bluuebunny/crossref_metadata_2025 huggingface dataset:
Individual inflammatory response of human blood monocytes to mesh biomaterials
Authors: Schachtrupp A , Klinge U , Junge K , Rosch R , Bhardwaj R S , Schumpelick V
Published: January 2003

Background

Alloplastic implants such as those employed in hernia repair induce distinct local inflammation and seroma production. As monocytes take a key position in the inflammatory foreign body reaction, their specific release of cytokines was investigated in vitro after incubation with alloplastic materials.

Methods

Human blood monocytes were isolated from buffy coats of 42 healthy blood donors. Cells were cultivated in polystyrene culture wells (4 × 106 cells/well) on polypropylene–polyglactin mesh, on polytetrafluoroethylene, in control wells with the addition of 1 µg lipopolysaccharide (LPS) and on pure polystyrene. Supernatant was taken after 1 h and 5 days, and concentrations of tumour necrosis factor (TNF) α, interleukin (IL) 6 and IL-10 were determined. Donors were defined as ‘high’ or ‘low’ responders when concentrations of TNF-α were above the 75th or below the 25th percentiles, respectively.

Results

In contact with biomaterials, the monocytes liberated TNF-α, IL-6 and IL-10, similar to levels observed after stimulation with LPS. Median cytokine concentrations were not normally distributed and were influenced by donor, timepoint and applied stimulus. One donor matched the criteria for low responder and three for high responder.

Conclusion

The individual was identified as an independent factor for the inflammatory response of monocytes to biomaterials. Moreover, high and low responders could be identified. The variability of cytokine release and the lack of a normal distribution suggest that a larger sample size should be used in future studies of cellular response.
The value of magnetic resonance cholangiopancreatography in predicting common bile duct stones in patients with gallstone disease
Authors: Topal B , Van de Moortel M , Fieuws S , Vanbeckevoort D , Van Steenbergen W , Aerts R , Penninckx F
Published: January 2003

Background

The application of available predictive scoring systems for the detection of common bile duct (CBD) stones has not reduced the number of patients who undergo unnecessary endoscopic retrograde cholangiopancreatography. The aim of this study was to create a predictive model for CBD stones and to assess the value of magnetic resonance cholangiopancreatography (MRCP) in prediction.

Methods

In 1998, 366 patients with gallstone disease (118 males, 248 females; mean age 57 (range 8–84) years) underwent cholecystectomy. Statistical analysis was performed on patient data obtained at the time of first presentation.

Results

CBD stones were demonstrated in 43 (12 per cent) of 366 patients. The predictive model for common duct stones included ultrasonography showing CBD stones or bile duct dilatation, age greater than 60 years, fever, serum alkaline phosphatase level above 670 units/l and serum amylase level above 95 units/l. In patients with a predicted probability greater than 5 per cent, CBD stones were present in 11 per cent, compared with 1 per cent in patients with a probability of 5 per cent or less. MRCP had an observed sensitivity of 95 per cent, specificity of 100 per cent, positive predictive value of 100 per cent and negative predictive value of 98 per cent.

Conclusion

In patients with a predicted probability for CBD stones of more than 5 per cent, MRCP is recommended in order to confirm the presence or absence of stones and as guidance in further management.
Right lobe living donor liver transplantation with or without venovenous bypass
Authors: Fan S T , Yong B H , Lo C M , Liu C L , Wong J
Published: January 2003

Background

Venovenous bypass was considered necessary to maintain haemodynamic stability and avoid splanchnic and retroperitoneal congestion during the anhepatic phase of liver transplantation. It was essential for right lobe living donor liver transplantation (LDLT) in which the inferior vena cava needed to be cross-clamped to construct wide and short hepatic vein anastomoses. However, many complications related to venovenous bypass have been reported. This study aimed to determine whether venovenous bypass was necessary for right lobe LDLT.

Methods

Between June 1996 and June 2001, 72 patients underwent right lobe LDLT. The outcomes for the first 29 patients who had venovenous bypass during the operation were compared with those of the remaining 43 patients who did not have venovenous bypass. In patients without bypass, blood pressure was maintained during the anhepatic phase by boluses of fluid infusion and vasopressors.

Results

Compared with patients undergoing operation without venovenous bypass, patients who had venovenous bypass required significantly more blood, fresh frozen plasma and platelet infusion, and had a lower body temperature; their postoperative hepatic and renal function in the first week was worse than that in patients who did not have a bypass. The time to tracheal extubation was longer and the incidence of reintubation for ventilatory support was higher with venovenous bypass. Six of the 29 patients with venovenous bypass died in hospital, compared with two of the 43 patients without a bypass (P = 0·05). By multivariate analysis, the lowest body temperature during the transplant operation was the most significant factor that determined hospital death.

