bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification of the monochromatic photon flux of refractive x‐ray monochromators in the energy range from 10 to 30 keV
Authors: Ebel Horst 
Published: October 2002

AbstractThe refractive properties of matter at incidence angles close to total reflection are used for monochromatization of continuous x‐radiation. Possible radiation sources are standard diffraction tubes with different target materials and either regular line focus or with fine focus. Theoretical considerations include Snell's law, dispersion theory and Fresnel's equations. The results of Monte Carlo calculations are as follows. The photon flux of the band‐shaped monochromatic beam with thicknesses of 20–40 µm, divergence of 0.01° and width of 10 mm depends on the x‐ray source, the refractor material, the angular combination of incidence and take‐off angle and, thus, on the pass energy of the monochromator. Numerical values of 104 photons s−1 were obtained with a tube with Mo anode, fine focus, 45 kV and 40 mA. Pass energies of 5–30 keV and widths of the pass energy range of 0.2–3.5 keV were obtained. The refractor materials were Si and n‐C33H68. The hydrocarbon refractor is characterized by a comparably much smaller photoelectric absorption and, consequently, better efficiency. Copyright © 2002 John Wiley & Sons, Ltd.
Neuroleptic-induced extrapyramidal symptoms are accompanied by cognitive dysfunction in schizophrenia
Authors: Krausz M. , Moritz S.H. , Naber D. , Lambert M. , Andresen B. 
Published: October 2002

SummaryCognitive impairments in schizophrenics have been found to precede tardive dyskinesia and to co-exist with other motor deficits. However, little is yet known about the prevalence of cognitive disturbances in patients with neuroleptic-induced parkinsonism. From the literature on idiopathic parkinson, it was inferred that extrapyramidal symptoms (EPS) are accompanied by cognitive dysfunction. 85 schizophrenic in-patients were divided into EPS high and low scorers according to an established criterion (Simpson Angus Scale, cut-off score: 0.4). Cognitive impairments were assessed using a self-rating instrument measuring disturbances of information processing.Patients with high EPS exhibited significantly elevated scores in six of ten cognitive and perceptual subscales (t = 2.1—3.1) as compared to low EPS patients. It is concluded that high EPS patients suffer from cognitive disturbances which are assumed to possess high relevance for both psycho-social and medical treatment. Cognitive problems may, when not considered, disturb compliance, insight of illness and transfer of learnt skills into everyday life.
Mechanism of superoxide anion production by hepatic sinusoidal endothelial cells and Kupffer cells during short‐term ethanol perfusion in the rat
Authors: Hasegawa Tadashi , Kikuyama Masataka , Sakurai Kazushi , Kambayashi Yasuhiro , Adachi Masakazu , Saniabadi Abby R. , Kuwano Hiroyuki , Nakano Minoru 
Published: October 2002

Abstract:  Background/Aims: The aim of this study was to clarify the candidate cells for and the mechanism of superoxide anion (O2·−) release into the hepatic sinusoids during short‐term exposure to ethanol.Methods: The rat liver was perfused continuously with ethanol (a substrate for alcohol dehydrogenase) or tert‐buthanol (not a substrate for alcohol dehydrogenase) for 20 min at a final concentration of 40 mM. In order to detect O2·− production, MCLA (2‐methyl‐6‐[p‐methoxyphenyl]‐3,7‐dihydroimidazo[1,2‐a]pyrazin‐3‐one), a Cypridina luciferin analogue, was simultaneously infused and MCLA‐enhanced chemiluminescence was measured. The effects of gadolinium chloride (GdCL3) (a suppressor of Kupffer cells (KCs)), staurosporine (ST) (an inhibitor of serine–threonine kinases, including protein kinase C), diphenyleneiodonium chloride (DPI) (an inhibitor of NADPH oxidase), ibuprofen (IB) (an inhibitor of cyclooxygenase) and 4‐methylpyrazole (4MP) (an inhibitor of ethanol metabolism) on the ethanol‐induced chemiluminescence were also evaluated. Sites where O2·− could be released were determined by histochemical detection of nitro blue tetrazolium reduction.Results: Both ethanol and tert‐buthanol rapidly caused O2·− release. GdCL3 suppressed the ethanol‐induced O2·− release by 61%. Staurosporine and DPI, but neither IB nor 4‐MP, also significantly inhibited the ethanol‐induced O2·− release. In the histochemical examination, ethanol‐stimulated liver showed blue formazan precipitate on both sinusoidal endothelial cells (SECs) and Kupffer cells (KCs), whereas the GdCl3‐pretreated liver had the precipitate only on SECs.Conclusions: This study shows that ethanol itself stimulates both SECs and KCs to release O2·− via activation of NADPH oxidase probably involving protein kinase C (PKC).
Evaluation of serum eosinophil cationic protein as a predictive marker for asthma exacerbation in patients with persistent disease
Authors: Sorkness C. , McGill K. , Busse W. W. 
Published: October 2002

