9.3 mg/kg). Probenecid provoked a statistically significant dose‐dependent reduction in the total clearance of acamprosate (from 5.8±0.7 ml/min in the control group to 2.6±0.1 ml/min in the animals treated with 66 mg/kg of probenecid) demonstrating the existence of a tubular secretion process on the renal excretion of acamprosate in the rat. Copyright © 2002 John Wiley & Sons, Ltd.
Out of Africa with regional interbreeding? Modern human origins
Authors: Satta Yoko , Takahata Naoyuki 
Published: October 2002

AbstractA central issue in paleoanthropology is whether modern humans emerged in a single geographic area and subsequently replaced the preexisting people in other areas. Although the study of human mitochondrial DNAs supported this single‐origin and complete‐replacement model, a recent paper1 argues that humans expanded out of Africa more than once and regionally interbred. However, both the genetic antiquity and the impact of the African contribution to modern Homo sapiens are so great as to view Africa as a central place of human evolution. Despite the possibility that out‐of‐Africa H. sapiens interbred with other populations, this evidence is more consistent with the uniregional hypothesis than the multiregional hypothesis of modern human origins. BioEssays 24:871–875, 2002. © 2002 Wiley Periodicals, Inc.
Bioreduction and biocrystallization of palladium by Desulfovibrio desulfuricans NCIMB 8307
Authors: Yong Ping , Rowson Neil A. , Farr J. Peter G. , Harris I. Rex , Macaskie Lynne E. 
Published: October 2002

AbstractThe reduction of Pd(II) to Pd(0) was accelerated by using the sulfate‐reducing bacterium Desulfovibrio desulfuricans NCIMB 8307 at the expense of formate or H2 as electron donors at pH 2–7. With formate no reduction occurred at pH 2, but with H2 50% of the activity was retained at pH 2, with the maximum rate (1.3–1.4 μ mol min−1 mg dry cells−1) seen at pH 3–7, which was similar to the rate with formate at neutral pH. Excess nitrate was inhibitory to Pd(II) reduction using formate, but not H2. Chloride ion was inhibitory as low as 100 mM using formate but with H2 only ca. 25% inhibition was observed at 500 mM Cl− and H2 was concluded to be the electron donor of choice for the potential remediation of industrial wastes. Deposited Pd was visible on the cells using transmission and scanning electron microscopy and analysis by energy dispersive X‐ray microanalysis (EDAX) identified the deposit as Pd, confirmed as Pd(0) by X‐ray powder diffraction analysis (XRD). The crystal size of the biodeposited Pd(0) was determined to be only 50% of the size of Pd(0) crystals manufactured chemically from Pd(II) at the expense of H2 and, unlike the chemically manufactured material, the biocrystal size was independent of the pH. The “biological” Pd(0) functioned as a superior chemical catalyst in a test reaction which liberated hydrogen from hypophosphite. Pd, and also Pt and Rh, could be recovered by resting cell suspensions under H2 from an industrial processing wastewater, suggesting a possible future application of bioprocessing technology for precious metals. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 369–379, 2002.
Scale‐up and optimization of an acoustic filter for 200 L/day perfusion of a CHO cell culture
Authors: Gorenflo Volker M. , Smith Laura , Dedinsky Bob , Persson Bo , Piret James M. 
Published: October 2002

AbstractAcoustic cell retention devices have provided a practical alternative for up to 50 L/day perfusion cultures but further scale‐up has been limited. A novel temperature‐controlled and larger‐scale acoustic separator was evaluated at up to 400 L/day for a 107 CHO cell/mL perfusion culture using a 100‐L bioreactor that produced up to 34 g/day recombinant protein. The increased active volume of this scaled‐up separator was divided into four parallel compartments for improved fluid dynamics. Operational settings of the acoustic separator were optimized and the limits of robust operations explored. The performance was not influenced over wide ranges of duty cycle stop and run times. The maximum performance of 96% separation efficiency at 200 L/day was obtained by setting the separator temperature to 35.1°C, the recirculation rate to three times the harvest rate, and the power to 90 W. While there was no detectable effect on culture viability, viable cells were selectively retained, especially at 50 L/day, where there was a 5‐fold higher nonviable washout efficiency. Overall, the new temperature‐controlled and scaled‐up separator design performed reliably in a way similar to smaller‐scale acoustic separators. These results provide strong support for the feasibility of much greater scale‐up of acoustic separations. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 438–444, 2002.
Purification of a functional gene therapy vector derived from Moloney murine leukaemia virus using membrane filtration and ceramic hydroxyapatite chromatography
Authors: Kuiper Marcel , Sanches Raquel M. , Walford James A. , Slater Nigel K.H. 
Published: October 2002

AbstractThe ability of membrane ultra‐ and diafiltration and two chromatography media, Matrex⌖ Cellufine™ Sulfate (Millipore) and Macro‐Prep⌖ ceramic hydroxyapatite (Bio‐Rad), to adsorb, elute, and purify gene therapy vectors based on Moloney murine leukaemia virus (MoMuLV) carrying the 4070A amphotropic envelope protein was studied. Membrane ultra‐ and diafiltration provided virus concentration up to 160‐fold with an average recovery of infectious viruses of 77 ± 14%. In batch experiments, Macro‐Prep⌖ ceramic hydroxyapatite (type 2, particle size 40 μm) proved superior to Matrex⌖ Cellufine™ Sulfate for MoMuLV vector particle adsorption. Furthermore, functional vector particles could be eluted using phosphate buffer pH 6.8 (highest titres from ≥300 mM phosphate) from the Macro‐Prep⌖ adsorbent, with higher specific titres (cfu/mg protein) than the starting material. Similar results were obtained when this ceramic hydroxyapatite was packed into a column and used in a liquid chromatography system. Recovery of transduction‐competent virus was between 18 and 31% for column experiments and 32 and 46% for batch experiments. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 445–453, 2002.
Solvent selection for solid‐to‐solid synthesis
Authors: Ulijn Rein V. , De Martin Luigi , Gardossi Lucia , Janssen Anja E. M. , Moore Barry D. , Halling Peter J. 
Published: October 2002

