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Biomedical subjects

L G Larsson

Publications and source records attributed to L G Larsson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Organization of radiotherapy and clinical oncology in Sweden. A historical review.

The organization of radiotherapy and oncology in Sweden is described, from the first small pioneer roentgen institutes, via the early Radiumhemmet and King Gustav V's Jubilee Clinics, up to the present organization with its regional coordinating oncologic centers and departments of oncology and radiotherapy at the regional hospitals, as well as some large central county hospitals. The great importance of Gösta Forssell's early organizing work and foresight for this development is underlined.

Health Facilities↗
PubMed1994

Preclinical evaluation of the reliability of a 50 MeV racetrack microtron.

PURPOSE: A 50 MeV racetrack microtron has been installed and tested at Memorial Sloan-Kettering Cancer Center. It is designed to execute multi-segment conformal therapy automatically under computer control using scanned X ray and electron beams from 10 to 50 MeV. Prior to acceptance of the machine from the manufacturer, formal reliability testing was carried out. Only in this way could confidence be gained in its usefulness for routine 3D computer-controlled conformal therapy. MATERIALS AND METHODS: To assess reliability, a set of 25 multi-segment test cases, each consisting of 10 to 17 fixed segments, was developed. The field arrangements and modalities for some of the test cases were identical to 3D conformal treatments that were being delivered with multiple static fields on conventional linear accelerators at our institution. Other cases were designed to explore reliability under more complex sets of conditions. These cases were "treated" repeatedly during a total period of 45 hours, over 5 days. During the treatments, ion chambers attached to the head of the machine provided dosimetric data for each field. Data from sensors connected to every set-up parameter (for example, couch positions, gantry angle, collimator leaf positions, etc.) were recorded and verified by an external computer. RESULTS: While preliminary tests indicated an interlock rate of 5%, final reliability test results demonstrated an interlock fault rate of approximately 0.5%. The reproducibility of dosimetric data and geometric setup parameters was within specifications. As an example, leaf position reproducibility in the patient plane was within 0.5 mm for 97% of the setups. The times required to carry out treatments were recorded and compared with the times to carry out identical treatments on a conventional linear accelerator with cerrobend blocks. Areas where additional time savings can be achieved were identified. CONCLUSIONS: As an integral part of acceptance testing, the Scanditronix MM50 was rigorously tested for reliability. The machine successfully passed these tests, providing increased confidence in its usefulness for routine 3D conformal therapy.

Humans↗
PubMed1994

Ectopic expression of myc or myn down-regulates immunoglobulin transcription.

Co-transfection of expression vectors for c-myc or myn down-regulated the expression from a reporter plasmid containing the chloramphenicol-acetyl-transferase (CAT) gene, under the control of an immunoglobulin kappa promoter and the immunoglobulin heavy-chain enhancer. The effect was dose-dependent and an additive effect was seen when both expression vectors were transfected simultaneously. Deletion mutants lacking the leucine zipper region of c-myc were unable to down-regulate the transcription from the reporter construct. Reporter genes where the immunoglobulin enhancer had been exchanged with a SV40 enhancer or an immunoglobulin minimal enhancer were still down-regulated by a cotransfection with c-myc expression vectors. A minimal promoter containing an octamer motif responded to myc expression while a minimal promoter containing a SP1 motif did not. No direct interactions between myc, myn and Oct proteins could be detected either by band-shift analysis, or by co-translation in vitro followed by precipitation with SP6 kappa promoter bound to magnetic carriers. Furthermore, B cells from mice transgenic for myc showed aberrant expression of transcription factors.

Animals↗
PubMed1994

Expression of mad, mxi1, max and c-myc during induced differentiation of hematopoietic cells: opposite regulation of mad and c-myc.

