Distribution of complement receptors on human normal and malignant mononuclear cells

Mononuclear cells from normal human subjects and patients with chronic lymphocytic leukemia (CLL), chronic lymphosarcoma cell leukemia (LCL), and hairy cell leukemia (HCL) were labeled with fluoresceinated, purified human C3b (FI-C3b) and analyzed using the fluorescence- activated cell sorter (FACS). FI-C3b labeled 17.6% +/- 6.0% of peripheral blood mononuclear cells (PBM) from 20 normal subjects, which, when separated by the FACS, consisted of B lymphocytes and approximately 5% monocytes. Analyses in which either monocytes or B lymphcoytes were excluded from consideration demonstrated that both these cell types were labeled by the FI-C3b with a heterogeneous distribution of fluorescence intensity, indicating either heterogeneity of CR density or variable avidity of individual CR for the FI-C3b. FACS profiles of PBM ( < 5% monocytes) from 14 of 15 patients with CLL showed a homogeneous distribution of very low fluorescence intensity, with > 60% of the cells being slightly more fluorescent than unlabeled controls. This low, homogeneous distribution of fluorescence is strikingly similar to profiles of CLL cells labeled with anti-Ig reagents and suggests homogeneity of low CR density and/or avidity. Similarly, CR+ mononuclear cells from five patients with HCL and three patients with LCL displayed more homogeneous FI-C3b labeling than normal CR+ PBM. Homogeneity of FI-C3b binding to CLL, LCL, and HCL cells further supports the concept for a clonal origin for these disorders.     

Increased ascorbic acid content in chronic lymphocytic leukemia B lymphocytes.

Human lymphocyte extracts analyzed by high-performance liquid chromatography reveal a major UV-absorbing peak that was shown to be ascorbic acid by spectral, chemical, and enzymatic criteria. Because this peak appeared very prominent in the elution profile of chronic lymphocytic leukemia (CLL) lymphocyte extracts, we measured the ascorbic acid content in lymphocytes from the blood of normal subjects and untreated patients with chronic lymphocytic leukemia. A significantly higher concentration of 111 +/- 15.3 nmol per 10(8) cells (mean +/- SEM) was found in CLL lymphocytes than in normal blood lymphocytes, which contained 42.2 +/- 3.3 nmol per 10(8) cells. Selective enrichment with B and T cells showed that this difference was limited to the chronic lymphocytic leukemia B cell, which had a 5- to 15-fold higher content of ascorbic acid than normal B cells had. In contrast, the ascorbic acid level was similar in normal and CLL T cells. The very high ascorbic acid content provides the chronic lymphocytic leukemia B cell with a reducing substance that could react with oxidants or free radicals.     

Increased tyrosine protein kinase activity in hairy cell and monocytic leukemias.

Tyrosine protein kinases (TPK) help regulate cellular growth and differentiation. Several proto-oncogenes encode for protein products with associated tyrosine kinase activity. An assay for TPK activity was performed in cell extracts using a synthetic peptide substrate and [32P] adenosine triphosphate (ATP). TPK activity was elevated in K-562 cells, which possess an amplified c-abl oncogene, compared to normal blood mononuclear cells (K-562 = 9.37 +/- 1.72 [mean +/- standard deviation] pmol ATP/10(6) cells/min; normal = 1.14 +/- 0.46, p less than 0.01). TPK activity was measured in peripheral blood mononuclear cells from patients with hairy cell leukemia (HCL), myelomonocytic leukemia (MOL), acute myeloblastic leukemia (AML), and chronic lymphocytic leukemia (CLL). In patients with clinically active disease, elevated TPK activity was measured in mononuclear cells from five HCL patients (range 3.76-24.15) and from seven MOL patients. These elevated levels appeared to parallel disease activity, as low levels of TPK activity were measured in patients with inactive (treated) disease. Low levels of TPK were measured in mononuclear cells from active AML and CLL patients. Elevated TPK levels in patients with HCL and MOL may reflect the overexpression of a proto-oncogene or increased growth factor activity in immature or rapidly dividing leukemic cells. Serial TPK levels in HCL and MOL patients correlated with change in disease activity.     

