Biomedical subjects
Publications and source records attributed to C Sundström.
A high titer of hepatitis B antigen (HBsAg) was found in a patient with acute hepatitis B infection complicated by bone marrow aplasia. A possible antimitotic effect of HBsAg as an aetiological factor of the aplasia in this patient is discussed.
53 patients with the myelodysplastic syndromes (MDS) were classified according to the proposals of the FAB cooperative group 1982. 29 patients had refractory anaemia (RA), 10 refractory anaemia with excess of blasts ( RAEB ), 5 RAEB in transformation, 7 RA with ringed sideroblasts and 2 chronic myelomonocytic leukaemia ( CMML ). Counting blast cells type I and II involved no difficulties. 4 of 15 patients who developed acute myeloid leukaemia (AML) according to the FAB classification of 1976 did not fulfill the new 1982 criteria for AML. A redefinition of the blast cell type II to include a more granulated blast cells, without the characteristics of promyelocytes, would solve this problem. We conclude that a redefinition of the blast cell type II might turn out to be useful.
Different types of human cells which normally grow as monolayers or suspension cultures were tested for their capacity to form and grow as spheroids. Sixteen out of the 27 tested tumour cell lines formed spheroids. Nearly all of these spheroids also grew. With only two exceptions the doubling times were longer when the tumour cells grew as spheroids than when they grew in conventional mass culture. Eleven out of 13 tested human non-tumour cells formed small spheroids but of these only the spheroids of lymphoid origin could grow. These lymphoid cells grew faster when aggregated to spheroids than when in single-cell suspension culture. None of the other non-tumour cells, which normally grew as monolayers, could grow as spheroids. The normally monolayer-cultured tumour cells formed symmetrical spheroids with smooth surfaces while the normally suspension-cultured cells formed irregular spheroids with rough surfaces. All large spheroids had a necrotic centre surrounded by a shell of viable cells. The thickness of the viable cell layer varied depending on cell type. The shape and organization of cells within the spheroids also varied largely. The results show that many types of human cells can be cultured as spheroids and that a wide spectrum of morphological appearances and growth rates can be obtained.
U-937 represents a well established permanent human hematopoietic cell line. Electron microscopical and enzyme cytochemical studies as well as the analysis of surface glycoproteins have provided ample evidence for the monocytic origin of U-937. Upon stimulation with the tumour promotor 12-O-tetradecanoylphorbol-13-acetate (TPA), U-937 cells evolve into macrophage-like cells with phagocytic capacities. Since human blood monocytes (BM) are characterized by five acid esterase (AcE; EC 3.1.1.6) isoenzymes which are cell-specific in terms of isoelectric points (pI) and antigenicity, attempts were made in the present study to identify identical isoenzyme patterns in non- and TPA-stimulated U-937 cells. BM, cultured BM, non- and TPA-stimulated U-937 cells, as well as samples of resident human peritoneal macrophages (PM) as clearly-defined functional derivatives of BM, were subjected to isoenzyme analysis using isoelectric focusing (IEF). The five monocyte specific isoenzymes of AcE were identified in both populations of U-937. TPA-stimulated samples showed two additional bands, identical to those appearing in cultured BM after 4 days of glass-adherence and characteristic of resident human PM. Antisera raised against AcE of BM immunoprecipitated the two additional isoenzymes of TPA-stimulated U-937. It is concluded (1) the isoenzyme mapping of AcE documents the monocytic origin of U-937. (2) TPA-stimulation caricatures transformation of BM into resident tissue macrophages as far as pure morphology and AcE isoenzyme patterns are concerned. Thus, AcE isoenzyme mapping is apt for establishing reproducible and standardized criteria of different activation/differentiation states within the monocyte-macrophage lineage.
Immunohistochemical double-staining was performed on frozen sections from synovial biopsies obtained at arthroscopy from 22 patients with different kinds of synovitis. Not only in specimens from patients with rheumatoid arthritis and seronegative chronic polyarthritis, but also in those from patients with synovitis due to psoriasis, trauma, or crystals, were seen many alpha Leu-1-positive T lymphocytes--in most cases predominantly of the alpha Leu-3a-positive T "helper" cell type--in close contact with HLA-DR-positive macrophages/dendritic cells. Presence of many HLA-DR-positive, often OKM1-negative, and irregular sublining cells characterized all forms of chronic arthritis.
