bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-μ-opioid-receptor IgG antibodies are commonly present in serum from healthy blood donors: evidence for a role in apoptotic immune cell death
Authors: Macé Gaëtane , Jaume Martial , Blanpied Catherine , Stephan Lionel , Coudert Jérôme D. , Druet Philippe , Dietrich Gilles 
Published: October 2002

AbstractWe previously observed the presence of anti-human μ-opioid-receptor (anti-hMOR) autoantibodies in IgG pools prepared from several thousand healthy blood donors. These autoantibodies behaved agonistically because of their ability to bind to the first and third extracellular loops of the receptor. In this study, we found that each healthy donor's serum contained anti-hMOR IgG autoantibodies with a specific activity against both the first and the third extracellular loops of the receptor. Because of the inability of IgG to cross the blood-brain barrier, we investigated the effects of the expression of anti-hMOR autoantibodies on immune cells. In analogy to studies of the effects of morphine, we investigated the ability of antibodies to sensitize splenocytes to Fas (CD95)-mediated apoptosis. We took advantage of the high sequence homology between murine MOR and hMOR extracellular loops to estimate the effect on murine splenocytes of anti-hMOR antibodies raised by immunizing mice. Splenocytes from mice injected with Chinese hamster ovary (CHO) cells expressing MOR were sensitized to Fas-mediated apoptosis, whereas those from mice injected with CHO cells or phosphate-buffered saline were not. Similar sensitization to Fas-mediated apoptosis was observed in splenocytes from mice undergoing passive transfer either with IgG from mice previously immunized against CHO cells expressing MOR or with IgG directed against the first and third extracellular loops of the receptor. Together, our data show that anti-MOR autoantibodies are commonly expressed in healthy humans and could participate in the control of lymphocyte homeostasis by promoting Fas-mediated apoptosis.
KSHV- and EBV-associated germinotropic lymphoproliferative disorder
Authors: Du Ming-Qing , Diss Tim C. , Liu Hongxiang , Ye Hongtao , Hamoudi Rifat A. , Cabeçadas José , Dong Henry Y. , Harris Nancy Lee , Chan John K. C. , Rees John W. , Dogan Ahmet , Isaacson Peter G. 
Published: October 2002

Abstract
Kaposi sarcoma–associated herpesvirus (KSHV) is known to be associated with 3 distinct lymphoproliferative disorders: primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and MCD-associated plasmablastic lymphoma. We report 3 cases of a previously undescribed KSHV-associated lymphoproliferative disorder. The disease presented as localized lymphadenopathy and showed a favorable response to chemotherapy or radiotherapy. Histologically, the lymphoproliferation is characterized by plasmablasts that preferentially involved germinal centers of the lymphoid follicles, forming confluent aggregates. They were negative for CD20, CD27, CD79a, CD138, BCL6, and CD10 but showed monotypic κ or λ light chain. Clusters of CD10+CD20+ residual follicle center cells were identified in some of the follicles. The plasmablasts were positive for both KSHV and EBV, and most of them also expressed viral interleukin-6 (vIL-6). Unexpectedly, molecular analysis of whole tissue sections or microdissected KSHV-positive aggregates demonstrated a polyclonal or oligoclonal pattern of immunoglobulin (Ig) gene rearrangement. The plasmablasts showed somatic mutation and intraclonal variation in the rearranged Ig genes, and one case expressed switched Ig heavy chain (IgA), suggesting that they originated from germinal center B cells. We propose calling this distinctive entity “KSHV-associated germinotropic lymphoproliferative disorder.”
Protection against thrombosis in mice lacking PAR3
Authors: Weiss Ethan J. , Hamilton Justin R. , Lease Katy E. , Coughlin Shaun R. 
Published: October 2002