SummaryBackground Eosinophilic inflammation is a feature of asthma. However, serological markers to indicate eosinophil activation in this process are not fully defined.Objective To evaluate the relationship of serum eosinophil cationic protein (ECP) to asthma worsening and a marker for treatment effectiveness, 26 adult patients with an asthma exacerbation were identified.Methods Identified asthma subjects were treated with oral corticosteroids (prednisone) for 14 days. The lung function variables, forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF), were determined as percentage of predicted and the blood total eosinophil count and serum ECP levels were measured. Patients were re‐evaluated after 14 days of corticosteroid treatment and then every 3 months thereafter during a 12‐month period.Results Eighteen patients responded to prednisone treatment, whereas eight did not, assessed as improvement of their lung function parameters. Different serum ECP patterns could be seen in the responders compared with the non‐responders. All 18 responders had considerably increased serum ECP at the time of exacerbation, whereas the non‐responders had lower serum ECP levels. The serum ECP levels decreased to a greater extent in the responder patient group than in the non‐responder patients following prednisone treatment. This difference in patterns was not seen with total blood eosinophil counts.Conclusion Our findings suggest that serum ECP may be used to predict a response to corticosteroid therapy in adult patients with asthma.
Non‐allergenic antigen in allergic sensitization: responses to the mite ferritin heavy chain antigen by allergic and non‐allergic subjects
Authors: Epton M. J. , Smith W. , Hales B. J. , Hazell L. , Thompson P. J. , Thomas W. R. 
Published: October 2002

SummaryBackground The majority of house dust mite proteins are non‐allergenic. There is, however, no information on the type of immune responses produced to these proteins and if the responses are affected by allergic sensitization.Objective To identify and produce a non‐allergenic antigen of the house dust mite and compare antibody and T cell responses with the responses to allergens in sensitized and non‐sensitized individuals.Results Ferritin heavy chain was cloned from a cDNA library as a candidate non‐allergen of the house dust mite. It bound IgG but not IgE in the sera of allergic and non‐allergic subjects and induced high T cell proliferative responses that correlated highly with the responses to the major allergen Der p 2. The cytokine response to the non‐allergen was characterized by the release of high levels of both Th1 and Th2 cytokines from the PBMC of both allergic and non‐allergic subjects. In contrast, the response to Der p 2 showed the expected high level of Th2 cytokine release from the PBMC of allergic subjects, while the Th2 cytokine production from PBMC of non‐allergic subjects was low and even lower than that induced by ferritin heavy chain. The levels of IFN‐γ release were similar for all groups. Der p 2 induced significantly more IL‐10 than ferritin in the non‐allergic group.Conclusion The T cell responses to a non‐allergenic protein of the house dust mite were high and strongly correlated with the response to the major allergen. The non‐allergenic protein induced high levels of Th1 and Th2 cytokine in both allergic and non‐allergic subjects, while the allergen induced high levels of Th2 cytokine in allergic subjects and low levels in non‐allergic subjects. The responses to the allergen were thus independently up‐ and down‐regulated with no evidence of bystander regulation.
Elastic properties of irradiated RBCs measured by optical tweezers
Authors: Barjas‐Castro M.L. , Brandão M.M. , Fontes Adriana , Costa F.F. , Cesar C.L. , Saad S.T.O. 
Published: October 2002