Intracellular and serum levels of aldolase activity in B chronic lymphocytic leukemia.

Intracellular and serum activities of aldolase (ALS) were biochemically determined in lymphocyte subpopulations from normal subjects and patients with B-chronic lymphocytic leukemia (B-CLL). Aldolase activity was significantly lower in T cells of CLL than in normal T cells (2.9 +/- 1.5 vs. 4.7 +/- 2.1 Sigma Units (SU)/6 x 10(6) cells, p < 0.05). The aldolase activity also was significantly (p < 0.001) lower (3.1 +/- 1.9 SU/6 x 10(6) cells) in CLL B lymphocytes than in normal B lymphocytes (18.1 +/- 6.5 SU/6 x 10(6) cells). Moreover, the serum levels of ALS in all patients with B-CLL were higher than that in normal subjects (8.1 +/- 5.8 vs. 2.2 +/- 0.8 SU/ml, p < 0.02). Our findings demonstrate that T lymphocytes from patients with B-CLL display enzyme activity different from that of normal T cells. This may reflect the abnormal maturity of the residual T cell population in B-CLL.     

Homeostatic chemokines drive migration of malignant B cells in patients with non-Hodgkin lymphomas

This study investigated the role of several chemokines and their receptors on malignant B lymphocytes recovered from 13 patients with chronic lymphocytic leukemia (CLL), 9 with hairy cell leukemia (HCL), 5 with mantle cell lymphoma (MCL), 5 with marginal zone B-cell lymphoma (MZL), 6 with small lymphocytic lymphoma (SLL), and 5 with follicular cell lymphoma (FCL). Flow cytometry analysis demonstrated that CXCR4 and CXCR5 were expressed on all malignant and normal B cells. Considering CC receptors, CCR1 was expressed in 70% of patients with CLL and 40% of those with HCL but was lacking in patients with MCL, MZL, SLL, and normal B cells. CCR2 showed a heterogeneous pattern of expression. CCR3 was found in almost all patients with CLL and in the majority of those with HCL, whereas it was usually lacking in patients with MZL and SLL and in healthy subjects. CCR5 was expressed in patients with HCL and MCL. Migration assays showed that different chemokines, mainly CXCL12 and CXCL13, are able to trigger migration of malignant B lymphocytes. Some of these chemokines induce calcium mobilization. These data indicate that different patterns of chemokine receptor expression identify different malignant B-cell subsets and that these receptors are functional and might play a role in malignant B-cell circulation.     

Monoclonal antibody-defined T-cell subsets in hairy-cell leukaemia

In 17 tests in 14 patients with hairy-cell leukaemia (HCL), peripheral blood Leu 2a+ and 3a+ suppressor and helper cells were present in normal mean percentage (3a+ 63 +/- 15%, normal 64 +/- 8%; 2a+ 39 +/- 16%, normal 34 +/- 8%), absolute (3a+ 0.8 +/- 0.4 x 10(9)/1, normal 0.6-1.4 x 10(9)/1; 2a+ 0.5 +/- 0.4 x 10(9)/1, normal 0.2-0.6 x 10(9)/1), and relative (3a+/2a+) (2.2 +/- 1.3, normal 1.9 +/- 0.7) numbers. In all the 9 untreated patients, 3a+ helper cells were normal or increased in percentage numbers, while 2a+ suppressor cells were normal or slightly reduced. It is suggested that these data explain, at least in part, the lack of immuneparesis of HCL as compared with chronic lymphocytic leukaemia (CLL) which is consistently associated with immuneparesis and an excess of Leu 2a+ suppressor cells. In individual splenectomised patients, some variations in Leu 2a+ and 3a+ numbers were observed, and it is suggested that the spleen, known to be important in the natural history of HCL, may have an influence on peripheral T-cell subsets. Although HCL is clearly shown to differ from CLL and myeloma regarding T-cell subset numbers, the fundamental mechanism underlying this difference remains unknown.     