AbstractThe recent observation that knock-out of protease-activated receptor-4 (PAR4) ablates thrombin signaling in mouse platelets and protects against ferric chloride–induced thrombosis of mouse mesenteric arterioles suggests that thrombin's actions on platelets can play an important role in thrombosis. Complete ablation of thrombin signaling would be difficult to achieve in human beings because human platelets have 2 thrombin receptors that are each capable of mediating transmembrane signaling. However, it is possible that complete ablation of thrombin signaling in platelets is not necessary for an antithrombotic effect. In mouse platelets, PAR3 functions as a cofactor that binds thrombin and promotes productive cleavage of PAR4, and thrombin responses are decreased but not absent inPar3−/− platelets. We now report thatPar3−/− mice were protected against ferric chloride–induced thrombosis of mesenteric arterioles and against thromboplastin-induced pulmonary embolism. Surprisingly,Par3−/− and Par4−/−mice showed similar degrees of protection in these models and similar prolongation of tail bleeding times. Thus, even a partial decrease in mouse platelet responsiveness to thrombin protected against thrombosis and impaired hemostasis in some settings. These results demonstrate the importance of PAR3's unusual cofactor function and underscore the relative importance of thrombin's actions on platelets in vivo. They also suggest that PAR inhibition might be explored for the prevention or treatment of thrombosis in human beings.
Functional β1 - and β2-adrenoceptors in the left and right atrium of pre-hypertensive rats
Authors: Doggrell Sheila A 
Published: October 2002

Abstract
There is a small increase in the functional β2-adrenoceptor response on the spontaneously hypertensive rat (SHR) left atrium in the early stages of hypertension. In the present study, the functional β1 - and β2-adrenoceptors of the left and right atrium in SHR pre-hypertension and age-matched (5-week-old) Wistar Kyoto (WKY) rats were characterized. Contractility methods with isoprenaline, T-0509 (a selective β1-adrenoceptor agonist) and procaterol (a selective β2-adrenoceptor agonist) were used. At 5 weeks, the SHRs were pre-hypertensive. Isoprenaline was more potent on the left atrium of 5-week-old SHRs than WKY rats. Bisoprolol, a selective β1-adrenoceptor antagonist, was more potent against isoprenaline and T-0509 on the SHR than WKY rat left atrium. ICI 118,551, a selective β2-adrenoceptor antagonist, was more potent against procaterol and T-0509 on the SHR than WKY rat left atrium. The results with bisoprolol and ICI 118,551 suggest that there are more functional β1- and β2-adrenoceptors on the left atrium of 5-week-old SHRs than WKY rats. Isoprenaline, T-0509 and procaterol were equipotent on the right atrium of 5-week-old WKY rats and SHRs. Bisoprolol was more potent against isoprenaline, T-0509 and procaterol on the SHR than WKY rat right atrium. ICI 118,551 was more potent against T-0509, but not isoprenaline and procaterol, on the SHR than WKY rat left atrium. This suggests there are more functional β1-adrenoceptors, and probably more functional β2-adrenoceptors, on the right atrium of 5-week-old SHRs than WKY rats. These functional differences in β1 - and β2-adrenoceptor-mediated responses of the left and right atria of pre-hypertensive SHRs cannot be caused by hypertension, and may be associated with the onset of hypertension.
In-vitro transfer of nitazoxanide across the intestinal epithelial barrier
Authors: Matysiak-Budnik Tamara , Mégraud Francis , Heyman Martine 
Published: October 2002

Abstract
Nitazoxanide is a thiazolide compound that exhibits antimicrobial properties against helminths, protozoa, anaerobic bacteria and also Helicobacter pylori. The mucosal diffusion of this new drug has not been studied. The aim of this study was to examine the transport of radiolabelled nitazoxanide across the epithelial barrier according to the mode (mucosal or serosal) of drug administration. HT29-19A intestinal epithelial cells, grown as monolayers on microporous filters, were used as an epithelial model. In a short-term (100 min) transport study, the apical to basal and the basal to apical transport of nitazoxanide across the monolayers was studied in an Ussing chamber. In a long-term (24 h) study, the transport of the drug and its intracellular accumulation were studied in filter-grown epithelial monolayers kept in culture plates. In the short-term transport study, both the apical and basal fluxes achieved a steady state after 70 min and there was no significant difference between the apical to basal (3991 ± 1001 ng h−1 cm−2) and the basal to apical (4246 ± 856 ng h−1 cm−2) nitazoxanide fluxes. In the long-term transport study, after apical or basal drug application, a gradual increase in the drug concentration in the opposite compartment was noted, which reached similar values for apical and basal fluxes (2497 ± 125 and 2309 ± 81 ng mL−1, respectively) after 24 h. Moreover, a rapid, although transitory, intracellular accumulation of nitazoxanide was observed at 10 min after apical (299 ± 25 ng/106 cells) and basal (124 ± 10 ng/106 cells) drug application, but decreased thereafter. There is an important transepithelial transport of nitazoxanide across the digestive epithelial monolayer with a rapid intracellular accumulation of the drug. No difference between the apical to basal and basal to apical fluxes of the drug was observed, suggesting that both topical and systemic modes of action of this antibiotic are successful.
Functionalization of Carbon Material by Surface Grafting of Polymers
Authors: Tsubokawa Norio 
Published: October 2002

