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C Sundström

Publications and source records attributed to C Sundström.

At least 73 records · Page 4Linked to original sources
PubMed1993

Immunohistochemical characteristics of Hodgkin and Reed-Sternberg cells in relation to age and clinical outcome.

One hundred and fifty-four cases of Hodgkin's disease diagnosed between 1985 and 1988 from an unselected population were stained with a panel of six monoclonal antibodies; LN1, MB2, L26 (CD20), all B-cell antibodies, UCHL1 (CD45 RO), mainly T-cell antibody, Leu M1 (CD15), Ber H2 (CD30) and the polyclonal CD3, T-cell antibody. The results were related to age, histopathological subgroup and prognosis. There was no significant difference in staining patterns in the 90 patients below the age of 60 compared with the 54 patients above that age. In the entire group, significantly fewer mixed cellularity cases were positive with Ber H2 and Leu M1 compared to nodular sclerosis. Disease-free survival tended to be better for cases stained with T-cell related antibodies. This study thus indicated differences in behaviour between T-cell positive and negative Hodgkin's disease and that there are antigenic differences between nodular sclerosis and mixed cellularity subgroups. We could not, however, show any phenotypic differences between the tumour cells in young and old patients.

Adult↗
PubMed1992

Expression of the bcl-2 gene in human multiple myeloma cell lines and normal plasma cells.

The bcl-2 gene, encoding a mitochondrial membrane protein suggested to play an important role in cell survival, is translocated into the Ig loci in about 80% of human follicular lymphomas, which results in a high level of expression. This report shows that bcl-2 was expressed in eight of eight human multiple myeloma cell lines and in normal lymph node and bone marrow plasma cells. In the majority of the myeloma lines, the level of expression was comparable with that observed in Karpas 422, a follicular lymphoma cell line carrying a 14;18 translocation of the bcl-2 gene. DNA rearrangements of the bcl-2 locus were evident in only one of the myeloma cell lines, U-266-1970. In this cell line, which exhibited the highest bcl-2 expression, a fourfold increased copy number of the bcl-2 gene was estimated by Southern analysis. This amplification was lost in cells of later passages (U-266-1984), suggesting that bcl-2 might possibly have played a role in the tumor development in vivo. Our results are in contrast to previous observations in murine plasmacytoma, in which bcl-2 was shown to be silent. The results also contradict the published observation that bcl-2 is not expressed at terminal stages of B-cell differentiation. It is at present unclear whether the high expression of bcl-2 in human myeloma is the result of a deregulated expression associated with the malignant phenotype or a mere reflection of the bcl-2 expression typical of normal plasma cells.

Blotting, Southern↗
PubMed1992

Characterization of a U-937 subline which can be induced to differentiate in serum-free medium.

We report the selection and characterization of a U-937 subline which is capable of long-term growth in serum-free medium and can be induced to differentiate. The subline (U-937-1SF) can be maintained in standard RPMI-1640 medium supplemented by antibiotics only. As compared to the serum-dependent U-937 parental cell line, U-937-1SF produced lower amounts of lysozyme and elastase and had a decreased surface expression of complement receptor 1 (CD35) and myeloid antigens CDw17 and CD38. Apart from these alterations, the U-937-1SF cells appear to be morphologically, cytogenetically and phenotypically similar to the parental U-937 clone-1 cells. The capacity of U-937 clone-1 cells to undergo phorbol myristic acid (PMA)-, vitamin D3 (VitD3)- and retinoic-acid (RA)-induced differentiation was retained in the U-937-1SF cells as evidenced by the induced growth arrest, development of a monocyte/macrophage morphology and increased expression of differentiation-associated antigens, e.g. CD11b, CD11c, CD14 and CD18. The growth-inhibitory response to cytokines involved in the activation and differentiation of monocytes, IFN-gamma, TNF-alpha, IL-1 beta, IL-6 and GM-CSF, was normal. Our results suggest that the U-937-1SF subline can be used as a serum-free model system for studies on various aspects of monocyte differentiation.