BACKGROUND : Gamma irradiation of RBCs results in the production of reactive oxygen capable of initiating the process of membrane lipid peroxidation and accelerates the leakage of potassium ions from RBCs, resulting in an increase of internal viscosity. STUDY DESIGN AND METHODS : The elastic properties of irradiated and stored RBC units were studied using laser optical tweezers. The laser trapped the cell and the membrane elasticity was analyzed, measuring the cell deformation in six different drag velocities. Five RBC units were split into two portions. One portion received a gamma irradiation dose of 25 Gy, and the second one was used as a control and was not irradiated. All units were stored (4°C), and the elasticity was examined on Days 1, 14, 21, and 28. RESULTS
: Elastic properties (μ) from irradiated RBCs stored for 21 and 28 days were significantly affected compared with control cells (21 days: control, 0.3 ± 0.03 × 10
−3
; irradiated, 3.5 ± 1.3 × 10
−3
dyn/cm; p < 0.001; and 28 days: control, 0.5 ± 0.09 × 10
−3
; irradiated, 14 ± 3.2 × 10
−3 dyn/cm; p < 0.001). CONCLUSION : The sensitivity of the laser optical tweezers method showed that there is no significant change in elasticity over time for up to 14 days of storage, regardless of whether the unit was irradiated or not. However, beyond 21 days of storage, irradiated units demonstrate decreased elasticity.
Diadenosine pentaphosphate vasodilates the forearm vascular bed: Inhibition by theophylline and augmentation by dipyridamole
Authors: van Ginneken Egidia E. M. , Rongen Gerard A. , Russel Frans G. M. , Smits Paul 
Published: October 2002

BackgroundIn rats, diadenosine pentaphosphate (AP5A) has been implicated in the pathogenesis of essential hypertension. This study describes for the first time the vasomotor action of AP5A in humans by means of the “perfused forearm technique.”ResultsAP5A evoked a dose‐dependent forearm vasodilator response equal to that of adenosine but less than that of adenosine triphosphate (ATP) at equimolar doses. The P1‐purinoceptor antagonist theophylline (0.28 μmol/min per deciliter) reduced the percentage decrease in forearm vascular resistance (FVR) to AP5A (0.6, 6, and 20 nmol/min/dL): −8% ± 6%, −50% ± 6%, and −68% ± 4% during saline solution versus −7% ± 4%, −33% ± 5%, and −45% ± 6% during theophylline (mean ± standard error [SE]; ANOVA for repeated measures; P < .05 for the interaction between purine dose and theophylline; n = 10). An inhibitor of equilibrative nucleoside transport, dipyridamole (7.4 nmol/min per deciliter), augmented the AP5A (0.6 and 6 nmol/min per deciliter)‐induced reduction in FVR as follows: −34% ± 6% and −67% ± 5% during saline versus −49% ± 5% and −80% ± 3% during dipyridamole (P < .05 for the effect of dipyridamole; n = 6). The bivalent cation chelator ethylenediaminetetra‐acetic acid (EDTA) inhibited the rapid degradation of AP5A in vitro. In vivo, the highest tolerated intra‐arterial EDTA dose was not sufficient to inhibit AP5A metabolism.ConclusionIntra‐arterial AP5A caused a dose‐dependent reduction in FVR. This is, at least in part, mediated by its degradation product adenosine. The data do not support an in vivo vasoconstrictor action of AP5A, and as such AP5A does not seem likely to contribute to the pathogenesis of primary hypertension in humans.Clinical Pharmacology & Therapeutics (2002) 71, 448–456; doi: 10.1067/mcp.2002.124469
Pharmacokinetics of plasma enfuvirtide after subcutaneous administration to patientswith human immunodeficiency virus: Inverse Gaussian density absorption and 2‐compartment disposition*
Authors: Zhang Xiaoping , Nieforth Keith , Lang Jean‐Marie , Rouzier‐Panis Regine , Reynes Jacques , Dorr Albert , Kolis Stanley , Stiles Mark R. , Kinchelow Tosca , Patel Indravadan H. 
Published: October 2002

