Search PubMed⌕ Search

Biomedical subjects

N E Kay

Publications and source records attributed to N E Kay.

At least 91 records · Page 5Linked to original sources
PubMed1986

Immune abnormalities in renal failure and hemodialysis.

Considerable work needs to be done in order to understand the immunosuppressive effect of 'uremia' and the lymphocyte changes induced by hemodialysis. For example, the lymphocyte population dynamics can be further defined using monoclonal antibodies specific for lymphocyte subgroups. In vitro assays are available for lymphokine detection (i.e. IL-1, IL-2 which are important for T cell function) and may be correlated with both the clinical state and overall immunobiological status of hemodialyzed patients. The possibility of specifically delineating the extent of the immune system dysfunction in renal failure patients (on or off dialysis) is at hand. With this knowledge it will be possible to manipulate their management so as to minimize function alterations.

Antibody Formation↗
PubMed1986

Clinical trial of recombinant leukocyte A interferon as initial therapy for favorable histology non-Hodgkin's lymphomas and chronic lymphocytic leukemia. An Eastern Cooperative Oncology Group pilot study.

Twenty patients with disseminated favorable histology non-Hodgkin's lymphomas (16 patients) or chronic lymphocytic leukemia (four patients) who had not received previous chemotherapy were treated with recombinant leukocyte A interferon (IFL-rA) (Hoffmann-La Roche, Nutley, NJ). Treatment was administered in a moderate dose (12 X 10(6) U/m2) by intramuscular (IM) injection three times weekly for 8 weeks, followed by weekly maintenance therapy for an additional 16 weeks in patients responding to therapy. Five patients with stable disease at 8 weeks received four additional weeks of three-times-weekly treatment at an escalated dose (25 X 10(6) U/m2). Interferon was tolerated without severe toxicity by most patients, although treatment was discontinued prematurely due to side effects in four patients. Objective tumor responses (one complete response [CR] and six partial responses [PRs]) were seen in seven of 16 patients with lymphoma (44%). One of four patients with chronic lymphocytic leukemia also experienced a PR. Median time-to-progression from initiation of therapy among responding patients was 26 + weeks (range, 7 + to 84 + weeks). This study has demonstrated single agent antitumor activity of IFL-rA given in a tolerable outpatient dosage regimen in patients with advanced favorable histology non-Hodgkin's lymphomas, and serves as a basis for further trials of IFL-rA combined with chemotherapy as initial therapy for such patients in the future.

Adult↗
PubMed1986

Natural killer cells.

It is proposed that this article will encompass a review of primarily the human natural killer cell. The following parameters of the human natural killer (NK) cell will be reviewed: its ontogeny; surface membrane characteristics including monoclonal antibody reactivity, cell lineage, the natural killer sensitive targets, and the proposed mechanism of action of natural killer cells cytotoxicity against these NK sensitive targets; the status of natural killer cell in relationship to clinical disease; the alteration of natural killer cells both in vitro and in vivo; and finally postulate relevance of the natural killer cell in context of the evolution or pathophysiology of human disease. There will be an attempt through this review to encompass the more recent publications that pertain to the various sections.

Biological Products↗
PubMed1986

Defective T cell responsiveness in chronic lymphocytic leukemia: analysis of activation events.

Chronic lymphocytic leukemia (CLL) is a B cell disorder in which major T cell proliferative defects are present. We investigated the nature of this deficit by studying several parameters known to be crucial in normal T cell proliferative response to mitogen. Purified peripheral blood T cells from B-CLL patients were analyzed for the presence of T3 antigen. We observed that CLL T cells have a direct correlation between levels of T3 membrane antigen and proliferative response to mitogen. The appearance of activation antigens (transferrin, HLA-DR, and interleukin 2 [IL 2] receptor) was normal in CLL T cells post-mitogen exposure. Despite the normal presentation of IL 2 receptor on CLL T cell membrane, there was decreased production of IL 2 by CLL patients (v controls) (39.6 +/- 10.2 cells per milliliter v 64.6 +/- 11.0 cells per milliliter). Finally, we were able partially, but not fully, to reconstitute CLL T proliferative response to mitogen by adding purified exogenous IL 2. These findings suggest that CLL T cells have multiple defects that may impact on their proliferative potential. Further insight into these deficits may result in strategies that will facilitate immunologic restoration in T cells of these patients.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1985

Simultaneous presentation of relapsing Hodgkin's disease and treatment-related non-Hodgkin's lymphoma.

