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Biomedical subjects

R B Slease

Publications and source records attributed to R B Slease.

27 records · Page 2Linked to original sources
PubMed1980

Augmentation of human K-cell activity with interferon.

Our laboratory recently reported that interferon (IF) could augment human antibody-dependent cellular cytotoxicity (ADCC) and cytotoxicity by natural killer (NK) cells. Although there is general agreement that IF can boost the activity of human NK cells, two laboratories have reported a failure to boost ADCC. We have therefore examined in more detail the effects of IF on human ADCC. We have found, by several lines of evidence, that IF can indeed appreciably augment the activity of K cells, the subpopulation of lymphocytes that mediate ADCC: (1) human leucocyte IF, purified to homogeneity, boosted ADCC: (2) IF augmented ADCC against target cells that were completely resistant to NK activity; and (3) the ADCC activity of leukaemic cells from a patient with chronic lymphocytic leukaemia (CLL) which lacked any detectable NK activity was boosted by IF. These results are consistent with the hypothesis that human NK and K cells are the same subpopulation of lymphocytes and that the mechanisms regulating their activity are similar. However, the absence of NK activity in the CLL patient strongly supports the idea that not all FcR-positive cells are NK and that ADCC effectors devoid of NK may exist. However, further evidence is required to analyse this point.

Animals↗
PubMed1980

Characterization of a suppressor T-cell chronic lymphocytic leukemia with ADCC but not NK activity.

A patient with T-cell chronic lymphocytic leukemia (T-CLL) is reported whose cells demonstrate in vitro suppression of normal lymphocyte mitogen stimulation. The patient, who remains in Rai's clinical stage 0 on no therapy after more than 24 mo of observation, has shown a less aggressive clinical course than is usually attributed to T-CLL. His peripheral blood lymphocytes (PBL) were characterized by functional assays as well as surface markers. Over 90% of the patient's PBL formed rosettes with sheep erythrocytes and were lysed by two T-cell-specific antisera plus complement, while less than 1% bore surface immunoglobulins, and only 3% had complement receptors. In addition, 45% of the PBL demonstrated Ia-like antigens, more than 50% expressed a receptor for the Fc portion of IgG(T gamma), and most of the sheep erythrocyte rosettes were inhibited by theophylline. The patient's cells failed to respond to several mitogens and they caused marked suppression of lymphoproliferative responses to normal PBL to phytohemagglutinin (PHA) and concanavalin A (Con-A). The patient's lymphocytes also exhibited antibody-dependent cytotoxic activity (ADCC) against antibody-coated nucleated target cells, but lacked demonstrable natural killer (NK) activity. This patient's T-CLL cells appear to represent the clonal expansion of a subset of T cells with a previously undescribed pattern of suppressor and cytotoxic activities.

Adult↗
PubMed1980

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.

Blood Cells↗
PubMed1979

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.

Fluorescent Antibody Technique↗
PubMed1977

Deficiency of coagulation factors VII and XII in a patient with Hodgkin's disease.

A patient with Hodgkin's disease is described in whom deficiencies of coagulation factors VII and XII were discovered. Depressed levels of these factors appear to reflect increased Hodgkin's disease activity and returned to normal when chemotherapy was instituted. There was no evidence of accelerated fibrinolysis, intravascular coagulation, or circulating anticoagulants in the patient. Possible mechanisms for the abnormality include impaired production and/or increased consumption of coagulation factors. This observation suggests that all patients with lymphoreticular neoplasms should be screened carefully for clotting disturbances prior to treatment.

Adolescent↗
PubMed1976

Metastatic renal cell carcinoma 24 years after nephrectomy.

Recurrence of renal carcinoma 20 years after primary resection is uncommon. A patient is reported in whom two pulmonary metastases developed 24 years following nephrectomy for renal carcinoma. After a left lower lobectomy and a right pulmonary wedge resection were performed, he survived an additional two years before dying from metastatic disease.

Adenocarcinoma↗