Volume 50 (2004) No. 2

Volume 50 (2004) No. 2
Reviews
Non-immune Functions of MHC Class I Glycoproteins in Normal and Malignant Cells
D. FISHMAN, S. ELHYANY, S. SEGAL ...............................................35
Department of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University Cancer Research Center, Ben-Gurion University of the Negev Beer-Sheva, Israel
Corresponding author: Segal Shraga, Department of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University Cancer Research Center, Ben-Gurion University of the Negev POB 653, Beer-Sheva 84105, Israel.     
Tel.: 972-8-6477149; Fax: 972-8-6477626;  e-mail: ssegal(zavináč)bgumail.bgu.ac.il.
Abstract.
Full text. 35-42

Comparative Gene Map of Hypertriglyceridaemia
O. ŠEDA .................................43
Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic
Department of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Centre de Recherche, Centre Hospitalier de l´Université de Montréal, Montréal, Quebec, Canada
Corresponding author: Ondřej Šeda, Institute of Biology and Medical  Genetics, First Faculty of Medicine,
Charles University, Prague, Albertov 4, 12800 Prague 2, Czech Republic. Tel.: (+420) 224 968 154, fax: (+420) 224 918 666, 
e-mail: oseda(zavináč)lf1.cuni.cz

Abstract.
Full text. 43-57

Cytopathological Basis of Heart Failure – Cardiomyocyte Apoptosis, Interstitial Fibrosis and Inflammatory Cell Response
D. PETROVIČ
Institute of Histology and Embryology, Medical Faculty, University of Ljubljana

Corresponding author: Daniel Petrovič, Institute of Histology and Embryology, Medical Faculty of Ljubljana, Korytkova 2, 1105 Ljubljana, Slovenia. Tel.: +386 61 543 7367; Fax +386 61 1401 294; E-mail: daniel.petrovic(zavináč)mf.uni-lj.si
Abstract.
Full text. 58-62
Original Articles
Molecular Analysis of the Sex Hormone-Binding Globulin Gene in the Rat Hypodactylous Mutation (Hd)
F. LIŠKA1, C. GÖSELE2,3, V. KŘEN1,4, N. HÜBNER2, D. KŘENOVÁ1................................63
1Institute of Biology and Medical Genetics, Charles University, Prague, Czech Republic
2Max Delbrück Centre for Molecular Medicine, Berlin, Germany
3Max Planck Institute for Molecular Genetics, Berlin, Germany
4Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Corresponding author: František Liška,  Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University Prague, Albertov 4, 128 00 Praha, Czech Republic.
Abstract.
Full text. 63-68
Haemochromatosis-Causing Mutations C282Y and H63D Are Not Risk Factors for Coronary Artery Disease in Caucasians with Type 2 Diabetes
M. ZORC1, H. HRUŠKOVIČOVÁ2, M. GLOBOČNIK PETROVIČ3, M. MILČIČ2,
B. PETERLIN2, D. PETROVIČ1...........................................................69
1Institute of Histology and Embryology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia
2Division of Medical Genetics, Department of Obstetrics and Gynecology, Medical Centre Ljubljana, Ljubljana, Slovenia
3Eye Clinic, University Medical Centre Ljubljana, Ljubljana, Slovenia
Corresponding author: Daniel Petrovič, Institute of Histology and Embryology, Medical Faculty of Ljubljana, Korytkova 2, 1105 Ljubljana, Slovenia. Tel.: +386 61 543 7367; Fax +386 61 1401 294; e-mail: daniel.petrovic(zavináč)mf.uni-lj.si
Abstract.
Full text. 69-70
Comparison of the Expression of Langerin and 175 kD Mannose Receptor in Antigen-Presenting Cells in Normal Human
Skin and Basal Cell Carcinoma
Z. PLZÁKOVÁ1, M. CHOVANEC1, 2, K. SMETANA, Jr.1, J. PLZÁK1, 2, J. ŠTORK3, S. SAELAND4..........71
1Charles University, 1st Faculty of Medicine, Institute of Anatomy, Prague, Czech Republic
2Charles University, 1st Faculty of Medicine, Department of OtorhinOlaryngology, Head and Neck Surgery, Prague, Czech Republic
3Charles University, 1st Faculty of Medicine, Department of Dermatovenerology, Prague, Czech Republic
4Laboratory for Immunological Research, Schering-Plough, Dardilly, France
Corresponding author: Karel Smetana, Jr., Charles University, 1st Faculty of Medicine, Institute of Anatomy,
U Nemocnice 3, 128 00 Prague 2, Czech Republic.
Abstract.
Full text. 71-73

Reviews
Non-immune Functions of MHC Class I Glycoproteins in Normal and Malignant Cells
D. FISHMAN, S. ELHYANY, S. SEGAL

MHC class I glycoproteins play a pivotal role in the regulation of immune responses by presenting antigenic peptides to cytotoxic
T lymphocytes and by regulating cytolytic activities of natural killer cells. Cells originating in malignant tumours are often characterized by a profound immune escape phenotype. This phenotype is frequently associated with alterations in MHC class I-related antigen processing and presentation that enable tumours to escape immune surveillance. However, it now becomes clear that MHC class I molecules do not only provide a mechanistic framework for the presentation of antigenic peptides but, rather, possess broader biological functions due to their
ability to regulate cell-to-cell communication and receptor-mediated trans-membrane signal transduction. In the present review we made an attempt to re-evaluate the significance of an altered MHC class I phenotype for tumour progression in view of the current state of knowledge concerning the aforementioned non-immune functions performed by these membrane glycoproteins.
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Comparative Gene Map of Hypertriglyceridaemia
O. ŠEDA