The Myc proto-oncoprotein family is considered to play an important role in the control of cell growth and differentiation. It appears that the interaction of Myc with its heterodimeric partner Max is essential for Myc function. Recently two other partners of Max, called Mad and Mxi1, have been identified. In an effort to gain insight into the network of these four proteins we have started to analyse the expression of the c-myc, max, mad and mxi1 genes at the mRNA level during hematopoietic cell growth and differentiation. In the human myeloid cell lines U-937, HL-60 and ML-1 c-myc expression was down-regulated as shown previously after induction of differentiation, whereas the expression of max was only slightly affected. In contrast to these two genes the expression of mad was induced upon differentiation in the three cell lines by TPA, retinoic acid, vitamin D3, dimethyl sulfoxide, and interferon-gamma and remained elevated for at least 3 days. A kinetic analysis showed that the induction of mad in U-937 in response to TPA was rapid (15 min) and at least in part transcriptional, reminiscent of immediate early genes. The expression of mxi1 was induced in U-937 by some inducers but not in HL-60 or ML-1. Its induction occurred slowly, peaking around 48 h. These analysis thus suggest that the expression of mad and c-myc is inversely regulated during induced hematopoietic differentiation.

Cell Differentiation↗
PubMed1993

Benefits and disadvantages of joint hypermobility among musicians.

BACKGROUND: Joint hypermobility is considered to be both an advantage and a disadvantage. However, the degree of hypermobility in members of particular occupations requiring intense physical activity and the nature of the association between symptoms referable to specific joints and their hypermobility are unknown. METHODS: We interviewed 660 musicians (300 women and 360 men) about work-related symptoms such as joint pain and swelling and examined them for joint hypermobility according to a standard protocol. We then determined the relation between the mobility of their fingers, thumbs, elbows, knees, and spine and any symptoms referable to these regions. RESULTS: Five of the 96 musicians (5 percent) with hypermobility of the wrists, mostly instrumentalists who played the flute, violin, or piano, had pain and stiffness in this region, whereas 100 of the 564 musicians (18 percent) without such hypermobility had symptoms (P = 0.001). Hypermobility of the elbow was associated with symptoms in only 1 of 208 musicians (< 1 percent), whereas 7 of 452 (2 percent) without this hypermobility had symptoms (P = 0.45). Among the 132 musicians who had hypermobile knees, 6 (5 percent) had symptoms, whereas only 1 of 528 (< 1 percent) with normal knees had symptoms (P < 0.001). Of the 462 musicians who had normal mobility of the spine, 50 (11 percent) had symptoms involving the back, as compared with 46 of the 198 musicians (23 percent) who had hypermobility of the spine (P < 0.001). CONCLUSIONS: Among musicians who play instruments requiring repetitive motion, hypermobility of joints such as the wrists and elbows may be an asset, whereas hypermobility of less frequently moved joints such as the knees and spine may be a liability.

Adolescent↗
PubMed1993

Hypermobility: prevalence and features in a Swedish population.

In this investigation, parallel to an earlier study [1] of 660 musicians from the USA, 606 individuals from a factory in Ostersund, Sweden, were studied to determine the prevalence and nature of their hypermobility. They were examined using the same protocol and by the same examiner as in the earlier study for the presence of five well recognized features of hypermobility. In this mostly middle-aged population of workers, as in the earlier population of mostly young musicians, joint laxity was found to be far more common among females. In both sexes hypermobility is seen to decline with age, the rate of fall being about the same for men and women.

Adult↗
PubMed1993

Expression of a mast cell tryptase in the human monocytic cell lines U-937 and Mono Mac 6.