Animals↗
PubMed1992

In vitro analysis of drug resistance in tumor cells from patients with acute myelocytic leukemia.

A 72 hours fluorometric microculture cytotoxicity assay (FMCA) was used for the study of chemotherapeutic drug resistance in tumor cell suspensions from patients with acute myelocytic leukemia (AML). A marked heterogeneity with respect to sensitivity was observed for a panel of cytotoxic drugs tested in 76 samples from 60 patients with treated or untreated AML. Primary resistance to vincristine (Vcr) and prednisolone in untreated AML was observed as well as 'acquired' resistance to several other antileukemic drugs. Cross resistance patterns for AML active drugs revealed significant positive relationships between anthracyclines, VP16 and amsacrine (Amsa), whereas mitoxantrone (Mitox) was more weakly correlated. Sensitivity to cytosine arabinoside was unrelated to the anthracyclines, VP16, Amsa and Mitox but showed a significant relationship to 6-thioguanine. Several resistance modifying agents, including the novel non-immunosuppressive cyclosporin A analogue PSC 833, were able to potentiate the effects of doxorubicin and Vcr at concentrations achievable in the clinic. However, the pattern of activity was heterogenous and the frequency of responsive samples was higher in relapse compared to de novo cases. Individual in vitro/in vivo correlations based on quartile distributions of all accumulated drug sensitivity data from AML patients indicated a high specificity with respect to the identification of drug resistance. The results suggest that the FMCA may provide clinically valuable information on chemotherapeutic drug resistance in AML.

Antineoplastic Agents↗
PubMed1992

Lymphoma incidence in a Swedish county during 1969-1987.

The incidence of lymphoid malignancies (acute leukemias and myelomatosis excluded) during 1969-1987 in the County of Uppsala was calculated on the basis of the regional cancer register and local registers from the only oncological, hematological, dermatological and pathological departments in this well-defined geographical area. Of the 774 patients included, 639 had histopathological specimens available, all of which were re-examined. Seventy-nine patients were diagnosed on the basis of bone marrow investigations (greater than 70% re-examined, all had a low-grade non-Hodgkin's lymphoma = NHL) and 54 on fine-needle aspiration biopsies (not re-examined). Seventy-nine of the lymphoma diagnoses were based on autopsy specimens. The overall age standardized incidence was 16.2/100,000/year (NHL: 13.6, Hodgkin's disease = HD: 1.5) according to the Swedish 1970 census (according to world standard population: 10.2); male: 20.9 (12.9) and female: 12.4 (7.9). The annual change in trend was +3.0% +/- 2.6 (NHL: +3.6% +/- 2.4, HD: no change). The omission of the 54 'fine needle cases' led to an overall incidence of 15.0 (9.7) and an annual change in trend of +3.5% +/- 1.9. Among the histopathological specimens, an NHL was found in 524 patients and HD in 69. In 46 registered patients, the diagnosis malignant lymphoma was wrong. The diagnosis changed to NHL in 43 patients registered as HD.

Adult↗
PubMed1992

alpha-Interferon inhibits spontaneous and induced DNA synthesis in hairy cell leukemia.

The effect of alpha-interferon (alpha-IFN) on spontaneous or induced proliferation of isolated peripheral blood mononuclear cells from 5 hairy cell leukemia patients was studied. alpha-IFN inhibited the low spontaneous proliferation of B-ly7 positive hairy cells (HCs) and also the proliferation induced by tumour necrosis factor (TNF). Interleukin-2 did not affect HCs, but induced CD4 positive T cells to proliferate, an effect which alpha-IFN antagonized. The stimulatory effect of TNF on the growth of HCs proved to be reversible and was partially blocked with either anti-TNF receptor or anti-lymphotoxin antibodies. Cellular or secreted thymidine kinase levels reflected the proliferative state of HCs in response to different in vitro treatments, as confirmed by thymidine incorporation and cell cycle studies.

