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P D Zalewski

Publications and source records attributed to P D Zalewski.

49 records · Page 3Linked to original sources
PubMed1982

Two maturation-associated mouse erythrocyte receptors of human B cells. I. Identification of four human B-cell subsets.

Using rosetting tests with untreated mouse erythrocytes (M) and pronase-treated M (pro M), four human B cell subsets can be identified. Three of these, possessing the phenotypes BM+ pro M+, BM- pro M+ or BM- pro M-, constitute 17%, 61% and 22% of normal blood B cells respectively. The fourth subset, BM+ pro M-, does not occur in normal tissues but was found in the pre-B-cell line of Raji cells, indicating that this phenotype may be a marker for early B cells. Some differences in the proportion of each subset were found in cord blood, lymph nodes and tonsils. Surface-immunoglobulin-positive (SIg+) and -negative (SIg-) non-T cells were present in each subset. M and pro-M rosetting tests were applied to cells from blood of 27 cases of chronic lymphocytic leukaemia (CLL) and to cells from involved nodes, spleen or marrow in five cases of non-Hodgkin's lymphoma (NHL). In 15 cases of CLL, there was considerable increase in the BM+ pro M+ subset (BM+ pro M+ type CLL); in seven cases, there was a predominance of BM- pro M+ cells and in another four cases, BM- pro M- cells predominated. All five cases of NHL were greatly enriched in BM- pro M- cells. There was no obvious correlation between rosetting and other surface markers but BM- pro M- clones in CLL or NHL always stained brightly with FITC-anti-Ig. This was not found in BM+ pro M+ or BM- pro M+ clones. Rosette formation of neuraminidase-treated B cells with M identifies the same subset as B-pro-M rosetting in normals and CLL. Evidence is presented that two types of receptors are involved in M and pro-M rosetting, designated R1 and R2, binding to corresponding M ligands L1 and L2. M rosetting is due to R1-L1 binding while R2-L2 binding mediates B-pro-M rosetting. Shifts between subsets within the same clone in some cases of CLL suggest that the subsets are distinct maturational stage of B-cell development rather than families of B cells of different lineage. The following B-cell maturation sequence is proposed: R1+ R2- lead to R1+ R2+ leads to R1- R2+ leads to R1- R2-.

Adult↗
PubMed1982

Two maturation-associated mouse erythrocyte receptors of human B cells. II. Isolation and partial characterization of a B-cell lectin with specificity of R1.

Trypsin treatment of chronic lymphocytic leukaemia (CLL) cells which have the capacity to rosette with mouse erythrocytes (M), the BM+ subtype, inhibits their capacity to rosette and releases a substance into the supernatant which agglutinates mouse and rat erythrocytes but not erythrocytes of five other species tested. This substance has been named immature B-cell lectin (IBL). The specificity of IBL was further demonstrated by fluorescence labelling, absorption and latex rosetting. IBL does not bind to pronase-treated M (pro M), indicating that it has the specificity of R1 as distinct from R2 which binds to a pronase-resistant ligand on M. Other evidence that IBL is associated with B-cell membrane receptors for mouse erythrocytes is as follows: (1) The amount of IBL released into the supernatant correlated with the trypsin sensitivity of M rosetting with different clones of BM+ CLL cells. (2) Only small amounts of IBL were released from non-rosetting cells (T cells and mature B cells). (3) Binding properties of IBL were inhibited by extract of M but not extract from ox erythrocytes. (4) High-titre solutions of IBL conferred the capacity to form M rosettes on certain types of non-rosetting B cells. IBL has a dual binding specificity. Its binding to M is inhibited by fetuin and mannan, while its binding to B cells is not inhibited by these substances. The relationship of IBL to other membrane lectins including fibronectin is discussed. Preliminary characterization indicates a high-molecular-weight (at least 300,000 daltons) glycoprotein which has a pronounced tendency to aggregate in solution. The relationship of IBL to stages of human B-cell maturation is discussed.

Animals↗
PubMed1981

Loss of receptor activity for mouse erythrocytes precedes tumour promoter-induced maturation of chronic lymphocytic leukaemia cells.

The tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induced differentiation in lymphocytes from patients with chronic lymphocytic leukaemia (CLL). The differentiation was detected by the appearance of cytoplasmic immunoglobulin (CIg) and a plasmacytoid morphology, and was accompanied by the loss of the ability of the CLL cells to rosette with mouse erythrocytes (M). Loss of M rosetting occurred rapidly (within 10 min), was not prevented by cycloheximide or actinomycin D and was elicited by low concentrations of TPA (ED50 8 X 10(-10) M). Inhibition of rosette formation was induced by other phorbol diester promoters, but not non-promoting derivatives. Loss of the capacity to form M rosettes occurs before events which are evidently related to genome activation.

Animals↗
PubMed1981

B lymphocyte specificity of lectins of Cepaea nemoralis and Dolichos biflorus: paradoxical binding of anti-A active lectins to human lymphocyte subclasses.