ObjectiveEnfuvirtide (T‐20) is the first of a novel class of human immunodeficiency virus (HIV) drugs that block gp41‐mediated viral fusion to host cells. The objectives of this study were to develop a structural pharmacokinetic model that would adequately characterize the absorption and disposition of enfuvirtide pharmacokinetics after both intravenous and subcutaneous administration and to evaluate the dose proportionality of enfuvirtide pharmacokinetic parameters at a subcutaneous dose higher than that currently used in phase III studies.MethodsTwelve patients with HIV infection received 4 single doses of enfuvirtide separated by a 1‐week washout period in an open‐label, randomized, 4‐way crossover fashion. The doses studied were 90 mg (intravenous) and 45 mg, 90 mg, and 180 mg (subcutaneous). Serial blood samples were collected up to 48 hours after each dose. Plasma enfuvirtide concentrations were measured with use of a validated liquid chromatography‐tandem mass spectrometry method.ResultsEnfuvirtide plasma concentration‐time data after subcutaneous administration were well described by an inverse Gaussian density function‐input model linked to a 2‐compartment open distribution model with first‐order elimination from the central compartment. The model‐derived mean pharmacokinetic parameters (±SD) were volume of distribution of the central compartment (3.8 ± 0.8 L), volume of distribution of the peripheral compartment (1.7 ± 0.6 L), total clearance (1.44 ± 0.30 L/h), intercompartmental distribution (2.3 ± 1.1 L/h), bioavailability (89% ± 11%), and mean absorption time (7.26 hours, 8.65 hours, and 9.79 hours for the45‐mg, 90‐mg, and 180‐mg dose groups, respectively). The terminal half‐life increased from 3.46 to 4.35hours for the subcutaneous dose range from 45 to 180 mg.ConclusionsAn inverse Gaussian density function‐input model linked to a 2‐compartment open distribution model with first‐order elimination from the central compartment was appropriate to describe complex absorption and disposition kinetics of enfuvirtide plasma concentration‐time data after subcutaneous administration to patients with HIV infection. Enfuvirtide was nearly completely absorbed from subcutaneous depot, and pharmacokinetic parameters were linear up to a dose of 180 mg in this study.Clinical Pharmacology & Therapeutics (2002) 72, 10–19; doi: 10.1067/mcp.2002.125945
Low‐dose ritonavir moderately enhances nelfinavir exposure
Authors: Kurowski Michael , Kaeser Benoite , Sawyer Anthony , Popescu Matei , Mrozikiewicz Alexander 
Published: October 2002

BackgroundThe protease inhibitor ritonavir is increasingly administered at subtherapeutic doses in highly active antiretroviral treatment, to utilize its potential for drug interactions and to enhance the plasma concentrations of other concomitantly prescribed protease inhibitors. The addition of low doses of ritonavir to nelfinavirwas investigated to describe the extent of pharmacokinetic interaction.MethodsIn this randomized, open‐label, one‐sequence crossover study, nelfinavir 1250 mg twice a day was dosed for 17 days, followed by 14 days of nelfinavir 1250 mg twice a day plus low doses of ritonavir of either 100 mg or 200 mg orally. Twenty‐four healthy volunteers were evaluated for pharmacokinetics of nelfinavir, its metabolite M8, andritonavir. Plasma concentrations were measured up to 12 hours after morning and evening dosing, respectively, on days 14 and 31.ResultsRitonavir increased the area under the plasma concentration‐time curve(AUC) of nelfinavir by 20% (P =.024) and 39% (P =.001) after morning and evening administration, respectively. The AUC of nelfinavir metabolite M8was increased by 74% and 86% after morning and evening dosing (P <.001 for both).ConclusionDuring ritonavir combination therapy a clear although minor drug effect on nelfinavir pharmacokinetics was demonstrated but no dose effect was shown.Clinical Pharmacology & Therapeutics (2002) 72, 123–132; doi: 10.1067/mcp.2002.126178
Comparison of rofecoxib, celecoxib, and naproxen on renal function in elderly subjects receiving a normal‐salt diet
Authors: Schwartz J. I. , Vandormael K. , Malice M. P. , Kalyani R. N. , Lasseter K. C. , Holmes G. B. , Gertz B. J. , Gottesdiener K. M. , Laurenzi M. , Redfern K.‐J. , Brune K. 
Published: October 2002

