bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality in early inflammatory polyarthritis: Cardiovascular mortality is increased in seropositive patients
Authors: Goodson Nicola J. , Wiles Nicola J. , Lunt Mark , Barrett Elizabeth M. , Silman Alan J. , Symmons Deborah P. M. 
Published: October 2002

AbstractObjectiveTo determine the degree and causes of any excess mortality observed during the early years of inflammatory polyarthritis (IP).MethodsBetween 1990 and 1994, a total of 1,236 patients were registered with the Norfolk Arthritis Register, a primary care–based inception cohort. All patients were tracked on the National Health Service Central Register for notification of death. The vital status of each patient was determined as of December 31, 1999. Causes of death were coded according to the International Classification of Diseases, Ninth Revision. Expected death rates were calculated using annual death rates for the Norfolk population. Standardized mortality ratios (SMRs) were calculated for all IP patients and for the subgroups of patients who did and did not satisfy the American College of Rheumatology (ACR) 1987 criteria for rheumatoid arthritis (RA) at baseline, as well as for the subgroups who were and were not rheumatoid factor (RF) positive at baseline.ResultsBy December 31, 1999, 160 patients (13%; 79 women and 81 men) had died. The median duration of followup in the entire cohort was 6.9 years. Mortality rates were not significantly increased in the entire group of patients with IP or in the subgroup who met the ACR 1987 criteria for RA at baseline. In contrast, RF‐positive patients had an increased rate of death from all causes (SMR in men 1.51, in women 1.41). Cardiovascular disease was the most common cause of death. The majority of the excess mortality in the RF‐positive patients could be attributed to cardiovascular causes (SMR in men 1.34, in women 2.02).ConclusionExcess mortality in the early years of IP is confined to patients who are seropositive for RF. While excess cardiovascular mortality has been described in patients with established RA, this is the first report of premature death from heart disease in the early years of IP.
Effect of Wegener's granulomatosis on work disability, need for medical care, and quality of life in patients younger than 40 years at diagnosis
Authors: Reinhold‐Keller Eva , Herlyn Karen , Wagner‐Bastmeyer Rosemarie , Gutfleisch Joachim , Peter Hartmut H. , Raspe Heiner H. , Gross Wolfgang L. 
Published: October 2002

AbstractObjectivesTo evaluate the effects of Wegener's granulomatosis (WG) on employment status, work disability, and need for medical care of 60 consecutive WG patients aged ≤40 years at diagnosis.MethodsSixty WG patients (26 male, 34 female) with a median age of 36 years (range 17–48 years) and a median duration of disease of 39 months (range 0–228 months) completed self‐administered questionnaires on hospitalization, medical care, and employment status plus the Medical Outcomes Study‐Short Form‐36 (SF‐36) estimating their health‐related quality of life.ResultsThirty‐two of the 60 patients reported full‐ or part‐time employment more than 3 years after diagnosis. Only 14 of the 51 patients employed at diagnosis (27%) were currently receiving a permanent work disability pension due to WG. Two additional patients had lost work because of WG. Women who were employed at diagnosis had a nearly 3‐fold higher risk of losing their jobs compared with men (P = 0.0006). There were no differences with regard to age at diagnosis, disease duration, disease severity, or education level between employed and unemployed patients. Employed patients had missed a median of 14 workdays (range 0–18 days) due to WG within the past 12 months. More than half of all patients (33 of 60) had been hospitalized during the previous 12 months because of WG. Ninety‐three percent of all patients had visited their physician once or more per month, more than half of them at least once per week, regardless of employment status, severity of disease, or type of current medication. Unemployed WG patients experienced significant reductions in social and physical function and in their perceived degree of general health as assessed by the SF‐36.ConclusionsTwenty‐seven percent of WG patients younger than age 40 who were employed at diagnosis received permanent work disability within a disease duration of 39 months. Unemployment is followed by a considerable reduction in disease‐related quality of life compared with employed patients, independent of severity and extent of disease. Furthermore, because patients were followed closely by an interdisciplinary team, a high rate of hospitalization and frequent visits to physicians resulted.
Identification of synovium‐specific homing peptides by in vivo phage display selection
Authors: Lee Lewis , Buckley Christopher , Blades Mark C. , Panayi Gabriel , George Andrew J. T. , Pitzalis Costantino 
Published: October 2002

