bluuebunny/crossref_metadata_2025_split huggingface dataset:
Production of hemo- and immunoregulatory cytokines by erythroblast antigen+ and glycophorin A+ cells from human bone marrow
Authors: Sennikov Sergey V , Injelevskaya Tatyana V , Krysov Sergey V , Silkov Alexandr N , Kovinev Igor B , Dyachkova Natalya J , Zenkov Anton N , Loseva Mary I , Kozlov Vladimir A 
Published: October 2004

Abstract
Background
Erythroid nuclear cells (ENC) of the bone marrow (BM) have not previously been considered as important producers of wide spectrum of haemo- and immunoregulatory cytokines. The aim of the current work was to confirm the production of the main hemo- and immunoregulatory cytokines in human ENC from BM.

Results
We used native human BM ENC in our experiments. We for the first time have shown, that the unstimulated erythroblasts (Gl A+ or AG-EB+) produced a wide spectrum of immunoregulatory cytokines. Human BM ENC produce cytokines such as interleukn (IL)-1β, IL-2, IL-4, IL-6, interferon (IFN)-γ, transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α and IL-10. They can be sub-divided into glycophorin A positive (Gl A+) and erythroblast antigen positive (AG-EB+) cells. To study potential differences in cytokine expression between these subsets, ENC were isolated and purified using specific antibodies to Gl A and AG-EB and the separated cells were cultivated for 24 hours. The cytokine contents of the supernatant were measured by electrochemiluminescence immunoassay. Quantitative differences in TGF-β1 and TNF-α production were found between Gl A+ and AG-EB+ BM ENC. Furthermore, in vitro addition of erythropoietin (EPO) reduced IFN-γ and IL-2 production specifically by the AG-EB+ ENC. Thus, Gl A+ and AG-EB+ ENC produce IL-1β, IL-2, IL-4, IL-6, IFN-γ, TGF-β1 and TNF-α. Gl A+ ENC also produce IL-10.

Conclusion
Cytokine production by erythroid nuclear cells suggests that these cells might be involved in regulating the proliferation and differentiation of hematopoietic and immunocompetent cells in human BM.
Patterns of use, dosing, and economic impact of biologic agent use in patients with rheumatoid arthritis: a retrospective cohort study
Authors: Gilbert Thomas D , Smith Daniel , Ollendorf Daniel A 
Published: October 2004

Abstract
Background
Variability in dosing and costs of biologics among patients with rheumatoid arthritis (RA) is of interest to healthcare descision-makers. We examined dosing and costs among RA patients newly treated with infliximab or etanercept under conditions of typical clinical practice.

Methods
Integrated pharmacy and medical claims data were obtained from 61 U.S. health plans. RA patients newly treated with infliximab or etanercept between July 1999–June 2002 were selected. A maintenance number of infliximab vials was determined after the "loading period" (2–3 infusions); those with ≥ 2 occurrences of an increase in vials or an interval between infusions of <49 days were considered to have had escalated. For etanercept patients, escalation was based on ≥ 2 instances of increased average daily dose. Multiple logistic regression analyses were conducted to assess variables associated with dose escalation. RA-related costs at one year post-initiation also were examined; comparisons were made using generalized linear models.

Results
A total of 1,548 patients were identified (n = 598 and 950 for infliximab and etanercept respectively). Infliximab recipients were somewhat older (50.5 vs. 46.6 years for etanercept). Nearly 60% of infliximab patients increased their dose at one year, compared to 18% for etanercept. Infliximab patients who escalated dose incurred a 25% increase in mean one-year costs ($20,915 vs. $16,713 for no increase; p < 0.0001). Costs among etanercept patients did not substantially differ based on dose escalation ($14,482 vs. $13,866 respectively).

Conclusions
Infliximab is associated with higher rates of dose escalation relative to etanercept, which contributes to substantially higher one-year medical costs.
Use of polyethyleneimine polymer in cell culture as attachment factor and lipofection enhancer
Authors: Vancha Ajith R , Govindaraju Suman , Parsa Kishore VL , Jasti Madhuri , González-García Maribel , Ballestero Rafael P 
Published: October 2004

Abstract
Background
Several cell lines and primary cultures benefit from the use of positively charged extracellular matrix proteins or polymers that enhance their ability to attach to culture plates. Polyethyleneimine is a positively charged polymer that has gained recent attention as a transfection reagent. A less known use of this cationic polymer as an attachment factor was explored with several cell lines.

