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Biomedical subjects

C Sundström

Publications and source records attributed to C Sundström.

At least 91 records · Page 5Linked to original sources

Primarily asymptomatic low-grade non-Hodgkin lymphomas: prediction of symptom-free survival and total survival.

Low-grade non-Hodgkin lymphomas (NHL) constitute a group of tumours with an often long survival time but, at present, with little--or no--chance of cure if the disease is not strictly local. In primarily asymptomatic patients, treatment may either be started immediately after diagnosis or deferred until symptoms occur. The possibility of predicting the symptom-free time was investigated in 64 non-selected initially asymptomatic patients with advanced low grade NHL, all of whom had treatment deferred until symptoms occurred. The most powerful predictor was the histopathological subgroup. Lymphocytic (LC) and follicular centroblastic-centrocytic (fCBCC) lymphomas had a median symptom-free period of 2 years, which was four times longer than that for immunocytoma (IC) and follicular and diffuse CBCC (fdCBCC). In addition, the serum levels of deoxythymidine kinase (S-TK) and lactic dehydrogenase (S-LDH) could predict the symptom-free period. This did not apply to S-Haptoglobin, S-Orosomucoid or stage. In a multivariate analysis, only S-TK gave additional information to histopathology. The only variable that predicted the overall survival time was the length of the symptom-free period.

Follow-Up Studies↗

Immunophenotype analysis of B-CLL lymphoma and immunocytoma.

The differential diagnosis between lymphocytic lymphoma of the B-CLL type and immunocytoma (IC) can be difficult when it is based only upon morphological criteria. With the aim of improving the distinction between these subgroups, frozen sections of lymph nodes or other biopsied tissues from 14 cases of B-CLL and 16 cases of IC were investigated according to immunophenotype. A panel of 13 B cell-associated and 2 T cell-associated monoclonal antibodies was used. All but one of the B-CLL cases were FMC7-, while 14/16 IC cases were FMC7+ (p less than 0.001). The two negative IC cases were both of the lymphoplasmacytic type, claimed to be "more differentiated" than the lymphoplasmacytoid type. We suggest that the cells in these cases are mature enough to have lost their FMC7 positivity, similar to plasma cells. There was also a statistically significant (p less than 0.01) difference, although not as pronounced, for the anti-CD38 antibody (Leu-17, B-CLL: 3/14, IC: 10/16 positive). No significant difference in expression of determinants was found for any of the other antibodies.

ADP-ribosyl Cyclase↗

Prognostic factors in non-Hodgkin lymphoma stage I treated with radiotherapy.

The results of treatment in 175 consecutive patients with nonHodgkin lymphoma (NHL) clinical stage I treated between 1969 and 1984 were analysed according to different pretreatment prognostic variables. Treatment consisted of radiotherapy in 166 of the 175 patients. The estimated 5 and 10-year disease-free survival rates (DFS) were 63% and 60% and the survival rates at 5 and 10 years 82% and 76% respectively. Lymphomas arising from gut-associated lymphoid tissue, i.e. Waldeyer's ring, the thyroid and the gastrointestinal tract had a more favourable clinical course (10-year projected DFS 83%) than nodal (50%) and other extranodal lymphomas. Although the number of patients with other extranodal sites was small, sites such as testis, nasal cavity, paranasal sinus and extradural space seemed to have a high relapse rate. Unfavourable clinical courses were also observed among nodal high-grade NHL if the lymph nodes were larger than 5 cm in diameter. Chemotherapy before radiotherapy may be recommended in NHL subgroups with a high relapse rate and which today are potentially curable with chemotherapy, i.e. highgrade NHL. This study indicates that large nodal lymphomas and some extranodal sites belong to this group.

Adult↗

Primary aneuploid lymphoma of the uterine cervix: a case report.

A primary, diffuse, centroblastic lymphoma of the uterine cervix is described. The patient is a 77-year-old V-parous woman, who presented with postmenopausal bleeding, but no systemic symptoms. Gynecologic examination revealed a 4 x 8-cm tumor extending from the uterine cervix to the anterior vaginal wall and elevating the bladder neck, but with no sign of mucosal infiltration. According to the FIGO classification, the tumor was classified as stage IIIA. Flowcytometric analysis showed a grossly aneuploid tumor, with a DNA content of 3.5c. The S-phase rate was 30.6%. The patient was treated with external pelvic irradiation to 46 Gy. Six weeks later the therapy was completed with seven courses of a cyclophosphamide-vincristine-prednisolone (COP) regimen. Complete tumor response was achieved and 3 years later there is no sign of relapse. Despite unfavorable prognostic parameters: large tumor volume, diffuse growth pattern, aneuploidy, and a high S-phase rate, a combination of radiotherapy and chemotherapy was found to be a successful treatment of this rare form of advanced primary lymphoma of the uterine cervix.

