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Biomedical subjects

F R Davey

Publications and source records attributed to F R Davey.

At least 91 records · Page 5Linked to original sources
PubMed1983

The in vitro effects of vincristine on peripheral blood leukocyte progenitor cells (CFU-C) in patients in blast crisis of chronic granulocytic leukemia: correlation with clinical response.

The in vitro sensitivity of circulating progenitor cells (CFU-C) of 20 patients in blast crisis of chronic granulocytic leukemia (CGL) to vincristine was correlated with the clinical response to vincristine in vivo. Eleven patients who achieved either a good or partial clinical response displayed a reduction in the number of colonies or clusters formed by their peripheral blood leukocytes in a double layer agar culture assay following incubation with vincristine. The CFU-C of five of six patients who failed to respond clinically to vincristine and prednisone were not suppressed following incubation with up to 12 microM vincristine. Three additional patients were not evaluable due to early post-treatment deaths. In vitro assay of the effects of vincristine on CFU-C appears to have predictive value for in vivo response in blast crisis of CGL.

Adult↗
PubMed1983

Acute nonlymphocytic leukemia complicated by severe cytophagocytosis of formed blood elements by nonmalignant histiocytes: cause of significant clinical morbidity.

A 52-year-old female presented with Philadelphia chromosome-positive acute nonlymphocytic leukemia and a morphologically benign-appearing histiocytosis with intramedullary cytophagocytosis of formed blood elements. No cause of the reactive histiocytosis could be found. Despite initial successful therapy of the acute nonlymphocytic leukemia with induction of a cytological remission, pancytopenia with marked cytophagocytosis persisted. Therapy aimed at reducing the degree of cytophagocytosis by the histiocytes, in the form of vinblastine-treated platelets and, subsequently, prednisone, was instituted. There was no significant clinical response to either therapeutic maneuver. Cytophagocytosis persisted until leukemic relapse and death ensued.

Acute Disease↗
PubMed1983

Separation of human T-lymphocyte colony-forming cells on Percoll gradients.

Formation of T-lymphocyte colonies in semi-solid agar by mitogen-stimulated peripheral blood mononuclear cells is a sensitive indicator of a proliferative response. The exact identity of the T-lymphocyte colony forming cell (T-CFC) is not known, nor is it known if more than one T-CFC exists. It is possible that different subsets of mononuclear cells, each responding to diverse mitogens, give rise to different T-CFC. In this study, we separated mononuclear cells into seven subsets based on their density utilizing Percoll at concentrations of 40% to 55%. Following separation, the cells from each fraction were stimulated by phytohemagglutinin (PHA), pokeweed mitogen (PWM), concanavalin A (Con A), or staphylococcal protein A (SPA), and cultured in a semi-solid agar system. Each fraction was fully characterized by immunologic and cytochemical cell markers. Monocytes were found in the light density fraction, whereas T-lymphocytes and large granular lymphocytes were predominantly seen in the heavier density fractions. B lymphocytes were concentrated in the middle density fractions. Cells from fraction 1 (the lightest density fraction) formed significantly more T-cell colonies when stimulated by PHA than did fractions 4, 5, 6, or 7. This effect was not observed when other mitogens were used. We conclude that mononuclear cells can be separated into enriched cell subpopulations by Percoll fractionation and that PHA-stimulated T-CFC may also be enriched by Percoll fractionation. In addition, the data suggest that different subsets of T-CFC may exist.

Adult↗
PubMed1983

Prognostic significance of the revised French-American-British classification for acute lymphocytic leukaemia.

The French-American-British (FAB) classification of acute lymphocytic leukaemia (ALL) has recently been modified to improve its reproducibility. We therefore thought it beneficial to test the utility of this modified classification in the prognosis of children with ALL. Eighty-eight patients of less than 18 years of age with ALL were subtyped according to the modified FAB classification by two independent observers. The initial concordance was 86%. Seventy per cent of the patients were subtyped as L1, 27% as L2 and 3% as L3. Patients with L3 subtype were not analysed further. No significant differences were observed between L1 and L2 subtypes when the distribution of other prognostic factors were examined. No differences were observed between L1 and L2 subtypes in the achievement of complete remission. Patients with L1 morphology demonstrated no significant increased duration of first remission or survival when compared to patients with L2 morphology. We conclude that the morphology of lymphoblasts may not be an independent prognostic variable in patients with ALL.

