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Biomedical subjects

M F Greaves

Publications and source records attributed to M F Greaves.

At least 19 recordsLinked to original sources

Relation of "lymphoid" phenotype and response to chemotherapy incorporating vincristine-prednisolone in the acute phase of Ph1 positive leukemia.

Forty-four patients with Ph positive leukemia (36 developing blast crisis after chronic phase and eight presenting in acute leukemia) were classified into subgroups on the basis of reactivity of blasts with an anti-serum made against non-T,non-B acute lymphoid leukemia (ALL+), levels of terminal transferase enzyme (TdT+) and morphology. Positivity with anti-ALL serum was the most sensitive and reliable marker, and TdT was an important aid. The presence of "lymphoid" blasts in blast crisis of CML was related to the response to chemotherapy incorporating Vincristine and Prednisolone (VP). Patients with ALL+ blasts frequently (14 of 15 cases) responded to therapy while 21 of 25 patients who had no ALL+ blasts failed to respond. The clinical course of the ALL+ patients was variable: eight patients remitted with return to the appearances of the chronic phase; four patients demonstrated elimination of the Ph1 positive clone with hypoplasia and this was followed by normal (Ph1 negative) marrow regeneration in two. Subsequent relapse was of either the ALL+ "lymphoid" or the ALL-myeloid type. A regimen incorporating VP should be the treatment of choice in "lymphoid" blast crisis of CML.

Antigens, Neoplasm

"Ia-like" antigens on human T cells.

Human T lymphocytes have been tested for cell surface p. 28,33 "Ia-like" heteroantigen and DRw alloantigens. Small numbers (1--5%) of sheep (E) rosette or T antigen-positive, surface immunoglobulin-negative (E+, T+, smIg-) T cells were Ia+; these cells appeared to be restricted to the TG subset. Following activation by allogeneic lymphocytes or sperm, or by purified protein derivative of tuberculin (PPD), the proportion of positive T cells increased substantially. DRw typing indicated that Ia specificities on activated T cells were not acquired passively from the stimulator cells, suggesting therefore that either "selection" of a small DRw+ cell subset or derepression and/or exposure of DR locus gene products occurs during T cell activation.

Antigens, Surface

Immunological analysis of human microglia: lack of monocytic and lymphoid membrane differentiation antigens.

While it is certain that reactive microglia (phagocytes in damaged brain tissue) originate from monocytes, the derivation of resting microglia (argentophilic cells in undamaged brain tissue) is not clear. In order to examine a possible lymphocytic and/or monocytic origin for resting microglia, cryostat sections of presumably normal human brain tissue were treated with anti-lymphocyte, anti-monocyte and anti-beta 2-microglobulin sera and then stained with the immunoperoxidase technique. No positive reaction was obtained. It must be concluded that resting microglia are not derived from mononuclear blood cells.

Antigens, Surface

Terminal transferase-positive human bone marrow cells exhibit the antigenic phenotype of common acute lymphoblastic leukemia.

Combined immunologic assays for TdT enzyme and membrane markers show that TdT+ cells in nonleukemic human bone marrow carry ALL-associated and Ia-like antigens but no thymocyte markers or surface Ig. These cells could be precursors involved in acute lymphoblastic leukemia of the "common" or non-T, non-B type and in lymphoid blast crisis of Ph' positive chronic myeloid leukemia. A few TdT+, Ia+ cells express cytoplasmic IgM, indicating that some pre-B cells may be TdT positive.

Antigens

Lymphoid blast crisis in chronic myeloid leukaemia and Philadelphia positive acute lymphoid leukaemia.

Membrane markers (anti-ALL and anti-Ia antisera) and an enzyme marker (terminal transferase) have been used to define an L-type or "lymphoid" type of acute transformation in chronic myeloid leukaemia and Ph1 positive acute leukaemia. Patients with L-type ("lymphoid") blasts responded to regimens including vincristine and prednisolone (VP). The markers showed better correlation with survival than did the morphology of blasts. The clinical course of patients was variable; elimination Ph1 positive clone (and hypoplasia), return to the chronic phase and relapses (including meningeal leukaemia) were observed. In contrast, patients with myeloid blasts ("M" type of blast crisis) failed to respond to vincristine and prednisolone.

Antineoplastic Agents

Acid-phosphatase reaction in acute lymphoblastic leukaemia.

The diagnostic value of the acid-phosphatase reaction was assessed double-blind in 148 cases of acute lymphoblastic leukaemia (A.L.L.) classified by surface-membrane markers and entered into the M.R.C. U.K. A.L.L. trials. 90% of cases of T-A.L.L. showed a positive reaction in the majority of blast cells, while only 2% of common-A.L.L. and 10% of null-A.L.L. were positive. This cytochemical reaction distinguished the more aggressive form of A.L.L. any may aid the choice of therapy.

Acid Phosphatase

Expression of hexosaminidase isoenzymes in childhood leukemia.

Because differences in hexosaminidase isoenzyme profiles of granulocytes and lymphoyctes suggested that such profiles might help to distinguish between various types of leukemia, was examined leukocyte extracts from 55 untreated children and 12 controls by automated anion-exchange chromatography. In 23 of 27 cases of the common form of childhood acute lymphoblastic leukemia, the activity of hexosaminidase component I was greatly increased; the activity ratio of hexosaminidase I to hexosaminidase A was greater than 0.5 in 18 of these cases, whereas for other types of leukemia and for all normal cells tested, the ratio was less than 0.2. A raised hexosaminidase I was shown to be associated with leukemic cells by the finding of normal isoenzyme profiles of bone-marrow cells from 17 patients in remission who had such an increase either at diagnosis or in relapse. Hexosaminidase isoenzyme analysis had diagnostic value and may provide a new marker for study of leukocyte differentiation.

Adult

Maturation linked expression of a myeloid cell surface antigen.

An antiserum raised against myelomonocytic and monocytic leukaemia cells has been used to define a cell surface antigen shared by normal and leukaemic cells of the granulocyte and monocyte cell lines. The quantitative expression of this antigen was investigated using the Fluorescence Activated Cell Sorter and was shown to correlate with the degree of morphological maturation.

Animals