AbstractObjectiveTo identify homing peptides specific for human synovium that could be used as targeting devices for delivering therapeutic/diagnostic agents to human joints.MethodsHuman synovium and skin were transplanted into SCID mice. A disulfide‐constrained 7–amino acid peptide phage display library was injected intravenously into the animals and synovial homing phage recovered from synovial grafts. Following 3–4 cycles of enrichment, DNA sequencing of homing phage clones allowed the identification of specific peptides that were synthesized by a‐fluorenylmethyloxycarbonyl chemistry and used in competitive in vivo assays and immunohistochemistry analyses.ResultsWe isolated synovial homing phages displaying specific peptides that distinctively bound to synovial but not skin or mouse microvascular endothelium (MVE). They retained their tissue homing specificity in vivo, independently from the phage component, the original pathology of the transplanted tissue, and the degree of human/murine graft vascularization. One such peptide (CKSTHDRLC) maintained synovial homing specificity both when presented by the phage and as a free synthetic peptide. The synthetic peptide also competed with and inhibited in vivo the binding of the parent phage to the cognate synovial MVE ligand.ConclusionThis is the first report describing peptides with homing properties specific for human synovial MVE. This was demonstrated using a novel approach targeting human tissues, transplanted into SCID mice, directly by in vivo phage display selection. The identification of such peptides opens the possibility of using these sequences to construct joint‐specific drug delivery systems that may have considerable impact in the treatment of arthritic conditions.
Trends in incidence and mortality in rheumatoid arthritis in Rochester, Minnesota, over a forty‐year period
Authors: Doran Michele F. , Pond Gregory R. , Crowson Cynthia S. , O'Fallon W. Michael , Gabriel Sherine E. 
Published: October 2002

AbstractObjectiveTo determine time trends in the epidemiology of rheumatoid arthritis (RA) in a population‐based cohort.MethodsAn inception cohort of residents of Rochester, Minnesota ≥18 years of age who first fulfilled the American College of Rheumatology 1987 criteria between January 1, 1955 and December 31, 1994 (applied retrospectively, as appropriate) was assembled and followed up until January 1, 2000. Incidence rates were estimated and were age‐ and sex‐adjusted to the 1990 white population of the US. A birth cohort analysis was performed, and survival rates over time were examined.ResultsThe incidence cohort comprised 609 patients, 445 (73.1%) of whom were female and 164 (26.9%) were male, with a mean age at incidence of 58.0 years. The overall age‐ and sex‐adjusted annual incidence of RA among Rochester, Minnesota, residents ≥18 years of age was 44.6/100,000 population (95% confidence interval 41.0–48.2). While the incidence rate fell progressively over the 4 decades of study, from 61.2/100,000 in 1955–1964, to 32.7/100,000 in 1985–1994, there were indications of cyclical trends over time. Birth cohort analysis showed diminishing incidence rates through successive cohorts following a peak in the 1880–1890 cohorts. Incidence rates increased with age until age 85, but peaked earlier in women than in men. The survival rate in RA patients was significantly lower than the expected rate in the general population (P < 0.001), and no improvement was noted over time.ConclusionThe secular trends demonstrated in this study population, including the progressive decline in the incidence of RA over the last 40 years, suggest that an environmental factor may play a role in the etiology of RA.
Risk and rationality: the influence of decision domain and perceived outcome control on managers' high‐risk decisions
Authors: Forlani David 
Published: October 2002

AbstractThe issue of when managers will undertake different forms and amounts of risk in their new business creation decisions is still not fully understood. To address one facet of this issue, this paper advances the proposition that decision domain and perceived outcome control interact to impact managers' new‐product introduction decisions. Employing a causal method, a nested experimental design and indicators of risk's probability of loss and magnitude of loss elements, the study's results demonstrate that the manager's level of perceived outcome control combines with decision domain to determine subsequent levels of risk taking that are specific to each element of risk. Implications for theory, including prospect theory, and practice, especially firms wanting to pursue today's high‐risk new‐economy based initiatives, are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Eliminating recency with self‐review: the case of auditors' ‘going concern’ judgments
Authors: Ashton Robert H. , Kennedy Jane 
Published: October 2002