Bone Marrow↗
PubMed1983

T lymphocyte colonies stimulated by different mitogens require diverse culture conditions.

Normal human peripheral blood mononuclear cells form colonies of T lymphocytes in a semi-solid agar matrix when stimulated by a variety of mitogens. In this report, we attempt to determine the optimal conditions for the formation of T lymphocyte colonies by cells stimulated with phytohemagglutinin (PHA), pokeweed mitogen (PWM), Concanavalin A (Con A), or Staphylococcal protein A (SPA). We conclude that optimal conditions differ for each mitogen used. Cultures stimulated by PWM or Con A showed a significant requirement for feeder layers composed of human peripheral blood mononuclear cells. Two-mercaptoethanol significantly enhanced the number of T-cell colonies when PWM, Con A, or SPA, but not PHA, were added as mitogens. Fetal calf serum (FCS) was required for optimal conditions when Con A or SPA but not PWM or PHA were used to stimulate mononuclear cells. Cells stimulated by PHA or PWM produced more T-cell colonies in a 2-step assay than a 1-step assay, whereas the reverse was true with Con A or SPA. Optimal cell concentrations, mitogen doses, and culture kinetics also differed for each mitogen used in the T-cell colony assay.

Cell Division↗
PubMed1983

Mouse rosette positive B cells fail to synthesize immunoglobulin following incubation with pokeweed mitogen.

Mouse erythrocytes form spontaneous rosettes with a population of B lymphocytes from normal individuals and from patients with B cell chronic lymphocytic leukaemia (CLL). Since lymphocytes from patients with CLL respond poorly to pokeweed mitogen (PWM), we have compared mouse rosette positive (MR+), mouse rosette negative (MR-), and unfractionated B lymphocytes from normal individuals in their response to PWM. Mononuclear cells were fractionated into B, MR+ and MR- cell populations and then combined in 1:1 proportions with mitomycin-C treated T cells in culture media. Lymphocyte co-cultures were incubated for up to 10 days in the presence of PWM. Supernatant immunoglobulin (SIg) levels, percentage intracytoplasmic immunoglobulin (ICIg), and proliferative responses were determined. MR+ cells alone failed to produce significant levels of SIg (P less than 0.025) or percentages of ICIg positive cells This decreased synthesis of immunoglobulin by MR+ cells occurred in the presence of adequate T cells, macrophages and a satisfactory proliferative response.

Animals↗
PubMed1982

The presence of Burkitt-like cells in non-Burkitt's neoplasms.

In four cases, the morphology of neoplastic cells from the peripheral blood and bone marrow suggested the diagnosis of American Burkitt's lymphoma or acute lymphocytic leukemia (French--American--British--Classification; FAB-L3). Cytochemical and immunologic studies, however, indicated that the neoplastic cells in one case were characteristic of acute lymphocytic leukemia (non-B, non-T-cell type); in another case, metastatic carcinoma; and in two two cases acute myelomonocytic leukemia. We conclude that cytochemical and immunologic cell markers are necessary for the diagnosis of American Burkitt's lymphoma. In addition, neoplastic cells simulating lymphoblasts of acute lymphocytic leukemia, FAB-L3 may derive from non-B lymphocytic lineage.

Adult↗
PubMed1982

Splenic alterations in hairy-cell leukemia: II. an electron microscopic study.

Spleen from nine patients with hairy-cell leukemia (HCL) were studied for ultrastructural alterations. In all cases, hairy cells with typical ultrastructural characteristics were observed within splenic cords and sinuses. Hairy cells had numerous cytoplasmic processes that interdigitated with cytoplasmic processes of other hairy cells. Hairy cells also adhered to sinus endothelial cells and ring fibers and protruded into spaces between endothelial cells. Some normal sinuses were filled with aggregated hairy cells. Other sinuses appeared dilated. Many sinuses were lined by hairy cells that covered thinned endothelial cells and ring fibers. In these abnormal sinuses, endothelial cells were decreased and many appeared injured. The splenic cords were expanded by an infiltration of hairy cells and by large blood-filled spaces. These findings suggest that hairy cells adhere to many cell surfaces, produce endothelial cell injury and death, and impede the venous flow of blood in the spleen. All of the factors appear to influence the formation of the abnormal splenic sinuses and the blood-filled spaces that characterize HCL.