Binding of four blood group A-specific lectins, from Helix pomatia (HP), lucorum (HL), Cepaea nemoralis (CN) and Dolichos biflorus (DB) to human lymphocytes was determined. Use was made of lectins attached to latex particles, as convenient probes to detect binding of lectins to individual cells, Specificity of lectin-latex probes was demonstrated by comparison with agglutination and fluorescent lectin binding; experiments with untreated and enzyme-treated human and animal erythrocytes confirmed the specificity of the lectin-latex beads as did inhibition in the presence of N-acetyl-galactosamine, the immunodominant sugar of blood group A substance. The binding of HP to T cells and a proportion of B, and non-B, non-T cells is confirmed. Binding to B cells in chronic lymphocytic leukaemia (CLL) is also confirmed. HP-latex had the same specificity as soluble HP, but binding did not require pretreatment of lymphocytes with neuraminidase. HL-latex had the same specificity for erythrocytes, normal lymphocyte subpopulations and CLL lymphocytes as HP, but the binding was weaker and required pretreatment of the lymphocytes with neuraminidase to demonstrate it. Contrary to expectation, CN and DB bound to B lymphocytes and did not bind to T lymphocytes. CN binding was almost completely restricted to B cells, whereas DB bound to part of the non-B, non-T populations as well as to a substantial proportion of B cells. Neither CN nor DB labelled malignant T cells. Both CN and DB bound to B cells in CLL. As with HP, pretreatment of lymphocytes with neuraminidase increased the accessibility of receptors, but was not essential to demonstrate labelling with CN-, and DB-latex preparations. Binding of each lectin to lymphocytes was independent of ABO blood group of donor suggesting that ABO antigens may be expressed poorly, if at all, on lymphocytes. Binding is probably due to additional specificities possessed by these lectins. Protease treatment destroyed CN- and DB-binding sites but not HP receptors suggesting that at least two types of binding site are involved.

ABO Blood-Group System↗
PubMed1979

Null cell chronic lymphocytic leukaemia.

Lymphocytes lacking receptors for sheep erythrocytes and surface immunoglobulin were present in the blood in large numbers at some stage in four cases of chronic lymphocytic leukaemia (which included a mother and son), and formed a substantial proportion of the circulating lymphocytes in other cases. These null cells possessed receptors for mouse erythrocytes. Other B-cell markers were also found on these cells. Serial studies showed a great variation in the number of null cells during the course of the disease (which may be associated with treatment), suggesting variation in the the maturation of leukaemic cells, and indicating that the surface marker complement may not reflect the constitution of the cell undergoing the original malignant change.

Aged↗
PubMed1979

Surface marker studies in chronic lymphocytic leukaemia and non-Hodgkin's lymphoma.

Immunological surface marker techniques were applied in a study of 29 cases of chronic lymphocytic leumaemia and 22 of non-Hodgkin's lymphoma. Surface marker characteristics distinguished 2 subtypes of B lymphocytes. Chronic lymphocytic leukaemia was a monoclonal proliferation of B lymphocytes which produced spontaneous rosettes with mouse erythrocytes and had faintly immunofluorescent surface immunoglobulin. The majority of non-Hodgkin's lymphomas also had their origin from B lymphocytes but in contrast, this subtype did not show receptors for mouse erythrocytes and their surface immunoglobulin was brightly staining and demonstrated "capping". The clonal origin of nodular lymphomas could also be demonstrated on frozen sections stained for surface immunoglobulin. Two cases of true histiocytic lymphoma were identified. The current information available on surface marker characteristics of the leukaemias and lymphomas is reviewed.

Adult↗
PubMed1979

Studies of the human lymphocyte-mouse erythrocyte bond.

A subpopulation of human B lymphocytes forms rosettes with mouse erythrocytes through a glycoprotein-dependent bond. Further studies of this bond show that the lymphocyte receptor is not immunoglobulin, although the binding of antisera or staphylococci to surface immunoglobulin inhibits the formation of mouse rosettes. Rosette formation could not be induced in thymocytes by enzymatic modification of the surface, or in T cells by lectin-induced transformation. The capacity to bind mouse erythrocytes was lost after incubation in a serum-free medium of lymphcytes from most patients with chronic lymphocytic leukaemia (CLL) and normal subjects. This loss could be prevented by the addition of a variety of sera and glycoprotein-containing substances to the medium, including fetuin. Conditions conductive to the subsequent restoration of rosetting capacity could not be found, indicating that the loss of this capacity was not due to the shedding of a cell-surface receptor which could be re-synthesized. It is suggested that the functional receptors in B1 lymphocytes are held in aggregates by cross-linking peripheral glycoprotein molecules; disaggregation and consequent loss of the capacity to form rosettes with mouse erythrocytes occurs during incubation in serum-free media, and during maturation of lymphocytes to the B2 stage.

Animals↗
PubMed1979

Maturation in B lymphocytic leukaemia.

