bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cells in the lung of patients with hypersensitivity pneumonitis accumulate in a clonal manner
Authors: Facco Monica , Trentin Livio , Nicolardi Linda , Miorin Marta , Scquizzato Elisa , Carollo Davide , Baesso Ilenia , Bortoli Michela , Zambello Renato , Marcer Guido , Agostini Carlo , Semenzato Gianpietro 
Published: February 2004

AbstractHypersensitivity pneumonitis (HP) is characterized by an alveolitis sustained by CD8+ T lymphocytes showing a limited expression of the T cell receptor (TCR). We previously demonstrated that a bias in T cell selection occurs in the lower respiratory tract of patients with HP, with a compartmentalization in the lung of CD8+ T cells bearing (TCR)-β variable (TCRBV) #2, 3, 5, 6, 8, and 13 gene segments. We herein characterized the clonal T cell populations present in the lung and in the blood of patients with HP. Heteroduplex analyses, cloning, and sequencing T cells bearing TCR indicate oligoclonal expansions of T cells expressing homologous or identical complementary-determining region 3. Furthermore, T cell clones isolated from the two compartments expressed similar, sometimes identical, junctional regions. Removal from antigenic exposure led to the disappearance of T cell clones. Our findings indicate that expansions of T lymphocytes bearing clonal TCRBV region gene segments take place in the lung of patients with HP during exposure. The evidence that identical T cell clones are present in the lung and the blood of the same patient suggests that the immune reaction occurring at lung level gives rise to a systemic reaction.
Cross-regulation of CD86 by CD80 differentially regulates T helper responses fromMycobacterium tuberculosissecretory antigen-activated dendritic cell subsets
Authors: Balkhi Mumtaz Yaseen , Latchumanan Vinoth K , Singh Balwan , Sharma Pawan , Natarajan Krishnamurthy 
Published: February 2004

AbstractWe report that stimulation of Mycobacterium tuberculosis secretory antigen- and tumor necrosis factor α-matured BALB/c mouse bone marrow dendritic cells (BMDCs) with anti-CD80 monoclonal antibody up-regulated CD86 levels on the cell surface. Coculture of these BMDCs with naïve, allogeneic T cels now down-regulated T helper cell type 1 (Th1) responses and up-regulated suppressor responses. Similar results were obtained with splenic CD11c+/CD8a− DCs but not to the same extent with CD11c+/CD8a+ DCs. Following coculture with T cells, only BMDCs and CD11c+/CD8a− DCs and not CD11c+/CD8a+ DCs displayed increased levels of surface CD86, and further, coculturing these DCs with a fresh set of T cells attenuated Th1 responses and increased suppressor responses. Not only naïve but even antigen-specific recall responses of the Th1-committed cells were modulated by DCs expressing up-regulated surface CD86. Further analyses showed that stimulation with anti-CD80 increased interleukin (IL)-10 and transforming growth factor-β-1 levels with a concomitant reduction in IL-12p40 and interferon-γ levels from BMDCs and CD11c+/CD8a− DCs and to a lesser extent, from CD11c+/CD8a+ DCs. These results suggest that cross-talk between costimulatory molecules differentially regulates their relative surface densities leading to modulation of Th responses initiated from some DC subsets, and Th1-committed DCs such as CD11c+/CD8a+ DCs may not allow for such modulation. Cognate antigen-presenting cell (APC):T cell interactions then impart a level of polarization on APCs mediated via cross-regulation of costimulatory molecules, which govern the nature of subsequent Th responses.
Nitric Oxide Donor Increases Osteoprotegerin Production and Osteoclastogenesis Inhibitory Activity in Bone Marrow Stromal Cells from Ovariectomized Rats
Authors: Wang Feng-Sheng , Wang Ching-Jen , Chen Yeung-Jen , Huang Yu-Ting , Huang Hui-Chen , Chang Per-Rong , Sun Yi-Chih , Yang Kuender D. 
Published: February 2004

