bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phospholipases A2 in Gastric Juice of Helicobacter pylori – Positive and Negative Individuals
Authors: Huhtinen Heikki T. , Grönroos Juha M. , Haapamäki Markku M. , Nevalainen Timo J. 
Published: October 2004

Abstract
Gastric juice is known to have phospholipase A2 catalytic activity. Helicobacter pylori (H. pylori) has been reported to produce phospholipase A2, which is believed to hydrolyse the protective layer of gastric mucosal phospholipids and to promote mucosal damage. The current study aimed at identifying secretory phospholipase A2 subtypes (pancreatic group I phospholipase A2 and synovial-type group II phospholipase A2) in gastric juice and their relation to the presence of H. pyloriin gastric mucosal biopsies in the same individuals. Gastric juice was collected from 29 individuals during gastroscopy. Biopsies were taken from the antrum and body of the stomach to determine the H. pylori status. We found catalytically active phospholipase A2 and both group I and group II phospholipases A2 in the gastric juice samples. The catalytic activity and the mass concentrations of group I and group II phospholipases A2 correlated significantly with the pH value in gastric juice. The gastric juice of H. pylori positive individuals did not contain higher amounts of phospholipases A2 than the juice of H. pylori negative individuals. Rather, the mass concentration of group II phospholipase A2 in gastric juice seemed to be somewhat lower in individuals with H. pylori infection than in uninfected individuals. The results of the current study show that both group I and group II phospholipases A2 are present in gastric juice. The main sources of phospholipases A2 in gastric juice are probably other than H. pylori.
Low Levels of Plasma Proteins: Malnutrition or Inflammation?
Authors: Johnson Andrew Myron 
Published: October 2004

Abstract
Levels of several plasma proteins, including albumin, transferrin, and transthyretin (prealbumin), have been proposed as markers for protein energy malnutrition. However, many other factors, especially inflammatory disease and drug or hormone therapy, affect levels of these proteins. These factors probably account for the majority of low levels of transthyretin. Levels of albumin and other proteins may be helpful in determining increased risk of morbidity and mortality, but better markers are needed for diagnosis of protein energy malnutrition per se.
Laboratory Medicine: The Need for a Broader View. The “Multiple Bundle” Model of Clinical Laboratory Function
Authors: Dominiczak Marek H. 
Published: October 2004

Abstract
The essence of the nineties in health care, in business, in organizational management and in education, has been change. As always in a changing environment, there will be winners and losers. In the September issue of CCLM, Williamson wrote: “Poor clinical chemistry. It is a field trapped between pressures from increasing electronic automation of assays, simplified technology and reductionism of molecular genetics and the growing pressure of economic accountability and cost cutting. It may not survive” (1). Should we all be on Prozac and wait for the doomsday?
Our problems are not unique. Some time ago, traditional cardiology was “trapped” between the advent of new invasive techniques on the one hand and a pressure to increase emphasis on prevention on the other. How did it end? Most of today's cardiologists are invasive cardiologists and many became leaders in cardiovascular prevention in addition to their “traditional” tasks (2). This is a classical example of a paradigm shift.
The present article suggests that at least some of our problems may stem from too narrow a view of laboratory medicine that we present to decision makers who allocate funds to laboratory services.
The Use of Free Cortisol Index for Laboratory Assessment of Pituitary-Adrenal Function
Authors: Bonte Harry A. , van den Hoven Ron J. , van der Sluijs Veer Gertjan , Vermes István 
Published: October 2004

Abstract
We developed a time-resolved-fluoro-immunoassay to measure cortisol binding globulin (CBG) in serum. It is a microtitre plate, solid phase, reagent excess, sandwich assay in which the same polyclonal antiserum is used as a source of capture and labeled antibodies. The results of this assay were shown to be reliable and were fully comparable with those obtained by a commercially available kit. As a reflection of the free cortisol concentration we measured cortisol and CBG concentrations in serum and calculated the Free Cortisol Index (FCI) = [cortisol]serum/[CBG]serum · 100. The clinical use of this parameter, as a screening test for disturbances of the pituitary-adrenal axis, was investigated in different groups of subjects: healthy men and women, women using oral contraceptives, pregnant women at term, patients with thyroidal illnesses, patients using anti-epileptic drugs and patients suffering from adrenal diseases. In a number of groups we compared the FCI results with measurements of cortisol in saliva, another parameter used as an estimate of the concentration of free cortisol in blood. Our conclusion is that the FCI, in contrast to a total cortisol measurement alone, can prevent unnecessary further testing.
Isoenzmyes of Class I and II Alcohol Dehydrogenase in Chronic Hepatitis
Authors: Chrostek Lech , Szmitkowski Maciej 
Published: October 2004