AbstractThis paper examines the use of self‐review to debias recency. Recency is found in the ‘going concern’ judgments of staff auditors, but is successfully eliminated by the auditor's use of a simple self‐review technique that would be extremely easy to implement in audit practice. Auditors who self‐review are also less inclined to make audit report choices that are inconsistent with their going concern judgments. These results are important because the judgments of staff auditors often determine the type and extent of documentation in audit workpapers and serve as preliminary inputs for senior auditors' judgments and choices. If staff auditors' judgments are affected by recency, the impact of this bias may be impounded in the ultimate judgments and choices of senior auditors. Since biased judgments can expose auditors to significant costs involving extended audit procedures, legal liability and diminished reputation, simple debiasing techniques that reduce this exposure are valuable. The paper also explores some future research needs and other important issues concerning judgment debiasing in applied professional settings. Copyright © 2002 John Wiley & Sons, Ltd.
Gene expression of cytokine receptors in HL60 cells exposed to a 50 Hz magnetic field
Authors: Zhou Jiliang , Li Changlin , Yao Gengdong , Chiang Huai , Chang Zongliang 
Published: October 2002

AbstractThe effects of a 50 Hz extremely low frequency (ELF) sinusoidal magnetic field (MF) on the expression of genes relating to cytokine receptors were studied in HL60 cells. Transcription levels of tumor necrosis factor receptor (TNFR) p55 and p75, interleukin‐6 receptor‐α (IL‐6Rα) and transforming growth factor‐β receptor 1 (TGFβR1) were quantified in cells exposed to an intensity of 0.1 or 0.8 mT for periods ranging from 30 min to 72 h. Cells treated with 10 nM of phorbol 12‐myristate 13‐acetate (PMA) for 8 h served as a positive control. Gene expression values were assessed by the ribonuclease protection assay (RPA) and normalized to those of the noninducible gene GAPDH. The results showed that MF exposure at 0.1 and 0.8 mT for 72 h increased TNFR p75 and IL‐6Rα mRNA expression in HL60 cells. No significant change in gene expression levels of TNFR p55 and TGFβR1 was observed under any of the exposure conditions. In addition, we report here for the first time that IL‐6Rα mRNA expression can be suppressed by PMA in HL60 cells. Bioelectromagnetics 23:339–346, 2002. © 2002 Wiley‐Liss, Inc.
Effects of pulsed electromagnetic field (PEMF) stimulation on bone tissue like formation are dependent on the maturation stages of the osteoblasts
Authors: Diniz Pericles , Shomura Kenji , Soejima Kazuhisa , Ito Gakuji 
Published: October 2002

AbstractThe effects of pulsed electromagnetic field (PEMF, 15 Hz pulse burst, 7 mT peak) stimulation on bone tissue‐like formation on osteoblasts (MC3T3‐E1 cell line) in different stages of maturation were assessed to determine whether the PEMF stimulatory effect on bone tissue‐like formation was associated with the increase in the number of cells and/or with the enhancement of the cellular differentiation. The cellular proliferation (DNA content), differentiation (alkaline phosphatase activity), and bone tissue‐like formation (area of mineralized matrix) were determined at different time points. PEMF treatment of osteoblasts in the active proliferation stage accelerated cellular proliferation, enhanced cellular differentiation, and increased bone tissue‐like formation. PEMF treatment of osteoblasts in the differentiation stage enhanced cellular differentiation and increased bone tissue‐like formation. PEMF treatment of osteoblasts in the mineralization stage decreased bone tissue‐like formation. In conclusion, PEMF had a stimulatory effect on the osteoblasts in the early stages of culture, which increased bone tissue‐like formation. This stimulatory effect was most likely associated with enhancement of the cellular differentiation, but not with the increase in the number of cells. Bioelectromagnetics 23:398–405, 2002. © 2002 Wiley‐Liss, Inc.
Patterning the marginal zone of early ascidian embryos: localized maternal mRNA and inductive interactions
Authors: Nishida Hiroki 
Published: October 2002