Aged↗

Prognostic relevance of serum-markers in relation to histopathology, stage and initial symptoms in advanced low-grade non-Hodgkin lymphomas.

The prognostic relevance of 4 different serum markers (deoxythymidine kinase = S-TK, lactic dehydrogenase = S-LDH, S-Haptoglobin and S-Orosomucoid) in relation to histopathology according to the Kiel classification, stage and presence or absence of initial symptoms were investigated in 168 consecutive cases of low-grade non-Hodgkin lymphomas (NHL). All serum markers, as well as the other three parameters, gave prognostic information. Univariate analysis yielded a high predictive value (p less than 0.0002) for both S-TK and S-LDH. The best information regarding the probability of survival was, however, obtained from the presence or absence of symptoms from lymphoma manifestations other than those caused by a strictly local tumor mass. Since S-TK and S-LDH correlated well with each other, only the better of them, S-TK, gave information additional to initial symptoms in a multivariate test.

Aged↗

IgE-producing low-grade non-Hodgkin lymphoma.

An unusual case of IgE-producing non-Hodgkin lymphoma (NHL) is presented. The patient's history included a 6-year period of increasing IgE level before a low grade NHL was diagnosed. The patient developed lymph node, skin, bone marrow and lung infiltrations. With a cytostatic combination therapy a temporary improvement was achieved, but the patient died from progressive disease after 2 yr. The morphological appearance of the tumour varied between that of LP immunocytoma and a centrocytic lymphoma. Immunophenotype studies showed intracytoplasmic IgE lambda in tumour cells and B-cell surface phenotype (BB-1 pos; OKT 10 pos; PCA weakly pos and SIgE lambda).

Aged↗

Aggressive treatment improves survival in adult acute lymphoblastic leukemia.

20 consecutive adult patients with acute lymphoblastic leukemia were treated with an intense induction regimen including vincristine, doxorubicin, prednisolone, L-asparaginase and cyclophosphamide. 16 patients (80%) achieved complete remission and were then given CNS prophylaxis and 3 years of maintenance therapy. With minimum follow-up of 24 months, the median duration of first remission is 37+ months. Out of 10 patients who have completed maintenance therapy, 2 have relapsed after 14 and 22 months, respectively, and 7 are in continuous complete remission 1+-55+ months off therapy.

Adolescent↗

Phorbol ester and B cell-stimulatory factor synergize to induce B-chronic lymphocytic leukemia cells to simultaneous immunoglobulin secretion and DNA synthesis.

This paper discusses the response of two B cell-type chronic lymphocytic leukemia (B-CLL) clones, 173 and 183, to the phorbol ester TPA combined with a B cell-stimulatory factor (BSF) derived from a T helper cell hybridoma (MP6). Previous studies with 173 and 183 cells have consistently shown that TPA alone induces differentiation but no proliferation. However, when the two clones were exposed to TPA plus BSF-MP6, not only differentiation but also DNA synthesis was observed. Compared with TPA exposure alone, the fraction of cells with induced lymphoblastoid-plasmacytoid morphology increased and Ig secretion was enhanced. By a 1-hr TPA pulse followed by BSF-MP6, the DNA synthesis was further augmented, but less maturation was observed. T cell and monocyte removal, using cell sorting, showed that the DNA synthesis induced was independent of these cell types, also under serum-free conditions. Quantitation of several cell cycle-associated surface Ags showed that the 4F2, Ba, Bac-1, and cD23 Ags increased while the CD37 decreased in expression upon addition of BSF-MP6. We conclude that B-CLLs are inducible by TPA and BSF-MP6 not only to differentiation, but also to DNA synthesis even under serum-free conditions in vitro. The results furthermore suggest that the very low proliferation activity in B-CLL tumors in vivo may reflect a relative deficiency of proper growth and differentiation factors or a subnormal response of B-CLL cells to such factors.