Expression of a mast cell tryptase mRNA was detected in two human monocytic cell lines, the U-937 and the Mono Mac 6, and in normal human peripheral blood (PB) monocytes. In the U-937 cell line but not in normal PB monocytes, the tryptase expression was upregulated 3-50 fold following phorbol ester (PMA)-induced differentiation, but no such induction was seen after retinoic acid, interferon-gamma or vitamin D3 exposure. The tryptases expressed in PMA-induced and non-induced U-937 and in Mono Mac 6 were characterized by PCR amplification and nucleotide sequence analysis. The U-937 cell line was found to express a tryptase identical to one of the previously cloned mast-cell beta tryptases (Tryptase I), and the tryptase expressed in Mono Mac 6 was found to be nearly identical to the previously cloned alpha tryptase. By northern blot analysis with oligonucleotide probes specific for the alpha and beta tryptases both cell lines were found to express only one type of tryptase. Densitometric quantifications of tryptase mRNA levels, in the two cell lines, showed approximately 80 times higher mRNA levels in Mono Mac 6 compared to non-induced U-937. Immunohistochemical staining for tryptase showed a marked heterogeneity in the Mono Mac 6 cell line. Only one out of 10 cells were positive for the protein but the levels in these cells were very high, equivalent, or even higher than the levels seen in the human mast cell line HMC-1. This shows that the expression of a single tryptase, in this case the alpha tryptase, is sufficient for the production of a stable protein and probably also a stable proteolytically active tetramer. The family of human mast-cell tryptases has been considered to represent a class of proteases specifically expressed in mast cells and basophilic leucocytes. The expression of tryptases in two monocytic cell lines and in normal PB monocytes indicate that in humans, the lineage specificity of these serine proteases is less restricted than earlier expected. The cloning of a full length cDNA for the murine counterpart to the human mast cell tryptases, the MMCP-6, is presented. No expression of the MMCP-6 was detected in a panel of mouse monocyte or macrophage cell lines indicating a species difference in the lineage specificity of the 'mast cell tryptases'.

Animals↗
PubMed1993

The role of Bcl-2 in the pathogenesis of B chronic lymphocytic leukemia.

At least three categories of genes are envisaged to be involved in the natural history of B-CLL. First, the genes that are responsible for the transforming event(s) in the (presently unknown) target cell; second, the gene(s) that help the progressive accumulation of malignant cells and finally the gene(s) that cause the progression toward a more aggressive lymphoma. The possibility that the clonal expansion of B-CLL is due to a prolonged life-span of monoclonal B cells rather than to an acceleration of their proliferative activity may now be reinterpreted by taking into account some recent findings on the expression of Bcl-2 gene in B-CLL cells. The Bcl-2 gene product regulates programmed cell death and a number of experiments suggest that Bcl-2 is involved in the selection and maintenance of long-lived memory B cells rescuing them from apoptotic death and leading to their accumulation in the GO phase of the cell cycle. Variant chromosomal translocations have been detected in a small fraction (5-10%) of B-CLL, involving Bcl-2 and the Ig light chain gene. Despite the low percentage of Bcl-2 rearrangements the expression of mRNA and protein is appreciable in most samples of fresh B-CLL cells in an amount comparable to that observed in Karpas 422 cells, which contain a t(14;18).(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗
PubMed1993

Interleukin-2 enhances the production of tumor necrosis factor-alpha in activated B-type chronic lymphocytic leukemia (B-CLL) cells.

Tumor necrosis factor-alpha (TNF-alpha) has recently been implicated as a regulator growth and differentiation of normal and malignant B cells. We utilized a selected clone (I-83) of primary resting B-type chronic lymphocytic leukemia (B-CLL) cells, inducible to activation, growth and differentiation in vitro, as a model system to study the possible role of TNF-alpha as an autocrine growth factor for such cells. Our results show that unstimulated I-83 B-CLL cells produced a low level of TNF-alpha mRNA, as shown by Northern blot analysis, and cytoplasmic TNF-alpha, determined in individual cells by immunocytochemistry. Secreted TNF-alpha could, however, not be detected in the medium by ELISA. TNF-alpha synthesis and secretion was, however, induced to high levels by stimulation of the B-CLL cells with interleukin-2 (IL-2) after activation by 12-O-tetradecanoylphorbol-13-acetate (TPA) or Staphylococcus aureus Cowan strain I (SAC) and B-cell stimulatory factor-MP6 (thioredoxin). A moderate increase in TNF-alpha secretion was also induced by TPA or IL-2 alone. IL-4 did not have any major effects on the production of TNF-alpha in activated cells, but inhibited the IL-2-induced production of TNF-alpha in SAC-activated cells. The cell surface expression of TNF-alpha receptors (TNF-R), as determined by binding assay using 125I-labelled recombinant TNF-alpha (rTNF-alpha), was also induced after SAC or TPA activation, but shed receptors (TNF-binding proteins) were only observed after TPA activation. Exogenously added rTNF-alpha in combination with TPA or SAC induced a high level of DNA synthesis in I-83 B-CLL cells. The increased endogenous production and secretion of TNF-alpha during induced growth stimulation, the induced expression of TNF-R, and the mitogenic effect of TNF-alpha on activated B-CLL cells raise the question whether TNF-alpha may function as an autocrine co-stimulator of B-CLL cell growth as recently suggested. anti-TNF-alpha and anti-TNF-R antibodies, however, failed to inhibit the IL-2- and IL-4-induced proliferation of activated I-83 B-CLL cells.