Cell Cycle↗
PubMed1992

Feasibility of the fluorometric microculture cytotoxicity assay (FMCA) for cytotoxic drug sensitivity testing of tumor cells from patients with acute lymphoblastic leukemia.

The automated fluorometric microculture cytotoxicity assay (FMCA) was used for chemotherapeutic drug sensitivity testing of fresh and cryopreserved tumor cells from patients with acute lymphoblastic leukemia (ALL) at diagnosis and relapse. The technique success rate was 87% for fresh and 81% for cryopreserved samples. Up to 16 different cytotoxic drugs were routinely tested, but neither asparaginase nor methotrexate produced dose-response related cell kill. FMCA data showed good correlation to the well established Disc assay and the drug sensitivity reported by the FMCA was in good agreement with known clinical activity. Samples from children and initial ALL tended to be more drug sensitive than those from adults and ALL at relapse, respectively. For 36 samples clinical outcome was correlated to the quartile position in comparison to all other samples for the most in vitro active drug actually given to the patient. For patients with samples in the first, second, third, and fourth quartiles, the probabilities of complete remission were 89, 57, 38, and 0%, respectively. Using the median value as cut-off line, the sensitivity and specificity of the assay were 87 and 62%, respectively. It is concluded that the FMCA with a minimum of effort and with high success rate report clinically relevant drug sensitivity profiles for ALL.

Antineoplastic Agents↗
PubMed1991

Association between histamine-containing mast cells and sensory nerves in the skin and airways of control and capsaicin-treated pigs.

The association between mast cells (visualized by routine staining and immunohistochemistry for histamine) and capsaicin-sensitive nerves (containing calcitonin gene-related peptide (CGRP) and substance P (SP] was studied in the pig. In the 1-ethyl-3(3-diethylaminopropyl)carbodiimide (EDCDI)-fixed skin tissue, histamine-containing mast cells and CGRP/SP-positive nerves were found in close association around blood vessels. In the EDCDI-fixed airway mucosa, only single histamine-containing mast cells were detected. However, many alcian blue-positive mast cells were found, sometimes close to the airway epithelium where CGRP SP-containing nerve were abundant. The CGRP/SP-containing nerve fibres were absent 2 days after systemic capsaicin pretreatment, but no changes in the number and distribution of tissue mast cells, granulocytes or lymphocytes, or the number of blood leukocytes were detected. Local injection of allergen, histamine and capsaicin into the skin of pigs actively sensitized with ascaris antigen caused a rapid light red-flare (vasodilation) reaction. Allergen and histamine, but not capsaicin, also produced plasma protein extravasation. In contrast to the absent flare, the protein extravasation response still occurred in capsaicin-treated pigs. The sensitivity to ascaris antigen was mediated by an IgE-like antibody. We conclude that a functional and morphological relationship exists between histamine-containing mast cells and capsaicin-sensitive sensory nerves in the pig skin. Mast cells and sensory nerves are also found in the airway mucosa and appear to be closely associated with the epithelium.

Animals↗
PubMed1991

Effect of alpha-IFN on cytokine-induced antigen expression and secretion of TNF, LT and IgM in HCL.