Conclusion

Venovenous bypass is not necessary and is probably harmful to patients undergoing right lobe LDLT, and should therefore be avoided.
Blood oxygenation level dependent functional magnetic resonance imaging
Authors: Mcintyre Michael , Richter Wolfgang , Morden Dara , Wennerberg Anders , Frankenstein Uta
Published: January 2003

The objective of the present article is to provide an introduction to the most widely used method of imaging the functional neuroanatomy of the human brain. The inferential relationship between neural activation and a magnetic resonance signal change is described in detail. The contrast between an active state and a baseline depends on an increased ratio of oxyhemoglobin to deoxyhemoglobin, a longer transverse relaxation time (T), decreased levels of paramagnetically induced dephasing, and a consequently stronger signal in the active state. Issues pertaining to image interpretation, spatial and temporal resolution, and image stability are described. © 2003 Wiley Periodicals, Inc. Concepts Magn Reson 16A: 5–15, 2003
Perfusion‐based functional magnetic resonance imaging
Authors: Silva Afonso C. , Kim Seong‐Gi
Published: January 2003

The measurement of cerebral blood flow (CBF) is a very important way of assessing tissue viability, metabolism, and function. CBF can be measured noninvasively with magnetic resonance imaging (MRI) by using arterial water as a perfusion tracer. Because of the tight coupling between neural activity and CBF, functional MRI (fMRI) techniques are having a large impact in defining regions of the brain that are activated due to specific stimuli. Among the different fMRI techniques, CBF‐based fMRI has the advantages of being specific to tissue signal change, a critical feature for quantitative measurements within and across subjects, and for high‐resolution functional mapping. Unlike the conventional blood oxygenation level dependent (BOLD) technique, the CBF change is an excellent index of the magnitude of neural activity change. Thus, CBF‐based fMRI is the tool of choice for longitudinal functional imaging studies. A review of the principles and theoretical backgrounds of both continuous and pulsed arterial spin labeling methods for measuring CBF is presented, and a general overview of their current applications in the field of functional brain mapping is provided. In particular, examples of the use of CBF‐based fMRI to investigate the fundamental hemodynamic responses induced by neural activity and to determine the signal source of the most commonly used BOLD functional imaging are reviewed. © 2003 Wiley Periodicals, Inc. Concepts Magn Reson 16A: 16–27, 2003
Functional magnetic resonance imaging of the human brain and spinal cord by means of signal enhancement by extravascular protons
Authors: Stroman P.W. , Tomanek B. , Malisza K.L.
Published: January 2003

A review of functional magnetic resonance imaging (fMRI) signal changes in spin–echo image data is presented. Spin–echo fMRI data from the human brain and spinal cord show a consistent departure from that expected with blood oxygen level dependent (BOLD) contrast. Studies to investigate this finding demonstrate fMRI signal changes of 2.5% in the spinal cord and 0.7% in the brain at 1.5 T, which is extrapolated to an echo time of zero. Consistent evidence of a non‐BOLD contrast mechanism arising from a proton‐density change at sites of neuronal activation is demonstrated. A mathematical model and physiological explanation for signal enhancement by extravascular protons is also presented. © 2003 Wiley Periodicals, Inc. Concepts Magn Reson 16A: 28–34, 2003
Hardware considerations for functional magnetic resonance imaging
Authors: Silva Afonso C. , Merkle Hellmut
Published: January 2003

Functional magnetic resonance imaging (fMRI) techniques based on changes in blood oxygenation or regional cerebral blood flow or volume have had great impact in mapping the regions of the brain that are activated by specific stimuli. The basic strategy of fMRI paradigms is to acquire data during two different brains states: one state usually comprises a resting condition, while in the other state the subject is performing a specific sensory or cognitive task. The signal difference between the activated and resting signals is on the order of only a few percent, and therefore the reliability and reproducibility with which it can be detected limit both the temporal and spatial resolution of fMRI experiments. The era of fMRI has significantly contributed to advancing the state of the art of MRI scanners. Every hardware component in modern MRI scanners, from the magnet itself to the gradient, shim, and RF coils to peripheral stimulus delivery equipment, has been (re)designed to perform to the limit of currently available technology and to improve the quality of MRI data, particularly fMRI data. The current state of the art of MRI scanners is described in light of their use in fMRI experiments. © 2003 Wiley Periodicals, Inc. Concepts Magn Reson 16A: 35–49, 2003
Peer mediation training and program implementation in elementary schools: Research results
Authors: Bickmore Kathy
Published: January 2003

This research examines the implementation and effects of a peer mediation program in twenty‐eight urban elementary schools. The Center for Conflict Resolution, a program of the Cleveland, Ohio, public schools, provided intensive training and follow‐up support for teams of peer mediators and adult advisers at each school. Trainers were youths from the same community. Qualitative and quantitative evidence indicate that this program significantly improved the average eight‐ to eleven‐year‐old students understanding of and inclination to use nonviolent conflict resolution and his or her capacity to achieve in school. The study outlines the specific commitments from administrators and other staff members that were required to develop and implement equitable, effective, and sustainable programs.
Structural sources of conflict in a university context
Authors: Barsky Allan Edward
Published: January 2003

Universities present an interesting setting for the analysis of conflict because of their unique organizational structures. They combine hierarchical administration with a peer philosophy that views professors as self‐governing colleagues (or a community of scholars), a tenure system for job security, an ethic of academic freedom within a highly regulated and bureaucratized system, decentralized departments that often operate independently rather than as part of an organization, and myriad constituencies served by the university (Baldridge, 1971; Douglas, 1998; Hartman, 1977; Ostan 1995).