Antigens, Differentiation, B-Lymphocyte↗

Low cytidine deaminase levels in human hematopoietic cell lines.

Purine and pyrimidine enzyme profiles of human cell lines have been investigated. A novel observation was the finding that most of the cell lines showed very low or undetectable levels of cytidine (deoxycytidine) deaminase, while they possessed pyrimidine 5'-nucleotidase, cytidine and deoxycytidine kinase activities. Most cell lines showed high levels of adenosine deaminase and purine nucleoside phosphorylase activities and low levels of purine 5'-nucleotidase. We propose that high adenosine deaminase and purine nucleoside phosphorylase activities and low cytidine deaminase activity may be of importance for immature hematopoietic cells in order to ensure a balanced synthesis of the DNA precursors.

Cell Line↗

Diagnostic and prognostic significance of serum measurements of lactoferrin, lysozyme and myeloperoxidase in acute myeloid leukemia (AML): recognition of a new variant, high-lactoferrin AML.

92 patients with acute myeloid leukemia were classified according to the FAB classification (M1 n = 20, M2 n = 43, M3 n = 1, M4 n = 19, M5a n = 2, M5b n = 2, and M6 n = 5 patients). Serum measurements of lactoferrin (LF), myeloperoxidase (MPO) and lysozyme (LYS) were performed before the start of treatment. LF was significantly lower in M1 when compared with M2 but not as compared to M4, MPO was significantly higher in M2 and M4 than in M1, but comparable MPO levels were found in M2 and M4. LYS was significantly elevated in M2 in comparison with M1, and in M4 when compared to both M1 and M2. Polymorphonuclear granulocytes (PMNs) in M1 were significantly reduced when compared with M2 and M4, whereas mononuclear cells were significantly increased in M4 in comparison with both M1 and M2. FAB classification did not generate any prognostic information. When the patients were, instead, subdivided according to LF levels were found prognostically significant differences. Of patients below 100 micrograms/l, 44% went into remission as compared to 77% with LF from 101 to 400 micrograms/l. In patients with LF levels above 400 micrograms/l the remission frequency was only 14%. Multivariate statistical analysis on the data further suggested that lactoferrin may be used as an independent prognostic indicator. We conclude that although determination of the serum-levels of lactoferrin, lysozyme and myeloperoxidase in certain cases may be valuable as a supplement to the morphological examination of acute myeloid leukemia, it is evident that none of the three determinations can be used alone to distinguish between the FAB groups.

Adult↗

Functional and morphological characterization of cultures of Kupffer cells and liver endothelial cells prepared by means of density separation in Percoll, and selective substrate adherence.

This paper presents a study on the structure and function of Kupffer cells (KC) and liver endothelial cells (LEC) isolated by a simple and rapid technique involving 1) perfusion of the liver with collagenase; 2) cell separation by means of density centrifugation in Percoll; and 3) cell culture, taking advantage of the fact that KC and LEC differ in their preferences for growth substrate. The KC, which attach and spread under serum-free conditions on surfaces of glass or plastic during the first 15 min in culture exhibit a typical macrophage-like morphology including membrane ruffling and a heterogenous content of vacuoles. Moreover, these cells express (a) Fc receptors (FcR) for binding and phagocytosis of erythrocytes covered with immune globulin G (E-IgG), and (b) complement receptors (CR) for binding and serum dependent phagocytosis of erythrocytes covered with either human C3b or mouse inactivated C3b (iC3b). The cells also bind fluid phase fluoresceinated C3b. Approximately 30% of the KC express immune response-associated (Ia)-antigens. The LEC attach and spread on fibronectin coated surfaces, but not on glass or plastic surfaces, during the first two hours in culture with or without serum, and are morphologically distinct from KC. Cultured LEC are well spread out with no membrane ruffling and with numerous large vesicles surrounding the regularly shaped nucleus. These cells bind, but do not ingest E-IgG via the FcR, but no binding of fluid phase C3b or particle fixed C3b or iC3b can be observed. Incubation of LEC with fluorescein amine conjugates of ovalbumin or formaldehyde treated serum albumin, but not with fluoresceinated native serum albumin, results in accumulation of fluorescence specifically localized in the large perinuclear vesicles. Neither KC nor any other cell types tested have the ability to accumulate fluorescence upon incubation with these compounds. Ia-antigens are not present on the LEC. Cytochemical demonstration of unspecific esterase, acid phosphatase, and peroxidase reveals different patterns and intensities of staining in KC as compared to LEC.