In order to investigate the possible mechanisms for the effect of alpha-interferon (alpha-IFN) in hairy cell leukaemia (HCL), blood cells from 4 cases were treated in vitro with alpha-IFN, tumour necrosis factor (TNF) and interleukin 2 (IL-2). Changes in the antigen expression, immunoglobulin (Ig) secretion and the production of TNF and lymphotoxin (LT) were investigated. TNF induced expression of CD4 and CD71, increased the intensity of HLA-DR, CD25, CD11c and CD13 expression and decreased both the intensity and frequency of sIg and cIg positivity. alpha-IFN decreased CD25 expression, the tartrate-resistant acid phosphatase activity (TRAP), reduced the TNF-induced CD4 and CD71 expression and antagonized the TNF effect on the Ig expression. Spontaneous TNF or LT production could not be detected in culture supernatants. However, TNF was found to induce LT production, an effect which alpha-IFN antagonized and IL-2 augmented. The reduction of CD25, TNF-induced CD71 and TRAP caused by alpha-IFN seems to represent a deactivation of the activated state of hairy cells (HCs). The failure of alpha-IFN to induce Ig secretion or CD38 expression in HCs speaks against a differentiation induction effect. The LT secretion induced by TNF suggests that other cytokines than TNF might be involved in the proliferation of HCs and that alpha-IFN by blocking the production of LT and perhaps other cytokines causes a growth arrest in HCs.

Adult↗
PubMed1991

Treatment outcome in Hodgkin's disease in patients above the age of 60: a population-based study.

All persons in three Swedish counties afflicted with Hodgkin's disease between 1979 and 1988 were traced. The objective was to analyze, in unselected, population-based material, whether an assumed worse prognosis in the elderly could be due to differences in staging procedures, treatment intensity, decreased tolerance to therapy or to a more aggressive disease. After histopathological revision, 163 of 202 patients (autopsy cases excluded) were accepted as HD, 61 (37%) of them above the age of 60. Although staging procedures had been more intense in the young, the elderly patients had a more advanced stage at diagnosis, and tended more often to have B-symptoms. The intensity of staging procedures did not seem to influence survival. The 5-yr relative survival was 37% above and 85% below the age of 60. Radiotherapy was the primary treatment in 12 (20%) above and 41 (41%) below the age of 60 with 5-yr relative survival figures of 84% and 85%, respectively. Thirty-seven patients (61%) above and 61 (59%) below 60 were treated with combination chemotherapy (MOPP/ABVD, MOPP, ChlVPP/OPEC) with curative intent. The 5-yr relative survival was 33% and 86%, respectively. The majority of the elderly patients (54%) received less than 40% of the planned chemotherapy dose. The main reason for this pronounced reduction was intolerance to therapy, with 8 treatment-related deaths. We conclude that tolerance to combination chemotherapy in the elderly patients with HD is poor and could be the major reason for poor treatment outcome in this age group.

Adolescent↗
PubMed1990

Myeloperoxidase in human lung lavage. I. A marker of local neutrophil activity.

The origin of myeloperoxidase (MPO) in bronchoalveolar lavage (BAL) was investigated in the first part of the study. Radioimmunoassay of the cellular and supernatant MPO content as well as the peroxidase-antiperoxidase (PAP) technique were employed to determine the cellular source of MPO. The concentrations of MPO were measured in serum and BAL in the second part of the study. The aim was to determine whether the capillary bed was also a source of MPO. Neutrophil numbers in BALs obtained from 20 healthy subjects correlated significantly to the concentrations of MPO in cell-free BAL supernatants (r = 0.643, P less than or equal to 0.01). The cellular content of MPO in mixed BAL cells was significantly correlated to the number of neutrophils in the mixture (r = 0.536, P less than 0.05), but not to the number of any other cells. Moreover, the PAP-technique identified MPO in lung tissue neutrophils in resection specimens obtained from three patients undergoing surgery. This technique also revealed strong MPO activity in all BAL neutrophils and a weak activity in merely 4% of the alveolar macrophages in cytospin preparations obtained from seven BALs. High BAL/serum ratio of MPO concentrations suggests that MPO is of local origin, rather than passively diffused from the circulating pool. We therefore conclude that strong evidence suggests that MPO in BAL originates from lung neutrophils and that BAL MPO content may be used to estimate the neutrophil presence or activation in epithelium lining fluid.

Adult↗
PubMed1990

Myeloperoxidase in human lung lavage. II. Internalization of myeloperoxidase by alveolar macrophages.