This ethnographic study has explored experiences of conflict from the perspective of university students, professors—including both tenure‐and non‐tenure‐stream faculty members, administrators, and support staff members. Accordingly, the purposes of this article are to (1) describe the manner in which structural factors lead to the expression of conflict within a university setting and (2) describe the implications of structural sources of conflict, including ways in which universities and other organizations can try to address these sources of conflict.
What mediators do with words: Implementing three models of rational discussion in dispute mediation
Authors: Jacobs Scott , Aakhus Mark
Published: January 2003

This study identifies three models of rationality that mediators employ in interpreting conflict situations and formulating the most sensible and appropriate way to proceed. These models, critical discussion, bargaining, and therapy articulate what mediators presume about the nature of conflict and the framework of activity required to manage the conflict. The models were developed through a close analysis of a corpus of forty‐one mediation sessions. The analysis shows that the substance, direction, and outcome of mediation is shaped by the framework of activity implemented by the mediator. This can be seen by the way in which arguments are deflected and discouraged in bargaining and therapy models. These models suggest that mediation competence can be understood in terms of two issues: which model to implement when and how best to implement any model in a stream of discourse.
Disputing neutrality: A case study of a bias complaint during mediation
Authors: Garcia Angela Cora , Vise Krist , Whitaker Stephen Paul
Published: January 2003

Researchers find that some participants in mediation hearings report that the mediator was unfair or biased, but disputants rarely communicate these perceptions to the mediator, and very rarely do they do so during the mediation hearing itself. During data collection for a study of mediation hearings, a videotape of a small‐claims mediation hearing was made in which a disputant did make such an accusation during the hearing. This serendipitous capture of an accusation of bias on videotape enables us to examine how a mediator's actions during the hearing may have contributed to a disputants perception of unfairness. Narrative analysis is used to show how mediation techniques such as empowerment, representation of disputant positions, story summarizing, and emotion work can cause a perception of bias if they are applied unequally.
Discourses in the use and emergence of organizational conflict
Authors: Kusztal Iwona I.
Published: January 2003

Four discourses in use were identified in a grounded theory study of organizational conflict. This article discusses how these different discourses in use were involved in the emergence of organizational conflicts. Discourses in use determine what conflicts arise in the organization and how they are understood and managed. In this article, the practical implication of this approach for assessing and managing conflict processes in organizations is considered.
On the circuit paradigm in quantum networks
Authors: Mahler Günter , Otte Alexander , Stollsteimer Marcus
Published: January 2003

Physics is not scale invariant. As we reach the quantum domain not only new computational modes, but also fundamental control limits, are expected to appear. We investigate, to what extent some variant of the circuit paradigm may remain applicable, despite the qualitative change in function. Copyright © 2003 John Wiley & Sons, Ltd.
Decoherence in quantum systems and the network paradigm
Authors: Mathis W. , Pahlke K. , Zou XuBo
Published: January 2003

Since quantum systems interact with their environment permanently or within a measurement process, there is much interest in concepts of open quantum system modelling. In this paper we give an overview on three different concepts in order to address this problem in the context of the network paradigm. Furthermore the modelling of spatially localized decoherence processes within the stochastic diffusion wave equation approach of Gisin et al. is briefly discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Solid state coherent quantum dot system for quantum computing and quantum transmission
Authors: Matsueda Hideaki
Published: January 2003

Recent progress in nano‐metre structure and measurements is capable of providing us with the freedom to harness fast and seemingly weak correlations between atoms in an ensemble, manifesting them at macroscopic level. So we have investigated a prospective model of solid state integrated circuits for quantum computation, based on our coherence retentive resonance dynamic dipole–dipole interaction (RDDDI) theory. In this model, each qubit is a block consisting of an ensemble of quantum dots, and the energetics of which suggests stability up to room temperature. Here, we propose a qubit swap (∏4) gate applying our RDDDI. Moreover, integration of the ∏4 gate is proposed to form quantum circuits that can transfer a qubit state to any position within them, realizing bit reversal permutation circuits with even and odd bits, and a shuffling circuit. Copyright © 2003 John Wiley & Sons, Ltd.
CrossNets: possible neuromorphic networks based on nanoscale components
Authors: Türel Özgür , Likharev Konstantin
Published: January 2003

Extremely dense neuromorphic networks may be based on hybrid 2D arrays of nanoscale components, including molecular latching switches working as adaptive synapses, nanowires as axons and dendrites, and nano‐CMOS circuits serving as neural cell bodies. Possible architectures include ‘free‐growing’ networks that may form topologies very close to those of cerebral cortex, and several species of distributed crossbar‐type networks, ‘CrossNets’ (including notably ‘InBar’ and ‘RandBar’), with better density and speed scaling. Numerical modelling show that the specific signal sign asymmetry used in CrossNets allows self‐excitation of recurrent networks with long‐range cell interaction, without a symmetry‐breaking global latchup. Our next goal is to develop methods of globally supervised teaching of extremely large networks with no external access to individual synapses. Such development would open a way towards cerebral‐cortex‐scale networks (with ∼1010 neural cells and ∼1014 synapses) capable of advanced information processing and self‐evolution at a speed several orders of magnitude higher than their biological prototypes. Copyright © 2003 John Wiley & Sons, Ltd.
Signal processing by pulse‐driven molecular arrays
Authors: Csurgay Árpád I. , Porod Wolfgang , Rakos Balázs
Published: January 2003

In this paper cellular array processors composed of weakly Coulomb coupled molecules are studied. Equivalent circuits for molecules performing optically induced electron and proton transfer are presented, and pulse‐driven computing architectures are proposed. The polymer‐like molecular array is processing signals if it is subjected to a sequence of electromagnetic pulses of well‐defined frequency, envelope and length. Programming is accomplished by selecting proper sequence of pulses. Universality of the proposed architecture for computing is demonstrated. Copyright © 2003 John Wiley & Sons, Ltd.
A computing architecture composed of field‐coupled single domain nanomagnets clocked by magnetic field
Authors: Csaba György , Porod Wolfgang , Csurgay Árpád I.
Published: January 2003

Next neighbour field coupling of nanodevices is emerging as an alternative way to integrate nanoelectronic devices (Nanotechnology1993;4: 49). In this paper, integrated circuits composed of single domain nanomagnets are proposed. New magnetic field‐coupled devices with multiple equilibrium states are introduced. The devices are made locally active by exposing them to external magnetic fields. Non‐reciprocity is achieved by proper design of the nanomagnet's shape together with its clocking.

