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Biomedical subjects

R Foa

Publications and source records attributed to R Foa.

At least 145 records · Page 8Linked to original sources
PubMed1982

Chronic T-cell leukaemias. III. T-colonies, PHA response and correlation with membrane phenotype.

The functional capacity of T lymphocytes from 28 cases of chronic T-cell leukaemia--T-CLL, T-PLL, T-LCL and Sézary syndrome--was evaluated in a T-colony forming system and in a PHA response assay. Reduced or absent T-colony growth was observed in 23 cases (82%) while in five the growth was normal. Although a good correlation was generally observed between colony formation and PHA transformation, in a few cases a low PHA response was accompanied by moderate colony growth and vice versa. Characterization of the leukaemic T lymphocytes using monoclonal antibodies (OKT series) indicates that cases with a helper/inducer phenotype (OKT4+) showed moderately reduced or near-normal T-colony numbers, whilst cases with a suppressor/cytotoxic phenotype (OKT8+)--confined to T-CLL in this study--had a very low or absent colony growth. The functional abnormalities reported here suggest that neoplastic T-cells with a helper/inducer phenotype show a low proliferative response in the assay systems used, although expressing mature T-cell characteristics. The low growth observed in T-CLL confirms that cells with a suppressor/cytotoxic phenotype form few T-cell colonies.

Cell Division↗
PubMed1982

Reduced T-colony forming capacity in B-chronic lymphocytic leukaemia.--II. Correlation with clinical stage and findings in B-prolymphocytic leukaemia.

The T-colony forming capacity of T-lymphocytes from 33 cases of B-chronic lymphocytic leukaemia (B-CLL) and five of B-prolymphocytic leukaemia (B-PLL) was studied. An absent or reduced (less than 50) colony growth was observed in 21 of the 33 B-CLL and in four of the five B-PLL studied. Seven of the nine stage 0 patients (77.7%) according to Rai's clinical staging) gave rise to more than 50 colonies, compared with five out of 24 (20.9%) in stages I-IV patients. Furthermore, the mean number of colonies was significantly (p less than 0.01) higher in stage 0 patients (57 +/- 33.6), compared with more advanced stages (22 +/- 29.9). Since in normal peripheral blood, T-colony formation appears to be a property of T mu lymphocytes, and T gamma cells are significantly increased in B-PLL and B-CLL, mainly in advanced disease, the T-colony growth was correlated with the percentage of T gamma cells. Despite a negative trend, a statistical correlation was not observed. Our findings are suggestive of a functional defect of the T-cell population in the majority of cases of B-CLL, with a partial sparing in stage 0 patients. This abnormality, apparently unrelated to the T mu: T gamma ratio, is probably due to an intrinsic defect of the T mu cell population.

B-Lymphocytes↗
PubMed1982

Production of immunoreactive calcitonin by myeloid leukaemia cells.

Raised plasma levels of immunoreactive human calcitonin (i-HCT) have been found in patients with chronic granulocytic leukaemia (CGL) in chronic phase and myeloblastic transformation and in patients with acute myeloid leukaemia at presentation and in relapse. In CGL levels were significantly higher in myeloblastic transformation than in the chronic phase. Leukaemia cells were cultured in a short-term liquid culture system in which little cell proliferation occurs and in a two layer blast-cell colony system which permits blast-cell proliferation. i-HCT was identified in supernatant media from cells cultured in both systems but levels were substantially higher in media collected from cells cultured in the latter system. These results suggest that i-HCT is synthesized by proliferating blast cells.

Calcitonin↗
PubMed1982

Characterization of T-lymphocyte subsets in hairy-cell leukaemia (HCL) by monoclonal antibodies: comparison with Fc gamma, Fc mu receptors and correlation with disease activity.