AbstractThermolysin catalyzed solid‐to‐solid synthesis of the model peptide Z‐L‐Phe‐L‐Leu‐NH2 is practically feasible in water and a range of organic solvents with different physicochemical properties. Excellent overall conversions were obtained in acetonitrile, ethyl acetate, n‐hexane, methanol, 2‐propanol, tert‐amyl alcohol, tetrahydrofuran, toluene and water, while no product precipitation was observed in dichloromethane resulting in a much lower yield. In precipitation driven synthesis the product accumulates both in solution and in the solid phase. It was shown that the highest overall yields (yield in the liquid plus yield in the solid) can be expected in solvents where the substrate solubilities are minimized. The best yields of solid product can be expected in solvents where both product and substrate solubilities are lowest. This was in agreement with experimental observations and should be generally valid. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 509–515, 2002.
Changing a culture: a brief program analysis of a social learning program on a maximum‐security forensic unit
Authors: Goodness Kelly R. , Renfro Nancy S. 
Published: October 2002

AbstractThis report presents outcome data collected for a three‐year period from a maximum‐security forensic psychiatric program. Admission and discharge variables, restraint/seclusion, and client abuse/neglect data are presented from a one‐year period that preceded the advent of the Behavior Management Treatment Program's (BMTP's) Social Learning Diagnostic Program to two years after implementing the Social Learning Diagnostic Program. Significant overall progress and improvement was observed in all variables analyzed after instituting a social learning program paradigm. This report provides a brief summary of the BMTP's Social Learning Diagnostic Program along with a discussion of the role played by Dangerousness Management Plans in the treatment of patients within the social learning milieu. Additionally the patient population served, and the rationale for implementation of a program based in social learning theory, are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Intravascular ultrasound catheter entrapment after coronary artery stenting
Authors: Sasseen Brett M. , Burke James A. , Shah Rakesh , Costa Marco A. , Zenni Martin , Gilmore Paul , Bass Theodore A. 
Published: October 2002

AbstractIntracoronary ultrasound (IVUS) facilitates optimal stent deployment in the treatment of coronary artery disease, which may favorably improve long‐term outcome after stenting. Complications associated with IVUS include coronary vasospasm and rarely more serious adverse events such as vessel perforation or stent deformation. We report an IVUS catheter tip entrapment within a self‐deploying nitinol stent. Cathet Cardiovasc Intervent 2002;57:229–233. © 2002 Wiley‐Liss, Inc.
Percutaneous transcatheter coil embolization of two coronary fistulas originating from the left main ostium and left anterior descending artery
Authors: Boccalandro Fernando , Awadalla Hany , Smalling Richard W. 
Published: October 2002

AbstractWe report a successful case of percutaneous transcatheter coil embolization of a coronary fistula originating from the ostium of the left main, simultaneously with a second fistula arising from the left anterior descending artery, in a patient with exercise‐related angina and evidence of myocardial ischemia. Cathet Cardiovasc Intervent 2002;57:221–223. © 2002 Wiley‐Liss, Inc.
A new Amplatzer device to maintain patency of Fontan fenestrations and atrial septal defects
Authors: Amin Zahid , Danford David A. , Pedra Carlos A.C. 
Published: October 2002

AbstractThis study evaluated use of Amplatzer fenestrated device to maintain patency of the Fontan fenestration and atrial septal defect. Fenestrations are routinely created in patients with lateral tunnel or extracardiac Fontan. Spontaneous closure of the fenestration can lead to Fontan circulation failure. Other patients without single‐ventricle physiology may benefit from a small communication between the left and right atria for decompression if closure of the atrial septal defect leads to failure of a dysfunctional ventricle. Amplatzer septal occluder device was modified to create a fenestration through the disks. Three patients with modified Fontan and one patient with a large atrial septal defect underwent placement of the device by transcatheter technique. The device deployment was guided by transesophageal echocardiography. The procedure was successful in all patients. Contrast injection after placement revealed patent fenestration with free flow. Follow‐up ranged from 3 months to 1 year. All devices were patent by transthoracic echocardiography. These preliminary results suggest that the Amplatzer fenestrated device can serve as a valuable tool in failing Fontan circulation and may help to avoid surgical intervention. More studies are needed to assess long‐term efficacy of the device. Cathet Cardiovasc Intervent 2002;57:246–251. © 2002 Wiley‐Liss, Inc.
Architecture and function of atropisomeric molecular triads
Authors: Gawroński J. , Kacprzak K. 
Published: October 2002

AbstractMolecular triads, B‐A‐B, in which the central unit A is aromatic or heteroaromatic, can exist as syn or anti conformers or atropisomers of correspondingly C or S shape. These stereoisomers are either discrete conformer species, often distinguished by NMR spectroscopy, or can be separated at ambient temperature as stable atropisomers. In the latter case syn and anti stereoisomers exhibit different (e.g., complex‐forming) properties. Practical applications of atropisomeric triads as ligands in asymmetric dihydroxylation are also discussed. Chirality 14:689–702, 2002.