PubMed HealthSearch

Biomedical subjects

A Polliack

Publications and source records attributed to A Polliack.

At least 37 records · Page 2Linked to original sources

Phorbol esters and hairy cell leukemia: effects on cell morphology and surface membrane features and comparison with other B cell leukemias.

Hairy cell leukemia (HCL) mononuclear cells were incubated with the phorbol ester TPA in an attempt to induce further maturation and were compared with B cell chronic lymphocytic leukemia, prolymphocytic leukemia, and non-Hodgkin's lymphoma cells. Morphology, surface features, membrane markers, tartrate-resistant acid phosphatase, and Ig secretion were examined. HCL cells spread and adhered firmly after TPA, producing elongated filopodia. Cells still retained ribosomal lamellar complexes, and increased numbers of dense bodies were seen. TPA enhanced the adherent and phagocytic properties of HCL cells, producing a modest increase in the expression of membrane Ig, GP-70, and Leu-M5 markers, tartrate-resistant acid phosphatase, and Ig secretion. Other neoplastic B cells behaved differently, forming readily detachable clumps without elongated filopodia. Maturation to plasma cells and hairy cell features were readily evident in all cases. These differences in growth patterns were consistent and may be used to distinguish HCL from other B cell neoplasias.

Acid Phosphatase

Phorbol ester induction of plasmacytoid and hairy cell leukemia features in B-type lymphocytic leukemias: the relation to B-cell differentiation and maturation.

Mononuclear cells concentrated from 11 patients with chronic lymphocytic leukemia (CLL), 7 with non-Hodgkin's lymphoma in leukemic phase (NHL), 5 with hairy cell leukemia (HCL), 1 with prolymphocytic leukemia (PLL), and 1 with plasma cell leukemia (PCL) were induced to differentiate with various doses of TPA. The degree of induction was followed for up to 6 days by measuring the expression of surface membrane markers (SmIg and GP-70) and Ig secretion, the induction of tartrate-resistant acid phosphatase (TRAP) and by recording ultrastructural changes as seen by electronmicroscopy. The results show a dose and time dependency of the TPA effect and a great heterogeneity in the cellular response, particularly in cells obtained from B-CLL patients. TPA induced two main features, namely the development of "plasmacytoid" or "hairy cell" leukemia features that clearly depended on the dose and duration of treatment with the phorbol ester. The plasmacytoid features were more frequently encountered with lower doses (1 ng/ml) of TPA and were more evident after shorter exposures to TPA (1-2 days). Nevertheless, the hairy cell features were more striking after incubation with higher concentrations of TPA (10-100 ng/ml) after longer periods of incubation (up to 6 days) with lower doses of TPA. The various features of differentiation measured including cell morphology, surface membrane markers, Ig secretion, and TRAP staining, were frequently independent of each other, suggesting an autonomous pathway of differentiation for some of these features. Furthermore, in most of the cases, hairy cell leukemia features were obtained more frequently following TPA exposure than plasmacytic changes.

Acid Phosphatase

Heterogeneity in TPA-induced differentiation of B-chronic lymphocytic leukemia cells: development of hairy cell or plasmacytoid features are time and dose dependent.

Cells from 11 chronic lymphocytic leukemic (CLL) patients were induced to differentiate with various doses of tetradecanoyl phorbol-13-acetate (TPA) and the degree of induction was followed up to six days by measuring the expression of two surface membrane markers (SmIg and GP-70), Ig secretion, tartrate-resistant acid phosphatase (TRAP), and ultrastructural changes. The results indicate dose and time dependency of the TPA effect and a great heterogeneity in the response to TPA among cells from different CLL patients. Furthermore, the two main TPA-induced features, the "plasmacytoid" or "hairy cell" features depended on the dose and duration of treatment with the phorbolester. The plasmacytoid features were more frequently encountered at low doses (1 ng/ml) of TPA and were evident after short exposures to TPA (1-2 days). The hairy cell features were more obvious after incubation with higher doses of TPA (10-100 ng/ml) or at Day 6 with lower doses of TPA. The differentiation features measured, including cell morphology, surface membrane markers, Ig secretion, and TRAP staining, appeared to be independent of each other suggesting an autonomous pathway of differentiation for some of these features.

Acid Phosphatase

Parameters affecting the in vitro maturation of human monocytes to macrophages.