Cytoskeleton↗
PubMed1982

Diminished autologous mixed lymphocyte reaction in patients with Hodgkin disease: evidence for non-T cell dysfunction.

In the autologous mixed lymphocyte reaction (AMLR), T lymphocytes are stimulated to proliferate by autologous non-T mononuclear cells. In five untreated patients with Hodgkin disease, the AMLR was diminished. In addition, in the same five patients, T cell response PHA was inhibited by a cell in the non-T cell fraction, the response of non-T cells to PWM was diminished, and there was a diminished ability of the non-T cell population to stimulate in allogeneic MLR. However, the response of T cells from patients with Hodgkin disease to allogeneic antigen was normal. The AMLR and allogeneic MLR were then studied in an additional five untreated patients before and after monocyte depletion of the stimulating non-T mononuclear cell population. In this second group of Hodgkin disease patients, the AMLR was again diminished when T cells were incubated either with non-T cells or non-T cells depleted of monocytes. In the Hodgkin patients, monocyte depletion did not alter the T cell response in the AMLR. In the controls, monocyte depletion greatly diminished the proliferative response. The diminished AMLR in untreated Hodgkin disease patients may be the result of a failure of adequate monocyte stimulation of autologous T cells.

Cell Separation↗
PubMed1982

Non-Hodgkin's lymphoma with immunologic phenotype similar to non-T, non-B acute lymphocytic leukemia.

A diagnosis of diffuse poorly differentiated lymphocytic lymphoma was made from a biopsy of a scapular mass on a 24-month-old child. The bone marrow and peripheral blood were not involved in the neoplastic process. Neoplastic cells stained negatively for Sudan black B, myeloperoxidase, periodic acid-Schiff reagent, alpha-naphthyl acetate esterase, and acid phosphatase. In addition, neoplastic cells did not form nonimmune rosettes with sheep erythrocytes or contain surface membrane immunoglobulin. However, neoplastic cells were positive for terminal deoxynucleotidyl transferase and "Ia-like" antigen. We conclude that this non-Hodgkin's lymphoma has a cytochemical and immunologic phenotype similar to that of lymphoblasts from cases of non-T, non-B acute lymphocytic leukemia.

Bone Neoplasms↗
PubMed1982

Mouse erythrocyte formation. A marker for resting B lymphocytes.

The ability of peripheral blood lymphocytes to form rosettes with mouse erythrocytes was examined using lymphocytes from normal healthy individuals of various ages and of neoplastic lymphoid cells from patients with a variety of lymphoproliferative disorders. Our results indicated that only B lymphocytes form mouse rosettes (MR). The percentage of MR varied slightly according to the strain of mouse erythrocytes used in the assay. Little variation in the mean percentage of MR was observed when lymphocytes from various age groups of healthy individuals were studied. When neoplastic lymphoid cells were incubated with mouse erythrocytes only lymphocytes from patients with chronic lymphocytic leukemia formed an increased number of MR. Peripheral blood B lymphocytes lost their ability to form MR following incubation with pokeweed mitogen. These findings supported the view that the determinant on B lymphocytes which binds to mouse erythrocytes was present only at a resting stage of B cell maturation.

Animals↗
PubMed1982

Effects of vitamin E on mixed lymphocyte cultures.

When lymphocytes from individuals ingesting vitamin E were used as responding cells in the mixed lymphocyte culture (MLC) the proliferative response was normal indicating that T lymphocyte reactivity to allogeneic antigen was undisturbed. However, the use of lymphocytes from individuals receiving vitamin E as stimulating cells in the MLC resulted in a diminished proliferative response suggesting that large doses of vitamin E may effect B cells and/or macrophages as they interacted with T lymphocytes.

Adult↗
PubMed1982

Mouse rosette positive B cells stimulate poorly in the autologous and allogeneic mixed lymphocyte reaction.