In a retrospective survey of 334 cases of non-Hodgkin lymphoma (NHL), 250 cases could be classified according to both Rappaport's classification and the Kiel classification. All patients initially in stage I had an excellent prognosis irrespective of histology, whereas patients in stages II, III and IV had a worse prognosis that did not significantly differ between stages. Rappaport's classification could separate stages II-IV into 2 different prognostic groups, one favourable and one unfavourable group. According to the Kiel classification, 3 prognostic groups - favourable, intermediate and unfavourable - were found. The survival rate for favourable Rappaport fell in between favourable-Kiel and intermediate-Kiel. Both subgroups within favourable-Rappaport (nodular lymphomas and diffuse well differentiated lymphomas) could actually be subdivided by the Kiel classification into one group with a more truly favourable behaviour and one with an intermediate behaviour. The extent of follicularity among nodular lymphomas and the presence of plasmacytoid differentiation among the small lymphocytic lymphomas were found to be of prognostic importance. In conclusion, we found that the Kiel classification separated the more indolent lymphomas better than Rappaport's classification. No preference was found concerning the high grade lymphomas.
A myeloproliferative condition in blastic phase is described in an 18-year-old male who was also found to have a mediastinal malignant teratoma. Myeloid metaplasia was found in the lymph nodes and spleen, and an infiltration of granulocytic blast cells was observed in the bone marrow and the lymph nodes. Aneuploidy with an extra chromosome (trisomy 8) was present in bone marrow cells. To our knowledge the combination of a myeloproliferative disorder and a malignant teratoma has not been earlier described.
The surface glycoprotein patterns of leukaemic B lymphocytes from 20 patients with clinically progressive or non-progressive chronic lymphocytic leukaemia (CLL) were investigated. Cells were labelled by the neuraminidase-galactose oxidase-tritiated sodium borohydride technique and the radioactive proteins were separated by polyacrylamide slab gel electrophoresis and visualized by fluorography. A total of 13 to 16 bands were detected. A common surface glycoprotein pattern for CLL cells was seen in all patients consisting of 7 proteins with the apparent molecular weights of 210, 200, 185, 150, 135, 110 and 90 kilodaltons, respectively. Interesting differences were, however, observed as cells from patients with progressive CLL in general lacked the glycoproteins 120, 72 and 67 K, which were found on cells from inactive CLL. The possible biological and clinical significance of these findings is discussed.
The Leukaemia Group of Middle Sweden recently started a new multicentre study of treatment of adult patients with acute leukaemia from 6 centres. The criteria for the diagnosis, subclassification, degree of leukaemic bone marrow infiltration, remission and relapse are to be used by the morphologists of 6 different pathology departments. The reproducibility of the criteria has been studied by 3 of the morphologists concerned, in a retrospective review of a strictly consecutive series of 79 adult patients treated at Södersjukhuset, Stockholm, Sweden, in the years 1978 to 1981. The results show that the reproducibility of the criteria and the concordance of the morphologists when using them increased when the criteria were made more detailed and precise.
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Fresh neoplastic B cells from 14 untreated patients with naturally occurring B-cell leukemias were found to be susceptible to lysis by human natural killer (NK) cells. The observed lysis of the fresh, non-cultured, neoplastic B cells was mediated by a population of interferon-augmentable, FcR-positive, non-adherent lymphoid cells, which were also able to kill the "standard" NK target K562. A further finding was the correlation of NK susceptibility with disease activity in 11 patients with chronic lymphocytic (CLL) and one patient with lymphosarcoma cell leukemia (LSCL). Enriched neoplastic B cells from seven untreated patients with non-progressive CLL, whose disease activity was stable throughout the 6 month period of study, exhibited persistent and essentially unchanged NK susceptibility profiles. In contrast, four untreated patients with progressive CLL also had a measurable fraction of NK-susceptible, neoplastic targets, but these cells subsequently disappeared after successful cytoreductive therapy, and later re-emerged when these patients again developed progressive disease. Furthermore, one patient with LSCL was found to have persistent, measurable NK susceptibility in his tumor-enriched fraction after unsuccessful cytoreductive therapy. An additional finding in the peripheral blood of patients with chronic B-cell leukemias was the presence of significantly lower NK effector-cell activity against K562 as compared to normal donor peripheral blood lymphocytes (PBLs). The implications of these findings are discussed.
Normal and rheumatoid synovial cells have been analyzed in frozen sections and in suspension. HLA-DR-expressing, macrophage-like cells are demonstrated in normal synovial intima and in rheumatoid tissue. Suspended normal synoviocytes equaled peripheral blood non-T lymphocytes as stimulators of mixed lymphocyte reactions, whereas adherent rheumatoid synovial cells were extremely efficient as such stimulators and in presenting soluble antigens to autologous T lymphocytes. This HLA-DR-dependent T lymphocyte regulation might provide a cellular basis for the HLA-D haplotype-arthritis associations.