Abstract
Nitric oxide (NO) has emerged as a potent regulator useful in alleviating estrogen deficiency bone loss. Osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) play important roles in regulating osteoclastogenesis. Although recent studies have reported NO donor attenuation of bone loss, the effect of NO donor on OPG and RANKL expression of osteogenic stromal cells and bone microenvironment in ovariectomized rats is not fully understood. Here, we showed that optimal NO donor treatment [2,2′-(hydroxynitrosohydrazino)bis-ethanamine; 15 μm] increased OPG, but not RANKL, levels in bone marrow stromal cells from ovariectomized rats. NO donor augmentation of OPG synthesis was transcriptionally mediated. The stimulatory action of NO donor on OPG expression appeared to be regulated by tyrosine kinase-dependent activation of Cbfa1/Runx2 binding to the OPG promoter, because cell cultures pretreated with tyrosine kinase inhibitor (herbimycin A), but not with protein kinase A inhibitor (calphostain C) or protein kinase C inhibitor [(Rp)-cAMP] significantly reduced NO-augmented Runx2 activation and OPG levels. Conditioned medium from NO donor-treated cells inhibited macrophage-colony-stimulating factor and RANKL-induced osteoclast formation of macrophage-colony-stimulating factor-dependent bone marrow macrophages. Neutralization with anti-OPG antibodies abolished the inhibitory effect of conditioned medium on osteoclastogenesis. Immunohistochemical observation also showed that 2,2′-(hydroxynitrosohydrazino)bis-ethanamine increased OPG expression of osteochondral cells located at metaphyseal endosteum and calcified cartilage of proximal femurs in ovariectomized rats. These findings suggest that NO donor can be an alternative pharmacological strategy for regulating bone resorption.
Dimensional accuracy of injection-moulded components produced in an enhanced silicone rubber mould
Authors: Dunne P , Byrne G 
Published: February 2004

The inherent technical limitations of rapid prototyping systems have led to the development of rapid tooling techniques. These techniques are capable of producing prototypes in final materials by the intended manufacturing process. One rapid tooling process that provides a low cost and rapid route to the manufacture of injection-moulded thermoplastic components is enhanced silicone moulding. During the moulding cycle the mould deforms under the pressures and temperatures experienced and components produced suffer a loss of dimensional accuracy. An analytical and experimental investigation was undertaken to quantify the dimensional accuracy of components produced by the process, and to identify the moulding parameters which contribute to the loss of dimensional accuracy. A mould was produced from a stereolithography master pattern and used to injection-mould components in high-impact polystyrene under various moulding conditions. Moulded components produced were typically oversized with a loss of dimensional accuracy of the order of 0.3–0.6 mm. Two parameters, namely injection pressure and mould temperature, were found to have an influence on dimensional accuracy. The injection pressure causes the mould cavity to expand and results in manufacture of components which are oversized. Components produced at an injection pressure of 16MPa were on average 0.34 mm (1.3 per cent) oversized in width and 0.36 mm (11.3 per cent) oversized in depth. Those produced at an injection pressure of 20 MPa were oversized by an average of 0.45 mm (1.8 per cent) in width and 0.59 mm (18.6 per cent) in depth. An increase in mould temperature caused a reduction in the size of the mould cavity. This was because the rubber mould was restricted in a metal mould frame. The rubber mould expands into the free space of the cavity. Components produced at mould temperatures of 50, 70 and 90°C were oversized in width by an average of 0.37mm (1.5 per cent), 0.34 mm (1.3 per cent) and 0.20 mm (0.8 per cent) respectively.
Anti-inflammatory effect of erythromycin on histamine-induced otitis media with effusion in guinea pigs
Authors: Aktan Bülent , Gundogdu Cemal , Ucuncu Harun , Unal Bunyami , Sütbeyaz Yavuz , Altas Sare 
Published: February 2004

In this study, the anti-inflammatory effect of erythromycin was investigated in a model of histamine-induced otitis media with effusion (OME). OME was induced in guinea pigs by the transtympanic injection of histamine solution into the middle-ear cavity. Guinea pigs were randomly assigned to one of three groups: control, erythromycin treatment, or methylprednisolone treatment. After histamine injection, the animals were treated with intraperitoneal medication for five days consecutively. Afterwards, the animals were sacrificed and the temporal bones were removed. The samples were examined stereologically.In the erythromycin-treated group, it was observed that neutrophil infiltration was significantly inhibited when compared to the control group. This result shows that erythromycin may produce a significant anti-inflammatory effect in this model of OME.
Effects of the chorda tympani damage on submandibular glands: scintigraphic changes
Authors: Yagmur C. , Miman M. C. , Karatas E. , Akarcay M. , Erdem T. , Ozturan O. 
Published: February 2004