Bronchial wash and bronchoalveolar lavage were performed in 12 healthy subjects (five smokers), in order to elucidate whether or not material of neutrophil origin may be phagocytized by lung macrophages in vivo. Cells from different levels in the bronchial tree were obtained by sequential injection and subsequent aspiration of either four 50-ml or five 10-ml aliquots. Each aliquot was used for the determination of total and differential cell counts. The proportion of myeloperoxidase-positive alveolar macrophages was determined by specific immune histochemical staining. The percentage of myeloperoxidase-positive macrophages was highest (median 94.8%, range 37-98.5%) in the 10-ml aliquots and lowest in the last three 50-ml aliquots (median values 1-2.5%) (P less than 0.001). A significant correlation was obtained between the fraction of myeloperoxidase-positive macrophages and the percentage count of bronchoalveolar lavage neutrophils (r = 0.466, P less than 0.05). Furthermore, the cellular myeloperoxidase showed a significant inverse correlation (r = -0.46, P less than 0.05) to the viability of the bronchoalveolar lavage cells. Our findings are compatible with previous demonstrations in animals of neutrophil phagocytosis by lung macrophages and show that this phenomenon in particular occurs in the more proximal airways. The internalization of neutrophils or neutrophil components by airway macrophages may be an important scavenger mechanism for protection of the lung from the deleterious effects of activated neutrophils.

Adult↗
PubMed1990

Myelosarcoma without acute leukaemia: immunohistochemical and clinico-pathologic characterization of eight cases.

Eight cases of myelosarcoma without acute leukaemia at time of diagnosis were reviewed and biopsies were immunostained using antibodies reacting with myeloid/monocytic markers. Initial tumour location included lymph nodes, paranasal sinuses, nasopharyngeal and/or orbital regions and other extranodal locations. Three cases developed acute myeloblastic leukaemia within 1-9 months. Diagnosis was correct in four of the cases, in the other cases a non-Hodgkin's lymphoma was initially diagnosed. Morphological examination showed a blastic but variable appearance of the tumours. In a few cases cytoplasmic granulation was present. Chloroacetate esterase was present in all cases. In paraffin sections cathepsin G. elastase or lysozyme were present in all cases except one. In frozen material from four of the cases, the myeloid markers CD 11c and CD 33 were present (all cases) and CD 13 and Ki M8 in 3/4 cases.

Adolescent↗
PubMed1990

Immunophenotype of hairy-cell leukemia.

15 cases of HCL were studied with a panel of monoclonal antibodies against different leukocyte antigens. A B-cell phenotype different from that of B-CLL was observed (CD10-, CD19+, CD20+, CD21-, CD22+, CD37+, CD38-, FMC7+, LN1+, PCA-1+, BLy7+ and CD5-). As expected, CD11c and CD25 were positive and, in addition, a My7 and My9 positivity in varying degree was noted. 3 weeks of in vitro incubation did not significantly alter the phenotype. We conclude that HCL exhibits a unique phenotype among chronic B-cell leukemias, which is closer to the plasma cell stage of differentiation than that of B-CLL. The BLy7 monoclonal antibody seems to be a promising marker for HCL.

Antigens, CD↗
PubMed1989

Interleukin 4 strongly augments or inhibits DNA synthesis and differentiation of B-type chronic lymphocytic leukemia cells depending on the co-stimulatory activation and progression signals.