Kinetic studies on lymphocytes labelled with indium 111-oxine in patients with chronic lymphocytic leukaemia

The kinetics of 111Indium-oxine-labelled autologous blood lymphocytes were studied in normal subjects and 10 patients with chronic lymphocytic leukaemia (CLL). In both normal and leukaemic subjects, intravascular survival of lymphocytes was characterized by two exponential decreases, the first being a rapid one and the second slow phase. T 1/2 of the second phase for normal T lymphocytes (52.0 +/- 3.2 h: mean +/- SEM) was longer than that for B lymphocytes (31.6 +/- 2.8 h). T 1/2 of the second phase in patients with CLL was 15.1 to 192.6 h, which correlated well with the clinical stage of CLL by the Rai classification. Body surface scanning revealed prominent splenic accumulation of labelled cells in normal individuals and patients with CLL. Lymph node visualization was recognized in all patients with T-cell CLL; however, there was no visualization in 8 of the 9 patients with B-cell CLL. The longer survival time and splenic and lymph node visualization suggest that an expansion of the extravascular lymphocyte pool may be important in the pathophysiology of CLL.     

Surface immunoglobulin density on human peripheral blood mononuclear cells.

The densities of surface immunoglobulin (slg) on peripheral blood mononuclear cells (PBM) of normals and patients with chronic lymphocytic leukemia (CLL), chronic lymphosarcoma cell leukemia (LCL), and hairy cell leukemia (HCL) were analyzed using the fluorescence-activated cell sorter (FACS). PBM were labeled with fluorescein conjugates of F(ab')2 fragments of affinity chromatography-purified anti-Fab or class-specific anti-mu, anti-delta, anti-gamma, or anti-alpha. Histograms of relative cell fluorescence, rems of relative cell fluorescence, reflecting slg density, were prepared with the FACS. Anti-Fab-labeled normal PBM demonstrated a homogeneous low-density peak that when separated by the FACS and analyzed cytochemically consisted predominantly of monocytes, whereas brighter-staining cells were predominantly lymphocytes. Anti-mu and anti-delta labeled 9.0% and 8.5% of normal PBM, respectively, the slg+ cells being virtually all lymphocytes. Cells labeled by anti-gamma exhibited low homogeneous slg density and consisted of more than 80% monocytes. No normal or leukemic PBM were labeled by anti-alpha. All slg-positive cells (less than 5% monocytes) from 12 of 13 patients with CLL had very low homogeneous densities of slg and bore slgM, Whereas cells from 9 of 13 and 2 of 13 patients bore slgD and slgG, respectively. Similarly, PBM from 2 patients with HCL exhibited low and homogeneous densities of algM, slgD, and slgG, whereas those from a third patient bore only slgG. By contrast, the density of slgM and PBM derived from 3 patients with LCL was very high; slgD and slgG densities varied from very high to undetectable in these patients. The different homogeneous densities of slg on peripheral blood lymphocytes from patients with CLL, HCL, and LCL suggest that these diseases represent malignant transformation of different B-lymphocyte subpopulations.     

An antigen common to chronic lymphocytic and hairy cell leukemia cells not shared by normal lymphocytes or by other leukemic cells

Rabbit xenoantisera and mouse monoclonal antibodies prepared against human chronic lymphocytic leukemia (CLL) B cells were found to react against a single polypeptide chain with a mol wt of 69 kd found on leukemic cells of all CLL (N = 40) and B type hairy cell leukemia (HCL) patients (N = 9) examined. This common CLL-associated antigen (cCLLa) was not detectable on circulating T or B lymphocytes, thymocytes, lymph node and splenic lymphocytes, or bone marrow leukocytes from normal persons. In addition, the cCLLa was not detectable on cultured T or B lymphoblastoid cell lines or on malignant cells from other forms of lymphocytic or myelocytic leukemia. Non-Hodgkin's lymphoma cells also failed to express the antigen. Autologous cultured lymphoblastoid cell lines were established from residual normal B cells from a CLL patient whose cells were used to generate one of the antisera. Absorption of the antibody with these cultured polyclonal B cells did not affect the anti-CLL activity, which suggests that the cCLLa is not HLA related. Unlike the T cell differentiation complex gp65-71, the cCLLa was not expressed on fetal or cord blood lymphocytes or on mitogen-stimulated normal lymphocytes and was distinct from the antigen recognized by the LEU-1 antibody in spite of their similar mol wt. The cCLLa was also determined to be unrelated to the human T cell leukemia lymphoma virus (HTLV-1). One of the monoclonal antibodies generated against the cCLLa was a complement binding IgG which exhibited highly selective cytotoxic activity against 100% of cells bearing the cCLLa. Such an antibody might prove clinically useful in early diagnosis and treatment of CLL and HCL.     