Abstract
Using class-specific fluorogenic substrates, the activities of class I and II alcohol dehydrogenase (ADH) isoenzymes were determined in the sera of patients with chronic hepatitis. The activity of the total alcohol dehydrogenase and indicator enzymes of liver damage were also investigated. We found a statistically significant increase of class I alcohol dehydrogenase isoenzymes in the total tested group which included those with the viral hepatitis. The (2-fold) increase in the activity of class I isoenzymes was similar to the increase of aminotransferases. The serum activity of class II isoenzymes was unchanged. Here an increase in total enzyme activity was not statistically significant. Class I isoenzymes and total enzyme activity correlated well with aminotransferases. These results demonstrate that serum activity of class I ADH measured with fluorogenic substrates confirms liver cell damage and may be useful in the diagnosis of chronic hepatitis.
Mechanisms of Antigen Presentation
Authors: Jensen Peter E. 
Published: October 2004

AbstractT-lymphocytes recognize short peptide antigens bound stably to polymorphic major histocompatibility complex (MHC)-encoded glycoproteins expressed on the surface of antigen-presenting cells (APC). Two general pathways have evolved to generate peptide-MHC complexes. The MHC class II antigen processing pathway provides a mechanism for sampling proteins present in endosomal compartments. CD4+ regulatory T-cells recognize peptides bound to MHC class II molecules, which are selectively expressed in specialized APC that have efficient mechanisms for uptake of microbial antigens, and express costimulatory molecules required for activating naive T-cells. CD8+ T-cells recognize peptides bound to MHC class I molecules. Class I molecules are widely expressed and bind peptides derived from the normal turnover of cellular proteins, providing a mechanism to display a sampling of cellular components to be monitored for abnormalities by cytotoxic T-cells. Specialized accessory proteins influence the efficiency of antigen presentation and the specificity of immune responses through their roles in generating peptides, targeting antigen and MHC glycoproteins to selected intracellular compartments, and by direct participation in the peptide-loading mechanism. It has recently been discovered that some viruses have evolved ways to inhibit or subvert discrete steps in antigen processing, providing a mechanism to evade immune recognition.
Immunostimulatory CpG Motifs Trigger a T Helper-1 Immune Response to Human Immunodeficiency Virus Type-1 (HIV-1) gp160 Envelope Proteins
Authors: Deml Ludwig , Schirmbeck Reinhold , Reimann Jörg , Wolf Hans , Wagner Ralf 
Published: October 2004

AbstractBacterial DNA sequences containing unmethylated CpG motifs have recently been proposed to exhibit immunostimulatory effects on B-, T- and NK cells, leading to the induction of humoral and cell-mediated immune responses. In the present study we investigated the immunomodulatory effects of a CpG-containing oligodeoxynucleotide (CpG ODN) to the HIV-1 gp160 envelope (Env) protein in the BALB/c mouse model. Priming and boosting of mice with gp160 adsorbed to aluminium hydroxide (Alum) induced a typical T helper-2 (Th2)-dominated immune response with high titers of gp160-specific immunoglobulin (Ig)G1 isotypes but a weak IgG2a response. Specifically re-stimulated splenocytes from these mice predominantly secreted interleukin (IL)-5 but only minute amounts of interferon-γ (IFN-γ) upon specific re-stimulation. In contrast, a boost immunisation of gp160/Alum primed mice with a gp160/Alum/CpG combination resulted in a seven times higher production of IgG2a antibodies, without affecting the titers of IgG1 isotypes. Furthermore, approximately 10-fold increased levels of IFN-γ, but significantly reduced amounts of IL-5, were secreted from gp160-restimulated splenic cells. A further greater than 30-fold increase in the levels of specific IgG2a responses and a substantially elevated secretion of IFN-γ were observed when the mice received gp160/Alum/CpG combinations for priming and boost injections. Thus, CpG ODNs are useful as an adjuvant to induce a typical Th0/Th1 response to HIV gp160 proteins. However, despite the induction of a more Th1-like immune response, gp160/Alum/CpG combinations were not sufficient to prime an Env-specific cytotoxic T-cell (CTL) response.
Activation and Regulation of NFκB during Acute Inflammation
Authors: Lentsch Alex B. , Ward Peter A. 
Published: October 2004

