EXTRAVASAL FIBRIN STABILIZATION BY FACTOR XIII IN LYMPH NODES WITH HODGKIN’S DISEASE

1987 ◽  
Author(s):  
R Adày ◽  
A Szegedi ◽  
Z Nemes ◽  
L Muszbek
Keyword(s):  
Lymph Nodes ◽  
Hodgkin's Disease ◽  
Factor Xiii ◽  
Mononuclear Cells ◽  
Hodgkin’S Disease ◽  
Tumor Stroma ◽  
Urea Solution ◽  
Immunoperoxidase Technique ◽  
Long Time ◽  
Covalently Linked

The formation of extravasal fibrin deposits in various tumors has been recognized a long time ago and it has been implicated in various aspects of tumor growth. However, no adequate information is available on the nature of intratumoral fibrin. In this study we attempted to find out if fibrin deposit in human lymph nodes with Hodgkin’s disease is stabilized and made resistant to fibrinolysis by factor XIII /FXIII/ of blood coagulation. The two main tasks for FXIII in fibrin stabilization is to attach a^antiplas-min the main phyiological inhibitor of fibrinolysis to fibrin strands and crosslink fibrin chains. By double immunofluorescent labeling for fibrin and α2-antiplasmin a complete colocalization of the two antigens could be observed. A part of fibrin strands also stained for α2-antiplasmin-plasmin-complex-neoantigen revealing that α2-antiplasmin covalently linked to fibrin inhibited intratumoral fibrinolysis. The finding that immunolabeling for fibrin was preserved following the treatment of sections by concentrated urea solution clearly demonstrates that fibrin chains became crosslinked by FXIII. These results were further supported by SDS PAGE analysis of intratumoral fibrin deposits. There are two theoretical possibilities for the appearance of FXIII in the interstitial space: 1/ plasmatic FXIII can get acrossthe vessel wall when increased permeability is induced 2/ FXIII can be produced and released by certain cells of the tumorous tissue. We explored the secondpossibility by various immunomorphological and enzymcytochemical techniques. Alarge number of FXIII positive cells were detected by immunoperoxidase technique in the follicular and interfollicular region of malignant, but not in normal lymph nodes. These relatively large, multipolar, mononuclear cells possesseda macrophage-like appearance and showedANAE-positivity,i.e.,they belong to thegroup of tumor associated macrophages. FXIII containing cells were labeled by monoclonal anti-Leu M3 (a monocyte/macrophage marker), but not by anti-HLA-DR.They were often found in the immediate vicinity of malignant Hodgkin’s cells and also showed an intimate relationshipwith extravasal fibrin formation.lt is suggested that FXIII secreted byintactor released from damaged macrophages might be involved in the stabilization offibrin in the tumor stroma or around tumor cells.

Fibrinolysis Resistant Fibrin Deposits in Lymph Nodes with Hodgkin's Disease

1988 ◽  
Vol 60 (02) ◽  
pp. 293-297 ◽  
Author(s):  
Róza Ádány ◽  
Andrea Szegedi ◽  
Richard J Ablin ◽  
László Muszbek
Keyword(s):  
Tumor Growth ◽  
Lymph Nodes ◽  
Hodgkin's Disease ◽  
Factor Xiii ◽  
Hodgkin’S Disease ◽  
Tumor Stroma ◽  
Fluorescent Labelling ◽  
Fibrin Deposition ◽  
Adequate Information ◽  
Covalently Linked

SummaryExtravasal fibrin deposition is frequently observed within and around tumorous tissues and has been implicated in various aspects of tumor growth. However, no adequate information has been available on the mechanism how intratumoral interstitial fibrin deposits escape a prompt elimination by the fibrinolytic system. In this study we provide immunomorphological evidence showing that fibrin deposits in lymph nodes with Hodgkin's disease are stabilized and made resistant to fibrinolysis by factor XIII (FXIII) of blood coagulation. By double immuno- fluorescent labelling systems fibrin deposits were simultaneously stained for α2-antiplasmin (α2-AP), the main physiological inhibitor of fibrinolysis and in a number of nodular areas they were also labelled for plasmin (ogen). The detection of α2-antiplasmin-plasmin complex-neoantigen (α2-AP-P-Neo) revealed that α2-AP reacted with plasmin, i.e., α2-AP covalently linked to fibrin indeed inhibited intratumoral fibrinolysis. In addition to fibrin deposits FXIII was also found in cellular elements characterized earlier as tumor associated macrophages. These cells were attached to fibrin strands suggesting that they are involved in the intratumoral fibrin formation and might be a source of fibrin stabilizing factor in the tumor stroma.