This study describes the opposing effects that interleukin (IL) 4 exerts on the B cell stimulatory factor (BSF-MP6) and IL 2-dependent proliferation and differentiation of cells of one selected B-type chronic lymphocytic leukemia cell clone (I83), which depend on the nature of the activation inducer. In I83 cells activated by a 1-h pulse of 12-O-tetradecanoylphorbol 13-acetate, the BSF-MP6-dependent DNA synthesis was strongly enhanced by 50-100 U/ml of recombinant IL 4. Recombinant IL 2 stimulation was necessary only when a suboptimal dose of BSF-MP6 was used. The differentiation was also markedly enhanced by IL 4 as measured by quantitation of IgM secretion both at the population (enzyme-linked immunosorbent assay analyses of the supernatant) and single-cell level (enzyme-linked immunospot technique), by morphological examination of the maturation stage and flow cytometric analysis of differentiation-associated surface antigens (CD11c, FMC7, PCA-1 and CD38). No Ig isotype switch was found. In contrast, DNA synthesis and differentiation of I83 cells, activated by Staphylococcus aureus Cowan strain I (SAC) and co-stimulated with BSF-MP6 plus IL 2, were strongly inhibited by IL 4, both when it was added simultaneously with SAC or after 2 days of SAC exposure. Analysis of the cell-cycle progression of SAC and BSF-MP6 plus IL 2 and IL 4-stimulated cells by acridine orange staining and fluorescence-activated cell sorter (FACS) analysis demonstrated an arrest of a minor cell population in G0 and a block of the transition of G1 cells to S phase. Neither the enhancing nor the inhibitory effect of IL 4 on the proliferation and differentiation of I83 cells was an indirect effect via IL 4-induced activation of contaminating T cells, monocytes or natural killer cells, as shown by experiments where these cell types were depleted by FACS sorting. Furthermore the expression of CD23 and CD25 was not inhibited by IL 4. The results thus demonstrate contrasting biological effects of IL 4 on clonal leukemic B cells depending on the nature of the activation and progression stimuli. This adds to the emerging picture of a very complex cytokine and cell-to-cell contact-mediated regulation of the activation and subsequent growth and/or differentiation of human B cells.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

Bone marrow morphology during alpha-interferon treatment in hairy cell leukemia.

14 patients with HCL were started on alpha-interferon (IFN) treatment. Bone marrow changes were followed in trephine biopsies every 3rd month. Differential counting was performed according to the point counting method and fiber content was evaluated. At the start of treatment all patients had 80% or more of tumor cells in the bone marrow. The reduction of granulopoiesis was more pronounced than for erythropoiesis. During treatment cellularity decreased in 6/13 patients already after 3 months; later, cellularity was normalized in most patients. Only 1 patient showed a complete remission. 12/14 patients showed a significant but slow reduction of tumor cells. Also, between 12 and 18 months an improvement was seen in some patients. The megakaryocytes improved rapidly and the erythropoiesis was normalized before the granulopoiesis. Only 1 patient did not show a bone marrow response. 5/14 patients showed a reduction of bone marrow fibers, first seen after 6 months of treatment. IFN was discontinued in 9/14 patients. 7 of these relapsed during the observation period (18 months).

Adult↗
PubMed1989

Acute lymphoblastic leukaemia in adults in Sweden 1977-84: a retrospective analysis. Swedish ALL-Group.

The present study is a retrospective analysis of the outcome in 210 patients diagnosed and treated as having acute lymphoblastic leukaemia (ALL) in Sweden during 1977-84. 131 patients were morphologically rediagnosed as ALL. For the ALL-patients, nine different remission induction regimens were used. Remission frequency was 69%, without statistical difference according to induction treatment. However, the reasons for remission failure differed among therapy groups. The number of responders was significantly higher among patients who received a remission induction therapy with an anthracycline and/or L-asparaginase. Maintenance therapy consisted in most cases of 6-mercaptopurine and methotrexate with reinduction courses for 2-3 years. Median survival time was 13 months and median duration of first remission (MRD) 11 months. For a subgroup of patients (n = 29) treated with the most intense remission induction regimens, including at least 4 cytostatic drugs with both an anthracyclilne and L-asparaginase, the MRD is not yet reached, the shortest follow up time is 43 + months, and the probability of remaining in complete remission is 66%. We conclude that aggressive cytostatic therapy, with induction regimens including both an anthracycline and L-asparaginase, may cure a considerable number of adult ALL-patients.

Adolescent↗