AbstractDuring the acute inflammatory response, there is induction of a mediator cascade which functions to activate residential macrophages and recruit blood leukocytes to the site of the inflammatory insult. Dysregulation of this process can cause an exaggerated inflammatory response and lead to tissue injury. Recent studies have focused on the transcription factor NFκB, which controls the gene expression of many pro-inflammatory mediators. Under normal conditions, NFκB is retained in the cytosol by inhibitory proteins of the IκB family. In response to an inflammatory insult, IκB proteins are degraded and the free NFκB complex translocates to the nucleus where it initiates gene transcription. An understanding of thein vivomechanisms leading to the activation of NFκB, and the regulatory mechanisms that exist to limit this activation, may lead to the development of novel new therapeutic options for inflammatory injury. In this review we will discuss the current knowledge of the role of NFκB in the development of acute inflammation, as well as the regulatory mechanisms that exist to prevent the activation of NFκB and resolve inflammatory tissue injury.
CD 14++Monocytes, CD14+/CD16+Subset and Soluble CD14 as Biological Markers of Inflammatory Systemic Diseases and Monitoring Immuno-suppressive Therapy
Authors: Scherberich Juergen E. , Nockher Wolfgang A. 
Published: October 2004

AbstractThe majority of peripheral blood monocytes strongly positive for the lipopolysaccharides (LPS)-receptor CD14 are negative for Fcγ receptor type III (CD16). However, a subset of monocytes coexpressing CD14 and CD16 accounts for about 8% of all monocytes. This population exhibits features of tissue macrophages, and is largely expanded (> 20 %) during acute and chronic inflammatory diseases including cases with pararheumatic systemic vasculitis. In addition, compared to normal controls, soluble CD14 (sCD14) is elevated (> 3 μg/ml) in serum specimens of these patients. CD14+/CD16+monocytes show a higher phagocytosis rate than CD14+/CD16 negative cells, and express higher levels of interleukin-1 and major histocompatibility complex, such as histocompatibility antigens HLA-DR, -DP and -DQ antigens. Glucocorticoids downregulate expression of CD14 and rapidly deplete CD14+/CD16+monocytes from peripheral blood. Patients under chronic immunosuppressive therapy exhibit low CD14/+/CD16+ rates, which may rise during infectious and non-infectious inflammatory complications, however. Thus, serial analyses for sCD14 and the proinflammatory CD14+/CD16+subset of monocytes suggest a valuable tool monitoring patients under immunosuppressive and/or antiinflammatory therapy.
Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions
Authors: Weber Christian , Erl Wolfgang , Weber Kim S. C. , Weber Peter C. 
Published: October 2004

AbstractThe integrin heterodimer CD11b/CD18 (αMβ2, Mac-1, CR3) expressed on monocytes or polymorphonuclear leukocytes (PMN) is a receptor for iC3b, fibrinogen, heparin, and for intercellular adhesion molecule (ICAM)-1 on endothelium, crucially contributing to vascular cell interactions in inflammation and atherosclerosis. In this report, we summarize our findings on the effects of lipid mediators and lipid-lowering drugs. Exposure of endothelial cells to oxidized low density lipoprotein (oxLDL) induces upregulation of ICAM-1 and increases adhesion of monocytic cells expressing Mac-1. Inhibition experiments show that monocytes use distinct ligands, i.e. ICAM-1 and heparan sulfate proteoglycans for adhesion to oxLDL-treated endothelium. An albumin-transferable oxLDL activity is inhibited by the antioxidant pyrrolidine dithiocarbamate (PDTC), while 8-epi-prostaglandin F2α (8-epi-PGF2α) or lysophosphatidylcholine had no effect, implicating yet unidentified radicals. Sequential adhesive and signaling events lead to the firm adhesion of rolling PMN on activated and adherent platelets, which may occupy areas of endothelial denudation. Shear-resistant arrest of PMN on thrombin-stimulated platelets in flow conditions requires distinct regions of Mac-1, involving its interactions with fibrinogen bound to platelet αllbβ3, and with other platelet ligands. Both arrest and adhesion strengthening under flow are stimulated by platelet-activating factor and leukotriene B4, but not by the chemokine receptor CXCR2. We tested whether Mac-1-dependent monocyte adhesiveness is affected by inhibitors of hydroxy-methylglutaryl-Coenzyme A reductase (statins) which improve morbidity and survival of patients with coronary heart disease. As compared to controls, adhesion of isolated monocytes to endotheliumex vivowas increased in patients with hypercholesterolemia. Treatment with statins decreased total and low density lipoprotein (LDL) cholesterol plasma levels, surface expression of Mac-1, and resulted in a dramatic reduction of Mac-1-mediated monocyte adhesion to endothelium. The inhibition of monocyte adhesion was reversed by mevalonate but not LDLin vitro, indicating that isoprenoid precursors are crucial for adhesiveness of Mac-1. Such effects may crucially contribute to the clinical benefit of statins, independent of cholesterol-lowering, and may represent a paradigm for novel, anti-inflammatory mechanisms of action by this class of drugs.
Mycophenolic Acid Influences T Helper 2 (Th2) Cytokine Induced Expression of Intercellular Cell Adhesion Molecule -1 (ICAM-1) on Human Endothelial Cells
Authors: Weigel Guenter , Bertalanffy Peter , Dubsky Peter , Griesmacher Andrea , Wolner Ernst 
Published: October 2004