Abstract
Recent advances in surface grafting of polymers onto carbon materials, such as carbon black, graphite powder, and carbon fiber, and the application of polymer-grafted carbon materials as a novel functional materials have been mainly reviewed. The grafting of polymers onto the surface was achieved by (1) grafting onto process, (2) grafting from process, (3) polymer reaction process, and (4) stepwise growth by dendrimer synthesis methodology. For the grafting, surface functional groups, such as carboxyl and phenolic hydroxy groups, were used as grafting sites. For example, in the living cationic polymerization initiated by carbon black/ZnCl2 system, carboxyl groups on the surface acted as initiating site and grafting site. In the surface grafting, polycondensed aromatic rings of carbon materials could be used as grafting sites by using ligand exchange reaction of polymers containing ferrocene moieties. It was demonstrated that, by the grafting of polymers onto carbon black surface, the dispersibility in solvent and the surface wettability were readily controlled by pH and temperature. By postgrafting of hydrophilic polymer to grafted hydrophobic chain on carbon black, amphiphilic carbon black was obtained. The applications of crystalline polymer-grafted carbon black as a novel gas sensor material and a positive temperature coefficient material are summarized.
Effect of Water and Oxygen Contents on the Decomposition of Gaseous Trichloroethylene in Air under Electron Beam Irradiation
Authors: Hakoda Teruyuki , Hashimoto Shoji , Kojima Takuji 
Published: October 2002

Abstract
An electron beam (EB) treatment of gaseous trichloroethylene (TCE) in air was studied as a purification method of off-gases containing gaseous chloroethylenes. The model air containing TCE at input concentrations of 5–75 ppmv, detected mostly in actual off-gases, was irradiated with 1-MeV EBs in a gas-flow vessel at 10 L/min under the conditions of atmospheric pressure, 298 K, and different H2O contents. The decomposition of 75 ppmv TCE was also examined in humid air under different O2 contents of 1 × 103–2.1 × 105 ppmv. In the existence of H2O and O2 contents with ≥ 3 × 102 ppmv and ≥ 5 × 103 ppmv, respectively, the decomposition ratios of TCE were enhanced and TCE was decomposed into 83.0 ± 1.5% of dichloroacetyl chloride (DCAC) and 17.5 ± 0.6% of carbonyl chloride (COCl2) independently of the input TCE concentrations based on the carbon balance. Trichloroethylene of 5–75 ppmv was effectively decomposed by the OH radical through Cl-radical chain oxidation under the above-mentioned air conditions.
Evaluation of a rapid micro-scale assay for tacrolimus by liquid chromatography-tandem mass spectrometry
Authors: Keevil BG , McCann SJ , Cooper DP , Morris MR 
Published: October 2002

Background: The immunosuppressive drug tacrolimus has complex and unpredictable pharmacokinetics, therefore regular monitoring is required in patients receiving tacrolimus therapy. We have developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring tacrolimus concentrations in whole blood and have compared it with a microparticle enzyme immunoassay. Methods: For the LC-MS/MS assay, samples were prepared in a 96-deep well microtitre plate by adding 10 µL of blood to 40 µL of 0·1 mol/L zinc sulphate solution. Proteins were precipitated by adding 100 µL acetonitrile containing ascomycin internal standard. After vigorous mixing and centrifugation, 20 µL of the supernatant was injected into the LC-MS/MS system. A C18 cartridge (3 mm × 4 mm) was eluted with a step gradient of 50% to 100% methanol containing 2 mmol/L ammonium acetate and 0·1% (v/v) formic acid, at 0·6 mL/min. The column was maintained at 55°C. Results: The retention times were 0·98 min for ascomycin and 0·98 min for tacrolimus. Cycle time was 2·5 min, injection to injection. The analytes were monitored using a Quattro micro tandem mass spectrometer operated in multiple reaction monitoring mode using the following transitions: m/z821 > 768 (tacrolimus) and m/z809 > 756 (ascomycin). The limit of quantitation was 0·5 µg/L and the assay was linear up to 30 µg/L. Precision of the method, over the concentration range 2·5-15·0 µg/L, was < 7% within-batch and < 6% between-batch. Total time to analyse 24 samples including result generation was 90 min. Conclusion: We conclude that the LC-MS/MS method is quick, precise and robust and will provide a fast turn around of results for the transplant physician.
Stability of ascorbic acid in serum and plasma prior to analysis
Authors: Ching Simon YL , Prins Alex W , Beilby John P 
Published: October 2002