DNA, Neoplasm↗
PubMed1992

Suppression of basal, PMA- and IFN-alpha-, but not IFN-gamma-induced expression of HLA class I in v-myc-transformed U-937 monoblasts.

Recent studies have suggested that certain oncogenes, in particular members of the myc family, may be involved in the down-regulation of HLA class-I antigen expression observed in many types of tumor. We report that constitutive expression of an OK10 v-myc gene in human monoblastic U-937 cells results in a reduced expression of HLA class-I cell-surface expression and decreased levels of HLA class-I protein and mRNA. All class-I alleles, with the possible exception of HLA A3, were affected, as shown by one-dimensional isoelectric focusing (ID-IEF). Basal expression of the beta 2m chain was also reduced, although to a lesser extent. In addition, we show that the PMA-, and at least partially the IFN-alpha-induced increase in HLA class-I antigen expression, was inhibited in U-937-myc cells both at the protein and the mRNA level. In contrast, the response to IFN-gamma was normal. Another important difference in the response to IFN-gamma and alpha was that, while IFN-gamma abrogated the v-myc block of PMA-induced differentiation of U-937 cells, as previously reported, IFN-alpha did not. Our data show that v-myc negatively affects the regulation of both basal and inducible HLA class-I antigen expression.

Alleles↗
PubMed1992

Growth- and differentiation-associated expression of bcl-2 in B-chronic lymphocytic leukemia cells.

The bcl-2 gene is translocated into the Ig loci in about 80% of human follicular lymphomas and in 10% of B-type chronic lymphocytic leukemias (B-CLL), resulting in a high level of expression. We have compared the expression of bcl-2 transcripts and protein in B-CLL cells in their normal equivalent CD5+ B cells and in normal B-cell populations representative of different in vivo and in vitro stages of activation and proliferation. We report here that bcl-2 was expressed in 11 of 11 cases of CD5+ B-CLL clones, contrasting with the absent expression in normal CD5+ B cells. Activation of 173 and 183 B-CLL cells by phorbol esters (12-O-tetradecanoylphorbol-13-acetate [TPA]) to IgM secretion without concomitant DNA synthesis resulted in a rapid but transient downregulation of bcl-2 expression. In contrast, the reduction of bcl-2 at both the messenger RNA and protein levels was sustained after mitogenic stimulation, suggesting that bcl-2 expression and proliferation are inversely related in these cells. This notion was further supported by immunocytochemical analysis showing that bcl-2 was primarily expressed in small resting lymphocytes and in cells differentiating to the plasma cell stage, but less expressed in Ki67-positive proliferating B blasts. Moreover, it was also supported by the low level of bcl-2 in exponentially growing Epstein-Barr virus-carrying lymphoblastoid and B-CLL cell lines. The regulation of bcl-2 expression in B-CLL resembled that of normal tonsillar follicular B cells, in which a high level of expression was found in resting mantle zone B cells but not in the proliferating germinal center B cells. Based on these findings and the role of bcl-2 in maintaining B-cell memory, we propose that the phenotype of B-CLL cells corresponds to a mantle zone memory-type B cell.

Aged↗
PubMed1992

Expression of myc-family genes in established human multiple myeloma cell lines: L-myc but not c-myc gene expression in the U-266 myeloma cell line.