Results
Polyethyleneimine compared favorably to traditional attachment factors such as collagen and polylysine. PC-12 and HEK-293 cells plated on dishes coated with polyethyleneimine showed a homogeneous distribution of cells in the plate, demonstrating strong cell adhesion that survived washing procedures. The polymer could also be used to enhance the adherence and allow axonal outgrowth from zebrafish retinal explants. The effects of this coating agent on the transfection of loosely attaching cell lines were studied. Pre-coating with polyethyleneimine had the effect of enhancing the transfection yield in procedures using lipofection reagents.

Conclusion
Polyethyleneimine is an effective attachment factor for weakly anchoring cell lines and primary cells. Its use in lipofection protocols makes the procedures more reliable and increases the yield of expressed products with commonly used cell lines such as PC-12 and HEK-293 cells.
Gastric T-cell lymphoma associated with hemophagocytic syndrome
Authors: Fukui Rika , Hata Fumitake , Yasoshima Takahiro , Denno Ryuuichi , Okazaki Minoru , Kasai Kiyoshi , Sato Masaaki , Homma Toshio , Ohno Keisuke , Yanai Yoshiyuki , Sogahata Katsuya , Nishimori Hidefumi , Hirata Koichi 
Published: October 2004

Abstract
Background
Lymphoma-associated hemophagocytic syndrome (LAHS) occurs in mostly extra nodal non-Hodgkin's lymphoma. LAHS arising from gastrointestinal lymphoma has never been reported. Here we report a case of gastric T-cell lymphoma-associated hemophagocytic syndrome.

Case presentation
A 51-year-old woman presented with pain, redness of breasts, fever and hematemesis. Hematological examination revealed anemia. Gastroscopy revealed small bleeding ulcers in the stomach and the computed tomography scan showed liver tumor. She underwent total gastrectomy for gastrointestinal bleeding and the histopathology revealed gastric T-cell lymphoma. She continued to bleed from the anastomosis and died on the 8th postoperative day. Autopsy revealed it to be a LAHS.

Conclusions
If Hemophagocytic syndrome (HPS) occurs in lymphoma of the gastrointestinal tract, bleeding from the primary lesion might be uncontrollable. Early diagnosis and appropriate treatment are needed for long-term survival.
Epidemiology in conflict – A call to arms
Authors: Tam Clarence C , Lopman Ben A , Bornemisza Olga , Sondorp Egbert 
Published: October 2004

AbstractIn this first special theme issue, Emerging Themes in Epidemiology publishes a collection of articles on the theme of Epidemiology in conflict. Violent conflict is an issue of great sensitivity within public health, but more structured research and reasoned discussion will allow us to better mitigate the public health impacts of war, and place the public health community in a more informed position in discussions about possible interventions in future conflicts.
Extravascular lung water assessed by transpulmonary single thermodilution and postmortem gravimetry in sheep
Authors: Kirov Mikhail Y , Kuzkov Vsevolod V , Kuklin Vladimir N , Waerhaug Kristine , Bjertnaes Lars J 
Published: October 2004

Abstract
Introduction
Acute lung injury is associated with accumulation of extravascular lung water (EVLW). The aim of the present study was to compare two methods for quantification of EVLW: transpulmonary single thermodilution (EVLWST) and postmortem gravimetric (EVLWG).

Methods
Eighteen instrumented and awake sheep were randomly assigned to one of three groups. All groups received Ringer's lactate (5 ml/kg per hour intravenously). To induce lung injury of different severities, sheep received Escherichia coli lipopolysaccharide 15 ng/kg per min intravenously for 6 hours (n = 7) or oleic acid 0.06 ml/kg intravenously over 30 min (n = 7). A third group (n = 4) was subjected to sham operation. Haemodynamic variables, including EVLWST, were measured using a PiCCOplus monitor (Pulsion Medical Systems, Munich, Germany), and the last measurement of EVLWST was compared with EVLWG.

