Future Aspects

PNS research has progressed considerably during the past 20 years. The classification of separate disease entities and the improved diagnostic possibilities offered by antibody detection have contributed much to the increased clinical awareness of PNS. Progress made in the research of these diseases has not only elucidated the underlying mechanisms but has also brought new insight into tumor immunology in general. Nevertheless, many questions remain unanswered. The pathogenesis of the PNS and...

The Technology

There are a number of methods available for detecting and quantifying gene expression levels such as Northern blots, S1 nuclease protection assays, differential display, and serial analysis of gene expression (SAGE) 25 . However, such methods are often labor intensive, rather complex and designed to analyze only a small number of genes at a time. They have been augmented with the development of array-based technologies which expand the number of genes. It is possible to analyze at one time....

Differential Angiogenic Pathways

Complex angiogenic pathways involve the discrete regulation of each stage in this multistep process. Tissue- and disease-specific expression of angiogenic factors and inhibitors may vary through the different phases of a pathological process. For example, an angiogenic switch may turn slow growing neoplasms into aggressive, metastasizing tumors 44 . Sequential activation of various angiogenic and inhibitory pathways may coordinate the beneficial progression from hemostasis through successful...

Introduction

The PNS are interesting as excellent examples of naturally occurring tumor immunity 5, 6 . In PNS, the relevant tumor antigens belong to the group of antigens normally expressed in immunoprivileged sites only, such as the nervous system, and trigger both cellular and humoral responses 7 . These immune responses may limit tumor growth 8 and improve the response to oncological therapy 9, 10 . PNS are sometimes even associated with tumor eradication 11 . However, the immune response also targets...

Angiogenesis Biomarkers for Assessing Human Disease

Understanding the pathophysiological mechanisms of angiogenesis creates a number of clinical opportunities. Although most clinical attention focuses on the possibility of pharmacological treatment, another productive development leading from our increasing understanding of angiogenic pathways has been the design of biomarkers for use in human disease. Where angio-genesis contributes to pathology, biomarkers may usefully guide diagnosis, predict prognosis, demonstrate activity of pharmacological...

Prolamins as Cereal Storage Proteins

CD represents a malabsorption disorder induced by ingestion with food of cereal storage proteins of wheat, barley, and rye. Although oats are well tolerated by most CD patients 3, 4 , some concern remains 5, 6 . The cereal storage proteins toxic for CD patients are insoluble in aqueous salt solutions, but can be extracted from flour by aqueous alcohol. According to the classical definition 7, 8 , cereal storage proteins soluble in aqueous alcohol without reduction of intermolecular disulfide...

Endothelial Cells and the Initiation of Angiogenesis

Angiogenesis may be better regarded as a cascade rather than a linear process, with any of a variety of factors able to push the vessel through any single stage of its growth. Divergent consequences may result from stimulation by any one factor. Effects on blood vessel growth depend on what other angiogenic or antiangiogenic factors are available, on the precise expression of receptors and second messenger systems by the vessel itself, and on whether its matrix environment is either permissive...

Paraneoplastic Nervous System Syndromes of the Neuromuscular Junction

Myasthenia gravis, LEMS, and neuromyotonia affect the neuromuscular junction. These disorders are not necessarily associated with malignancy but are sometimes associated with tumors and are regarded as PNS in these patients. Eighty-five percent of patients with myasthenia gravis have antibodies to the acetylcholine receptor 133 , but only 10-15 of patients with myasthenia gravis have a thymoma. LEMS is much more commonly associated with cancer than myasthenia gravis. LEMS affects individuals in...

Preface

Volume 44 of Advances in Clinical Chemistry contains a series of chapters of diverse interest for clinical laboratory scientists. In this volume, the role of caspases as key effector molecules in apoptosis is explored with respect to their impact at multiple points in the evolution of myocardial infarction. Their use as potential targets for therapeutic intervention provides an attractive alternative for pharmacological modulation of this disease process. Advances in biochemical identification...

Functional Significance of Caspases

Role of Caspases During Embryonal Development Much knowledge concerning the function of caspases was gained from targeted gene disruption studies in animals, especially in mice 55, 56 . Deletion of individual caspase-related genes from cell lines or animals (i.e., knockout mice) is necessary to explore the functional significance of individual caspases in vivo. Many caspases-related genes have been deleted, yielding a variety of phenotypes, from embryonic or perinatal death to normal...

Gliadin Antibodies of CD Patients Recognize Deamidated Gliadin

Although the gliadin-deamidating activity of tTG toward gliadin was known since 1998 79-82 , attention was focused on the deamidation effect on binding of modified gliadin peptides to HLA molecules. This was due to the fact that the typical mucosal lesion in CD is basically regarded as a result of T-cell activation after presentation of gliadin peptides. Antibodies in CD were considered of relatively minor importance in disease pathogenesis and were generally viewed as side products of the...

Pathophysiology of

Bik analysis with dry chemistry strips has facilitated population studies for various groups and ages 15, 17-19 . Screening of presumed healthy school children and adults showed that Bik was associated with inflammation and or infection (Table 1). Reference ranges for general and specific populations have been established for daily and hourly excretion rates 4 . In normal children, the interday excretion of Bik is fairly constant (Table 1). Approximately 50 of patients with fever were positive...