Deregulated c-myc expression, as a consequence of translocation of the c-myc gene to one of the immunoglobulin loci, appears to play an important role in the pathogenesis of several B-cell tumors, including Burkitt's lymphoma, mouse plasmacytoma and rat immunocytoma. This study investigated the expression of c-myc and 2 other members of the myc gene family, L- and N-myc, at the mRNA and protein level, and analyzed for possible rearrangements of these genes in the human counterpart to the mouse plasmacytoma--multiple myeloma (MM). Nine well-characterized MM cell lines were examined by using Northern- and Southern-blot analysis and immunoprecipitation. The c-myc gene was found to be highly expressed in most MM cell lines. The level of expression was comparable to that observed in the COLO 320 and HL-60 cell lines, carrying amplified c-myc genes, and to that of B-cell lines with a higher proliferative activity than the MM cell lines. In the U-266 MM cell line, L-myc, but no c-myc mRNA or protein, was found. The L-myc gene was expressed in both early- and late-passage U-266 cells, suggesting that the L-myc expression was not the result of the in vitro cultivation. N-myc was not expressed in any of the MM cell lines. No rearrangements of c-myc or L-myc genes were found. We thus conclude that (a) in contrast to the corresponding mouse and rat B-cell tumors, c-myc is not frequently rearranged in MM; (b) c-myc is highly expressed in most MM lines; and (c) L-myc but not c-myc is expressed in the U-266 MM cell line.

DNA, Neoplasm↗
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

Molecular investigation of the cytokines produced by normal and malignant B lymphocytes.

Different normal and malignant human B-cell populations were studied with a twofold aim: to define which cytokines are produced in vivo, and to assess the relationship between cytokine production and kinetic state. To analyse normal B-cells representative of different stages of activation and proliferation in vivo, we purified germinal centre (GC)-B blasts and mantle B (M-B) cells from tonsils. To compare malignant B lymphocytes with their closest normal equivalent cells, we separated malignant CD5+B lymphocytes from the peripheral blood of patients with B-chronic lymphocytic leukemia (B-CLL) and normal CD5+B lymphocytes from cord blood. The expression of interleukins (IL) IL-1 alpha, IL-1 beta, tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), IL-2, IL-4, and IL-6 genes was analysed using Northern and Western blotting techniques. TNF-alpha mRNA is produced by resting (M-B) and actively proliferating (GC-B) normal B lymphocytes. TGF-beta mRNA is present at high levels in resting normal M-B cells, while the transcript levels are lower in proliferating GC-B and in activated CD5+B lymphocytes. IL-2 production is limited to the actively proliferating GC-B blasts, IL-1 beta and IL-6 to resting M-B cells. The cytokine production profile of CD5+ malignant B-CLL cells differs from that of their putative normal counterparts and is more like the profile of M-B cells, since B-CLL cells produce IL-1 beta, TNF-alpha, TGF-beta, and IL-6. These observations lead to the following conclusions: among normal B lymphocyte populations, resting M-B lymphocytes are the most active cytokine producers, and B-CLL malignant B cells reflect the production pattern of normal resting B lymphocytes.

Antigens, CD↗
PubMed1991

Cancer risk after iodine-131 therapy for hyperthyroidism.

Cancer incidence was studied in 10,552 patients (mean age, 57 years) who received 131I therapy (mean dose, 506 MBq) for hyperthyroidism between 1950 and 1975. Follow-up on these patients was continued for an average of 15 years. Record linkage with the Swedish Cancer Register for the period 1958-1985 identified 1543 cancers occurring 1 year or more after 131I treatment, and the standardized incidence ratio (SIR) was 1.06 (95% confidence interval = 1.01-1.11). Significantly increased SIRs were observed for cancers of the lung (SIR = 1.32; n = 105) and kidney (SIR = 1.39; n = 66). Among 10-year survivors, significantly elevated risks were seen for cancers of the stomach (SIR = 1.33; n = 58), kidney (SIR = 1.51; n = 37), and brain (SIR = 1.63; n = 30). Only the risk for stomach cancer, however, increased over time (P less than .05) and with increasing activity administered (P = not significant). The risk for malignant lymphoma was significantly below expectation (SIR = 0.53; n = 11). Overall cancer risk did not increase with administered 131I dose or with time since exposure. The absence of any increase in leukemia adds further support to the view that a radiation dose delivered gradually over time is less carcinogenic than the same total dose received over a short time. Only for stomach cancer was a possible radiogenic excess suggested.

Adolescent↗