Mouse erythrocytes form spontaneous rosettes with a population of B lymphocytes from normal individuals and in the majority of lymphocytes from patients with B cell chronic lymphocytic leukaemia (CLL). We have compared the ability of mouse rosette positive (MR+) cells with mouse rosette negative (MR-) cells and monocytes to act as stimulators in the autologous mixed lymphocyte reaction (AMLR) and allogeneic mixed lymphocyte reaction (MLR). Mononuclear cells from the peripheral blood of healthy individuals were fractionated into T cells, MR+ cells, MR- cells and monocytes. Lymphocyte cultures were harvested on days 6, 8 and 10 and the incorporation of tritiated thymidine was determined. MR- cells and monocytes were potent stimulators in the AMLR and MLR. In contrast MR+ cells, like B cells from patients with CLL, stimulated less in the AMLR and MLR. We conclude that MR+ cells from normal individuals function similarly to cells from CLL in the AMLR and MLR.

Animals↗
PubMed1981

The development of acute myelomonocytic leukemia in a patient with acute lymphocytic leukemia.

A diagnosis of acute lymphocytic leukemia (ALL) was made from a peripheral blood and bone marrow specimen from a 59-year-old woman. Typical-appearing lymphoblasts were positive for periodic acid-Schiff (PAS) reaction, but negative for peroxidase, Sudan black B (SBB) and non-specific esterase (NSE) stains. Lymphoblasts failed to form non-immune rosettes and had no surface membrane immunoglobulins. However, lymphoblasts exhibited an "Ia-like" membrane antigen and markedly stimulated allogeneic lymphocytes in a mixed lymphocyte reaction (MLR). These cytochemical and immunologic studies were considered characteristic of null-cell subtype of ALL. Thirteen months later, the peripheral blood and bone marrow specimens contained numerous myelomonoblasts characterized by a weak or negative PAS stain and strongly positive peroxidase, SBB, and NSE reactions. Electron micrographs of the bone marrow suggested that the majority of leukemic cells were myelomonocytic and a minority of cells were lymphoblasts. In addition, myelomonoblasts in liquid cultures appeared to differentiate into mature macrophages. These data suggest the development of acute myelomonocyte leukemia in a previous case of ALL.

Bone Marrow↗
PubMed1981

HLA antigens and childhood acute lymphocytic leukaemia.

HLA-A and -B antigens were determined for 94 children with acute lymphocytic leukaemia (ALL) and for 376 normal controls. Sixty-four of these 94 patients were typed for lymphocyte surface markers and 59 were defined as 'null cell' ALL. There was no difference in the distribution of the HLA-A or -B locus antigens between the control group and the entire group of patients with ALL or the 'null cell' subgroup. Patients with HLA-A9 determinants had a significant increase in early, first remission duration compared to patients without HLA-A9. This was particularly evident in the 'null cell' ALL subgroup. In addition, HLA-A9 appeared to be an independent factor affecting the length of first remission since there was no correlation between known prognostic factors such as patient age, sex or WBC and the presence or absence of the HLA-A9 antigen. Survival for the first 12-18 months was also greater in the HLA-A9 group than in the non-HLA-A9 population. Thus, the presence of HLA-A9 appears to be associated with some protective effect among patients with ALL.

Adolescent↗
PubMed1981

B lymphocyte function in B cell chronic lymphocytic leukaemia.

B-enriched lymphocyte populations from patients with chronic lymphocytic leukaemia (CLL) were compared to B-enriched lymphocyte populations from normal age-matched controls for their ability to stimulate a proliferative response and to generate cytotoxic cells in allogeneic mixed lymphocyte cultures (MLC). The proliferative responses of MLCs were less than normal when the stimulating cells originated from B cells of patients with CLL. The degree of stimulation provided by the B cells from the patients with CLL inversely correlated with the peripheral white cell count. Lymphocytes from patients providing a poor stimulatory signal in the MLC tended to have less "Ia-like" antigen than lymphocytes giving a moderate level of stimulation. B lymphocytes from patients with CLL which stimulated poorly in the MLC also failed to generate specific cytotoxic cells even when provided with a normal proliferative trigger. These data suggest that B lymphocytes from cases of CLL with markedly elevated leucocyte counts may have a diminished concentration of both "Ia-like" and serum defined antigens.

B-Lymphocytes↗