We demonstrate that (i) digital signal can propagate along a line of coupled single domain nanomagnets; (ii) and a family of logic circuits (inverter, majority gate, etc.) can be realized. Based on these observations we envision a new nanoelectronic computing architecture as a two‐dimensional array of field‐coupled nanomagnets. We estimate an integration density of 1010device/cm2, few hundred MHz operation speed, straightforward fabrication technology and robust operation in a wide temperature range. Copyright 2003 John Wiley & Sons, Ltd.
Circuit and application aspects of tunnelling devices in a MOBILE configuration
Authors: Glösekötter P. , Pacha C. , Goser K. F. , Prost W. , Kim S. O. , van Husen H. , Reimann T. , Tegude F. J.
Published: January 2003

In this paper, circuit and application aspects of different monostable–bistable transition logic elements (MOBILEs) are analysed. By taking advantage of the multi‐state behaviour of resonant tunnelling devices (RTD) the logic depth and the circuit complexity per logic function is reduced at the gate level. Both, simulation and measurement results prove correct circuit operation in the gigahertz regime and I–O compatibiliy of the logic voltage levels. The scaling laws of the different MOBILEs are compared to each other in terms of speed and power dissipation. Detailed SPICE simulations based on experimental data precisely analyse the impact of fluctuations on the circuit functionality and performance. This study demonstrates that RTD‐based MOBILEs are ready for use in digital circuitry such as linear threshold gates which offer a highly reduced circuit complexity. Copyright © 2003 John Wiley & Sons, Ltd.
Highly functional tunnelling devices integrated in 3D
Authors: Wernersson Lars‐Erik , Lind Erik , Lindström Peter , Andreani Pietro
Published: January 2003

We present a new technology for integrating tunnelling devices in three dimensions. These devices are fabricated by the combination of the growth of semiconductor heterostructures with the controlled introduction of metallic elements into an epitaxial layer by an overgrowth technique. First, we use a new type of tunnelling transistor, namely a resonant‐tunnelling permeable base transistor. A simple model based on a piece‐wise linear approximation is used in Cadence to describe the current–voltage characteristics of the transistor. This model is further introduced into a small signal equivalent circuit in order to optimize the performance of the device. In addition to the tunnelling structure below the grating, these transistors may be integrated in 3D by the introduction of another tunnelling structure directly over the metal grating. In the integrated device structure, the gate acts simultaneously on both tunnelling structures and the obtained characteristics are the result of the interplay between the two tunnelling structures and the gate. An equivalent circuit model is developed and we show how this interaction influences the current–voltage characteristics. The gate may be used to adjust the peak voltage of certain peaks in a controlled fashion, which creates a highly functional tunnelling device. These results show the need for a strong interaction between the development of circuit models and processing technology to develop new nano‐electronic devices and circuits. Copyright © 2003 John Wiley & Sons, Ltd.
Attachment, culture, and the caregiving system: The cultural patterning of everyday experiences among Anglo and Puerto Rican mother–infant pairs
Authors: Carlson Vivian J. , Harwood Robin L.
Published: January 2003

This investigation focuses on cultural differences in the relationship between maternal sensitivity, emotional expression, and control strategies during the first year of life and infant attachment outcomes at 12 months. Participants were middle‐class Puerto Rican and Anglo mother–infant pairs (N = 60). Ratings of physical control, emotional expression, and maternal sensitivity during mother–infant interactions in five everyday home settings, videotaped when the infants were 4, 8, and 12 months old, were examined in combination with 12‐month Strange Situation classifications. Results suggest that physical control shows a different pattern of relatedness to maternal sensitivity, emotional expression, and attachment outcomes among the Puerto Rican compared to the Anglo mothers in this study. These findings have implications for practitioners and researchers interested in normative parenting among diverse cultural groups. ©2003 Michigan Association for Infant Mental Health.
Selective use of transthyretin and retinol‐binding protein as markers in the postoperative assessment of protein nutritional status
Authors: Ihara Hiroshi , Matsumoto Takayuki , Shino Yoshio , Hashizume Naotaka , Takase Makoto , Nagao Jiro , Sumiyama Yoshinobu
Published: January 2003