In vitro maturation of human monocytes to macrophages was characterized by morphological criteria, cell size and lysosomal enzymes activity. Purified populations of monocytes were maintained in culture at either adherent or nonadherent conditions and their maturation to macrophages was observed in both cases. The addition of external factors such as hydrocortisone and vitamin D3 inhibited monocyte maturation. In the absence of external factors, nonadherent monocytes were inhibited in their maturation for up to 10 days when plated at crowded cell concentrations. In addition, the presence of human serum in the culture media had a higher inhibitory activity than similar concentrations of fetal calf serum. Supernates from crowded macrophages were also inhibitory for monocyte maturation. We suggest the possibility that cell crowding, as well as soluble factors found in the serum and probably secreted by macrophages, participate in the regulation of monocyte development by inhibiting their maturation. Once released from this inhibitory signal or environment, the monocytes mature to macrophages.

Adolescent

In vitro differentiation and establishment of cell lines derived from human myelomonocytic leukemia cells.

Primary cultures of cells derived from 13 patients with acute myelomonocytic leukemia (AMML) were studied with particular emphasis on in vitro proliferation, cell differentiation and the mode for establishment of cell lines. Using irradiated human macrophage monolayers to assist cell growth, we obtained four new cell lines of myelomonocytic origin. All the cell lines were characterized for cytochemical markers and response to phorbol esters (TPA), a differentiation inducing agent. In the absence of any inducing agent, spontaneous differentiation of blast cells into mature macrophages-like cells occurred in 8 out of the 13 primary cultures. Thus, maturation induction by agents such as TPA is not always required in order to obtain leukemic cell differentiation in vitro. The regulation of cell proliferation and differentiation by cellular interactions and by extrinsic soluble products is discussed in detail, in the light of these findings.

Cell Differentiation

Generation of a monoclonal anti-GP70 antibody and characterization of its reactivity with various human cell lines and cells from leukemia-lymphoma patients.

Monoclonal anti GP-70 antibodies (BI) were generated in mice and used for screening of various malignant and non-malignant cell lines. The reactivity of these monoclonal antibodies was compared with that obtained with the polyclonal anti GP-70 antibody described in earlier studies [1-3]. The results indicated complete similarity in reactivity of both of the antibodies used. Furthermore, the reactivity of BI antibodies with cell samples obtained from a variety of leukemia and lymphoma patients and with peripheral blood samples from healthy blood donors was also very similar to the pattern of specificity described in earlier reports for the polyclonal preparation. From these studies we conclude that the monoclonal antibodies can substitute the polyclonal anti GP-70 antibodies in the diagnosis and subtyping of B-type leukemias and lymphomas.

Antibodies, Monoclonal

Hairy cell leukaemia: effects of phorbol ester on cell morphology and adherence and comparison with other B-cell neoplasias.

This report documents phorbol ester-induced changes in cell morphology in 9 patients with hairy cell leukaemia (HCL) and contrasts them with those obtained in cells from 20 patients with B-type chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma in leukaemic phase (NHL). The phorbol ester caused hairy cells to adhere strongly and produce thin elongated cytoplasmic extensions. Other cells showed marked surface ruffling, and contained increased numbers of phagolysosomes, although cells still retained ribosomal lamellar complexes. This in vitro growth pattern differed from that observed in B-CLL and NHL cells, which readily detached in clumps with minimal adherence. CLL and NHL-cells did not show macrophage features but developed plasmacytoid and hairy cell-like features. It is suggested that these different growth patterns may aid in distinguishing HCL from other B-cell neoplasias.

B-Lymphocytes

Topical modes in the preparation of human spleen specimens for routine scanning electron microscopy studies.

Various preparatory techniques were used to improve scanning electron microscopy images of the fine structure of vascular, cellular, and cordalreticular components of normal human spleens. The progressive method of fixation (GTGO) applied in the present study, allowed air drying of the tissues and rendered the specimens conductive even in newly fractured surfaces. Vascular perfusion proved necessary only in studies of the splenic blood vessels, while a simple immersion of tissue blocks in the washing solution resulted in better images of the white pulps. Interstitial (transsplenic) perfusion was found to be superior to vascular perfusion for routine preparation of spleen tissues, and freeze-cracking did not necessarily lead to improved images of the specimen's surfaces. Combined with proper washing and shaping protocols, the GTGO procedure is shown to be a superior mode of specimen preparation, abolishing most traditional artifacts and obtaining clear images of the complex splenic tissue.