Introduction: The stability of ascorbic acid in serum and plasma prior to analysis was studied. Methods: Blood samples were collected from ten healthy subjects into Vacutainer tubes containing either dipotassium EDTA, lithium-heparin or no additive. Ascorbic acid was analysed following immediate separation and preservation of samples, following delayed separation for 2 h and after delayed deproteinization and preservation for 2, 5 and 8 h. Deproteinization and preservation were achieved using a solution containing perchloric acid, EDTA and dithiothreitol. Ascorbic acid was analysed by high-performance liquid chromatography. Results: Blood collected into EDTA and separated, deproteinized and preserved immediately gave the highest yield of ascorbic acid. Loss of analyte after delayed separation was least for EDTA tubes (median 7%, range 4-13%), followed by lithium-heparin (median 18%, range 10-32%) and serum (median 26%, range 14-50%). Immediate separation of samples but delayed deproteinization and preservation also resulted in substantial losses of ascorbic acid. Conclusion: Minimum loss of ascorbic acid is achieved if blood is collected into tubes containing dipotassium EDTA and separated within 2 h, followed by immediate deproteinization and preservation.
Evaluation of individually ventilated cage systems for laboratory rodents: occupational health aspects
Authors: Renström Anne , Björing Gunnar , Höglund A. Urban 
Published: October 2002

New ventilated caging systems for laboratory animals were compared with conventional caging regarding allergen distribution, ergonomic suitability, cage environment and animal welfare. This paper presents occupational health evaluations. Mice were placed in individually ventilated cage (IVC) systems, a ventilated cabinet, and in cages on open shelves (conventional husbandry). The IVC systems were studied at negative and positive airflow. Aeroallergens were sampled on filters ( n = 204, including controls) in undisturbed rooms and during cage changing. Concentrations of mouse urinary allergen (Mus m 1) in filter eluates were measured using sandwich ELISA. An ergonomic evaluation was performed with measurement of traction forces. Staff exposure during cage changing was high in all systems, range 116-4430 ng Mus m 1/m3. In undisturbed animal rooms, allergen levels were orders of magnitude higher when using conventional caging compared with ventilated systems; P < 0.001. At positive pressure, both IVCs leaked allergen (median Mus m 1 concentration was < 0.08 ng/m3 at negative, but 6.5 ng/m3 (IVC1) and 0.8 ng/m3 (IVC2S) at positive pressure). The IVC systems had ergonomic disadvantages compared with the conventional husbandry and the ventilated cabinet, for instance with cages in unsuitable working heights. Ventilated husbandry solutions reduce levels of airborne allergen substantially at negative pressure, but are ergonomically less suitable. To prevent allergen exposure during cage changing, we propose that this procedure should be performed under ventilated conditions. Producers and users must cooperate in optimizing animal caging systems for both animals and staff.
Metabolic flux measurements across portal drained viscera, liver, kidney and hindquarter in mice
Authors: Hallemeesch M. M. , Ten Have G. A. M. , Deutz N. E. P. 
Published: October 2002

A method was developed to measure metabolic fluxes across either portally-drained viscera (PDV) and liver or kidney and hindquarter (HQ) in anesthetized mice. The method includes a primed-constant infusion of ketamine-medetomidine anaesthesia to stabilize the mice for the surgical procedures. For measurement of metabolic fluxes across PDV and liver, blood sampling catheters were inserted in the carotid artery, portal vein and hepatic vein and infusion catheters in the jugular vein and mesenteric vein. For measurement of metabolic flux across kidney and HQ, blood sampling catheters were inserted in the carotid artery, renal vein and caval vein and infusion catheters in the jugular vein and abdominal aorta. 14C-PAH was infused to enable plasma flow measurement using an indicator dilution method. In addition, we developed a blood sampling procedure without waste of blood. We measured plasma flow and metabolic fluxes across PDV, liver, kidney and HQ. Mean plasma flow in post-absorptive mice was: PDV: 0.9 ± 0.2, liver: 1.2 ± 0.3, kidney:1.0 ± 0.1, HQ: 1.1 ± 0.3 ml/10 g body weight (b.w.)/min. Significant glutamine release by the HQ and uptake of glutamine by the kidney and PDV was observed. In PDV, citrulline is produced from glutamine and is in turn used by the kidney for the production of arginine. In conclusion, the described model enables measurement of metabolic fluxes across PDV, liver, kidney and HQ in mice. The availability of such a small animal model allows the potential for measuring metabolic parameters in transgenic and knockout mice, and therefore may lead to an important refinement in metabolic research.
The selection of marmoset monkeys (Callithrix jacchus) in pharmaceutical toxicology
Authors: Smith D. , Trennery P. , Farningham D. , Klapwijk J. 
Published: October 2002