We evaluated several markers to judge the postoperative state of protein nutriture in eight patients following surgery for cancer. Seven patients had a good prognosis and had no evidence of infections or other complications. Following surgery, all of the patients showed a shift toward abnormal values for the serum concentrations of albumin, transthyretin (TT), retinol‐binding protein (RBP), and the amino acid (AA) ratio of nonessential to essential amino acids. In patients without complications, the AA ratio returned to normal first. When blood specimens were collected at 7‐day intervals, concentrations of RBP and TT were revealed to be decreased and recovered at the same time, or TT was recovered after RBP was normalized. RBP and TT were usually abnormal until the AA ratio became normal. Although albumin moved toward normal concentrations after RBP and TT, the albumin concentrations in some patients were slightly above the lower reference value, whereas RBP and TT were significantly below their lower reference limits. In these patients, assessments over the next 7–14 days showed persistently low values for albumin, TT, and RBP. We recommend the selective use of TT and RBP for the postoperative assessment of protein nutriture in surgical patients. J. Clin. Lab. Anal. 17:1–5, 2003. © 2003 Wiley‐Liss, Inc.
Indices of obesity, dyslipidemia, and insulin resistance in apparently healthy Caribbean subjects
Authors: Ezenwaka Chidum E. , Kalloo Risha
Published: January 2003

Reports from developing countries indicate that a rise in the socioeconomic level is a risk factor for metabolic disorders. We aimed to assess the indices of obesity, dyslipidemia, and insulin resistance among fairly literate healthy adults in a multidisciplinary institution in Trinidad. The study included 156 volunteers (46 males and 110 females, 17–40 years old). The subjects provided information on age, ethnicity, educational attainment, and occupation in self‐administered, closed‐ended questionnaires. Waist and hip circumferences (cm), weight (kg), and height (m) were measured. Fasting blood samples were taken for glucose, insulin, and lipid determinations in 78 subjects who volunteered for laboratory measurements. Insulin resistance was determined with homeostasis model assessment (HOMA). Of the 156 subjects studied, 83% had received tertiary education, and had no previous record of body mass index (BMI); 8% were obese, 17% were overweight, and 27% were underweight. Laboratory measurements in 78 subjects revealed 28% hypercholesterolemia and 20% hyperinsulinemia. There were no significant gender‐related differences in these prevalence rates (P>0.05). The identification of obesity, underweight, hyperinsulinemia, and hypercholesterolemia in this healthy population suggests that screening for the indices of metabolic disorders in a healthy population would be potentially useful for the early identification and treatment of metabolic‐related disorders. J. Clin. Lab. Anal. 17:6–11, 2003. © 2003 Wiley‐Liss, Inc.
Automatic analysis of normal bone marrow blood cells using the XE‐2100 automated hematology analyzer
Authors: Shibata Hisako , Yamane Takahisa , Yamamura Ryousuke , Ohta Kensuke , Takubo Takayuki , Kamitani Tomio , Hino Masayuki
Published: January 2003

The bone marrow aspiration test conventionally has been performed by visual methods, using a light microscope, because automatic blood cell analyzers cannot adequately capture erythroblasts and immature granulocytes (IGs) (Tatsumi et al.: Osaka City Med J 1988;34:135–146; Tatsumi et al.: Am J Clin Pathol 1986;86:50–54). With the development of the XE‐2100 automatic blood cell analyzer (Sysmex Corporation, Kobe, Japan) in 1999, the classification of erythroblasts and IGs by means of flow cytometry (Zini et al.: Infus Ther Transfus Med 2001;28:277–279; Briggs et al.: Sysmex J Int 1999;9:113–119) became possible. In the present study we classified cells in 65 bone marrow aspiration specimens by the microscopic method and with the XE2100, and compared the results. A good correlation was found in the nucleated red blood cell (NRBC), white blood cell (WBC), and total nucleated cell (TNC) counts; the myeloid/erythroid ratio (M/E ratio); neutrophils, lymphocytes, eosinophils, and IGs in the immature myeloid information (IMI) channel; and the total cell count. These items can all be analyzed in about 54 sec with the XE2100, which is faster than with the microscopic method. Therefore, analysis of bone marrow aspiration specimens with this apparatus appears to be very useful for clinical screening as well as laboratory testing. J. Clin. Lab. Anal. 17:12–17, 2003. © 2003 Wiley‐Liss, Inc.
Genetic analysis of chromosome 22q11.2 markers in congenital heart disease
Authors: Shi Yi‐Ru , Hsieh Kai‐Sheng , Wu Jer‐Yuarn , Lee Cheng‐Chun , Tsai Chang‐Hai , Yu Ming‐Tseng , Chang Jeng‐Sheng , Tsai Fuu‐Jen
Published: January 2003

Congenital heart disease (CHD) is a common cardiac defect found in infants and children. Despite advances in diagnosis and treatment, our understanding of the causative mechanism and etiology of CHD is limited. To determine the genetic etiology of CHD, we selected 11 consecutive short tandem‐repeat polymorphic (STRP) markers located in the interval of the 22q11.2 region to perform genotype analysis on a large number of CHD patients (>120) and their normal relatives (>220). The results show that as regards the distribution of allelic size and frequency of these STRP markers, there were no significant differences between the CHD patients and the normal volunteers. This indicates that there is no linkage disequilibrium with these markers in CHD. In the level of heterozygosity for each marker in nonsyndromic CHD and conotruncal heart defect (CTD), there were no significant differences between the two populations. In syndromic CHD, the level of heterozygosity for D22S1648 was significantly lower than that observed in the unaffected population (χ2 = 11.25; P = 0.001). This suggests that there may be a deletion at the D22S1648 locus, and the low heterozygosity of D22S1648 indicates that this marker can be used as a genetic marker for detecting microdeletions in 22q11.2. With the use of fluorescence in situ hybridization (FISH) and real‐time quantitative polymerase chain reaction (PCR) performed on syndromic patients, we confirmed the molecular results. J. Clin. Lab. Anal. 17:28–35, 2003. © 2003 Wiley‐Liss, Inc.
Detection of apolipoprotein E phenotype in unconcentrated cerebrospinal fluid
Authors: Mehta P.D. , Patrick B.A. , Pirttila T. , Coyle P.K. , Aisen P.S.
Published: January 2003