Serum transferrin receptor measurements in hematologic malignancies

An enzyme-linked immunosorbent assay using specific monoclonal antibodies was used to measure circulating transferrin receptor (TR) in 87 patients with various hematologic malignancies. The mean serum TR was significantly elevated in patients with myeloproliferative disorders (15.47 +/- 12.54 micrograms/ml), whereas there were no differences in chronic granulocytic leukemia (7.89 +/- 3.56 micrograms/ml), myelodysplastic disorders (9.25 +/- 4.73 micrograms/ml), and acute nonlymphocytic leukemia (3.85 +/- 3.50 micrograms/ml) as compared to normal (5.63 +/- 1.42 micrograms/ml). Among patients with lymphoproliferative disorders, the mean level was normal in lymphoma (5.73 +/- 2.59 micrograms/ml), multiple myeloma (5.47 +/- 1.31 micrograms/ml), and hairy cell leukemia (7.04 +/- 3.69 micrograms/ml). The serum TR was significantly elevated in chronic lymphocytic leukemia (CLL; 14.17 +/- 12.29 micrograms/ml), and the serum levels reflected the clinical stage of the disease. These findings suggest that serum TR measurement may provide a useful laboratory index of disease activity in certain disorders such as CLL, whereas it most likely reflects the intensity of erythropoiesis in the remaining hematological disorders that were evaluated in this study.     

The binding of ouabain to normal and chronic lymphocytic leukemic lymphocytes

The binding of the cardiac glycoside, ouabain, to cells had been used to quantify the number of active cation pumps. In this study, lymphocytes were incubated with 3H-ouabain and the equilibrium binding analyzed for the maximal number of specific binding sites. Lymphocytes from normal peripheral blood bound 44,200 +/- 9920 molecules/cell, compared with 29,200 +/- 8370 molecules/cell for the lymphocytes of chronic lymphocytic leukemia (CLL) subjects. This difference was significant (p less than 0.01) and did not reflect a lower number of sites on B cells than T cells, since B-cell-enriched lymphocytes from normal peripheral blood showed the same ouabain binding characteristics as the standard T-cell-rich preparation. Although monocytes bind threefold more ouabain than lymphocytes, the small monocyte contamination (3.0%) in normal lymphocyte preparations could not account for the difference between normal and CLL. The fewer ouabain binding sites on CLL lymphocytes may reflect both their smaller size (by 10%) and lower mitotic activity compared with lymphocytes from normal peripheral blood.     

Specific receptors for phorbol diesters on freshly isolated human myeloid and lymphoid leukemia cells: comparable binding characteristics despite different cellular responses