Animals↗

Alpha interferon treatment of patients with hairy-cell leukaemia.

We have treated 10 patients with hairy-cell, or hairy-cell-like leukaemia, for more than 6 months, with alpha interferon 3 X 10(6) IV/day I.M. or subcutaneously. All patients were severely pancytopenic before treatment. 7 patients had a typical hairy-cell leukaemia, whereas 3 lacked hairy cells but had the characteristic bone-marrow infiltration. The peripheral blood counts improved in all patients during treatment and the lymphoid infiltration of the bone-marrow was shown to decrease. 1 patient obtained complete remission, 6 partial remission and 3 had a minor response. It is concluded that alpha interferon is effective in the treatment of patients suffering from hairy-cell leukaemia.

Aged↗

Excision biopsy of the spleen by ultrasonic guidance.

Excision biopsy of the spleen was performed in 32 patients, using a recently invented instrument, which consists of a spring-trigger system for firing the two parts of a Tru-Cut needle. The biopsies were carried out under the guidance of an ultrasonic scanner. This technique yields sufficient material of high quality for a proper evaluation both of individual cells and the internal structure of the spleen. Eight patients had parenchymal abnormalities found by ultrasonic scanning: five had multiple abnormalities whereas three had a single abnormal area. Seven of these eight patients had a pathological spleen biopsy, consisting of Hodgkin's disease (four patients), "high-grade" malignant non-Hodgkin's lymphoma (two patients) or tuberculosis (one patient). In the other 24 patients with a normal ultrasonic picture of the splenic parenchyma five biopsies were pathological (3 cases of hairy-cell leukaemia, 1 of Gaucher's disease and 1 of Hodgkin's disease). Side-effects were: slight to moderate pain (16/32 patients) and bleeding requiring transfusion (4/32 patients). In one of these patients splenectomy was performed because of the bleeding. Two of the patients with bleeding complications suffered from hairy-cell leukaemia. It is concluded from this study that excision biopsy of the spleen is a diagnostic method which in some patients can replace splenectomy. The method seems to be valuable especially in patients with parenchymal abnormalities shown by ultrasonic scanning.

Adolescent↗

Bimodal differentiation prospectives for promyelocytes.

In accordance with the long-range goal to demonstrate the direct derivation of blood monocytes from promyelocytes in human bone marrow, the promyelocytic cell line HL-60 in the present study was differently stimulated with various inducers for the purpose of documenting its capability to evolve into granulocytes or monocytes-macrophages. Each differentiation line was monitored with the use of marker enzymes, antigens, and cell-specific monoclonal antibodies. In addition, studies were done on normal human bone marrow and leukemias. The results provided strong evidence for the close cytogeneic relationship of granulocytes and monocytes and for a common progenitor at the maturation stage of promyelocytes-myelocytes for both cell lineages.

Antibodies, Monoclonal↗

Alternative myelomonocytic differentiation of HL-60 reflects dual prospective potency of promyelocytes in human.

The permanent promyelocytic cell line HL-60 was subjected to stimulation with dimethyl sulfoxide (DMSO) and retinoic acid (RA), as well as 12-O-tetradecanoylphorbol-13-acetate (TPA) and lymphokine conditioned media for the induction of granulocytic or monocytic differentiation, respectively. Cells were investigated cytochemically using alpha-naphthylacetate esterase (acid esterase; AcE), naphthol AS-D chloroacetate esterase, and peroxidase reactions. In addition, the granulocyte or monocyte specific isoenzyme patterns of AcE as an intracytoplasmic property and the immunoreactivity to monoclonal antibodies recognizing granulocytes and monocytes (Ki-M2, Ki-M5) or monocytes alone (Ki-M1) were considered. The results indicated that HL-60 cell line bear the potency to evolve into granulocytes as well as monocytes. Additional studies performed on normal human bone marrow stained for AcE led to the conclusion that the myeloid cell line remains bipolar until the maturation stage of promyelocytes. Myelocytes being AcE positive only in 11.5 +/- 5.0 are heterogeneous and display the first indications of separated monocytic or granulocytic differentiation.

Antibodies, Monoclonal↗