Elevated triglyceride levels in the circulation are currently recognized as an independent risk factor for coronary artery disease. Hypertriglyceridaemia represents one of the attributes of metabolic syndrome and is present in the most common genetic dyslipidaemia, the familial combined hyperlipidaemia. The factual concentration of triglycerides is determined by a complex interaction of environmental and
genetic components. Deeper understanding of the causative gene variants and the mode of their participation in the pathogenesis of hypertriglyceridaemia is required for devising efficient therapy of hypertriglyceridaemia. This is the first systematic review of linkage and
candidate gene studies dealing with the dissection of genetic determinants of (hyper)triglyceridaemia in human and two major mammalian
model species, mouse and rat. Based on the merged sets of data, a synthetic view of the genetic component of triglyceridaemia, the “hypertriglyceridaemia gene map”, is presented.
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Cytopathological Basis of Heart Failure – Cardiomyocyte Apoptosis, Interstitial Fibrosis and Inflammatory Cell Response
D. PETROVIČ

A characteristic feature of heart failure is progressive deterioration of the left ventricular function. The mechanisms responsible for
progression of heart failure are not known, but may be related to progressive loss of cardiomyocytes due to apoptosis or programmed
cell death. Apoptosis of cardiomyocytes can cause scattered loss of cardiomyocytes and, when sufficiently widespread, this might cause
 heart failure. Beside cardiomyocyte apoptosis, progressive accumulation of interstitial collagen fibres in the heart occurs in the failing
heart that may lead to ventricular diastolic or systolic dysfunction. Pathological processes in the failing heart (cardiomyocyte apoptosis,
changes in interstitial tissue of the heart) are accompanied by an inflammatory cell response.
In this paper cardiomyocyte apoptosis, inflammatory cell response and changes in interstitial tissue of the heart are reviewed as
potential factors responsible for progression of the left ventricular dysfunction in heart failure.
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Original Articles
Molecular Analysis of the Sex Hormone-Binding Globulin Gene in the Rat Hypodactylous Mutation (Hd)
F. LIŠKA, C. GÖSELE, V. KŘEN, N. HÜBNER, D. KŘENOVÁ

Sex hormone-binding globulin or ABP/SHBG is an extracellular androgen and oestrogen carrier. In the rat, ABP/SHBG is secreted by Sertoli cells of the testis and is thought to regulate androgen bioavailability in the male reproductive tract. During ontogenesis, ABP/SHBG is expressed in many mesoderm-derived tissues, including interdigital mesenchyme of the developing autopodium. Shbg is thus a candidate for Hd,
comprising autopodium (hand and foot) reduction and male sterility resulting from spermatogenesis impairment. Moreover, linkage mapping of Hd revealed that an intragenic marker for Shbg, D10Wox12, was non-recombinant with Hd. Sequencing of the entire coding sequence
 of Shbg failed to identify any variation in hypodactylous animals, distinct from two control strains. However, RT-PCR analysis revealed a significantly higher level of the Shbg transcript in hypodactylous rats compared to SHR controls. Whether Shbg expression is upregulated
 due to a cis-acting mutation in regulatory elements of the Shbg gene or it is a secondary result of spermatogenesis failure remains to be determined.
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Haemochromatosis-Causing Mutations C282Y and H63D Are Not Risk Factors for Coronary Artery Disease in Caucasians
 with Type 2 Diabetes

M. ZORC, H. HRUŠKOVIČOVÁ, M. GLOBOČNIK PETROVIČ, M. MILČIČ,
B. PETERLIN, D. PETROVIČ

Iron metabolism might be involved in the pathogenesis of CAD, and C282Y and H63D mutations in the HFE gene are associated with
 increased serum iron levels and net iron accumulation. The aim of this study was to look for a relationship between the C282Y and H63D
gene mutations of the HFE gene and coronary artery disease (CAD) in a group of patients with type 2 diabetes lasting more than 10 years.
The C282Y and H63D gene mutations were tested in 338 Caucasians with type 2 diabetes: 156 cases with CAD and 182 subjects with no history of CAD. The C282Y and the H63D HFE gene distributions in patients with CAD (C282Y: YY 0.6%, CY 9.0%, CC 90.4%; H63D: DD 3.8%, HD 21.8%, HH 74.4%) were not significantly different from those of diabetic subjects without CAD (C282Y: YY 0%, CY 8.2%, CC 91.8%; H63D: DD 2.2%, HD 20.3%, HH 77.5%). In conclusion, we failed to demonstrate that the C282Y and H63D HFE gene
 mutations were risk factors for CAD in Caucasians with type 2 diabetes lasting longer than 10 years.
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Comparison of the Expression of Langerin and 175 kD Mannose Receptor in Antigen-Presenting Cells in Normal Human
Skin and Basal Cell Carcinoma
Z. PLZÁKOVÁ, M. CHOVANEC, K. SMETANA, Jr., J. PLZÁK, J. ŠTORK, S. SAELAND

The presence of professional antigen-presenting cells in tumours can influence their further spreading. Location of cells exhibiting
a specific marker of Langerhans cells – Langerin, and the 175 kD mannose receptor as a marker of dendritic cells of non-Langerhans
 type and macrophages, was studied using double staining  in the normal human epidermis and in basal cell carcinomas. The Lagerin-positive
cells strictly colonized the epidermis and no cells were found in the dermis, where 175 kD mannose receptor-exhibiting cells were present.
Very rare elements in the epidermal/dermal interface were positive for both markers. A low incidence of Langerin-positive cells was
found in tumours and 1/3 of studied carcinomas were even Langerhans cell-free. The extraepithelial presence of Langerin-positive cells
forming contacts with dendrite-like protrusions of 175 kD mannose receptor-exhibiting cells was found in connective tissue surrounding
 the tumour epithelium and indicates possible cooperation of both elements.

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