Prior to controlled clinical trials in human volunteers or patients it is required that novel pharmaceuticals are evaluated for pre-clinical safety in a rodent and a non-rodent ('second') species. In most cases the rodent species used has been the rat and the second species has been the dog or macaque (usually cynomolgus or rhesus) monkey. However, there is an increasing trend within the United Kingdom (UK) pharmaceutical industry to use the common marmoset ( Callithrix jacchus) for pre-clinical toxicology programmes. This paper examines the practicality of using the common marmoset (henceforth referred to as 'the marmoset') in toxicological testing and reviews metabolic and pharmacodynamic similarities between this species and humans. It then discusses some of the advantages and disadvantages of the use of this species when compared with two other alternatives to the dog and macaque, namely the ferret and minipig. In particular, the marmoset has clear advantages over the macaque in terms of animal welfare and practicality. There is regulatory acceptance of this species for Investigational New Drug (IND), Clinical Trial Exemption (CTX), New Drug Application (NDA) and Marketing Authorization Application (MAA) registrations. Whilst the dog is likely to be maintained as the primary non-rodent species in toxicology, the marmoset has been, and will likely continue to be, adopted as an additional non-rodent species in pre-clinical toxicology programmes where appropriate.
Outcome of Contact Tracing for Chlamydia Trachomatis in a District General Hospital
Authors: Jarvis Ranjana Rani , Curless Eric , Considine Kay 
Published: October 2002

The outcome of contact tracing (partner notification) for Chlamydia trachomatis in a district general hospital during the 5-year period between 1991-1995 was surveyed. During the 5-year period 1027 cases of C. trachomatis were diagnosed. The health adviser saw 928 (90%) of cases who reported 1132 (1.2) sexual contacts. Out of 682 sexual contacts sought by the health adviser, 472 (69.5%) were seen. Following a consultation with the health adviser, over two-thirds (86%) of index cases chose to inform their contacts themselves. Over two-thirds (71%) of contacts informed by these index cases were seen. A higher proportion of regular and first or most immediate contacts were seen as a result of contact tracing. A significantly higher proportion of partners of index cases who themselves returned for test of cure were seen. A consultation with the health adviser facilitated uptake of partner notification by the index patients. Patient referral led to a majority of contacts being seen in a genitourinary medicine (GUM) clinic. Follow-up visits by index patients may improve outcome of contact tracing and should continue irrespective of need for test of cure.
Developing a model to enhance the capacity of statutory organisations to engage with lay communities
Authors: Pickin Christine , Popay Jennie , Staley Kristina , Bruce Nigel , Jones Christopher , Gowman Natasha 
Published: October 2002

Objective: To understand the processes that constrain the capacity of statutory organisations to work effectively with lay communities and to develop a model to enhance their capacity to do so. Methods: The research consisted of three elements: a review of relevant literature; in-depth interviews with a purposive sample of people who had recently been involved in community-statutory sector partnership; and a deliberative workshop involving ten expert witnesses, selected to reflect a range of sectors and levels within organisations. Results: Many factors contribute to a lack of effective strategic partnerships between lay communities and statutory organisations. These factors fall into five domains: the community's capacity to engage; the skills and competencies of organisational staff; the dominant professional service culture; the overall organisational ethos and culture; and the dynamics of the local and national political systems. A model of the relationships and/or interaction between these domains is postulated. There is potential for testing this model with statutory organisations to see whether it concurs with their reality and whether it is enhancing their organisational capacity. Conclusions: Commonly occurring constraints to effective partnerships between statutory organisations and lay communities need to be identified and addressed by applying a dynamic model of the type presented here.