A 55-year-old white man was diagnosed in 1975 with Hodgkin's disease stage IIA, mixed cellularity. He was treated with 4,500 rads to an inverted-Y field followed by six cycles of MOPP and remained in complete remission. In 1983 a right axillary lymph node biopsy showed recurrent Hodgkin's disease, mixed cellularity. While receiving his initial chemotherapy he developed persistent epigastric distress. Endoscopic gastric biopsy demonstrated a diffuse large-cell non-Hodgkin's lymphoma. Surface marker studies confirmed the separate identity of these two malignant lymphoproliferative processes. This represents the first reported simultaneous occurrence of relapsing Hodgkin's disease with treatment-related non-Hodgkin's lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Lymphocytotoxic T lymphocytes in a patient with B-chronic lymphocytic leukemia and pure red cell aplasia.

The peripheral blood T cells of a hypertransfused patient with B-chronic lymphocytic leukemia and pure red cell aplasic were found to exhibit unusual spontaneous cytotoxic activity in vitro. The patient's E-rosette positive cells were cytotoxic for K562 (cultured human erythroleukemia cells) and allogeneic B and T lymphocytes freshly isolated from the peripheral blood of normal and CLL donors. They failed to kill autologous B cells, erythroid progenitors present in allogeneic bone marrow, and a number of cultured human tumor cells (Malme, CAKI) even after prolonged (36 h) co-culture. Peripheral blood T cells isolated from normal controls, other CLL patients, and hypertransfused individuals (n = 13) did not exhibit spontaneous lymphocytotoxic activity. Circulating cytotoxic T cells having the ability to kill freshly isolated allogeneic lymphocytes have, heretofore, not been reported in humans. Our findings suggest that among this patient's peripheral blood T cells, there exists a subpopulation of lymphocytotoxic cells that closely resemble cytotoxic T cells generated in vitro after priming with allogeneic target cells. Although the lymphocytotoxic cells could have been induced in this patient by previous HLA-mismatched transfusions, it is possible they may have arisen spontaneously and underly the patient's erythroblastopenic state.

Anemia, Aplastic↗
PubMed1985

Monoclonal antibodies to the 140,000 mol wt glycoprotein of B lymphocyte membranes (CR2 receptor) initiates proliferation of B cells in vitro.

Several mouse monoclonal IgG antibodies (AB1, AB2, AB3, and AB5) were developed that reacted with a 140,000 mol wt glycoprotein on the surface of cultured RAJI B lymphoid cells. The antibodies reacted with purified normal human peripheral blood B cells and CLL Ig+ B cells and showed specific germinal center and mantle zone staining in tissue sections of secondary lymphoid organs. Immunodepletion studies using 125I surface-labeled Raji cell membrane antigens demonstrated that the antigen identified by AB5 is the same 140,000 mol wt glycoprotein detected by anti-B2 that has recently been shown to react with the C3d fragment or CR2 receptor. (Iida et al: J Exp Med 158:1021, 1983). Addition of the AB series and anti-B2 monoclonal antibodies to cultures of purified human peripheral blood B cells resulted in the uptake of 3H-thymidine at two to six times background control levels provided that irradiated autologous T cells were added to the culture. Stimulation was not evoked by other monoclonal antibodies to B cell surface molecules (ie, B1, BA-1, BA-2, and HLA-DR). Pepsin-generated F(ab')2 fragments of anti-CR2 antibodies were essentially as effective as the intact IgG molecule in stimulating B cells. Induction of B cell proliferation by antibody binding to CR2 suggests that the C3d receptor may have an integral role in regulation of humoral immune response.

Animals↗
PubMed1985

Human platelets exert cytotoxic effects on tumor cells.