The aim of this study is to compare the scintigraphic results of a denervated submandibular gland with the contralateral normal side in patients with unilateral chorda tympani damage. Sixteen patients (11 women and five men with a mean age of 27) with unilateral proven chorda tympani damage during their previous ear surgery were included in the study. The perfusion ratio (PR), concentration ratio (CR) and stimulated excretion ratio (SER) were calculated scintigraphically and the results from the salivary glands on opposite sides were compared.For submandibular glands, the perfusion ratio (PR), concentration ratio (CR) and stimulated excretion ratio (SER) were found to be 0.65 ± 0.21, 0.70 ± 0.21, 0.79 ± 0.37, respectively. All ratios resulted from statistically decreased radioactivity accumulation on the affected side (p<0.05).Chorda tympani damage negatively affects the function of the ipsilateral submandibular glands despite the absence of atrophy. Dynamic salivary gland scintigraphy is a practical and valuable method of disclosing the decreased capacity of perfusion, concentration and secretion function in unilateral neurological deprivation.
Transient Ischemic Attack Reported with Paroxetine Use
Authors: Manos Gail H , Wechsler Steven M 
Published: February 2004

OBJECTIVE To report the occurrence of a transient ischemic attack (TIA) temporally related to the initiation of paroxetine. CASE SUMMARY A 57-year-old white man with a history of intermittent atrial fibrillation and hypercholesterolemia developed slurred speech and a facial droop 3 days after starting paroxetine. He was diagnosed with a TIA, hospitalized, and given anticoagulation treatment. The presenting symptoms resolved, but recurred when paroxetine was restarted 2 days later. DISCUSSION Platelets secrete serotonin, which mediates vasoconstriction through stimulation of 5-HT2a receptors. This is counterbalanced by the release of the vasodilator nitric oxide upon serotonin stimulation of endothelial 5-HT1 receptors. In conditions such as atherosclerosis, the damage to the endothelium leads to a greater vasoconstrictive response. Paroxetine has been reported to weakly inhibit norepinephrine reuptake and nitric oxide production in addition to increasing serotonergic activity, potentially compounding the vasoconstrictive response. An objective causality assessment revealed that the TIA was probably an adverse event resulting from use of paroxetine. CONCLUSIONS Use of paroxetine and other selective serotonin-reuptake inhibitors may result in changes of the vasculature and subsequent ischemic events in predisposed patients.
Use of Epoetin Alfa in Critically III Patients
Authors: Pajoumand Mehrnaz , Erstad Brian L , Camamo James M 
Published: February 2004

OBJECTIVE To discuss the controversies regarding the use of epoetin alfa (EPO) for reducing red blood cell (RBC) transfusions in critically ill patients with anemia. DATA SOURCES A MEDLINE search (1966–July 2003) was conducted using the search terms anemia; critical illness; erythropoietin; epoetin alfa; and erythropoietin, recombinant. References of selected articles were reviewed for studies that may have been missed by the computerized search. STUDY SELECTION AND DATA EXTRACTION Studies pertaining to the use of EPO for anemia of critical illness with an emphasis on data obtained from controlled trials. DATA SYNTHESIS Anemia is a common complication in patients admitted to the intensive care unit (ICU). Two prospective, randomized studies have demonstrated decreased transfusion requirements associated with EPO administration in medical/surgical patients who were in the ICU for at least 3 days and had hematocrit concentrations <38%. No differences were found in length of stay or mortality. A multicenter trial found that a restrictive strategy of RBC transfusion (hemoglobin goal 7–9 g/dL) was associated with in-hospital mortality lower than that with a more liberal approach, which calls into question the 38% hematocrit goal in the EPO trials. Furthermore, preliminary results from an economic analysis of EPO use in the ICU setting have demonstrated that EPO is not cost-effective. CONCLUSIONS Given the controversies surrounding EPO administration in critically ill patients, institutions are encouraged to develop EPO guidelines to help ensure the most appropriate use of this expensive product. Additional studies regarding patients most likely to benefit from EPO therapy, the most effective dosing regimen, and use of adjunctive therapies are needed.
Methamphetamine and Amphetamine Pharmacokinetics in Oral Fluid and Plasma after Controlled Oral Methamphetamine Administration to Human Volunteers
Authors: Schepers Raf J F , Oyler Jonathan M , Joseph Robert E , Cone Edward J , Moolchan Eric T , Huestis Marilyn A 
Published: February 2004