Results
At the end of experiment, values for EVLWST (mean ± standard error) were 8.9 ± 0.6, 11.8 ± 1.0 and 18.2 ± 0.9 ml/kg in the sham-operated, lipopolysaccharide and oleic acid groups, respectively (P < 0.05). The corresponding values for EVLWIG were 6.2 ± 0.3, 7.1 ± 0.6 and 11.8 ± 0.7 ml/kg (P < 0.05). Ranges of EVLWIST and EVLWIG values were 7.5–21.0 and 4.9–14.5 ml/kg. Regression analysis between in vivo EVLWST and postmortem EVLWG yielded the following relation: EVLWST = 1.30 × EVLWG + 2.32 (n = 18, r = 0.85, P < 0.0001). The mean bias ± 2 standard deviations between EVLWST and EVLWG was 4.9 ± 5.1 ml/kg (P < 0.001).

Conclusion
In sheep, EVLW determined using transpulmonary single thermodilution correlates closely with gravimetric measurements over a wide range of changes. However, transpulmonary single thermodilution overestimates EVLW as compared with postmortem gravimetry.
Metabolic influences of fiber size in aerobic and anaerobic locomotor muscles of the blue crab,Callinectes sapidus
Authors: Johnson L. K. , Dillaman R. M. , Gay D. M. , Blum J. E. , Kinsey S. T. 
Published: October 2004

SUMMARYDiameters of some white locomotor muscle fibers in the adult blue crab, Callinectes sapidus, exceed 500 μm whereas juvenile white fibers are &lt;100 μm. It was hypothesized that aerobically dependent processes,such as metabolic recovery following burst contractions, will be significantly impeded in the large white fibers. In addition, dark aerobic fibers of adults,which rely on aerobic metabolism for both contraction and recovery, grow as large as the white fibers. These large aerobic fibers are subdivided, however,thus decreasing the effective diameter of each metabolic functional unit and enabling aerobic contraction. The two goals of this study were: (1) to characterize the development of subdivisions in the dark levator muscle fibers and (2) to monitor post-contractile metabolism as a function of fiber size in aerobic and anaerobic levator muscles. Dark levator muscle fibers from crabs ranging from &lt;0.1 g to &gt;190 g were examined with transmission electron microscopy to determine the density of mitochondria and subdivision diameters. Across all size classes, there was a constant mitochondrial fractional area(25% of the total subdivision area) and subdivision size (mean diameter of 36.5±2.7 μm). Thus, blue crab dark levator fibers are unusual in having metabolic functional units (subdivisions) that do not increase in size during development while the contractile functional units (fibers) grow hypertrophically. The body mass scaling of post-contractile lactate dynamics was monitored during recovery from anaerobic, burst exercise in white and dark muscle, and in hemolymph. There were no differences among size classes in lactate accumulation during exercise in either muscle. However, in white fibers from large crabs, lactate continued to increase after exercise, and lactate removal from tissues required a much longer period of time relative to smaller crabs. Differences in lactate removal among size classes were less pronounced in dark fibers, and post-contractile lactate accumulation was significantly higher in white than in dark fibers from large animals. These data suggest that the large white fibers invoke anaerobic metabolism following contraction to accelerate certain phases of metabolic recovery that otherwise would be overly slow. This implies that, in addition to the typical mass-specific decrease in oxidative capacity that accompanies increases in animal mass, aerobic metabolic processes become increasingly limited by surface area to volume and intracellular diffusion constraints in developing white muscle fibers.
The Plasminogen Activating System in Periodontal Health and Disease
Authors: Kinnby Bertil 
Published: October 2004

AbstractThe plasminogen activating system is important for extracellular proteolysis and plays a regulatory role in interactions with other tissue degrading systems. Studies on the plasminogen activating system in gingival crevicular fluid (GCF) as well as gingival tissue are reviewed. tPA, uPA, PAI-1 and PAI-2 have all been detected in GCF. Especially tPA and PAI-2 are found in high concentrations. In tissue studies fibrinolytic activity has been found in the gingival pocket epithelium in humans and in animal studies. tPA and PAI-2 have been detected there immunohistochemically. Local production of the PAs and PAIs has been verified with in situ hybridization. In inflammation, a more intense and widespread immunohistochemical staining of tPA and PAI-2 is seen. Higher concentrations of tPA and PAI-2 are found in GCF but the balance between them seems to be constant. A systemically disturbed balance of the plasminogen activating system in GCF has been observed during pregnancy, with a possible protective function of PAI-2. In studies of periodontitis, the production of PAI-2 seemed to be locally lowered at impaired sites. In a study of children, a higher inflammatory response to bacterial plaque was accompanied by a higher fibrinolytic ativity in GCF samples. Bacterial LPS has been found to change the ratio of tPA to PAI-2 in cultured gingival fibroblasts. Interactions between PAI-2 and a protease in the gingival epithelium has been verified through the immunohistochemical detection of relaxed PAI-2.
Inhibition of Receptor-Dependent Urokinase Signaling by Specific Ser to Glu Substitutions
Authors: Carriero Maria Vincenza , Franco Paola , Gargiulo Lucia , Vocca Immacolata , Cito Letizia , Fontana Laura , Iaccarino Ciro , Pozzo Giovanna Del , Guardiola John , Stoppelli Maria Patrizia 
Published: October 2004