Animals

Adhesion, spreading and fragmentation of human megakaryocytes exposed to subendothelial extracellular matrix: a scanning electron microscopy study.

Platelet agonists and subendothelial extracellular matrix (ECM) induce morphological and biochemical changes in animal megakaryocytes, reminiscent of the response of platelets to the same substances. We have examined the behavior of human megakaryocytes exposed for up to 36 hours to the ECM produced by cultured bovine corneal endothelial cells. By phase contrast and scanning electron microscopy these megakaryocytes demonstrated non-reversible adherence and flattening with formation of long filopodia, thus confirming that human megakaryocytes acquire platelet functional capacities. In addition, megakaryocyte fragmentation into prospective platelets was apparently induced by the ECM. Up to 50% of the adherent megakaryocytes underwent spontaneous fragmentation into small particles which individually reacted like platelets on the ECM. The interaction of the megakaryocytes with the ECM was specific since no adherence, flattening or fragmentation occurred upon incubation of the megakaryocytes on regular tissue culture plastic or glutaraldehyde fixed ECM. Thus we have demonstrated platelet like behaviour of human megakaryocytes in response to this physiological basement membrane and a possible role of the subendothelium in platelet production which may occur in vivo as megakaryocytes cross the sinusoid walls and enter the blood stream.

Animals

Phorbol ester (TPA)-induced surface membrane alterations in B-type hairy cell and lymphocytic leukemia cells.

This report documents phorbol ester (TPA)-induced changes in cell morphology, and in vitro growth patterns in 9 patients with hairy cell leukemia (HCL), 21 with B-type CLL and non-Hodgkin's lymphoma in leukemic phase (NHL), and 10 with acute non lymphoblastic leukemia (ANLL). TPA caused cells from HCL to adhere strongly and produce elongated cytoplasmic extensions. Many of these cells had an appearance resembling fibroblasts, while others showed marked surface ruffling and spreading containing increased dense bodies, and phagolysosomal vacuoles as seen by transmission electron microscopy. This HCL in vitro growth pattern after TPA exposure differed from that seen in B-CLL and NHL cells, which only adhered moderately after 72 hours and readily detached in clumps. CLL and NHL-cells did not show ultrastructural features of macrophages but had either plasmacytic or HCL features. It is suggested that these different growth patterns may aid in distinguishing HCL from other B-cell neoplasias. The expression of surface markers, tartrate resistant acid phosphatase (TRAP) and Ig secretion were studied in some B-CLL, NHL and HCL cells after exposure to different concentrations of TPA for up to 6 days. Results showed that the documented changes were frequently both dose and time dependent and the most striking HCL-features were encountered after 6 days incubation with higher concentrations of TPA. However, individual variation from case to case was noted. Nevertheless, it seems that TPA induces neoplastic B-cells to mature into secreting plasmacytoid lymphocytes, and cells with features of HCL with variable expression of surface markers and TRAP.

Acute Disease

Non-Hodgkin's lymphoma associated with pregnancy. A report of six cases, with a review of the literature.

Six patients with non-Hodgkin's lymphoma diagnosed during late pregnancy or shortly thereafter are reported. Three patients had high-grade lymphoma and three, intermediate-grade histologic features. Five of the six patients were in Stage 4 and one was Stage 1. Only three had the diagnosis of non-Hodgkin's lymphoma during pregnancy, and in these three cases the disease appeared to progress rapidly after delivery. The other three women probably had lymphoma during pregnancy; lymphoma was widespread at the time of their diagnosis, but the diagnosis was only established on biopsy specimens after delivery in all three instances. Five patients had full-term natural deliveries with normal infants. A single patient with Burkitt's lymphoma had a premature delivery with a cesarean section in the 29th week because of abruptio placentae probably due to lymphoma of the uterine wall. In this case both mother and child died within 48 hours of delivery. The other five patients were treated soon after delivery. Published literature dealing with this topic is scanty and inconclusive; accordingly this report attempts to discuss management of lymphoma in pregnancy, based on the authors' limited experience with these six patients.

Adult

Establishment of the Amsalem T-cell line from a patient with acute lymphoblastic leukemia. Expression of E-receptor-associated antigens in cells incapable of forming E-rosettes.