BackgroundThis study compared directly the renal effects of two selective cyclooxygenase (COX)‐2 inhibitors (rofecoxib and celecoxib) with naproxen (dual COX‐1/COX‐2 inhibitor) and placebo in healthy elderly subjects on a sodium‐replete diet.MethodsA total of 67 elderly subjects stabilized in the clinic for weight andurinary sodium on a controlled 200‐mEq sodium diet were randomized in a double‐blind fashion to receive rofecoxib, 25 mg daily (n = 17); celecoxib, 200 mg twice daily (n = 17); naproxen, 500 mg twice daily (n = 17); or matching placebo (n = 16) for 28 days. Subjects were sequestered in the clinic for the first 14 treatment days on the controlled diet.ResultsDaily urinary sodium excretion during the first 72 hours of treatment (primary endpoint) significantly decreased in rofecoxib, celecoxib, and naproxen groups compared with baseline (P ≤ .05). Rofecoxib and celecoxib decreases in urinarysodium excretion rates that were comparable with each other, on the basis of predefined boundaries (−39.5 versus −27.1 mEq/d, respectively) and to naproxen (−40.6, mEq/d). Rofecoxib, celecoxib, and naproxen increased mean systolic blood pressure to a similar degree (3.4, 4.3, and 3.1 mm Hg, respectively, versus −1.3 mm Hg for placebo) after 14 days of treatment; small changes also occurred in diastolic blood pressure (0.3, 0.8, and −0.4 mm Hg, respectively, versus −1.4 mm Hg for placebo). Changes from baseline in creatinine clearance, body weight, and urinary potassium excretion among active treatments were similar. After 28 days of treatment, findings were generally consistent with those at 14 days. No subject reported edema or discontinued treatment as the result of an adverse experience.ConclusionIn healthy elderly subjects on a sodium‐replete diet, the COX‐2 inhibitors rofecoxib and celecoxib did not differ from a nonselective nonsteroidal anti‐inflammatory drug (naproxen), in influencing renal function as measured by urinary sodium excretion, systolic and diastolic blood pressure, creatinine clearance, or weight change.Clinical Pharmacology & Therapeutics (2002) 72, 50–61; doi: 10.1067/mcp.2002.126182
Severe 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) intoxication: Insights into the measurement of hepatic cytochrome P450 1A2 induction*
Authors: Abraham Klaus , Geusau Alexandra , Tosun Yalcin , Helge Hans , Bauer Steffen , Brockmöller Jürgen 
Published: October 2002