Monocytes are thought to play a role in host resistance to tumor cell growth in animals and humans. In addition, platelets are known to be involved in tumor metastases. To investigate the interaction of these two cell types and their effect on tumor cells, human monocytes and platelets were examined using an in vitro monocyte-tumor cell cytotoxicity assay. Monocytes alone resulted in 32% +/- 1.5 (mean +/- SEM) tumor cell kill. When platelets were added to monocytes in a 1:1 ratio, an increase in cytotoxicity to 61% +/- 3.2 was observed. The cytotoxicity noted when platelets were added to a fixed number of monocytes and tumor cells was dependent on the number of platelets added. A decrease in cytotoxicity from 32% +/- 1.5 to 12% +/- 2.3 was observed when contaminating platelets were removed from monocyte preparations. Platelets added to tumor cells in the absence of any monocytes were also toxic, resulting in a maximum kill of 95% at a 4:1 platelet/tumor cell ratio. Secreted products of freshly isolated platelets may be responsible for much of the observed cytotoxicity, since supernatants from the platelets were toxic for tumor cells. Platelets pretreated with a cyclooxygenase inhibitor (ASA) or a lipoxygenase inhibitor had decreased cytotoxicity compared with untreated platelets. Our results indicate that products of platelet arachidonate metabolism are toxic for tumor cell lines. They also suggest that the role of the platelet must be considered when studying monocyte-tumor cell cytotoxicity.

Blood Platelets↗
PubMed1984

Establishment and characterization of a subclone (U-937-AG) from a permanent human monocyte cell line.

The human cell line U-937 has many features suggestive of the monocyte. It may be stimulated in vitro to develop attributes of an activated macrophage with increased phagocytosis and enhanced Fc receptor expression. We describe the establishment of a subclone designated U-937 AG through the use of a mutagenic agent. The features of this subclone include increased tumoricidal cytotoxicity, increased Fc receptor expression for IgG and enhanced phagocytosis of antibody coated erythrocytes, while retaining the usual light microscopic features. The mutant cell line is also capable of producing an erythroid potentiating factor while temporary production of a granulocyte macrophage colony stimulating factor was noted. The availability of a "resting" parent and a more "activated" subclone of this human monocyte cell line should assist in the study of human monocyte activation.

Cell Line↗
PubMed1984

Defective expression of T cell antigens in chronic lymphocytic leukaemia: relationship to T cell dysfunction.

In chronic lymphocytic leukaemia (CLL) peripheral blood T cells have a variety of functional abnormalities. To explore more extensively the T cell status of B-CLL patients, surface immunoglobulin-negative cells were isolated by sheep erythrocyte rosetting (ER) and the membrane phenotypes of the ER + cells defined by immunofluorescence utilizing monoclonal antibodies (MAb). In 11 of 18 CLL patients (CLL group I) there was excellent correlation between ER + and T3 (mature T cell marker) positivity. In the remaining patients (CLL group II), only 5-45% of ER + cells were T3 positive, suggesting that many rosetting cells were non-T. However, the ER +, T3 negative cells were nonreactive with OKM -1 (MAb which detects monocytes and 'null' lymphocytes) or with OKT11, 9.6, and 35.1, MAb against the T cell E receptor. Moreover ER +, T3 negative cells were not stained with OKT4, OKT8, OKT6, OKT9 , or OKT10 . Treatment of group II ER + cells with neuraminidase increased (from 27% to 74%) the mean percentages of T3 positive cells detected, but not other membrane antigens. ER + cells from group II patients, compared with normal and group I patients, exhibited diminished proliferative responses to PHA and Con-A (P less than 0.01) and supported poorly pokeweed mitogen-induced proliferation of normal allogeneic B cells (P less than 0.01). Thus, in approximately one-third of the CLL patients studied, many ER + cells poorly express a number of membrane antigens characteristic of normal mature T cells, one of which (T3) is unmasked by neuraminidase treatment. This phenotypic abnormality appears to be associated with significant T cell dysfunction in vitro and may, at least in part, contribute to the commonly encountered immunological defects present in these patients.