AbstractEarly animal embryos are patterned by localized egg cytoplasmic factors and cell interactions. In invertebrate chordate ascidians, larval tail muscle originates from the posterior marginal zone of the early embryo. It has recently been demonstrated that maternal macho‐1 mRNA encoding transcription factor acts as a localized muscle determinant. Other mesodermal tissues such as notochord and mesenchyme are also derived from the vegetal marginal zone. In contrast, formation of these tissues requires induction from endoderm precursors at the 32‐cell stage. FGF–Ras–MAPK signaling is involved in the induction of both tissues. The responsiveness for induction to notochord or mesenchyme depends on the inheritance of localized egg cytoplasmic factors. Previous studies also point to critical roles of directed signaling in polarization of induced cells and in subsequent asymmetric divisions resulting in the formation of two daughter cells with distinct fates. One cell adopts an induced fate, while the other assumes a default fate. A simple model of mesoderm patterning in ascidian embryos is proposed in comparison with that of vertebrates. BioEssays 24:613–624, 2002. © 2002 Wiley Periodicals, Inc.
p53 and ageing: too much of a good thing?
Authors: Kirkwood Thomas B.L. 
Published: October 2002

AbstractA recent report by Tyner et al.1 suggests that p53 is bad for longevity. Heterozygotic mice carrying a p53 mutation that apparently enhances the stability of the wild‐type protein showed shorter lifespans and faster ageing while also developing fewer tumours. This fits with the idea that cellular ageing is the price paid for better protection against unlimited proliferation of cancer cells. But other work shows that there is a strong positive association between DNA repair‐mediated protection against cancer and ageing. So what are we to make of the new data with regard to overall understanding of the mechanisms of ageing? BioEssays 24:577–579, 2002. © 2002 Wiley Periodicals, Inc.
Radiation‐induced chromosome aberrations: Insights gained from biophysical modeling
Authors: Hlatky Lynn , Sachs Rainer K. , Vazquez Mariel , Cornforth Michael N. 
Published: October 2002

AbstractEnzymatic misrepair of ionizing‐radiation‐induced DNA damage can produce large‐scale rearrangements of the genome, such as translocations and dicentrics. These and other chromosome exchange aberrations can cause major phenotypic alterations, including cell death, mutation and neoplasia. Exchange formation requires that two (or more) genomic loci come together spatially. Consequently, the surprisingly rich aberration spectra uncovered by recently developed techniques, when combined with biophysically based computer modeling, help characterize large‐scale chromatin architecture in the interphase nucleus. Most results are consistent with a picture whereby chromosomes are mainly confined to territories, chromatin motion is limited, and interchromosomal interactions involve mainly territory surfaces. Aberration spectra and modeling also help characterize DNA repair/misrepair mechanisms. Quantitative results for mammalian cells are best described by a breakage‐and‐reunion model, suggesting that the dominant recombinational mechanism during the G0/G1 phase of the cell cycle is non‐homologous end‐joining of radiogenic DNA double strand breaks. In turn, better mechanistic and quantitative understanding of aberration formation gives new insights into health‐related applications. BioEssays 24:714–723, 2002. © 2002 Wiley Periodicals, Inc.
DNA melting in the presence of fluorescent intercalating oxazole yellow dyes measured with a gel‐based assay
Authors: Bjorndal Michael T. , Fygenson D. Kuchnir 
Published: October 2002

AbstractWe measured the effect of the intercalating oxazole yellow DNA dye quinolinium,4‐[(3‐methyl‐2(3H)‐benzoxazolylidene)methyl]‐1‐[3‐(trimethylammonio)propyl]‐,diiodide (YO‐PRO) and its homodimer (YOYO) on the melting of self‐complementary DNA duplexes using a gel‐based assay. The assay, which requires a self‐complementary DNA sequence, is independent of the optical properties of the molecules in solution. The melting temperature of the DNA is observed to increase in direct proportion to the number of occupied intercalation sites on the DNA, irrespective of whether the dye molecules are in monomer or dimer form. The increase is ∼ 2.5°C for each intercalation site occupied in the presence of 38 mM [Na+], for dye/duplex ratios in which less than 1/5 of the available intercalation sites are occupied. © 2002 Wiley Periodicals, Inc. Biopolymers 65: 40–44, 2002
A two‐step, one‐pot enzymatic synthesis of cephalexin from D‐phenylglycine nitrile
Authors: Wegman Margreth A. , van Langen Luuk M. , van Rantwijk Fred , Sheldon Roger A. 
Published: October 2002