T lymphocytes from 22 patients with hairy-cell leukaemia (HCL) were assessed on the basis of their ability to bind the Fc receptors for IgM (T mu) or IgG (T gamma), and by the capacity to react with OKT monoclonal antibodies. T-cell subsets defined by the presence of Fc receptors for IgM or IgG showed an overall increase in the proportion of T gamma cells and a non-significant decrease of T mu cells, regardless of the clinical state of the disease. Results with monoclonal antibodies showed that in patients with HCL in clinical remission T-cell subsets were normally balanced, while in patients with active disease the distribution and absolute number of T-cell subpopulations appeared markedly impaired, with a significant increase of OKT8 positive cells (suppressor/cytotoxic) and a significant reduction of OKT4 positive cells (helper/inducer) compared both with active disease patients and with normal controls. The OKT4+/OKT8+ ratio was also significantly reduced in patients with active disease compared with those in clinical remission and with controls (0.96 v 1.63 and v 1.94, respectively). Our findings confirm the heterogeneity of T-cell subset positivity defined by monoclonal antibodies and by Fc mu and Fc gamma receptors and suggest that in patients with HCL the distribution of OKT4 and OKT8 positive cells is closely correlated to the clinical state of the disease.

Antibodies, Monoclonal↗
PubMed1982

Reduced T lymphocyte colonies in B chronic lymphocytic leukaemia. III. Evidence of a proliferative abnormality of the T helper cell population.

The functional capacity of T and T mu (helper) cells from six untreated cases of B cell chronic lymphocytic leukaemia (B-CLL) was assessed in a double layer T colony forming assay. T lymphocytes from B-CLL originated few T colonies compared with normal T cells (35 +/- 25.9 vs 118 +/- 33.7). After enrichment of the T mu cells, colony growth in B-CLL was still reduced compared with the same cell fraction from normal controls (55 +/- 28.6 vs 90 +/- 35.6). When analysed independently, the three B-CLL cases with the lowest colony forming capacity, after enrichment of the T mu cells showed only a slight increase in growth, still well below the normal range. The two cases with normal or near normal colony growth, gave rise to similar results after T mu enrichment, indicating that, as in normal blood, B-CLL residual T colony formation is a property of the T mu cell population. In only one case was a significant increase and a normalization of the colony growth observed. It is suggested that the functional abnormality of T lymphocytes frequently observed in B-CLL patients, is not due only to the marked imbalance in T cell subsets, with a significant increase in T suppressor/cytotoxic cells and a reduction in T helper/inducer cells, but in many cases to an intrinsic defect of the T mu (helper/inducer) cell population.

B-Lymphocytes↗
PubMed1981

Increase in T gamma lymphocytes in B-cell chronic lymphocytic leukaemia. II. Correlation with clinical stage and findings in B-prolymphocytic leukaemia.

The proportion of T gamma and T mu lymphocytes was studied in 40 cases of B-chronic lymphocytic leukaemia (B-CLL) and six of B-prolymphocytic leukaemia (B-PLL). The significant increase in T gamma cells, previously reported in two small B-CLL series, was confirmed and shown to be directly correlated with the clinical stages of the disease (P less than 0.01 to less than 0.001). The normal T mu:T gamma ratio (2.3:1) was reversed in B-CLL (1:1.4) and B-PLL (1:1.9). The proportion of T mu cells was decreased but was not related to stage. Our findings suggest that the increase in T gamma cells may be responsible for the hypogammaglobulinaemia of B-CLL. This is supported by two sets of observations. First, serum Ig levels were more often normal in cases in Stages 0 and I than in Stages II-IV (P less than 0.05), while the levels of two or three Ig classes were below normal in Stages II-IV twice as frequently. Secondly, splenic irradiation in one case was followed by a fall in the absolute number of T gamma lymphocytes, a reversion to normal of the T mu: T gamma ratio and an improvement in serum Ig levels. Thus, the imbalance in ;the regulatory T-cell subsets may provide an important clue to understand the pathogenic mechanism of the immunodeficiency in the chronic B-cell leukaemias.

B-Lymphocytes↗
PubMed1981

Inhibitory effect of cyclosporin A on peripheral blood and bone marrow T lymphocyte colony formation.

The effect of cyclosporin A on the formation of T lymphocyte colonies from human peripheral blood and bone marrow was tested using a double-layer technique. A moderate inhibition (27%) was observed on peripheral blood lymphocytes with concentrations of 0.1 microgram/ml of the drug; this increased to 57% with 1 microgram/ml and to almost 70% with 10 microgram/ml. Bone marrow cells were less sensitive to cyclosporin A. This was more evident at the lowest concentration of the drug (0.1 microgram/ml), with which a 14% inhibition was found. Higher concentrations (1--10 microgram/ml) produced 37 and 56% inhibition respectively. Overnight incubation with the drug followed by repeated washing of the cells did not influence colony growth. E-rosette formation was also not affected by cyclosporin A. The apparent greater sensitivity to the drug of peripheral blood than bone marrow T lymphocytes, possibly related to a different distribution of T colony-forming cells or of T lymphocyte subsets, may have some bearing on the clinical application of cyclosporin A in the prevention and treatment of graft-versus-host disease in man.