scholarly journals Atypical hodgkin and reed-sternberg cells in peripheral blood of a patient with advanced stage of Hodgkin's disease - a case report

2003 ◽  
Vol 131 (9-10) ◽  
pp. 400-402 ◽  
Author(s):  
Rajko Milosevic ◽  
Milica Colovic ◽  
Vesna Cemerikic-Martinovic ◽  
Natasa Colovic ◽  
Marina Bogunovic
Keyword(s):  
Bone Marrow ◽  
Lymph Nodes ◽  
Peripheral Blood ◽  
Hodgkin's Disease ◽  
Mononuclear Cells ◽  
Hodgkin’S Disease ◽  
Lymphoid Cells ◽  
High Dose ◽  
Advanced Stage ◽  
Neck Lymph Nodes

The occurrence of abnormal Hodgkin's and Reed-Sternberg cells in the peripheral blood in a patient suffering from Hodgkin's disease has been noticed exceptionally rare in a previous period, and especially rare in last ten years primarily due to successfull treatment of this disease. The presence of atypical mononuclear cells in peripheral blood which cytomorphologically resembled Reed-Sternberg cells was registered in 8 patients till 1966. During the last decade, the presence of atypical mononuclear cells in the peripheral blood was used for their isolation cultivation, and detailed immunophenotypic and genetic analysis. The analysis of mononuclear cells in rare patients with Hodgkin's disease was established that they belong to the B-lymphoid cells with expression of CD30 and CD15 antigens. The examination of presence of Hodgkin's cells in the peripheral blood of patients with Hodgkin's disease is important for patients with advanced stage of the disease in which autologous stem cell transplantation and high dose chmeotherapy is planned. The authors present a 33-year-old patient, who noticed enlarged neck lymph nodes in September 2000, high temperature and loss in weight. On physical examination enlarged neck lymph nodes 5x8 cm and hepatosplenomegaly were found. There was anemia and thrombo-cytopenia, and normal WBC count with 24% of lymphoid elements in differential formula. On histologic examination of lymph nodes Hodgkin?s disease, type nodular sclerosis with mixed cellularity was found. Histology of bone marrow showed nodal lymphomatous infiltration. Immunohistochemistry with monoclonal antibodies of concentrate of peripheral blood cells showed expression of CD30+ and CD15+, immunophenotypically and morphologically matching Reed-Sternberg cells. Cytogentic analysis of mononuclear cells of the bone marrow showed normal karyotype. The patient was in clinical stage IV/V of the disease and chemotherapy with 9 cycles of ABVD+Mp protocol was applied. He is still in remission.

scholarly journals In situ immunologic characterization of cellular constituents in lymph nodes and spleens involved by Hodgkin's disease

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 226-232 ◽  
Author(s):  
S Poppema ◽  
AK Bhan ◽  
EL Reinherz ◽  
MR Posner ◽  
SF Schlossman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Cytotoxic T Cells ◽  
Lymphoid Tissues ◽  
Immunoperoxidase Technique ◽  
Activated T Cells ◽  
Cytoplasmic Staining