AbstractA possible synergistic effect of mycophenolic acid (MPA) and the immunosuppressive cytokines IL-4, IL-10 and IL-13 was investigated in human umbilical vein endothelial cells (HUVEC). These cytokines, which are produced by Th2-lymphocytes, were shown to induce the expression of vascular cell adhesion molecule-1 (VCAM-1) and production of IL-6 in endothelial cells. In this study we found IL-4 to induce both intercellular cell adhesion molecule-1 (ICAM-1) and VCAM-1 expression, whereas IL-13 induced VCAM-1 only. The surface expression of E-selectin was not influenced by any of the cytokines tested. MPA on its own led to statistically significant ICAM-1 expression on HUVEC. The combination of MPA with IL-4 led to a significant ICAM-1 expression in an additive manner compared to the cytokine alone. In contrast, MPA neither induced VCAM-1 nor did it influence the effects of IL-4 and IL-13 on VCAM-1 expression. A clinically relevant concentration of mycophenolic acid (10 μmol/l) decreased intracellular guanosine-5′-triphosphate (GTP) levels significantly. Since intracellular nucleotides are responsible for the glycosylation of proteins, a disturbance of the endothelial nucleotide balance could be responsible for the effects of MPA on ICAM-1. Guanine and guanosine prevented and partially reversed the actions of MPA, on both intracellular GTP and ICAM-1 expression, which strongly implies that MPA by interfering with nucleotide metabolism, affects the adhesive properties of endothelial cells, and by acting synergistically with IL-4 probably influences Th2 cytokine effects.
C-Reactive Protein: Structural Biology and Host Defense Function
Authors: Szalai Alexander J. , Agrawal Alok , Greenhough Trevor J. , Volanakis John E. 
Published: October 2004

AbstractHuman C-reactive protein is a Ca2+-binding acute phase-protein with binding specificity for phosphocholine. Recent crystallographic and mutagenesis studies have provided a solid understanding of the structural biology of the protein, while experiments using transgenic mice have confirmed its host-defense function. The protein consists of five identical protomers in cyclic symmetry. On one face of each protomer there is a binding site for phosphocholine consisting of two Ca2+ions that ligate the phosphate group and a hydrophobic pocket that accommodates the methyl groups of phosphocholine. On the opposite face is a deep cleft formed by parts of the N and C termini and bordered by an α-helix. Mutational studies indicate that the C1q-binding site of the molecule is located at the open end of this cleft with Asp112and Tyr175representing contact residues. Using human C-reactive protein transgenic mice, we investigated the host defense functions of the protein. Transgenic mice infected withStreptococcus pneumoniaehad increased lifespan and lowered mortality compared to wild-type mice. This was attributable to an up to 400-fold reduction in bacteremia mediated mainly by the interaction of C-reactive protein with complement. A complement-independent host protective effect was also demonstrated.
Annexin V and Phospholipid Metabolism
Authors: Russo-Marie Françoise 
Published: October 2004