Nina Zidar Jeruc Jera Jerse Maja and Stajer Dusan

Institute of Pathology, Medical Faculty, University of Ljubljana, Korytkova 2,1000 Ljubljana, Slovenia Centre for Intensive Internal Medicine, University Medical Centre, ZaloSka 7,1525 Ljubljana, Slovenia 3. Apoptosis and the 5. Activation of 5.1. Extrinsic (Death Receptor) Pathway of Caspase 5.2. Intrinsic (Mitochondrial) Pathway of Caspase 6. Activation of Caspases in the 7. Functional Significance of 7.1. Role of Caspases During Embryonal 7.2. Role of Effector Caspases During 8. Caspases...

Application of Microarrays to Neuropsychiatry Disorders

Neuropsychiatric disorders such as schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) are complex diseases, whose exact etiology is unknown. Evidence suggests genetic, developmental, and environmental factors combine to create each disorder, with susceptibility loci for SZ, BD, and MDD identified throughout the genome. With an absence of clearly defined genetic factors on which cellular and animal models can be generated, to further the understanding of this spectrum...

Conclusions and Perspectives

UPAR is a multifunctional molecule, present in intact and cleaved forms and involved in extracellular proteolysis, cell adhesion, mobility, and cell signaling events 5-8, 155-157 . It is located mainly on stromal cells at the invasive front in breast and colorectal cancer and present in elevated levels in tumor tissue and blood from cancer patients as well as patients with infectious diseases. High levels of uPAR correlate with short survival in breast, colorectal, and lung cancer as well as in...

Finsen Laboratory Strandboulevarden 49 DK2100 Copenhagen 0 Denmark

Full-Length, Glycolipid-Anchored uPAR, 2.2. Cleavage of 2.3. Shedding of uPAR 3. Monoclonal Antibodies to 4. Immunoassays for the Quantification of 5. uPAR in 5.1. Breast 5.2. Colorectal Cancer 5.3. Lung Cancer 5.4. Prostate Cancer 5.5. Gynecologic Cancer 6. Other 7. Conclusions and

Conclusion

Angiogenesis contributes to physiological and pathological processes as diverse as the menstrual cycle and malignancy, wound healing, and arthritis. Angiogenesis may be either beneficial or harmful, depending on both the quantity and quality of the newly formed blood vessels. Endothelial cells play central roles in the initiation of angiogenesis, and VEGF may be viewed as a prototypical, direct-acting angiogenic factor. Its diverse effects on endothe-lial cell function are mediated by a...

Conclusions

Gliadin antibodies in sera of patients with active CD preferentially recognize several deamidated gliadin peptides. The amino acid sequence of the epitopes of gliadin antibodies is in agreement with data on substrate specificity of tTG showing that this enzyme is responsible for generation of the deamidated epitope motifs. Furthermore, the gliadin antibody epitope (B-cell epitope) is very similar to sequences described as strongly T-cell stimulatory (T-cell epitopes). Determination of...

Monoclonal Antibodies to uPAR

MAbs are important tools for functional, structural, and localization studies as well as for quantification of the antigen in question. mAbs were initially raised against uPAR(I-III) purified from U937 cell lysates by DFP-uPA affinity chromatography 1 . One of these mAbs, R3 was used to show that uPA binding to uPAR is required for cell-induced potentiation of plasminogen activation 1 . These mAbs react in Western blotting with uPAR under nonreducing conditions, but not after chemical...

Advances in Clinical Chemistry

Department of Pathology and Laboratory Medicine Hartford Hospital Hartford, Connecticut AMSTERDAM BOSTON HEIDELBERG LONDON NEW YORK OXFORD PARIS SAN DIEGO SAN FRANCISCO SINGAPORE SYDNEY TOKYO Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 525 B Street, Suite 1900, San Diego, California 92101-4495, USA 84 Theobald's Road, London WC1X 8RR, UK This book is printed on acid-free paper. Copyright 2007, Elsevier Inc. All Rights Reserved. No part of this publication...

Abbreviations

ATF amino-terminal fragment of uPA BPH benign prostatic hyperplasia DFP diisopropyl fluorophosphate ELISA enzyme-linked immunosorbent assay FPR formyl peptide receptor FPRL1 LXA4R FPR-like receptor-1 lipoxin A4 receptor G-CSF granulocyte colony-stimulating factor time-resolved fluorescence immunoassay urokinase-type plasminogen activator

Immunoassays for the Quantification of uPAR

The cell surface plasminogen activation system has an active role in cancer invasion. Thus, both uPA and PAI-1 have been shown to be prognostic markers mainly in breast cancer 117-119 . Therefore, it was early proposed that measurement of uPAR might also be of value in identifying patients with aggressive tumors and hence poor prognosis. This provided impetus for the establishment of immunoassays to be used for sensitive and specific measurements of uPAR in tumor tissue lysates and blood from...

Pathogenesis of CD

In genetically susceptible individuals, ingestion of cereal prolamins from wheat, barley, rye, and possibly oats initiates an inflammatory disorder during which the small intestinal mucosa is damaged. This process is accompanied by malabsorption, activation of the intestinal immune system, and Adaptive immune response, CD4 mediated, Th1 skewed Fig. 1. Brief survey of pathogenesis and diagnosis of CD. Food peptides from wheat and related cereals are partially digested and absorbed. Remaining...

Paraneoplastic Syndromes of the CNS

Paraneoplastic Encephalomyelitis PEM is one of the most frequent cancer-associated syndromes. This complex disorder usually affects several areas of the CNS. Cerebellar and brain stem disorders, as well as limbic encephalitis, are the most common clinical presentations of PEM 31, 32 . Focal involvement of the sensorimotor cortex has been described in a few cases 33 , and PEM may manifest as epileptic seizures or epilepsia partialis continua 33, 34 , or as extrapyramidal symptoms 35 ....