Abstract
Background: Methamphetamine (METH) and amphetamine (AMP) concentrations in 200 plasma and 590 oral fluid specimens were used to evaluate METH pharmacokinetics and pharmacodynamics after oral administration of sustained-release METH.
Methods: Eight participants received four oral 10-mg S-(+)-METH hydrochloride sustained-release tablets within 7 days. Three weeks later, five participants received four oral 20-mg doses. Blood samples were collected for up to 24 h and oral fluid for up to 72 h after drug administration.
Results: After the first oral dose, initial plasma METH detection was within 0.25–2 h; cmax was 14.5–33.8 μg/L (10 mg) and 26.2–44.3 μg/L (20 mg) within 2–12 h. In oral fluid, METH was detected as early as 0.08–2 h; cmax was 24.7–312.2 μg/L (10 mg) and 75.3–321.7 μg/L (20 mg) and occurred at 2–12 h. The median oral fluid-plasma METH concentration ratio was 2.0 across 24 h and was highly variable. Neutral cotton swab collection yielded significantly higher METH and AMP concentrations than citric acid candy-stimulated expectoration. Mean (SD) areas under the curve for AMP were 21% ± 25% and 24% ± 11% of those observed for METH in plasma and oral fluid, respectively. After a single low or high dose, plasma METH was &gt;2.5 μg/L for up to 24 h in 9 of 12 individuals (mean, 7.3 ± 5.5 μg/L at 24 h); in oral fluid the detection window was at least 24 h (mean, 18.8 ± 18.0 μg/L at 24 h). The plasma and oral fluid 24-h METH detection rates were 54% and 60%, respectively. After four administrations, METH was measurable for 36–72 h (mean, 58.3 ± 14.5 h).
Conclusions: Perceived advantages of oral fluid for verifying METH exposure compared with urine include simpler specimen collection and reduced potential for adulteration, but urine offers higher analyte concentrations and a greater window of detection.
Homogeneous Real-Time Detection of Single-Nucleotide Polymorphisms by Strand Displacement Amplification on the BD ProbeTec ET System
Authors: Wang Sha-Sha , Thornton Keith , Kuhn Andrew M , Nadeau James G , Hellyer Tobin J 
Published: February 2004

Abstract
Background: The BD ProbeTec™ ET System is based on isothermal strand displacement amplification (SDA) of target nucleic acid coupled with homogeneous real-time detection using fluorescent probes. We have developed a novel, rapid method using this platform that incorporates a universal detection format for identification of single-nucleotide polymorphisms (SNPs) and other genotypic variations.
Method: The system uses a common pair of fluorescent Detector Probes in conjunction with unlabeled allele-specific Adapter Primers and a universal buffer chemistry to permit analysis of multiple SNP loci under generic assay conditions. We used Detector Probes labeled with different dyes to facilitate differentiation of two alternative alleles in a single reaction with no postamplification manipulation. We analyzed six SNPs within the human β2-adrenergic receptor (β2AR) gene, using whole blood, buccal swabs, and urine samples, and compared results with those obtained by DNA sequencing.
Results: Unprocessed whole blood was successfully genotyped with as little as 0.1–1 μL of sample per reaction. All six β2AR assays were able to accommodate ≥20 μL of unprocessed whole blood. For the 14 individuals tested, genotypes determined with the six β2AR assays agreed with DNA sequencing results.
Conclusion: SDA-based allelic differentiation on the BD ProbeTec ET System can detect SNPs rapidly, using whole blood, buccal swabs, or urine.
HPLC Determination of Erythrocyte Methotrexate Polyglutamates after Low-Dose Methotrexate Therapy in Patients with Rheumatoid Arthritis
Authors: Dervieux Thierry , Orentas Lein Diana , Marcelletti John , Pischel Ken , Smith Katie , Walsh Michael , Richerson Russell 
Published: February 2004