Freshly isolated human leukemia cells have been shown in the past to display varying in vitro responses to phorbol diesters, depending on their cell type. Specific receptors for the phorbol diesters have been demonstrated on numerous different cells. This study was designed to characterize the receptors for phorbol diesters on leukemia cells freshly isolated from patients with different kinds of leukemia and to determine if differences in binding characteristics for tritium-labeled phorbol 12,13-dibutyrate (3H-PDBu) accounted for the different cellular responses elicited in vitro by phorbol diesters. Cells from 26 patients with different kinds of leukemia were studied. PDBu or phorbol 12- myristate 13-acetate (PMA) caused cells from patients with acute myeloblastic leukemia (AML), acute promyelocytic (APML), acute myelomonocytic (AMML), acute monocytic (AMoL), acute erythroleukemia (AEL), chronic myelocytic leukemia (CML) in blast crisis (myeloid), acute undifferentiated leukemia (AUL), and hairy cell leukemia (HCL) (n = 15) to adhere to plastic and spread. However, they caused no adherence or spreading and only slight aggregation of cells from patients with acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), or CML-blast crisis (lymphoid) (n = 11). All leukemia cells studied, irrespective of cellular type, displayed specific receptors for 3H-PDBu. The time courses for binding by all leukemia types were similar, with peak binding at 5-10 min at 37 degrees C and 120 min at 4 degrees C. The binding affinities were similar for patients with ALL (96 +/- 32 nM, n = 4), CLL (126 +/- 32 nM, n = 6), and acute nonlymphoid leukemia (73 +/- 14 nM, n = 11). Likewise, the numbers of specific binding sites/cell were comparable for the patients with ALL (6.2 +/- 1.3 X 10(5) sites/cell, n = 4), CLL (5.0 +/- 2.0 X 10(5) sites/cell, n = 6), and acute nonlymphoid leukemia (4.4 +/- 1.9 X 10(5) sites/cell, n = 11). Thus, the differing responses to phorbol diesters of various types of freshly isolated leukemia cells appear to be due to differences other than initial ligand-receptor binding.     

Phorbol ester induces abnormal chronic lymphocytic leukemia cells to express features of hairy cell leukemia

We have investigated the relationship between chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), and different normal B cell subsets: Mrbc+, T1+ and slgM+ tonsil cells; germinal center; mantle zone; and peripheral blood B lymphocytes. Both malignant and normal cells were incubated in vitro with the phorbol ester 12-O-tetradecanoyl- phorbol-13-acetate (TPA) for 72 hours and the morphology, cytochemical profile, and surface markers were evaluated. The results show that CLL cells TPA-induced become indistinguishable from HCL by four independent criteria: the morphology; the cytoplasmic tartrate resistant acid phosphatase (TRAP) enzyme activity; the membrane positivity with anti- Leu M5 (SHCL3); and anti-Tac monoclonal antibodies which, in the uninduced state, react only with HCL. The features of TRAP and Tac positivity are also expressed (though in variable degree) by different normal B cell populations activated with TPA or pokeweed mitogen (PWM). It is concluded that HCL might represent an aberrantly activated variant of CLL (or of a CLL-related disorder).     

Immunoregulation of B lymphocyte colony formation by T cell subsets in patients with chronic lymphocytic leukemia

Normal B lymphocytes are activated, proliferate, and then differentiate into plasma cells and secrete immunoglobulin (Ig). We have reported that chronic lymphocytic leukemia (CLL) T4 cells help and CLL T8 cells lack suppressor effects on Ig synthesis by normal B cells (Blood 62:767, 1983). We have now explored the earlier phase, proliferation, using B cell colony formation; in semisolid media. B lymphocyte colonies from normal individuals and from patients with CLL were grown in 0.3% agarose overlayed with T cells or T cell subsets and the B cell mitogen staphylococcal protein A. Enriched T cells, OKT4 or OKT8, were obtained either by sheep erythrocyte rosettes or depletion of OKT8 or OKT4 cells by monoclonal antibody or complement, respectively. Twenty thousand B cells from normal subjects yielded 65 +/- 9, 64 +/- 7, and 19 +/- 6 colonies with autologous unfractionated T-, OKT4-, or OKT8- positive cells, respectively. This compared to 29 +/- 11, 81 +/- 11, and 15 +/- 4 colonies from patients with CLL with added autologous unfractionated T-, OKT4-, or OKT8-positive cells. To determine whether the fewer number of colonies in both normal subjects and patients with CLL with OKT8-positive cells was due to suppression or lack of help, the number of OKT4-positive cells was held constant, and OKT8-positive cells were added in increasing numbers. No suppression of colony formation could be demonstrated. Furthermore, the addition of increasing numbers of concanavalin A (Con A)-activated OKT8-positive cells did not suppress colony formation. These results suggest that the CLL T cell subsets behave in a functionally similar manner to normal T cell subsets, namely, (1) that normal and CLL B cell colony growth is helped by OKT4 cells; and (2) in contrast to immunoglobulin secretion by B cells, neither normal nor CLL OKT8 cells, unstimulated or activated by Con A, suppress B cell colony growth.     