Bone Marrow↗
PubMed1980

Cell surface and enzyme markers of cord blood lymphocytes.

Human cord blood (CB) lymphocytes were studied with several markers for T- and B-cells and the results compared with those of adult peripheral blood (PB) samples. The proportion of E-rosettes was significantly lower in CB (mean 24.7+/-13.5 SD) than in PB (67.5+/-7.3 SD). Treatment with neuramidase produced a marked increase in the proportion of E-rosettes in CB (mean 47 +/-13.9 SD), still below the PB values. The proportion of CB lymphocytes showing block positivity with alpha-naphthyl-acetate-esterase correlated closely with the percentage of E-rosettes in neuraminidase treated cells. The percentage of H-rosettes (human RBC) was significantly higher in CB (7.2+/-6.0) than in PB (3.2+/-1.6 SD). Re-rosetting experiments showed that in CB about 30% of the E-positive cells formed H-rosettes, in contrast to 5% in PB. These findings indicate that in CB the real number of T-lymphocytes is higher than shown by conventional E-rosette formation. The proportion of B-lymphocytes, tested by surface immunoglobulins and by rosette formation with mouse RBC (M-rosettes), was similar in CB and in adult PB. A slight increase in cells with IgM on the surface was found in CB. The overall proportion of lymphocytes with negative B and T markers in CB is three times greater than in adult PB. Levels of the enzyme terminal deoxynucleotidyl transferase were marginally increased in CG; in two out of 41 samples the levels were above those found in normal bone marrow. CB may be a suitable model for the study of lymphocyte subsets with negative B and T markers in man.

Adult↗
PubMed1980

Increase in T gamma lymphocytes in B-cell chronic lymphocytic leukaemia.

A significant increase in the proportion (mean 38% +/- 9.3 SD) and absolute number of T gamma (suppressor) lymphocytes was observed in 13 patients with chronic lymphocytic leukaemia (CLL) compared with 20 normal controls (mean 19% +/- 6.5). Conversely, the proportion of T mu (helper) lymphocytes was lower in CLL (mean 27% +/- 9.3) than in the controls (mean 40% +/- 4), although the absolute numbers were normal or increased. It is suggested that an imbalance of T-lymphocyte subsets controlling B-lymphocyte differentiation may be relevant in the pathogenesis of CLL or some of its associated features.

B-Lymphocytes↗
PubMed1980

Inhibition of T-lymphocyte colony formation by inhibitors of mitochondrial protein synthesis.

A double layer technique which requires an underlayer of peripheral blood leucocytes, in addition to phytohaemmagglutinin (PHA) in the overlayer, to obtain good T-lymphocyte colony formation, was used to assess the effect of two inhibitors of mitochondrial protein synthesis, chloramphenicol and ethidium bromide. A significant inhibition of the colony growth of peripheral blood T lymphocytes was observed when either of the drugs was incorporated in the underlayer. The inhibitory effect was always smaller (c. 50%) when the drugs were added to the overlayer. These findings point to the existence of a T-lymphocyte colony stimulating factor(s), released mainly by the leucocyte-rich underlayer and essential for T-colony formation, the production of which is inhibited by these mitochonrial inhibitors.

Chloramphenicol↗
PubMed1980

Evidence that T colony formation is a property of T mu (helper) lymphocytes.

The T-colony-forming capacity of different T lymphocyte subsets was studied in normal peripheral blood. Unfractionated lymphocytes (after 'Lymphoprep' separation) gave rise to a mean of 150 +/- 27 . 7 s.d. T colonies per 1 x 10(5) cells, while purified T lymphocytes by sheep RBC rosetting formed 110 +/- 32 . 2 colonies. Two subpopulations of T lymphocytes were further isolated according to the presence of Fc receptors for IgG (T gamma) or IgM (T mu) by ox RBC rosetting. T gamma cells were found to have a very low or absent T colony-forming capacity (23 +/- 26 . 2), while T mu cells produced normal colony numbers (106 +/- 28 . 4). Co-culture experiments showed that T gamma cells do not inhibit the T colony growth of normal T cells in our system. Our findings indicate that in human peripheral blood not all T lymphocytes are capable of forming T colonies and that this property is confined to the T mu (helper) lymphocyte subset.

