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Biomedical subjects

M Bofill

Publications and source records attributed to M Bofill.

78 records · Page 5Linked to original sources

The reactivity of a monoclonal antibody against cells of the monocyte-macrophage series in sections of normal and inflamed human tissues.

FMC-17a monoclonal antibody reactive with peripheral blood monocytes was used to identify cells of monocyte origin in sections of normal and inflamed human tissues. FMC-17 + ve cells were found in all samples tested. The distribution, HLA-DR staining characteristics, and enzyme profiles (ACP and ATPase) of FMC-17 + ve cells indicated that interdigitating (dendritic) cells, Langerhans cells, tissue histiocytes, and the classical inflammatory phagocytic macrophages belonged to the reactive population. The antigen recognized by this antibody was found on monocytic and promonocytic cells in bone marrow, yet appeared to be lost following activation in the later stages of inflammatory conditions. Further studies are necessary to elucidate at what stage in the differentiation/maturation pathway the antigen is acquired and again whether or not FMC-17--ve cells are an activated or degenerating population.

Animals↗

Infrequent normal B lymphocytes express features of B-chronic lymphocytic leukemia.

An infrequent (2-3%) B lymphocyte subpopulation was found in the normal human tonsil and lymph nodes that shows the phenotypic characteristics of B-chronic lymphocytic leukemia (B-CLL) (rosette formation with mouse erythrocytes, weak expression of membrane Ig, staining for HLA-DR, and OKT1 or Leu-1 detecting a T cell-associated p65 antigen). Preliminary evidence suggests that at least a subpopulation of these cells is found, in small proportions, within the germinal centers. These cells were not observed in the human bone marrow. B-CLL may involve this peripheral B lymphocyte subset.

Animals↗

Enzyme histochemical analysis on cryostat sections of human bone marrow.

A recently developed procedure, that has been shown to be suitable for detailed immunohistological analysis, has been used to prepare cryostat sections of bone marrow to investigate whether enzyme-histochemical techniques are also feasible on such material. A selected group of enzymes, some of which are inhibited or destroyed in paraffin- or plastic-embedded samples, have been demonstrated. The morphological details obtained were satisfactory in the preparations. The enzymes were dipeptidyl(amino)peptidase IV (for T lymphocytes); tartrate-resistant acid phosphatase (for hairy cell leukaemia); acid phosphatase and non-specific esterase (for macrophages and monocytes); ATPase and 5'nucleotidase (for B lymphocytes); and peroxidase or chloroacetate esterase (for granulocytic cells). In these preparations strong enzyme activities were shown. In adjacent sections the immunological analysis of membrane markers could also be performed contributing to a comprehensive study of the normal and malignant bone marrow cells.

Bone Marrow↗

T cell subset abnormalities in tissue lesions developing during autoimmune disorders, viral infection, and graft-vs.-host disease.

The authors review a large body of contemporary immunohistologic findings on the tissue distribution of T lymphocytes in normal and pathological conditions. The suggestions for technological advances in this field are: signal amplification using mixtures of monoclonal antibodies directed against different epitopes on the same antigen (e.g. OKT4A+B+D), triple layer amplification systems using hapten-labelled antibodies, and informative double staining methods with combinations of antibodies labelled with different fluorochromes or enzymes. Review of histological observations in a series of human diseases suggests that imbalances of OKT4+ and OKT8+ subsets of T lymphocytes may represent different types of immunoregulatory disorders. Rheumatoid arthritis and sarcoidosis appear to involve a high level of OKT4+ subpopulation response coupled with an associated appearance of a special type of HLA-DR+ macrophages. It remains to be seen whether normal or self-limited immunological responses (early stages of bacterial infection or delayed-type hypersensitivity reactions) produce OKT4+ and macrophage responses that are characteristically different. Meanwhile, excessive levels of OKT8+ cells have been found in a wide range of recognized or presumed immunoregulatory disorders including: graft-vs.-host reaction and viral infections. These disorders, as well as primary biliary cirrhosis and lichen planus, appear to possess both overlapping and disparate clinical characteristics, and the immunohistological observations may reflect the functional heterogeneity of OKT8+ populations in these diseases. These studies show that histologically meaningful heterogeneity can already be demonstrated for the OKT8+ lymphocyte group.

Animals↗

Immunological analysis of the skin in graft versus host disease.

Immunohistochemical analysis was performed on skin biopsies from patients suffering from graft versus host disease (GVHD) following bone marrow transplantation for aplastic anaemia and leukaemia. Lymphoid cells infiltrating the skin were exclusively T cells with the OKT8+ phenotype and these are probably cytotoxic T cells. Langerhans cells were reduced in number in all specimens and a variable number of HLA-DR positive macrophages were seen in the dermis. In several cases HLA-DR antigens were expressed on keratinocytes. These results show consistent features which may help discriminate rashes in the skin in the post-transplant period.

Adolescent↗

Rheumatoid arthritis: a disease of T-lymphocyte/macrophage immunoregulation.

In rheumatoid arthritis the synovial membrane has many of the characteristics of a hyperactive, immunologically-stimulated lymphoid organ. The basis of this hyperactivity is poorly understood. Highly specific antisera to human Ia-like (HLA-DR) antigens and monoclonal antibodies (OKT series) to various T-lymphocyte subsets were used to analyse both the normal and the rheumatoid synovium and to compare it with normal lymph nodes. In rheumatoid arthritis the synovium acquires an infiltrate with microanatomical similarities to the paracortical area of the lymph node. Large, very strongly HLA-DR-positive macrophage-like interdigitating cells form close contacts with the OKT4+ (inducer-type) T-cells, while the OKT8+ population (T-cells of suppressor-cytotoxic type) between the macrophage-OKT4+ cell clusters is scanty (T4/T8 ratio = 9:1). By contrast, in the lymph node there are more OKT8 T-cells interspersed between the HLA-DR+ interdigitating cells and OKT4+ cells (T4/T8 ratio = 2:1). The large interdigitating cells and the OKT4+ T-cell population may be mutually stimulatory. In the absence of efficient suppression this stimulation may lead to activation of B-lymphocytes and oligoclonal or polyclonal immunoglobulin synthesis, as is found in the synovial membrane in rheumatoid arthritis.

Antibodies, Monoclonal↗