The cellular constituents in lymph nodes and spleens of patients with Hodgkin's disease were studied with a series of monoclonal antibodies directed against human thymocyte, peripheral T-cell, and la antigens. Utilizing both an immunoperoxidase technique on frozen tissue sections and indirect immunofluorescence on cell suspensions, wer found that a majority of lymphocytes were T cells, since they stained with anti-T1 and anti-T3 antibodies, which react with all peripheral T cells. In addition, most of these cells were reactive with anti-T4 antibody, which defines the helper/inducer T-cell population, whereas only a minority of cells stained with anti-T5 and anti-T8 antibodies, which are reactive with suppressor/cytotoxic T cells. Moreover, a large proportion of T cells expressed T10 antigen, which is found on activated T cells. A minority of the T cells also expressed la antigen(s), again suggesting that some of the T cells are activated. In contrast, the Reed-sternberg cells did not react with any of these anti- T-cell antibodies or with anti-IgM antiserum, but displayed strong membrane and cytoplasmic staining with anti-la antibody. Taken together, these findings suggest that Reed-Sternberg cells are not of T- cell lineage but may be derived from antigen-presenting reticulum cells in the thymus-dependent areas of lymphoid tissues; these cells are normally associated with T4+ cells.

scholarly journals Isolation of Reed-Sternberg cells from lymph nodes of Hodgkin's disease patients

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 222-229
Author(s):  
G Sitar ◽  
E Brusamolino ◽  
C Bernasconi ◽  
E Ascari
Keyword(s):  
Lymph Nodes ◽  
Hodgkin's Disease ◽  
Mononuclear Cells ◽  
Density Gradient Centrifugation ◽  
Hodgkin’S Disease ◽  
Gradient Centrifugation ◽  
Cell Types ◽  
Velocity Sedimentation ◽  
Single Cell Suspension ◽  
Final Yield

This study describes a simple and relatively rapid method of purifying Reed-Sternberg (R-S) cells and their morphologic variants from the lymph nodes of patients affected by Hodgkin's disease. Our initial studies defined the optimal procedure for a quantitative disaggregation of Hodgkin's lymph nodes and the densities of R-S cells in several donors. These preliminary steps were helpful in the development of strategies for selectively concentrating R-S cells by density gradient centrifugation. We layered a single-cell suspension over Percoll of appropriate density, centrifuged these samples for 15 minutes, and collected a fraction enriched in R-S cells. Most of the R-S cells were distributed between densities of 1.060 and 1.072, with a peak at approximately 1.066 g/mL. R-S cells are denser than many mononuclear cells present in the lymph nodes of Hodgkin's patients and lighter than reactive cells such as eosinophils, mast cells, and neutrophils. However, the ranges of densities of these cell types overlap, making purification of R-S cells by isopyknic centrifugation impossible. Nevertheless, when this enriched fraction is further processed by velocity sedimentation in order to take advantage of the larger size of R-S cells as compared with all other cells, a substantial purification is achieved. We used three different velocity-sedimentation chambers to find the optimal conditions for obtaining the highest purity with a high final yield. The cells isolated by this method are viable, appear to be morphologically normal, and have been further characterized biologically.

scholarly journals In situ immunologic characterization of cellular constituents in lymph nodes and spleens involved by Hodgkin's disease

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 226-232 ◽  
Author(s):  
S Poppema ◽  
AK Bhan ◽  
EL Reinherz ◽  
MR Posner ◽  
SF Schlossman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Cytotoxic T Cells ◽  
Lymphoid Tissues ◽  
Immunoperoxidase Technique ◽  
Activated T Cells ◽  
Cytoplasmic Staining

Abstract The cellular constituents in lymph nodes and spleens of patients with Hodgkin's disease were studied with a series of monoclonal antibodies directed against human thymocyte, peripheral T-cell, and la antigens. Utilizing both an immunoperoxidase technique on frozen tissue sections and indirect immunofluorescence on cell suspensions, wer found that a majority of lymphocytes were T cells, since they stained with anti-T1 and anti-T3 antibodies, which react with all peripheral T cells. In addition, most of these cells were reactive with anti-T4 antibody, which defines the helper/inducer T-cell population, whereas only a minority of cells stained with anti-T5 and anti-T8 antibodies, which are reactive with suppressor/cytotoxic T cells. Moreover, a large proportion of T cells expressed T10 antigen, which is found on activated T cells. A minority of the T cells also expressed la antigen(s), again suggesting that some of the T cells are activated. In contrast, the Reed-sternberg cells did not react with any of these anti- T-cell antibodies or with anti-IgM antiserum, but displayed strong membrane and cytoplasmic staining with anti-la antibody. Taken together, these findings suggest that Reed-Sternberg cells are not of T- cell lineage but may be derived from antigen-presenting reticulum cells in the thymus-dependent areas of lymphoid tissues; these cells are normally associated with T4+ cells.