We developed a simple method to detect apolipoprotein E (Apo E) polymorphism distribution in approximately 20 μL of unconcentrated cerebrospinal fluid (CSF). A combination of isoelectric focusing in 3 M urea gel and immunoblotting was employed. Apo E phenotypes were identified in CSF samples from 45 patients with probable Alzheimer disease (AD), 15 with multiple sclerosis (MS), and 25 with other neurological diseases (OND). When the data were compared with a set of matched plasma samples, the results were identical. The method is useful for Apo E phenotyping from fresh or frozen unconcentrated CSF, when blood or plasma is not available. J. Clin. Lab. Anal. 17:18–21, 2003. © 2003 Wiley‐Liss, Inc.
Effect of the traditional chinese medicines Chan Su, Lu‐Shen‐Wan, Dan Shen, and Asian Ginseng on Serum Digoxin measurement by Tina‐quant (Roche) and Synchron LX system (Beckman) digoxin immunoassays
Authors: Chow Leonard , Johnson Myrtle , Wells Alice , Dasgupta Amitava
Published: January 2003

Chan Su, Lu‐Shen‐Wan, Dan Shen, and Asian ginseng are traditionally used to treat a number of conditions, including cardiovascular disease. All of these traditional Chinese medicines exhibit cardioactive properties. Digoxin is a cardioactive drug with a narrow therapeutic range (0.8–1.9 ng/mL). A patient taking digoxin may also take these Chinese medicines for their cardiotonic effects. Moreover, the active components of these medicines that are responsible for cardiotonic effects bear structural similarities to digoxin. Therefore, we studied the potential interference of these Chinese medicines with two digoxin immunoassays—the Tina‐quant (Roche Diagnostics) and the Beckman (Synchron LX system)—and compared the values with the fluorescence polarization immunoassay (FPIA; Abbott Laboratories). When very small amounts (2–5 μL) of aqueous extract of Chan Su or Lu‐Shen‐Wan were added to drug‐free serum, we observed high digoxin‐like immunoreactivity with the FPIA. In contrast, when ethyl acetate extract of Dan Shen or microliter amounts of ginseng extract were added todrug‐free serum, we observed modest digoxin‐like immunoreactivity with the FPIA, but no apparent digoxin activity with the Roche and Beckman digoxin immunoassays. When aliquots of a digoxin pool prepared from patients receiving digoxin were supplemented with these Chinese medicines, we observed the most significant interference with the FPIA. The presence of endogenous digoxin‐like immunoreactive substances can have additive effects with these Chinese medicines and falsely increase apparent digoxin levels by the FPIA. On the other hand, the Roche and Beckman assays were free from interference from DLIS but showed significant interference from Chan Su and Lu‐Shen‐Wan. We conclude that the FPIA showed the most significant interference from all four of the Chinese medicines we studied. However, the Roche and Beckman assays showed no interference from two (Dan Shen and Asian ginseng) of the four Chinese medicines we studied. J. Clin. Lab. Anal. 17:22–27, 2003. © 2003 Wiley‐Liss, Inc.
Determination of pharmaceuticals in aqueous samples using positive and negative voltage switching microbore liquid chromatography/electrospray ionization tandem mass spectrometry
Authors: Miao Xiu‐Sheng , Metcalfe Chris D.
Published: January 2003

Analytical methods were developed for atorvastatin, novobiocin and roxithromycin using microbore liquid chromatography/electrospray ionization tandem mass spectrometry (microbore LC/ESI‐MS/MS) in positive and negative voltage switching mode. Atorvastatin and roxithromycin require the positive‐ion mode, whereas the negative‐ion mode is required for the determination of novobiocin. Using the positive and negative voltage switching function, the three analytes were determined with one injection, and the time required was half that required using separately run positive‐ and negative‐ion modes, without any reduction in sensitivity. A microbore LC column (100 × 1.0 mm i.d.) was chosen for chromatographic separation with mobile phase solvents acetonitrile and 10 mM aqueous ammonium acetate. The flow‐rate was 0.1 ml min−1 and the injection volume was 1 µl. The analytes were quantified in the multiple reaction monitoring mode with external standards. By switching the positive and negative voltage, the three analytes were determined with a 4 min chromatographic run and with instrumental detection limits of 1–3 pg. This analytical method, using a microbore LC column combined with solid‐phase extraction, was applied successfully to the determination of trace levels of the above pharmaceuticals in aqueous samples. Atorvastatin was detected in a sewage treatment plant final effluent. Copyright © 2003 John Wiley & Sons, Ltd.
Study of the collision‐induced radical cleavage of flavonoid glycosides using negative electrospray ionization tandem quadrupole mass spectrometry
Authors: Hvattum Erlend , Ekeberg Dag
Published: January 2003