Abstract
Background: Methotrexate (MTX) may produce antiarthritic effects through polyglutamation to methotrexate polyglutamates (MTXPGs), a process that covalently attaches sequential γ-linked glutamic residues to MTX. We sought to develop an innovative HPLC method for the quantification of these metabolites in erythrocytes.
Methods: Two alternative approaches were developed. In the first approach, MTXPGs from 50 μL of packed erythrocytes were converted to MTX in the presence of plasma γ-glutamyl hydrolase and mercaptoethanol at 37 °C. In the second approach, MTXPG species (up to the hepta order of glutamation) from 100 μL packed erythrocytes were directly quantified in a single run. In both methods, the MTXPGs were extracted from the biological matrix by a simple perchloric acid deproteinization step with direct injection of the extract into the HPLC. The chromatography used a C18 reversed-phase column, an ammonium acetate/acetonitrile buffer, and postcolumn photo-oxidation of MTXPGs to fluorescent analytes.
Results: Intra- and interday imprecision (CVs) were &lt;10% at low and high concentrations of analytes for both methods. The limit of quantification was 5 nmol/L. In 70 patients with rheumatoid arthritis receiving weekly low-dose MTX, the mean (SD) total MTXPG concentration measured after conversion of MTXPGs to MTX was similar to the total MTXPG concentration calculated from the sum of individual MTXPG species [117 (56) vs 120 (59) nmol/L; r = 0.97; slope = 1.0]. The triglutamate predominated over all other MTXPG species (36% of total), the pentaglutamate was the highest order of glutamation detected, and a stability study revealed no change in the polyglutamation pattern in erythrocytes 48 h after phlebotomy when the specimen was stored at 2–8 °C.
Conclusion: The proposed method for quantification of erythrocyte MTXPGs is rapid, sensitive, and accurate and can be applied to the routine monitoring of MTX therapy.
Evaluation of Cell-free Fetal DNA as a Second-Trimester Maternal Serum Marker of Down Syndrome Pregnancy
Authors: Farina Antonio , LeShane Erik S , Lambert-Messerlian Geralyn M , Canick Jacob A , Lee Thomas , Neveux Louis M , Palomaki Glenn E , Bianchi Diana W 
Published: February 2004

Abstract
Background: Second-trimester cell-free fetal DNA (studied only in pregnancies with male fetuses) is higher in maternal serum samples from women carrying Down syndrome fetuses than in unaffected pregnancies. In this study we evaluated the potential performance of fetal DNA as a screening marker for Down syndrome.
Methods: Data on maternal serum fetal DNA concentrations and the corresponding concentrations of the quadruple serum markers were available from 15 Down syndrome cases, each matched for gestational age and length of freezer storage, with 5 control samples. Analyte values were expressed as multiple(s) of the control or population median. Screening performance of fetal DNA, both alone and when added to estimates of quadruple marker performance, was determined after modeling using univariate and multivariate gaussian distribution analysis.
Results: The median fetal DNA concentration in Down syndrome cases was 1.7 times higher than in controls. In univariate analysis, fetal DNA gave a 21% detection rate at a 5% false-positive rate. When added to quadruple marker screening, fetal DNA increased the estimated detection rate from 81% to 86% at a 5% false-positive rate.
Conclusions: Cell-free fetal DNA, measured in maternal serum, can modestly increase screening performance above what is currently available in the second trimester. If and when maternal serum fetal DNA can be measured in pregnancies with both male and female fetuses, the utility and cost-effectiveness of adding it as a Down syndrome screening marker should be assessed.
Comparison of Two Assays for Human Kallikrein 2
Authors: Blijenberg Bert G , Wildhagen Mark F , Bangma Chris H , Finlay Judith A , Väisänen Ville , Schröder Fritz H 
Published: February 2004

Abstract
Background: We compared two recently developed research assays for the measurement of human kallikrein 2 (hK2) in serum: one fully automated assay (Beckman Coulter Access® immunoanalyzer) and one manual assay based on the DELFIA® technology.
Methods: We used two subsets of clinical specimens consisting of 48 samples from prostate cancer patients and 210 samples from participants in an ongoing screening study (ERSPC). Both subsets were measured in the Rotterdam laboratory, and the prostate cancer samples were used for analytical comparison with the originating sites for the assays: Beckman Coulter Research Department (San Diego, CA) and Turku University (Turku, Finland).
Results: Both the Beckman Coulter and the Turku assays performed very similarly between the Rotterdam laboratory and the originating sites: the R2 value for both comparisons was 0.99, and the slope difference between sites was &lt;20%. Deming regression analysis of the DELFIA (y) and Access (x) assays yielded the following: for the prostate cancer group, y = 1.17x − 0.01 (R2 = 0.88; n = 48); and for the ERSPC group, y = 0.62x − 0.01 (R2 = 0.77). Breakdown of the latter group into subgroups (nondiseased, benign prostatic hyperplasia, and prostate cancer samples) gave only minor differences. The Access calibrators were underrecovered by 13% in the DELFIA assay, whereas the DELFIA calibrators were overrecovered by 45% in the Access assay.
Conclusion: The DELFIA and Access assays for hK2, which have similar analytical features, show differences that cannot be explained by calibration.