Cell Separation↗
PubMed1980

T-lymphocyte colonies in human cord blood.

The capacity of human cord blood (CB) lymphocytes to form T-colonies was studied with a double layer technique. The mean number of colonies in CB was 91 +/- 70.5 SD (X 10(5) cells), significantly lower than in adult blood, mean 182 +/- 58.0 (X 10(5). In 28 of the 50 CB samples tested the colony numbers were below the normal range for adult lymphocytes. There was no direct correlation between number of colonies and percentage of E-rosette-forming cells in CB. Some CB samples with a high proportion of E-rosettes formed few T-colonies, suggesting that not all E-rosette positive cells are capable of producing T-colonies. On the other hand, some CB samples with a low proportion of E-rosettes formed normal numbers of T-colonies. Purification of two populations of T-cell enriched and T-cell depleted lymphocytes confined the T-colony growth in CB, as in adult blood, to the former fraction, excluding that T-colonies could be obtained from E-rosette negative lymphocytes. This indicates that, from birth onwards, T-lymphocyte colonies originate from E-rosette positive cells. Whether the low growth observed in CB results from lack of maturation of T-lymphocytes or from the presence of specific subsets of T-lymphocytes is not clear at the present time.

Colony-Forming Units Assay↗
PubMed1979

Immunoreactive calcitonin in leukaemia.

A radioimmunoassay was used to measure concentrations of immunoreactive human calcitonin (HCT) in plasma and leucocytes from patients with various leukaemic and myeloproliferative disorders. Plasma immunoreactive HCT concentrations were increased in 32 out of 33 patients with chronic granulocytic leukaemia (CGL) and in all eight patients with acute myeloid leukamia (AML) at presentation or in relapse. Out of 11 patients with other myeloproliferative disorders, eight had increased plasma immunoreactive HCT concentrations. Buffy-coat-cell extracts and culture media from peripheral leucocytes of patients with CGL also contained increased immunoreactive HCT concentrations. In contrast, plasma from patients with chronic lymphocytic leukaemia, acute lymphoblastic leukaemia, and AML in remission had low or undetectable immunoreactive HCT concentrations. Increased plasma and cellular concentrations of immunoreactive HCT may be a consequence of abnormal proliferation of myeloid cells and might prove to be valuable in predicting relapse in patients with myeloid leukaemias.

Calcitonin↗
PubMed1979

Alkaline phosphatase in human lymphocyte subpopulations.

The levels of membrane alkaline phosphatase have been measured on different lymphocyte fractions from human peripheral blood separated on bovine serum albumin discontinuous gradients. The peak in enzyme activity was observed in a non-T-, non-B-cell fraction, rich in "null" lymphocytes; the lowest values were found in the fraction with the highest proportion of T-cells.

Alkaline Phosphatase↗
PubMed1979

Clinical staging and immunological findings in chronic lymphocytic leukemia.

Several immunological markers were tested in 52 untreated cases of chronic lymphocyte leukemia (CLL) to see whether their frequency differed according to the clinical stage in Rai's system. The leukemic cells in all cases had B-cell features as shown by monoclonal immunoglobulins on the cell surface (SmIg) and/or a high percentage of mouse RBC (M)-rosettes. Of the two B-cell markers, the M-rosette test was the more consistently positive. The frequency of these markers did not correlate with clinical staging. The percentage of T-lymphocytes, low in all cases, was found to correlate inversely with the lymphocyte counts, which were higher in advanced stages. The absolute number of T-lymphocytes was above normal in most cases, but did not relat to staging. At least one of the serum Ig, most commonly IgA, was decreased in 87% of cases. Low Ig were slightly less common in Stages 0-I than in advanced stages (II-IV). The above features were also examined in two groups of CLL patients: with stable (9) or progressive (16) disease. The only difference observed between the two groups was that surface IgM only was present in 1 of the 9 stable cases as compared to 9 of the 16 progressive ones. Our findings do not support the suggestions that surface IgM is a feature of a benign form of CLL or that the absolute number of T-lymphocytes correlates with prognosis.

Adult↗