ABSTRACT
In humans, the pathogenesis of diabetes is characterised by two major pancreatic ß cell defects: a reduction in ß cell mass and the failure of ß cells to produce enough insulin. Over the past two decades, multiple studies involving cell cultures, animal models and human subjects have established the importance of the protein kinase RNA-like endoplasmic reticulum kinase (PERK) in the adaptive functional capacity of pancreatic ß cells during embryonic development and into adulthood. In this review, we will highlight major findings identifying PERK as a crucial player in ß cell physiology and in diabetes.
Subject(s)
Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 2/genetics , Epiphyses/abnormalities , Eukaryotic Initiation Factor-2/genetics , Homeostasis/genetics , Insulin-Secreting Cells/enzymology , Osteochondrodysplasias/genetics , eIF-2 Kinase/genetics , Activating Transcription Factor 4/genetics , Activating Transcription Factor 4/immunology , Adult , Animals , Diabetes Mellitus, Experimental/enzymology , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/immunology , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 1/enzymology , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 2/enzymology , Diabetes Mellitus, Type 2/immunology , Diabetes Mellitus, Type 2/pathology , Epiphyses/enzymology , Epiphyses/immunology , Epiphyses/pathology , Eukaryotic Initiation Factor-2/immunology , Gene Expression Regulation, Developmental , Homeostasis/immunology , Humans , Infant, Newborn , Insulin-Secreting Cells/immunology , Insulin-Secreting Cells/pathology , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/immunology , Osteochondrodysplasias/enzymology , Osteochondrodysplasias/immunology , Osteochondrodysplasias/pathology , Signal Transduction , eIF-2 Kinase/deficiency , eIF-2 Kinase/immunologyABSTRACT
The presence of a specific type of cell, highly expressing difucosyl type 2 chain (dimeric Lex; FH-4 antigen), was found in the epiphyseal bone marrow cells of affected joints from patients with active severe rheumatoid arthritis (RA). The antigen was defined by monoclonal antibody FH-4 which was previously found to be directed to the oncofetal marker. The FH-4(+) cell population was identified as myeloid cell lineage with usual morphology specifically found in bone marrow of patients with severe RA, but is virtually absent in the same cell fraction of patients with osteoarthritis, infectious arthritis, and from normal adult subjects.
Subject(s)
Antigens, Differentiation, Myelomonocytic/analysis , Arthritis, Rheumatoid/pathology , Bone Marrow/pathology , Epiphyses/pathology , Adult , Aged , Antibodies, Monoclonal , Arthritis, Infectious/immunology , Arthritis, Infectious/pathology , Arthritis, Rheumatoid/immunology , Bone Marrow/immunology , Epiphyses/immunology , Female , Humans , Lewis Blood Group Antigens/analysis , Male , Middle Aged , Osteoarthritis/immunology , Osteoarthritis/pathologyABSTRACT
A case of erosive sterile arthritis following meningococcal meningitis is described. High levels of immune complexes were detected in serum and synovial fluid. This is the first case in literature in which destruction of subchondral bone is documented. The erosion showed a progressive remineralization in the six months following clinical recovery.
Subject(s)
Arthritis, Infectious/immunology , Immune Complex Diseases/immunology , Meningitis, Meningococcal/immunology , Antigen-Antibody Complex/analysis , Epiphyses/immunology , Female , Femur/immunology , Humans , Infant , Neisseria meningitidis/immunologyABSTRACT
Several benign and malignant tumors of bone and cartilage were examined by means of type-specific collagen antibodies in connection with indirect immunofluorescence technique in order to determine wether there is a positive correlation between cell morphology and gene expression as refered to the synthesis of tissue- or cell-specific collagen. In general benign bone and cartilage tumors show the collagen type corresponding to the original maternal tissue. In malignant osteogenic tumors a strong positive correlation was found between morphologic differentiation of osteosarcoma cells and tissue specific collagen synthesarcomas. Unrelated to the grade of differentiation and the type of malignant tumor, collagen type III could be demonstrated in all tumors investigated, occurring rather from vascular stroma than from the tumor cell itself.
Subject(s)
Bone Neoplasms/immunology , Cartilage Diseases/immunology , Collagen/immunology , Epiphyses/immunology , Neoplasms/immunology , Cartilage, Articular/immunology , Chondroma/immunology , Chondrosarcoma/immunology , Fluorescent Antibody Technique , Humans , Osteosarcoma/immunologyABSTRACT
The stimulation of lymphocytes by allogeneic and syngeneic cells other than lymphocytes has been shown to result in poor or no stimulation. We have been able to demonstrate that lymphocytes and chondrocytes mixed in culture both allogeneically and syngeneically has resulted in siginificant lymphocyte stimulation. The inference from this data suggest the presence of histocompatibility antigen as well as tissue-specific antigen on the surface of chondrocytes.