Lactic dehydrogenase in normal and leukemia lymphocyte subpopulations: evidence for the presence of abnormal T cells and B cells in chronic lymphocytic leukemia

Lactic dehydrogenase (LDH) was quantitated and the isozyme pattern studied in lymphocyte subpopulations from normal people and patients with chronic lymphocytic leukemia (CLL). Normal T lymphocytes differed from normal B lymphocytes in having greater total LDH activity (597.2 versus 252.1). Total LDH activity in CLL T cells (347.1) was lower than normal T cells., but not significantly different than normal B cells. Total LDH activity in CLL B cells (124.6) was lower then normal B cells and normal T cells. The isozyme pattern of normal T lymphocytes showed a higher activity in the LDH-1 band (26.7% versus 5.4%) but showed a lower activity in LDH-5 band (4.3% versus 16.3%) compared to normal B cells. Chronic lymphocytic leukemia T cells could be distinguished from CLL B cells by a high LDH-5 band (22.3% versus 7.6%) and from normal T cells by a high LDH-5 band (22.3% versus 4.3%) and a low LDH-1 band (7.3% versus 26.7%). CLL B cells could be distinguished from normal B cells by a low LDH-5 band (7.6% versus 16.3%). Thus, the LDH isozyme pattern distinguishes normal T lymphocytes from normal B lymphocytes, and normal T and B lymphocytes from CLL T and B lymphocytes.     

Relationship of the clinical response and binding of recombinant interferon alpha in patients with lymphoproliferative diseases

Patients with hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL) were treated with recombinant interferon alpha A (rIFN- alpha A). The binding of iodinated recombinant interferon-alpha to baseline samples of peripheral blood mononuclear cells (PBMCs) from the leukemia patients was compared with clinical responsiveness to rIFN- alpha A. HCL patients (8/10) responded to rIFN-alpha A therapy, whereas none (0/10) of the CLL patients studied responded. The PBMCs from the eight responsive HCL patients bound approximately twice as much iodinated interferon as the PBMCs from nonresponsive CLL patients. This difference was due to more high-affinity receptors per cell with no difference in the affinity of the interferon-receptor interaction. However, because PBMCs from HCL patients were larger than PBMCs from CLL patients, the cell surface receptor density was similar. The leukemic cells from one of the two nonresponsive HCL patients bound iodinated interferon similarly to the cells from the responsive HCL patients, whereas the leukemic cells from the other nonresponsive HCL patient bound considerably less. The rapidity of response of the HCL patients did not correlate with the level of binding of iodinated interferon. Our results suggest that the absolute number of interferon receptors per cell may be only one of several important parameters in the response to rIFN-alpha A therapy, and that the responsiveness of a particular lymphoproliferative disease or a particular patient to rIFN- alpha A therapy cannot be predicted or explained solely by the degree of interaction between IFN and its cell surface receptor.     

Lymphocyte surface immunoglobulin density and immunoglobulin secretion in vitro in chronic lymphocytic leukemia (CLL)

Lymphocyte surface immunoglobulin (SIg) and immunoglobulin (Ig) secretion were studied in 14 patients with chronic lymphocytic leukemia (CLL) and 12 healthy subjects. The determination of SIgM-bearing (SIgM+) cells by immunofluorescent staining and the quantification of SIgM by radioimmunoassay (RIA) permitted the calculation of the SIgM density. In 12 normal subjects the percentage of SIgM+ cells averaged 8% (range 4%-12%) and the SIgM density 10.2 ng antigenic equivalent/10(6) SIgM+ cells (SD 4.3). In 12 patients with CLL the respective figures were 68% (range 35%-90%) and 0.68 ng (SD 0.57). Ig secretion from pokeweed mitogen-stimulated CLL cells was markedly diminished as compared with normal lymphocytes. In coculture experiments CLL cells had no suppressive effect on Ig secretion of normal lymphocytes and normal lymphocytes did not enhance Ig secretion leukemic lymphocytes. These results indicate that the impaired secretory activity of CLL cells results from an intrinsic anomaly of these cells.     