A new T-cell line (Amsalem) was established from the peripheral blood of a patient with pre-T leukemia. Amsalem cells are unique in that they possess antigenic determinants associated with the E-receptor, yet fail to form rosettes with sheep red blood cells (SRBC). Amsalem cells were found to possess morphological and cytochemical features characteristic of T-lymphocytes, and were sensitive to the cytotoxic effect of rabbit antisera specific for T-cell antigens. In immunofluorescent tests with monoclonal antibodies, Amsalem cells showed a strong reactivity with the OKT-11A and A-22 antibodies, specific for the E-receptor. The cells were reactive with OKT-4 and showed a very weak reactivity with OKT-6 and OKT-8. No reactivity was found with the OKT-3, Leu 7, Leu 11, and OKM1 antibodies. Amsalem cells failed to form rosettes with SRBC; however, mouse anti-Amsalem serum inhibited the formation of E-rosettes. It is concluded that the Amsalem cell line is a line of pre-T leukemia cells characterized by a dissociation between its inability to form E-rosettes and the presence of antigenic constituents of the E-receptor.

Antibodies, Monoclonal

Secondary myelofibrosis with metastatic breast cancer simulating agnogenic myeloid metaplasia: report of a case and review of the literature.

A patient with carcinoma of the breast, who developed a clinical syndrome resembling agnogenic myeloid metaplasia, is described. She was found to have secondary myelofibrosis with metastatic carcinoma of the marrow, extensive extramedullary hematopoiesis resulting in massive splenomegaly, and leukoerythroblastosis. These findings are rare and myeloid metaplasia with striking extramedullary hematopoiesis causing massive splenomegaly and mimicking agnogenic myeloid metaplasia is seldom seen in patients with metastatic carcinoma. Previous case reports of secondary extramedullary hematopoiesis simulating agnogenic myeloid metaplasia (AMM) in patients with solid tumors are also reviewed.

Adult

Hairy cell leukemia associated with carcinoma: report of two patients and review of the literature.

The association of carcinoma and hairy cell leukemia (HCL) in two patients is recorded. One of the cases was a 58-year-old male who developed carcinoma of the kidney, while the second patient was a 48-year-old woman with carcinoma in the breast. This rare association is probably coincidental, as it is not described in most of the larger reported series of patients with HCL. It is of interest to note that the first patient had received radiation therapy thirty years before the diagnosis of HCL and carcinoma was made.

Adenocarcinoma

Chronic T cell lymphocytosis with large granular lymphocytes of helper (OKT4) phenotype.

A 54-year-old asymptomatic male patient was followed for more than 7 y and presented a constant T cell lymphocytosis without skin involvement or bone marrow depression. No clinical or haematological aggravation was noted during this follow-up. Morphologically, the cells were large granular lymphocytes strongly positive for beta-D-glucuronidase, negative for acid phosphatase and with features of T cells on transmission and scanning electron microscopy. The immunological studies of the lymphocytes showed the following parameters: E rosettes+, mouse rosettes-, SmIg-, OKT3+, OKT4+, OKT8-, OKT6-, Ia-, TdT-, NK-, HTLV-, decreased PHA and PWM stimulation, no interleukin 2 production and failure to enhance Ig synthesis in a PWM driven system. The karyotype was normal. This case of chronic T cell lymphocytosis with large granular lymphocytes helper profile and defect of helper function, not reported in the literature, may correspond to a distinct entity in the heterogeneous group of chronic T cell disorders.

Antibodies, Monoclonal

Results of therapy in adult acute nonlymphoblastic leukemia: experience in Jerusalem, Israel, during 1975-1982.

78 previously untreated patients (aged 16-82 years) with acute nonlymphoblastic leukemia received intensive chemotherapy for induction of remission. In 64 patients, the combination used consisted of daunomycin and cytosine arabinoside with or without 6-thioguanine. The overall remission rate was 59 and 87% for those who received what was considered as adequate therapy. Patients who achieved remission received maintenance and, in part, late intensification. The median duration of remission was 9 months. The median survival of the patients who attained remission was 24 months, compared to 15 months for the entire patient group and 3 months for patients who failed to achieve remission. Age had no effect on the rate and duration of the remission obtained but the median survival was significantly longer in patients below the age of 50 years.

Adolescent