Surface markers were studied serially in two cases presenting as acute B cell lymphocytic leukaemia. The leukaemic lymphocytes in both cases had the mouse erythrocyte receptor (MER) and surface immunoglobulin (SIg) with lambda light chain. Changes interpreted as an increase in immunological differentiation were observed in both, during the course of the disease and its treatment. These changes were loss of MER, increase in density of SIg, and the acquisition of SIgA. Selection of therapy to influence differentiation may ultimately afford better control of the lymphocytic leukaemias.

Adult↗
PubMed1978

Erythroderma, an unusual manifestation of B cell lymphoma.

A case is described in which the initial manifestation of a malignant lymphoma was an erythematous skin rash over the face, scalp and trunk. Immunological surface marker analysis showed the malignant cells to be of B lymphocyte origin with a homogeneous secretion of IgM-K. Repeated skin and lymph node biopsies and finally post mortem documented the progression of the lymphoma from that of a mixed lymphocytic-histiocytic type with a nodular pattern of growth to a diffuse histiocytic lymphoma with frequently bizarre cells. The theory of ecotaxis or homing of lymphocytes to the skin and other non-lymphoid organs of the body is discussed in an attempt to explain the occurrence of cutaneous involvement as a primary manifestation of lymphoma.

Adult↗
PubMed1978

B cell leukaemia distinguished from chronic lymphocytic leukaemia by surface markers.

Four cases of lymphocytic leukaemia were distinguished from CLL by surface marker analysis. CLL cells have relatively little SIg and have the mouse erythrocyte receptor. Cells in these cases had denser Slg and lacked the mouse erythrocyte receptor. The group presented a fairly uniform picture with onset in sixth or seventh decade, very high lymphocyte counts, splenomegaly (gross in three), heavy infiltration of marrow, relative resistance to chemotherapy and response to splenectomy. The lymphocytes were somewhat larger than those usually found in CLL and histological examination showed a quasi-nodular pattern in lymph nodes with diffuse infiltration of the spleen. Difficulties of classification are discussed. The addition of surface marker analysis to clinical and morphological parameters allows these cases of B-lymphocytic leukaemia (mouse erythrocyte-negative B leukaemia) to be distinguished clearly from chronic lymphocytic leukaemia. The mouse erythrocyte receptor is particularly useful in making this distinction.

Aged↗
PubMed1976

A subpopulation of human B lymphocytes that rosette with mouse erythrocytes.

A proportion of human peripheral blood lymphocytes form rosettes with mouse erythrocytes (M-RFC). It is confirmed that the proportion of such rosette-forming cells is high in chronic lymphocytic leukaemia (CLL). Analysis of normal lymphocyte populations revealed that M-RFC belong to the B-lymphocyte subclass exclusively. Analysis of their surface markers showed: (a) complement receptors in 50% as compared to 71% of the total B-cell population; (b) a distribution of surface immunoglobulins G, A, M and E typical of the lymphocyte sources; (c) lack of sheep erythrocyte receptor. No differences in the ratio of M-RFC to total B cells was found between lymphocyte population from tonsils, bone marrow and peripheral blood although a significantly higher ratio was seen in cord blood and in chronic lymphocytic leukaemia. Investigation of the properties of mouse erythrocyte rosette formation revealed the following: (a) incubation of lymphocyte mouse erythrocyte mixtures at 37degreesC before centrifugation inhibited rosette formation when CLL lymphocytes were used; (b) treatment of mouse erythrocytes with neuraminidase or trypsin increased their adhesiveness to lymphocytes; (c) treatment of lymphocytes with neuraminidase promoted M-rosette formation but trypsin treatment had an inhibitory effect; (d) cyanide and fluoride at concentrations which strongly inhibited E-rosette formation had no inhibitory effect on M rosettes; (e) M-rosette formation was inhibited by anti-immunoglobulin serum but not by anti-lymphocyte serum; and (f) M-rosette formation was also inhibited by the presence of staphylococci. E-rosette formation was unaffected. The nature of the bond in mouse rosettes is discussed in the light of these findings. The evidence indicates that the lymphocyte receptor may be a part of an immunoglobulin molecule.

Animals↗
PubMedDate not supplied

The role of zinc in caspase activation and apoptotic cell death.

In addition to its diverse role in many physiological systems, zinc (Zn) has now been shown to be an important regulator of apoptosis. The purpose of this review is to integrate previously published knowledge on Zn and apoptosis with current attempts to elucidate the mechanisms of action of this biometal. This paper begins with an introduction to apoptosis and then briefly reviews the evidence relating Zn to apoptosis. The major focus of this review is the mechanistic actions of Zn and its candidate intracellular targets. In particular, we examine the cytoprotective functions of Zn which suppress major pathways leading to apoptosis, as well as the more direct influence of Zn on the apoptotic regulators, especially the caspase family of enzymes. These two mechanisms are closely related since a decline in intracellular Zn below a critical threshold level may not only trigger pathways leading to caspase activation but may also facilitate the process by which the caspases are activated. Studies by our laboratory in airway epithelial cells show that Zn is co-localized with the precursor form of caspase-3, mitochondria and microtubules, suggesting this Zn is critically placed to control apoptosis. Further understanding the different pools of Zn and how they interact with apoptotic pathways should have importance in human disease.

Animals↗