A permanent cell line, MN 60, was established from the peripheral blood of a patient with an acute lymphoblastic leukemia (ALL) classified morphologically as being of the L3 type. Cell growth started rapidly in vitro and no feeder cells were needed. Cells of the MN-60 line were identical to the original leukemic cells with respect to surface immunoglobulin (Ig) expression and karyotype, including the presence of four marker chromosomes [1q+, 6q-, t(8;14)]. Continuous proliferation was maintained in stationary suspension culture with a doubling time of 25 h. The cells were tumorigenic in athymic nude mice and had the capacity to form colonies in semi-solid medium in vitro. Monoclonal surface Ig (mu lambda) was demonstrated whereas no cytoplasmic immunoglobulin could be demonstrated. The MN-60 cells were Epstein-Barr virus (EBV) negative as evidenced by EBNA tests and by nucleic acid hybridization studies. The cells expressed HLA-A-C, HLA-DR. beta 2-Microglobulin and cALL, but not Fc gamma. C3, sheep and mouse red blood cell receptors. No reactivity was found with anti-glycophorin A or the anti-BL 38.13 monoclonal antibody. Cell growth was retarded in the G0/G1 phase of the cell cycle after incubation with leukocyte interferon, hydrocortisone, phorbol myristate acetate and dimethyl sulphoxide.
Langerhans cells were enriched from epidermal cell suspensions by a monolayer technique based on the association of Langerhans cells with solid matrix-bound anti-Ia antibodies or by flow cytometry sorting of fluorescein-isothiocyanate labeled anti-Ia reactive cells. The monolayer technique gave a moderate enrichment (15-37%) whereas considerably higher purity (73-87%) was obtained by flow cytometry sorting. The identity of the enriched anti-Ia reactive cells as Langerhans cells was established by histochemical techniques or electron microscopy. The monolayer-enriched Langerhans cells could function as stimulating cells in the mixed leukocyte culture reaction and as antigen-presenting cells.
A series of 147 patients, 99 in clinical stage I and 48 in stage II, with localized non-Hodgkin's lymphoma, exclusively given radiation therapy, was retrospectively analysed. Using the Kiel classification, 12 patients (8%) could not be subgrouped with certainty, 63 (43%) were designated as high-graded and 72 (49%) as low-grade malignancies according to the definitions of Gérard-Marchant et coll. (1974). Complete remission was obtained in 93 per cent of the patients in stage I and in 75 per cent in stage II. Most of the failures (68%) were high-grade malignancies. Actuarial and relapse-free survival was determined for stage I and II and stratified by microscopy and extranodal disease. All patients initially in stage I had a good prognosis irrespective of the microscopic type; 60 per cent have remained free from disease. In contrast, only 2 patients (4%, all low-grade) in stage II have remained disease-free. Thus, in stage II irradiation cannot be considered the best treatment, especially in patients with high-grade malignancy, in whom chemotherapy may be curable. In stage I, on the other hand, irradiation seems to be curative in the majority of patients irrespective of microscopic type.
In a retrospective analysis of 334 cases of non-Hodgkin's lymphoma observed between 1969 and 1978, 250 cases could be classified according to the Kiel classification. Clinicopathologic correlation was analysed for these latter cases. Irrespective of the morphologic appearance, all cases initially in stage I showed an excellent prognosis after radiation therapy alone, whereas the prognosis for stage II was similar to stages III and IV. For stages II-IV, 3 major prognostic groups with significantly differing survival curves were identified. The median survival times were one, 3 and more than 7 years, respectively. The pathologic and clinical significance of the Kiel classification is discussed.
Net enzyme activities of normal human blood cells were measured, and isoelectric focusing patterns of acid esterase (AcE) (EC 3.1.1.6) and acid phosphatase (AcP) (EC 3.1.3.2) were compared with corresponding data obtained for two acute T-lymphoblastic leukemia cell lines (JM, Molt-4), one acute B-lymphoblastic leukemia cell line (Ball-1), one acute non-B-non-T-lymphoblastic leukemia cell line (KM 3), and one promyelocytic leukemia cell line (HL-60). The AcE isozymes, found in the individual blood cell types, were regularly expressed by the corresponding cell lines. AcP was regularly expressed by lines HL-60 and KM 3, but lines JM, Molt-4, and Ball-1 showed additional isozymes and/or reduction of the intensity of the typical isozymes found in the presumed normal counterparts. This phenomenon resulted partly in an obscuration of the typical isozyme patterns. Our study documents the applicability of isozyme mapping to the characterization of permanent hematopoietic cell lines. The results suggest that long-term culture conditions can repress phenotypic properties and/or derepress gene activities.
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