AbstractWe have previously reported that phosphorylation of human urokinase on Ser138/303 abolishes its catalyticindependent motogen and proadhesive abilities, whereas receptor binding is not affected. Here we show that substitution of the two relevant serines with glutamic acid residues impairs the ability of urokinase to mobilize a variety of human and mouse cell lines as well as human primary T lymphocytes. Accordingly, urokinase receptordependent signaling, leading to cytoskeletal rearrangements and paxillin redistribution, does not occur in MCF-7 breast carcinoma cells exposed to phosphorylationlike urokinase. Unlike the wildtype form, disubstituted urokinase is unable to induce the physical association of urokinase receptor with αvβ5 vitronectin receptor, which is required for MCF-7 urokinasedependent cell migration. Finally, the disubstituted variant fails to activate p55fgr, a member of the Src tyrosine kinase family, which mediates cell migration and adhesion of U937 myelomonocytic cells. In conclusion, the finding that specific amino acid substitutions strongly interfere with the ability of urokinase to stimulate cell migration, and the associated intracellular events uncover a novel way to regulate urokinase receptordependent signaling.
Cultivation in Glucose-Deprived Medium Stimulates Mitochondrial Biogenesis and Oxidative Metabolism in HepG2 Hepatoma Cells
Authors: Weber K. , Ridderskamp D. , Alfert M. , Hoyer S. , Wiesner R.J. 
Published: October 2004

AbstractIn order to test the hypothesis that an imbalance between energy requirement and energy supply regulates mitochondrial genes and ultimately mitochondrial biogenesis, energy supply was challenged in HepG2 cells by withdrawal of glucose from the culture medium, making the cells exclusively dependent on mitochondrial ATP production. Such cells showed a 2-fold increase of cytochrome c oxidase activity, elevated levels of mitochondrial DNA, mitochondrial DNA encoded mRNAs and proteins, as well as the nuclear encoded mitochondrial transcription factor A. Lactate production was significantly reduced and glutamine was consumed as an alternative substrate for oxidative metabolism. Longterm adapted cells formed exclusively monolayers, while they normally grow in multilayers forming tumor spheroids. Also, longterm adapted cells proliferated significantly faster. No differences for the ATP/ADP ratio were observed, indicating that this is not the primary signal initiating the adaptative processes. These results show that mitochondrial biogenesis and oxidative metabolism are stimulated in HepG2 cells grown in the absence of fermentable glucose, probably in order to compensate for the diminished supply of glycolytic ATP.
Green Tea Extract Protects against Early Alcohol-Induced Liver Injury in Rats
Authors: Arteel G.E. , Uesugi T. , Bevan L.N. , Gäbele E. , Wheeler M.D. , McKim S.E. , Thurman R.G. 
Published: October 2004

Abstract
Oxidants have been shown to be involved in alcoholinduced
liver injury. This study was designed to test
the hypothesis that the antioxidant polyphenolic extract
of green tea, comprised predominantly of epigallocatechin
gallate, protects against early alcoholinduced
liver injury in rats. Male Wistar rats were fed
highfat liquid diets with or without ethanol (10 14 g
kg 1 day 1) and green tea (300 mg kg 1 day 1) continuously
for 4 weeks using an intragastric enteral feeding
protocol. Mean body weight gains (~4 g/day) were
not significantly different between treatment groups,
and green tea extract did not the affect average concentration
or the cycling of urine ethanol concentrations
(0 550 mg dl 1 day 1). After 4 weeks, serum ALT
levels were increased significantly about 4-fold over
control values (35±3 IU/l) by enteral ethanol (114±18);
inclusion of green tea extract in the diet significantly
blunted this increase (65±10). Enteral ethanol also
caused severe fatty accumulation, mild inflammation,
and necrosis in the liver. While not affecting fat accumulation
or inflammation, green tea extract significantly
blunted increases in necrosis caused by
ethanol. Furthermore, ethanol significantly increased
the accumulation of protein adducts of 4-hydroxynonenal,
a product of lipid peroxidation and an index
of oxidative stress; green tea extract blocked this effect
almost completely. TNFa protein levels were increased
in liver by alcohol; this phenomenon was also
blunted by green tea extract. These results indicate
that simple dietary antioxidants, such as those found
in green tea, prevent early alcoholinduced liver injury,
most likely by preventing oxidative stress.
Detection of Poly(ADP-Ribose) by Immunocytochemistry: A Sensitive New Method for the Early Identification of UVB- and H2O2-Induced Apoptosis in Keratinocytes
Authors: Chang H. , Sander C.S. , Müller C.S.L. , Elsner P. , Thiele J.J. 
Published: October 2004