Negative electrospray ionization tandem quadrupole mass spectrometry was used to study the collision‐induced dissociation (CID) of the O‐glycosidic bond from different commercially available flavonoid glycosides. Depending on the structure, flavonoid glycosides can undergo both a collision‐induced homolytic and heterolytic cleavage of the O‐glycosidic bond producing deprotonated radical aglycone ((Y0 − H)−·) and aglycone (Y0−) product ions. The relative abundance of the radical aglycone to the aglycone fragment from flavonol‐3‐O‐glycosides increased with increasing number of hydroxyl substituents in the B ring and in the order kaempferol − <quercetin − <myricetin‐3‐O‐glycoside. The nature and position of the sugar substitution of the flavonol glycosides also affected the fragmentation to the radical aglycone. Obtained under similar conditions, the product ion spectrum of kaempferol‐7‐O‐neohesperidoside showed only a minor radical aglycone product ion as opposed to kaempferol‐3‐O‐rutinoside. The relative abundance of the radical aglycone to the aglycone fragment from flavone‐7‐O‐glycosides was also dependent on the substitution in the B ring. CID of apigenin‐7‐O‐glucoside produced relatively more of the radical aglycone fragment than luteolin‐7‐O‐glucoside, while only the aglycone fragment was found from diosmetin‐7‐O‐rutinoside. The position of the sugar substitution also affected the fragmentation of the flavone glycosides, such that the product ion spectrum of luteolin‐4′‐O‐glucoside showed only the aglycone fragment as opposed to luteolin‐7‐O‐glucoside. No radical aglycone fragments were found from the flavanone‐7‐O‐glycosides and dihydrochalcone glycoside investigated in the study. Copyright © 2003 John Wiley & Sons, Ltd.
Secondary ion and laser ablation mass spectrometry for the quantitative characterization of styrene–butadiene copolymers
Authors: Ruch D. , Muller J. F. , Migeon H. N. , Boes C. , Zimmer R.
Published: January 2003

Styrene–butadiene copolymers were analyzed by static secondary ion mass spectrometry (S‐SIMS) and laser ablation Fourier transform ion cyclotron resonance mass spectrometry (LA‐FTICRMS) to obtain quantitative information based on specific ions. Silver deposition was performed on polystyrene, butadiene rubber and styrene–butadiene rubber. Under these experimental conditions, new secondary ions were detected, in particular silver‐cationized butadiene [Mbutadiene − Ag]+ and styrene [Mstyrene − Ag]+ monomers. In contrast, LA‐FTICRMS experiments did not require pretreatment. At high laser power density, UV photons (193, 266 and 355 nm) allowed the detection of styrene and butadiene monomers at m/z 104 and 54, respectively. The use of the observed ions by SIMS or LA‐FTICRMS ensures that quantitative information on the relative distribution of each monomer is obtained. However, the silver coating thickness in the SIMS experiment seems to have an important influence on the quantitative information obtained. For LA‐FTICRMS experiments, the best results are obtained at a wavelength of 355 nm. Copyright © 2003 John Wiley & Sons, Ltd.
Electron ionization‐induced fragmentation of N‐(alkoxymethyl)anilides
Authors: Danikiewicz Witold , Szmigielski Rafał , Olejnik Marian
Published: January 2003

Electron ionization‐induced fragmentation patterns of the series of N‐(alkoxymethyl)acetanilides and related formanilides and benzanilides have been studied. The main fragmentation reaction observed for all compounds studied is the loss of an alkyl radical from the N‐alkoxymethyl group leading to the appropriate protonated N‐acylformanilide derivatives. This reaction is accompanied by unusually high kinetic energy release. Other important fragmentations common for majority of the compounds studied are (i) loss of an aldehyde molecule derived from an alkoxyl group yielding an appropriate N‐acyl‐N‐methylaniline, (ii) elimination of a CnH2nO2 fragment derived from N‐alkoxymethyl group and carbonyl group oxygen atom and (iii) formation of N‐methyleneaniline radical cation. Copyright © 2003 John Wiley & Sons, Ltd.
Structural characterization of carcinogen‐modified oligodeoxynucleotide adducts using matrix‐assisted laser desorption/ionization mass spectrometry
Authors: Brown Karen , Harvey Chris A. , Turteltaub Kenneth W. , Shields Sharon J.
Published: January 2003

The aim of this study was to determine the chemical structure of in vitro 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)‐modified oligodeoxynucleotides (ODNs) by exonuclease digestion and matrix‐assisted laser desorption/ionization mass spectrometry. A single‐stranded 11‐mer ODN, 5′‐d(CCATCGCTACC), was reacted with N‐acetoxy‐PhIP, resulting in the formation of one major and eight minor PhIP–ODN adducts. A 10 min treatment of the major and one minor PhIP–ODN adduct with a 3′‐exonuclease, bovine intestinal mucosa phosphodiesterase (BIMP), and a 5′‐exonuclease, bovine spleen phosphodiesterase, results in inhibition of the primary exonuclease activity at deoxyguanosine (dG) producing 5′‐d(CCATCG(PhIP)) and 5′‐d(G(PhIP)CTACC) product ions, respectively. Post‐source decay (PSD) of these enzymatic end products identifies dG as the sole modification site in two 11‐mer ODN–PhIP adducts. PSD of the minor PhIP–ODN adduct digestion end product, 5′‐d(CCATCG(PhIP)), also reveals that the PhIP adducted guanine moiety is in an oxidized form. Prolonged treatment of the PhIP–ODN adducts at 37° C with BIMP induces a non‐specific, or endonuclease, enzymatic activity culminating in the formation of deoxyguanosine 5′‐monophosphate‐PhIP (5′‐dGMP–PhIP). The PSD fragmentation pattern of the 5′‐dGMP–PhIP [M + H]+ ion of the major adduct confirms PhIP binds to the C‐8 position of dG. For the minor adduct, PSD results suggest that PhIP binds to the C‐8 position of an oxidized guanine, supporting the hypothesis that this adduct arises from oxidative degradation, resulting in a spirobisguanidino structure. Copyright © 2003 John Wiley & Sons, Ltd.
Identification of formylglycine in sulfatases by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry
Authors: Peng Jianhe , Schmidt Bernhard , von Figura Kurt , Dierks Thomas
Published: January 2003