Antibodies, Monoclonal↗
PubMed1984

Impaired natural killer activity in patients with chronic lymphocytic leukemia is associated with a deficiency of azurophilic cytoplasmic granules in putative NK cells.

This study was undertaken to gain further insight into the severely impaired natural killer (NK) activity we and others have previously observed in patients with chronic lymphocytic leukemia (CLL). Normal individuals' NK cells are large granular lymphocytes (LGL) that (A) bind to and lyse NK-sensitive cells, including K562, (B) express receptors for the Fc portion of IgG (FcR+ cells), and (C) express cell surface antigens reactive with monoclonal antibodies OKM1, 9.6, and OKT11A. We thus examined lymphocytes depleted of monocytes and B cells, from 6 CLL patients and 6 normal individuals, that were identified on the basis of binding to K562, expressing OKM1, or expressing receptors for the Fc portion of IgG. In the CLL patients studied, lymphocytes that bind to K562 cells, as well as OKM1+ cells isolated by fluorescence activated cell sorting, were morphologically similar to LGL of normal individuals, with the exception that more than 75% of the patients' cells were deficient in azurophilic cytoplasmic granules, which typify normal individuals' LGL. Furthermore, although the percentages of the patients' FcR+ cells reactive with OKT11A, 9.6 and OKM1 were very similar to those of normals, the majority of the patients' FcR+ cells were deficient in azurophilic granules and lacked NK activity. These findings indicate that the impaired NK activity in CLL patients is associated with cells that are phenotypically and morphologically NK cells, but which lack azurophilic granules that are thought to play a role in NK-mediated lysis.

Antibodies, Monoclonal↗
PubMed1983

Human anti-lymphoma responses generated in vitro and in vivo following sensitization with allogeneic leukocytes.

Peripheral blood lymphocytes (PBL) from a patient with poorly differentiated lymphocyte lymphoma (PDLL), after stimulation for 7 days with X-irradiated allogeneic lymphocytes pooled from three or ten donors (poolx), were cytotoxic for autologous lymphoma cells. Some clones lytic for autologous lymphoma cells, that were derived from this patient's pool-stimulated cells, resembled cytotoxic T lymphocytes (CTL), while other clones resembled natural killer (NK)-like cells in that they also lysed NK-sensitive HLA-negative K562 cells. In a second patient with more advanced PDLL, PDL cultured with T-cell growth factor (which is produced following stimulation with mitogens or alloantigens) lysed autologous lymphoma cells. On the basis of these in vitro findings, we asked whether IV transfusions with X-irradiated allogeneic leukocytes would result in anti-lymphoma responses in vivo. Ten days after transfusions with X-irradiated leukocytes from four unrelated donors, the first patient's two previously palpable nodes were no longer palpable and he remained in complete clinical remission for 6 months. The second patient had a temporary partial remission with dramatic reduction in size of multiple cervical and axillary nodes within 2 weeks after receiving the leukocyte transfusions.

Cells, Cultured↗
PubMed1983

The influential T cell in B-cell neoplasms.

Investigations of human B-cell malignancies have generally focused on the monoclonal B-cell populations. Until recently there has been little emphasis on the thymus (T) lymphocyte in these disorders. Current studies, however, suggest that quantitative and qualitative disorders of T cells are generally seen both in chronic lymphocytic leukemia and in multiple myeloma. This review will focus on two major concepts. First, it will define the quantitative and functional T-cell abnormalities in B-cell malignancies including evidence suggesting a causal link between the T-cell abnormalities and certain observed disease manifestations in chronic lymphocytic leukemia and multiple myeloma. Secondly, it will review data demonstrating that these T cells may be influenced by in vivo and in vitro manipulations and will outline some of the possible resultant clinical effects.

B-Lymphocytes↗
PubMed1983

Effects of human T-cell subpopulations on B-cell proliferation as determined by (3H)-thymidine incorporation.