Abstract
Apoptosis is an active form of cell death that is initiated
by a variety of stimuli, including reactive oxygen
species (ROS) and ultraviolet (UV) radiation. Poly
(ADPribose) (PAR) is formed upon activation of the
DNA repair enzyme poly(ADPribose) polymerase
(PARP), and therefore was suggested as a new marker
of apoptosis. Since DNA of epidermal cells represents
a wellknown chromophore for UVB irradiation,
and UVB is known to generate H2O2 in keratinocytes,
we hypothesized that PAR is a very sensitive marker
of UVB and H2O2-induced apoptosis in keratinocytes.
In order to test this hypothesis, human immortalized
keratinocytes (HaCaT) were UVBirradiated or
treated with H2O2, and subsequently apoptosis was
identified by comparing conventional parameters
such as morphological analysis, DNA laddering, and
TUNEL assay, with PAR formation. Both, UVB and
H2O2 treatment induced PAR formation in HaCaT cells
in a dosedependent manner, and its formation was
detected as early as 4 h after irradiation, and at lower
UVB doses (10 mJ/cm2) than observed by DNA laddering
and the TUNEL assay. In conclusion, the detection
of PAR formation is a very sensitive and early
method for the identification of apoptotic cells in
UVBinduced apoptosis of human keratinocytes.
Biochemical Features, Molecular Biology and Clinical Relevance of the Human 15-Domain Serine Proteinase Inhibitor LEKTI
Authors: Walden M. , Kreutzmann P. , Drögemüller K. , John H. , Forssmann W.-G. , Mägert H.-J. 
Published: October 2004

AbstractBased on the isolation of a 55 amino acid peptide from human hemofiltrate, we cloned the cDNA for a novel human 15-domain serine proteinase inhibitor termed LEKTI. A trypsininhibiting activity was demonstrated for three different domains. High levels of expression of the corresponding gene were detected in oral mucosa, followed by the tonsils, parathyroid glands, thymus, and trachea. Hovnanian and coworkers recently found that certain mutations within the LEKTI gene are linked to the severe congenital disease Netherton syndrome and atopic manifestations (including asthma). Thus, a future therapeutic use of LEKTI is conceivable.
Zinc Ligands in an Astacin Family Metalloprotease Meprin A
Authors: Doll B. A. , Villa J. P. , Ishmael F. T. , Bond J. S. 
Published: October 2004

AbstractA conserved tyrosine residue in the astacin family of metalloproteases is one of five ligands proposed to coordinate zinc at the active site. Sitedirected mutagenesis of the conserved Tyr (Y226) of recombinant mouse meprin α was used to test the hypothesis that this residue is essential for zinc binding and enzymatic activity. In addition, another proposed zinc binding ligand, H167, in the conserved (HEXXH) zinc binding motif of the meprin α protease domain was replaced by an alanine residue. Both mutants were expressed and secreted with the same subunit mass as wild type (90 kDa). The Y226F mutant retained the capacity to oligomerize to higher covalently and noncovalentlylinked oligomers as the wild type, whereas H167A was predominantly a monomer. The kcat/Km for Y226F against a fluorgenic bradykinin substrate analog was approximately 15% of the wild type, while the H167A mutant had no detectable activity. Both Y226F and H167A were more susceptible to extensive degradation by trypsin compared with the wildtype protein. The zinc content in the wildtype and Y226F mutant proteins were similar, one molecule of zinc per subunit. The results indicate that Y226 is not essential for zinc binding, but Y226 and H167 are essential for full enzymatic activity and stability of the metalloproteinase.