ObjectiveThe correct in vivo quantification of aryl hydrocarbon receptor‐mediated induction of cytochrome P450 1A2 (CYP1A2) in humans is a long‐standing question. We compared the performance of several modifications of the caffeine test for measurement of CYP1A2 activity in subjects with exceptionally high, low, or absent enzyme induction.MethodsCYP1A2 activity was measured in 2 women highly exposed to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD), in 1 man moderately exposed, and in 50 control subjects (30 nonsmokers and 20 heavy smokers). After the application of a test dose, caffeine demethylation was detected with the carbon 13 breath test, the total clearance, and several serum and urinary metabolite ratios.ResultsIn the highly TCDD‐exposed persons, results of the breath test (cumulative 15‐minute dose), the total caffeine clearance, the serum metabolic ratio paraxanthine/caffeine (30 and 120 minutes after application), and the urinary metabolic ratio sum of5‐acetylamino‐6‐formylamino‐3‐methyluracil (AFMU), 1‐methyluric acid (1U), and 1‐methylxanthine (1X) over 1,7‐dimethyluric acid (17U) showed a CYP1A2 activity 8 to 10 times higher than the mean of nonsmokers. In contrast, two caffeine urinary metabolic ratios with the parent substance in the denominator did not reflect the CYP1A2 enzyme induction. These ratios strongly depended on urine flow. For the breath test, only results evaluated for ashort sampling period (eg, 15 minutes after application) revealed the high induction. Compared with nonsmokers, higher mean values (maximally 1.8 times) were observed in smokers with all tests.ConclusionAfter high TCDD exposure, hepatic CYP1A2 activity is inducible at least 10 times in humans. Moderate TCDD exposure (up to 1000 ppt in blood fat) does not cause a CYP1A2 induction that can be measured to differentiate from background exposure individually. Therefore direct quantification of such toxins is more specific and sensitive.Clinical Pharmacology & Therapeutics (2002) 72, 163–174; doi: 10.1067/mcp.2002.126408
Hypoxic pulmonary artery fibroblasts trigger proliferation of vascular smooth muscle cells‐role of hypoxia‐inducible transcription factors
Authors: Rose Frank , Grimminger Friedrich , Appel Jutta , Heller Mathias , Pies Volker , Weissmann Norbert , Fink Ludger , Schmidt Sebastian , Krick Stefanie , Camenisch Gieri , Gassmann Max , Seeger Werner , Hänze Jörg 
Published: October 2002

ABSTRACTChronic lung hypoxia causes vascular remodeling with pulmonary artery smooth muscle cell (SMCPA) hyperplasia, resulting in pulmonary hypertension and cor pulmonale. We investigated SMCPA and pulmonary artery adventitial fibroblasts (FBPA) for their proliferative response to hypoxia. Strong SMCPA growth occurred under hypoxic conditions in SMCPA/FBPA co‐cultures, but not in SMCPA monocultures. SMCPA growth was fully reproduced by transferring serum‐free supernatant from hypoxic cultured FBPA to normoxic SMCPA. Hypoxia‐inducible‐transcriptionfactor subtypes (HIF‐1α, HIF‐2α, HIF‐3α) and its dependent target genes, carrying the hypoxiaresponsive‐element as regulatory component, were strongly activated in both hypoxic FBPA and SMCPA. HIF‐transcription‐factor decoy technique, employed to FBPA during hypoxic culturing, blocked the mitogenic activity of FBPA conditioned medium on SMCPA. The data suggest that hypoxia‐driven gene regulation in pulmonary artery fibroblasts results in a mitogenic stimulus on adjacent pulmonary artery smooth muscle cells, and HIF‐transcription‐decoy may offer a new therapeutic approach to suppress these events.
Molecular Characterization of the Growth Phase-Dependent Expression of the
lsrA
Gene, Encoding Levansucrase of
Rahnella aquatilis
Authors: Seo Jeong-Woo , Jang Ki-Hyo , Kang Soon Ah , Song Ki-Bang , Jang Eun Kyung , Park Buem-Seek , Kim Chul Ho , Rhee Sang-Ki 
Published: October 2002

ABSTRACT

Expression of the
lsrA
gene from
Rahnella aquatilis
, encoding levansucrase, is tightly regulated by the growth phase of the host cell; low-level expression was observed in the early phase of cell growth, but expression was significantly stimulated in the late phase. Northern blot analysis revealed that regulation occurred at the level of transcription. The promoter region was identified by primer extension analysis. Two opposite genetic elements that participate in the regulation of
lsrA
expression were identified upstream of the
lsrA
gene: the
lsrS
gene and the
lsrR
region. The
lsrS
gene encodes a protein consisting of 70 amino acid residues (
M
r
, 8,075), which positively activated
lsrA
expression approximately 20-fold in a growth phase-dependent fashion. The
cis
-acting
lsrR
region, which repressed
lsrA
expression about 10-fold, was further narrowed to two DNA regions by deletion analysis. The concerted action of two opposite regulatory functions resulted in the growth phase-dependent activation of gene expression in
Escherichia coli
independent of the stationary sigma factor σ
S
.