Dopamine: its potential for inducing ischemic left ventricular dysfunction

As an agent potentially capable of inducing ischemia in patients with coronary artery disease, dopamine administered intravenously was evaluated as a pharmacologic stress agent by supine radionuclide angiography, and the results were compared with ergometer exercise. In a preliminary group of 11 subjects (4 normal subjects and 7 patients with coronary disease), dopamine alone was administered in increments of 2.5 micrograms/kg per min to a maximum of 15 micrograms/kg per min. There were significant differences between exercise and dopamine in maximal stress heart rates, 129.3 +/- 30.0 versus 88.0 +/- 35.8 beats/min (p less than 0.05) in normal subjects and 118.9 +/- 21.1 versus 87.6 +/- 22.6 beats/min (p less than 0.05) in patients with coronary disease, as well as in maximal stress rate-pressure products, 213.3 +/- 51.4 versus 155.0 +/- 52.5 mm Hg/min X 10(2) (p less than 0.02) in normal subjects and 216.0 +/- 45.6 versus 161.0 +/- 48.6 mm Hg/min X 10(2) (p less than 0.003) in patients with coronary disease. As a result, in these patients the ejection fraction response was significantly different: -3.3 +/- 4.5% with exercise versus + 6.3 +/- 4.6% with dopamine (p less than 0.05). In a second group of 41 subjects (9 normal subjects and 32 patients with coronary disease), atropine (0.6 mg) was administered intravenously before and after every second dopamine dose increment. This produced statistically similar maximal stress heart rates as compared with exercise in all subjects, rate-pressure products in normal subjects and slightly higher values with dopamine in patients with coronary disease: 200.3 +/- 47.2 versus 183.1 +/- 43.0 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Decreased actin content of lymphocytes from patients with chronic lymphocytic leukemia

Actin, a major cytoskeletal protein, was quantitated in normal and chronic lymphocytic leukemia lymphocytes. The actin content of normal human blood lymphocytes was 2.2 +/- 0.4 mg/10(9) cells and represented 6.6% +/- 1.8% of the total cellular protein. A significant decrease (p less than 0.001) was noted in chronic lymphocytic leukemia lymphocytes that contained 1.4 +/- 0.3 mg actin/10(9) cells, constituting 4.3% +/- 1.1% of the total protein. Normal T and B cells did not differ in actin content. Reduced actin levels were found in the T as well as in the B lymphocytes of "B-cell" chronic lymphocytic leukemia. The possible importance of the decreased actin level in the anomalous capping response and motility of chronic lymphocytic leukemia lymphocytes is discussed.     

Decreased 5''-nucleotidase activity in a T lymphocyte subpopulation from patients with B cell chronic lymphocytic leukemia

The activity of the ectoenzyme 5'-nucleotidase (5'N) was determined in the T lymphocyte subpopulations from patients with chronic lymphocytic leukemia (CLL). 5'N could be detected only in the T cells from patients whose B cells also had enzyme activity. The specific activity of CLL T4 cells was 0.17 +/- 0.02 micron/h/mg protein, similar to that of normal T4 cells, which was 0.13 +/- 0.08 micron/h/mg. The CLL T8 cells, however, had a significantly lower 5'N activity (0.17 +/- 0.02 micron/h/mg) than normal T8 cells (0.41 +/- 0.11 micron/h/mg) (P = .003). Normal null cells had very low activity, while much higher levels were found in the null cells of CLL patients whose B cells had activity. These findings document a difference in activity of an enzyme between the T8 cell population of patients with CLL and that of normal subjects.