Abstract
Annexins, protein kinases C and cytosolic phospholipase
A2 belong to three families of ubiquitous cytoplasmic
proteins involved in signal transduction. All
annexins share the property of binding to phospholipids
in the presence of calcium. Most annexins are substrates
for protein kinases C except annexin V, the
most ubiquitous and abundant annexin. Protein kinases
C (PKC) belong to three distinct groups of kinases,
conventional PKCs (cPKCs) that depend on
calcium, diacylglycerol and negatively charged phospholipids
for their activity, novel PKCs (nPKCs) and
atypical PKCs (aPKCs), that do not require calcium for
their activity, although they both require negatively
charged phospholipids. Cytosolic phospholipase A2
(cPLA2) depends on calcium for its catalytic activity as
well as on serine phosphorylation by MAP kinases. We
report that annexin V modulates the activity of cPKCs
as well as of cPLA2 by interfering with their ability to
bind to negatively charged phospholipids and calcium.
We propose that annexin V could interfere with the
calcium and phospholipid signalling pathway.
Regulation of Leukocyte Trafficking by Lipoxins
Authors: Diamond Pauline , McGinty Ann , Sugrue Declan , Brady Hugh R. , Godson Catherine 
Published: October 2004

AbstractLipoxins arelipoxygenaseinteraction products formed by transcellular metabolism during host defence and inflammation. In model systems, lipoxins modulate polymorphonuclear leukocytes (PMN) chemotaxis, adhesion molecule expression, inhibit PMN-endothelial cell adhesion, and attenuate cytokine release from epithelial cells. These observations raise the possibility that lipoxins are ‘stop signals’ for PMN-mediated tissue injury and promote the resolution of acute inflammation.
Lipoxin and Aspirin-Triggered 15-epi-Lipoxin Cellular Interactions Anti-Inflammatory Lipid Mediators
Authors: Serhan Charles N. , Takano Tomoko , Gronert Karsten , Chiang Nan , Clish Clary B. 
Published: October 2004

AbstractEicosanoids are known to play important roles in inflammation. Recent findings have given rise to several new concepts regulating the generation of eicosanoids, illustrated in Figure 1. Lipoxins (LX) are trihydroxytetraene-containing eicosanoids that are generated within vascular lumen by platelet-leukocyte interactions and at mucosal surfaces by leukocyte-epithelial cell interactions. During these cell-cell interactions, transcellular biosynthetic pathways are used as major routes, and thus, in humans, LX are formedin vivoduring multicellular responses such as inflammation, atherosclerosis, and thrombosis. This branch of the eicosanoid cascade generates specific tetraene-containing products that appear to function as stop signals, since they inhibit key steps in leukocyte-mediated inflammation. Of special interest, it appears that aspirin also functions in part via production of novel epimers of lipoxins or 15-epi-lipoxins (Figure 1). Here, we review recent developments on the cellular interactions of these novel anti-inflammatory mediators.
Polymorphonuclear Granulocyte Stimulation by Cellulose-Based Hemodialysis Membranes
Authors: Körmöczi Günther F. , Rosenkranz Alexander R. , Zlabinger Gerhard J. 
Published: October 2004

AbstractHemodialyis with cellulose-based membranes is associated with an array of adverse reactions, including leukopenia, pulmonary sequestration and dysfunction of leukocytes. Activation of the alternative pathway of complement due to direct contact of plasma with dialysis membrane is considered to be responsible for the induction of these side effects. In recent years, evidence has accumulated that other neutrophil effector functions such as reactive oxygen intermediate production play an important role as well. Here the importance of burst formation in cooperation with other inflammatory effector functions in the mechanisms of hemodialysis-related adverse effects will be discussed.
Reduction of Circulating Cholesterol and Apolipoprotein Levels during Sepsis
Authors: Fraunberger Peter , Schaefer Steffen , Werdan Karl , Walli Autar K. , Seidel Dietrich 
Published: October 2004

Abstract
Sepsis with multiple organ failure is frequently associated
with a substantial decrease of cholesterol levels.
This decrease of cholesterol is strongly associated
with mortality suggesting a direct relation between inflammatory
conditions and altered cholesterol homeostasis.
The host response during sepsis is mediated by
cytokines and growth factors, which are capable of influencing
lipid metabolism. Conversely lipoproteins
are also capable of modulating cytokine production
during the inflammatory response. Therefore the decrease
in circulating cholesterol levels seems to play a
crucial role in the pathophysiology of sepsis. In this review
the interaction between cytokines and lipid metabolism
and its clinical consequences will be discussed.