Human T-cell subgroups, fractionated by Fc receptor characteristics, have primarily been utilized to investigate their influence on B-cell immunoglobulin synthesis. We have investigated T subpopulation-B cell interaction by evaluating [3H]-thymidine incorporation of pokeweed mitogen-stimulated lymphocytes. DNA synthesis by B cells is dependent on T cells, but may be influenced by regulatory mechanisms that are distinct from those related to plasma cell differentiation. Peripheral blood mononuclear cells were divided into purified B cells, and three T-cell groups [T total (TI), T gamma (Fc receptors present for IgG), and T non-gamma (no Fc receptor on initial isolation)]. A fixed concentration of B cells (5 X 10(4) was then added to increasing concentrations of T gamma and irradiated TI or T non-gamma cells in the presence of PWM. The addition of irradiated T non-gamma enhanced [3H]-thymidine incorporation in a linear dose-dependent relationship. The addition of T gamma cells resulted in reduction in lymphocyte [3H]-thymidine incorporation is an alternative method for the evaluation of T-cell subgroup-dependent suppression or enhancement of human B-cell activity.

Antigens, Surface↗
PubMed1983

Chronic lymphocytic leukemia progenitor cells carry the antigens T65, BA-1, and Ia.

CLL B cells may be induced to form B-cell colonies in vitro. Colonies formed are monoclonal and appear to reflect the circulating malignant B-cell clone in vitro. Using hybridoma-produced monoclonal antibodies (MAB) and an in vitro B-cell colony assay, we have provided a characterization of the antigenic phenotype of the clonogenic CLL B cell. B-cell colony growth in both patients and normals was not altered by prior incubation with either MAB or complement (C') alone. CLL B-cell colony formation was markedly reduced after treatment with T101 and C', while normal colonies were unaffected (8 +/- 2 versus 107 +/- 10). None of the residual CLL B-cell colonies after T-101 and C' treatment reacted with T-101. However, BA-1 and la reactivity were still seen in residual CLL B-cell colonies following T-101 treatment. In contrast, a similar percentage reduction of B-cell colony growth was seen for both normals and CLL patients following treatment with BA-1 (76% versus 81%) and Q5/13 (89% versus 92%). These studies suggest that the CLL progenitor cell is characterized by the phenotype la+, BA-1+, T-101+. Better definition of the CLL progenitor cell has potential implications with regards to clinical utilization of MAB in the treatment of CLL.

Antibodies, Monoclonal↗
PubMed1983

Alterations in human natural killer cell activity and monocyte cytotoxicity induced by zinc deficiency.

Zinc deficiency alters lymphocyte and monocyte function in man and animals. A patient with isolated zinc deficiency was found to have lymphopenia (420 lymphocytes/microliter), depressed T-cell mitogen response (48% of normal control), increased numbers of circulating T-suppressor cells (OKT8 reactive cells) and decreased circulating T-helper cells (OKT4 reactive cells). Activity of the patient's natural killer (NK) cells was 1 lytic unit/10(6) cells (normal 10 to 40), and monocyte cytotoxicity (MC) was four times that of normal controls. Zinc repletion in vivo improved the peripheral lymphocyte count, corrected the abnormal OKT8-to-OKT4 ratio, normalized T-cell response to mitogen, improved NK function, and lowered MC to control values. A divalent cation chelator, 1,10-orthophenanthroline (OP), was used to simulate zinc deficiency in vitro. T-cells exposed to OP are nonresponsive to mitogen unless zinc is added. NK function of lymphocytes from normal donors exposed to OP was depressed in a time- and dose-dependent manner. NK activity of peripheral blood lymphocytes (PBL) from 12 normal donors exposed to 50 microM OP for 16 hr was 10.3 +/- 7 lytic units/10(6) cells (mean +/- S.E.M.) vs. 32.6 +/- 14 for cells incubated in medium alone. When monocytes were exposed for 16 hr to 50 microM OP, however, MC significantly increased to a range two to five times that of control. OP-induced alterations of lymphocyte and monocyte function was reversed by the addition of 50 microM zinc but not calcium or magnesium. Since NK activity and MC are thought to be important in host tumor immunity, alterations in zinc metabolism may have important implications for human tumor immune surveillance mechanisms.

Chlorides↗