scholarly journals Isolation of Reed-Sternberg cells from lymph nodes of Hodgkin's disease patients

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 222-229 ◽  
Author(s):  
G Sitar ◽  
E Brusamolino ◽  
C Bernasconi ◽  
E Ascari
Keyword(s):  
Lymph Nodes ◽  
Hodgkin's Disease ◽  
Mononuclear Cells ◽  
Density Gradient Centrifugation ◽  
Hodgkin’S Disease ◽  
Gradient Centrifugation ◽  
Cell Types ◽  
Velocity Sedimentation ◽  
Single Cell Suspension ◽  
Final Yield

Abstract This study describes a simple and relatively rapid method of purifying Reed-Sternberg (R-S) cells and their morphologic variants from the lymph nodes of patients affected by Hodgkin's disease. Our initial studies defined the optimal procedure for a quantitative disaggregation of Hodgkin's lymph nodes and the densities of R-S cells in several donors. These preliminary steps were helpful in the development of strategies for selectively concentrating R-S cells by density gradient centrifugation. We layered a single-cell suspension over Percoll of appropriate density, centrifuged these samples for 15 minutes, and collected a fraction enriched in R-S cells. Most of the R-S cells were distributed between densities of 1.060 and 1.072, with a peak at approximately 1.066 g/mL. R-S cells are denser than many mononuclear cells present in the lymph nodes of Hodgkin's patients and lighter than reactive cells such as eosinophils, mast cells, and neutrophils. However, the ranges of densities of these cell types overlap, making purification of R-S cells by isopyknic centrifugation impossible. Nevertheless, when this enriched fraction is further processed by velocity sedimentation in order to take advantage of the larger size of R-S cells as compared with all other cells, a substantial purification is achieved. We used three different velocity-sedimentation chambers to find the optimal conditions for obtaining the highest purity with a high final yield. The cells isolated by this method are viable, appear to be morphologically normal, and have been further characterized biologically.

Chemotherapy in hodgkin’s disease (lymphadenoma)

1973 ◽  
Vol 11 (15) ◽  
pp. 57-59
Keyword(s):  
Lymph Nodes ◽  
Young Women ◽  
Hodgkin's Disease ◽  
Important Determinant ◽  
Hodgkin’S Disease ◽  
X Rays ◽  
Single Factor ◽  
Node Biopsy ◽  
Choice Of Treatment ◽  
Choice Of Therapy

The extent of Hodgkin’s disease at the time of diagnosis is the most important single factor affecting prognosis and the choice of treatment.1 2 Thorough investigation is needed to determine the stage of the disease,3 and it is best to refer patients to a centre with special experience of the condition. The staging process requires haematological, biochemical and radiographic studies, including abdominal lymphography.4 Some patients may also need laparotomy with splenectomy and hepatic and node biopsy to localise any intra-abdominal spread, particularly into the liver which is ominous and an important determinant in the choice of therapy.5 6 Laparotomy is less usually performed in patients over 60. In children under 6 splenectomy should not be carried out because it makes them more susceptible to infection.7 In young women the ovaries may be sewn to the abdominal wall in the mid-line so that they can be shielded from x-rays directed at iliac lymph nodes.

Tissue T-lymphocytes in untreated Hodgkin's disease morphologic and functional correlations in spleens and lymph nodes

Cancer ◽  
1982 ◽  
Vol 50 (2) ◽  
pp. 259-268 ◽  
Author(s):  
Carlo D. Baroni ◽  
Luigi Ruco ◽  
Stefania Uccini ◽  
Antonio Foschi ◽  
Massimo Occhionero ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Lymph Nodes ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease
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