AbstractA cascade of two enzymatic transformations is employed in a one‐pot synthesis of cephalexin. The nitrile hydratase (from R. rhodochrous MAWE)‐catalyzed hydration of D‐phenylglycine nitrile to the corresponding amide was combined with the penicillin G acylase (penicillin amidohydrolase, E.C. 3.5.1.11)‐catalyzed acylation of 7‐ADCA with the in situ–formed amide to afford a two‐step, one‐pot synthesis of cephalexin. D‐Phenylglycine nitrile appeared to have a remarkable selective inhibitory effect on the penicillin G acylase, resulting in a threefold increase in the synthesis/hydrolysis (S/H) ratio. 1,5‐Dihydroxynaphthalene, when added to the reaction mixture, cocrystallized with cephalexin. The resulting low cephalexin concentration prevented its chemical as well as enzymatic degradation; cephalexin was obtained at 79% yield with an S/H ratio of 7.7. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 356–361, 2002.
Production of lipolyzed butteroil by a calf pregastric esterase immobilized in a hollow fiber reactor: III. Effect of glycerol
Authors: Lessard Louis P. , Hill Charles G. 
Published: October 2002

AbstractLipolysis of butter oil in a hollow fiber reactor containing an immobilized calf pregastric esterase was studied at 40°C, a pH of 6.0, and glycerol concentrations of 0, 150, and 500 g/L in the buffer solution. The concentrations of 10 fatty acid species in the lipolyzed product were determined using high‐performance liquid chromatography. The rate of loss of enzyme activity and the relative selectivities of this esterase depended on the glycerol concentration. By contrast, the overall rate of release of fatty acids was not affected by the glycerol concentration. Loss of enzyme activity was modeled using first‐order kinetics. The models for deactivation and reaction kinetics were fit simultaneously to the data. The model was successful in describing the rates of release of all 10 fatty acid species for a range of space times from 0 to 25 h. The parameters of the model were tested for dependence on glycerol concentration. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 323–333, 2002.
Purification of plasmid DNA by an integrated operation comprising tangential flow filtration and nitrocellulose adsorption
Authors: Kendall D. , Lye G. J. , Levy M. S. 
Published: October 2002

AbstractThere is an increasing interest in the development of scaleable and reproducible plasmid DNA purification protocols for vaccine and gene therapy. The use of an integrated unit operation, comprising tangential flow microfiltration coupled with the adsorption of contaminants onto nitrocellulose membranes as a single processing step was examined in this work. Experiments were performed using a custom‐built tangential flow microfiltration rig (membrane area=12.5 cm2). Tangential flow filtration–adsorption of E. coli lysates containing a plasmid product removed most solids (>75%) and decreased chromosomal DNA contamination by 75% w/w. Total plasmid DNA concentration and supercoiled content of the permeate were virtually identical to those of the feed, indicating a recovery yield of 100% (transmission equal to 1). Results were similar for E. coli lysates containing either a 6.9 kb or a 20 kb plasmid. Significant reductions in RNA, endotoxin, and protein levels were also observed. The reproducibility and potential for scale up of this integrated filtration–adsorption operation makes it at attractive option for intermediate‐ to large‐scale pharmaceutical‐grade plasmid processing. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 816–822, 2002.
Computer‐aided real‐time estimation of reaction conversion for lipase‐catalyzed esterification in solvent‐free systems
Authors: Won Keehoon , Jeong Jae Cheol , Lee Sun Bok 
Published: October 2002

AbstractReal‐time conversion estimation through macroscopic balancing was investigated for enzymatic esterification reactions in a solvent‐free system. In principle, the conversion of ester synthesis can be determined from the amount of water produced by the reaction because water is formed as a by‐product in the same molar ratio as the product. In this study, we show that the water production rate, and thereby the reaction conversion, can be estimated on‐line from measurements of the relative humidity of the inlet and outlet air and the material balances of water in the system. In order to test the performance of the real‐time conversion estimation method, the lipase‐catalyzed esterification reaction of n‐capric acid and n‐decyl alcohol in solvent‐free media was conducted while controlling the water activity at various values. When the reaction conversions estimated on‐line were compared with those analyzed off‐line by gas chromatography, good agreement was obtained: the average mean absolute error was ± 2.4% of the reaction conversion despite the simplicity of the method. The on‐line estimation method presented here requires no expensive or complicated analytical instruments and no sampling of reaction medium. It can be used for monitoring nonaqueous enzymatic reactions where water is produced or consumed during reaction. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 795–803, 2002.