ABSTRACT
THE PATHOPHYSIOLOGY of most autoimmune diseases is often poorly understood. EXPERIMENTAL CONSIDERATIONS and clinical experience suggest that high doses immunoablation followed by stem cell transplantation is a therapeutic option to consider for certain severe autoimmune disorders. THE CONCEPT OF RESTORING NORMAL IMMUNE REACTIVITY must in part br true since current results of 466 transplants (445 autologous, 21 allogeneic) patients suffering from various autoimmune diseases show a beneficial outcome in approximately 2/3 of the patients. TO IMPROVE THE EFFICACY AND SAFETY OF SUCH AN AGGRESSIVE PROCEDURE in patients with potentially affected vital organs by the underlying autoimmune disease, it is especially important to follow international consensus guidelines and to centrally collect clinical data for in depth analysis in the EBMT International Stem Cell Project for Autoimmune Disease in Basel, Switzerland. PHASE III STUDIES ARE RUNNING FOR SYSTEMIC SCLEROSIS (Astis, Autologous Stem cell Transplantation International Rheumatoid Arthritis Trial) started in 2003. A STUDY PROJECT IS PLANNED FOR MULTIPLE SCLEROSIS (Astims, Autologous Stem cell Transplantation International Multiple Sclerosis).
Subject(s)
Autoimmune Diseases/therapy , Stem Cell Transplantation , Adolescent , Adult , Age Factors , Aged , Animals , Autoimmune Diseases/immunology , Child , Child, Preschool , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Disease Models, Animal , Feasibility Studies , Humans , Infant , Mice , Middle Aged , Patient Selection , Prospective Studies , Randomized Controlled Trials as Topic , Registries , Transplantation, Autologous , Transplantation, Homologous , Treatment OutcomeABSTRACT
Tissue processing and analysis require good preservation of both the shape and content of cells. Lowicryl resin is one of the few embedding media that allow good preservation of both tissue architecture and cellular contents. Therefore, different histochemical and immunohistochemical reactions can be applied to semithin sister sections from one biopsy. Further examination of a zone of interest can be carried out under the electron microscope. The hydrophilic property of Lowicryl resins makes possible different histochemical reactions; however, the technique used for paraffin sections must be adapted for each reaction. Antigenic preservation of cells by low temperature embedding allows immunolabeling on either semithin sections or in the zone of interest on ultrathin sections. We have shown the application and adaptation of different histochemical and immunohistochemical reactions on semithin and ultrathin sections from hepatic biopsies that were large, but thin. The variety of techniques that can be used on sister Lowicryl sections of a single biopsy makes this medium useful for extensive pathological studies of precious needle biopsies.
Subject(s)
Acrylic Resins , Biopsy, Needle/methods , Kidney Diseases/metabolism , Liver Diseases/metabolism , Plastic Embedding/methods , Clinical Protocols , Histocytochemistry , Humans , Immunohistochemistry , Kidney/chemistry , Kidney/pathology , Kidney Diseases/pathology , Liver/chemistry , Liver/pathology , Liver Diseases/pathology , Plastic Embedding/instrumentationABSTRACT
Chronic graft-versus-host disease (cGvHD) is a disabling alloimmune disease. Acute flare-ups of alloimmune reactions can occur even at the chronic clinical stage necessitating modulation of immunosuppression therapy. We studied conjunctival lesions of a patient with an acute flare-up in cGvHD. Along with severe GvHD lesions, biopsies showed eosinophils with pathological signs of activation. Since eosinophil recruitment and activation is observed in flare-ups of patients with autoimmune or inflammatory bowel diseases, we suggest that activated eosinophils in target organs may be a marker of evolutive lesions in alloimmune reactions as in other kinds of inflammatory diseases.
Subject(s)
Conjunctival Diseases/etiology , Eosinophils/pathology , Graft vs Host Disease/pathology , Acute Disease , Bone Marrow Transplantation/adverse effects , Cell Movement , Chronic Disease , Conjunctival Diseases/drug therapy , Conjunctival Diseases/pathology , Graft vs Host Disease/diagnosis , Graft vs Host Disease/drug therapy , Humans , Immunosuppressive Agents/therapeutic use , Inflammation/drug therapy , Inflammation/etiology , Inflammation/pathology , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/therapy , Male , Middle Aged , Transplantation, Isogeneic/adverse effectsSubject(s)
Bone Marrow Transplantation/adverse effects , Eosinophilia/etiology , Lymphoma, T-Cell/etiology , Multiple Myeloma/therapy , Neoplasms, Second Primary/etiology , Adult , DNA, Neoplasm/genetics , Eosinophilia/genetics , Humans , Lymphoma, T-Cell/genetics , Male , Neoplasms, Second Primary/genetics , Time Factors , Tissue Donors , Transplantation, HomologousABSTRACT
For pathologists, tissu processing and analysis require good preservation of both the shape (morphology) and the content of the cells (antigens, nucleic acids). Low temperature embedding resins are the only inclusion substrate which allows both a fine morphological analysis and good preservation of antigens and nucleic acids. Automatic the technical processes and simplified protocols now allow the introduction of low temperature embedding resins in diagnostic procedures.
Subject(s)
Biomarkers , Cold Temperature , Histocytochemistry , Microscopy, Electron , Resins, Plant , Tissue Embedding , Coloring Agents , Humans , PolymersABSTRACT
BACKGROUND: Secondary malignant diseases are late complications after allogeneic bone marrow transplantation (BMT). Anogenital lesions associated with human papillomavirus (HPV) infection have been described in renal transplant recipients but not after BMT. HPV types 16 and 18 are strongly linked to the malignant transformation. METHODS: In a series of 238 patients with allogeneic BMT, three had anogenital lesions. We looked for HPV in DNA extracted from embedded tissue to study HPV genotypes, p53 expression, and ploidy. RESULTS: In two patients, HPV sequences were detected. One of them, with giant condyloma, had HPV type 18 and two aneuploid clones, but p53 expression was not found. CONCLUSION: As in solid organ transplant recipients, anogenital condyloma may develop after BMT. Because the oncoprotein of HPV is able to bind and to degrade p53, it may lead to genetic instability, and subsequently to malignant transformation.
Subject(s)
Anus Diseases/virology , Bone Marrow Transplantation/adverse effects , Condylomata Acuminata/virology , Genital Diseases, Female/virology , Genital Diseases, Male/virology , Papillomaviridae , Papillomavirus Infections/etiology , Tumor Virus Infections/etiology , Adult , Aneuploidy , DNA, Viral/analysis , Female , Gene Expression , Humans , Immunohistochemistry , Male , Middle Aged , Papillomaviridae/genetics , Papillomavirus Infections/genetics , Tumor Suppressor Protein p53/genetics , Tumor Virus Infections/geneticsSubject(s)
Leukemia, Monocytic, Acute/diagnosis , Lung Neoplasms/diagnosis , Neoplasms, Second Primary/diagnosis , Adolescent , Child, Preschool , Diagnosis, Differential , Humans , Leukemia, Monocytic, Acute/diagnostic imaging , Leukemia, Monocytic, Acute/pathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Male , Neoplasms, Second Primary/diagnostic imaging , Neoplasms, Second Primary/pathology , RadiographyABSTRACT
For pathologists, tissue processing and analysis require good preservation of both the shape (morphology) and the content of the cells (antigens, nucleic acids). Low temperature embedding resins are the only inclusion substrate which allows both a fine morphological analysis and good preservation of antigens and nucleic acids. Automatic the technical processes and simplified protocols now allow the introduction of low temperature embedding resins in diagnostic procedures.