Cα‐Formylglycine, the catalytic amino acid residue in the active site of sulfatases, is generated by post‐translational modification of a cysteine or serine residue. We describe a highly sensitive procedure for the detection of Cα‐formylglycine‐containing peptides in tryptic digests of sulfatase proteins. The protocol is based on the formation of hydrazone derivatives of Cα‐formylglycine‐containing peptides when using dinitrophenylhydrazine as a matrix for matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS). The hydrazone derivatives desorb and ionize with high efficiency and can be detected in the sub‐femtomole range. The presence of Cα‐formylglycine is indicated by a mass increment of 180.13 u, corresponding to the hydrazone moiety, and also by a unique C‐terminal fragment ion, characteristic of sulfatases, that becomes prominent in MALDI post‐source decay mass spectra of the hydrazone derivatives. Copyright © 2003 John Wiley & Sons, Ltd.
Effect of instrument tuning on the detectabilityof biopolymers in electrospray ionization mass spectrometry
Authors: Oberacher Herbert , Walcher Wolfgang , Huber Christian G.
Published: January 2003

Electrospray ionization mass spectrometry of multiply charged biopolymer ions of different molecular size revealed a strong influence of tuning parameters on their detectability in quadrupole ion trap and triple quadrupole mass spectrometers. Hence, after optimizing the ion optical parameters with the signal of the 4− charge state of (dT)24 (low charge state tuning), a tenfold increase in the signal‐to‐noise ratio for a mixture of oligodeoxythymidylic acids (n = 12–18) was obtained compared with the results achieved with tune parameters optimized with a synthetic 80‐mer oligodeoxynucleotide. By contrast, a detection limit in the upper femtomole region could only be reached for a 104‐mer oligodeoxynucleotide utilizing the 24− charge state of the 80‐mer (high charge state tuning). The same effect was observed for proteins investigated in the positive ion mode using low and high charge states of cytochrome c and carbonic anhydrase, respectively, for instrument tuning. By comparing the settings for low and high charge state tuning, it became obvious that the most significant difference was observed in the potential applied to the heated metal capillary used to transfer ions from the atmospheric pressure to the vacuum region of the ion source. Taking advantage of the optimized tuning procedure, the molecular mass of a 61 base pair product of polymerase chain reaction was accurately determined by electrospray ionization mass spectrometry on‐line interfaced to ion‐pair reversed‐phase high‐performance liquid chromatography. Copyright © 2003 John Wiley & Sons, Ltd.
STAT1 and STAT3 α/β splice form activation predicts host responses in mouse hepatitis virus type 3 infection
Authors: Ning Qin , Berger Lloyd , Luo Xiaoping , Yan Weiming , Gong Feili , Dennis James , Levy Gary
Published: January 2003

Signal transducer and activator of transcription 1α (STAT1 α) is reported to be essential for IFN‐γ and IFN‐α regulated gene expression, while STAT1 β, an alternate splice‐form, mediates only IFN‐α‐dependent gene expression. STAT3 α and STAT3 β splice forms are also differentially activated in response to cytokines including IL‐6 and IL‐10. The aim of this study was to investigate whether the STAT activation will predict the host immune response to viral infection and possibly a therapeutic target for the treatment of viral infection. Mouse hepatitis virus type 3 (MHV‐3) resistant strain (A/J) and sensitive mouse strains (BalB/cJ) were infected intraperitoneally (i.p.) with 100 plaque form units (pfu) of MHV‐3. The mice were sacrificed at the indicated times, and livers and spleens were immediately frozen in liquid nitrogen. Nuclear extracts proteins were detected by immunoblotting. STAT1 and STAT3 activation in spleen increased 24 to 72 hr following MHV‐3 infections in both sensitive and resistant mouse strains. However, over this time period, the ratio of activated α to β splice‐form for STAT1 and STAT3 increased above 1.0 in resistant A/J mice, while the ratio fell to <0.3 in MHV‐3 sensitive Balb/cJ and C3H/HeJ strains. Activated STAT1 α/β and STAT3 α/β ratio in liver were similar in resistant and sensitive mouse strains. Treatment of sensitive Balb/cJ mice with neutralizing anti‐TGF‐β antibody could increase the STAT1 α/β ratio to <1.0 in spleens, predicting enhanced rates of survival. These results suggested that ratio of activated STAT1 α/β and STAT3 α/β in mixed leukocytes from spleen predict the outcome to MHV‐3 infection, and may be an important marker and therapeutic target for modification of host immune response to virus infection. J. Med. Virol. 69:306–312, 2003. © 2003 Wiley‐Liss, Inc.