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S Pettersson

Publications and source records attributed to S Pettersson.

At least 55 records · Page 3Linked to original sources
PubMed1997

Extracorporeal shock wave lithotripsy for the treatment of renal stones. Treatment policy is as important for success as type of lithotriptor and patient selection.

OBJECTIVE: To compare the efficiency of different machines for extracorporeal shock wave lithotripsy (ESWL) of renal stones and to analyze treatment strategies and stone characteristics as determinants of treatment failure. DESIGN: Prospective cohort study. SETTING: Nationwide study in Sweden. All 11 hospitals in Sweden using 1 of 7 lithotriptors in 1991 were included. PATIENTS: The study cohort comprised 1171 (97.6%) of the 1200 patients in Sweden who underwent ESWL for the first time because of renal stones between February 18, 1991, and December 31, 1991. MAIN OUTCOME MEASURE: Treatment failure, defined as 1 or more residual renal stone fragments larger than 4 mm 1 of 3 months after the end of treatment, was analyzed after ESWL monotherapy and after ESWL plus auxiliary treatment using a multivariate analysis. RESULTS: Treatment failure varied by center from 12% to 48% (mean, 24%) after ESWL monotherapy and from 4% to 40% (mean, 18%) after ESWL plus auxiliary procedures. After adjusting for differences in the patient mix, the risk of treatment failure, measured as the odds ratio, varied by center almost 7-fold after ESWL monotherapy and 20-fold after ESWL plus auxiliary treatment. Substantial differences also existed for the same equipment used at different centers. The risk of treatment failure increased rapidly for renal stones larger than 15 mm, and it was at least 2-fold higher in patients who had multiple stones or a cavity. CONCLUSIONS: When ESWL is used for the treatment of renal stones, the treatment policy has as great an effect on the success rate and need for auxiliary treatment as optimal equipment and proper patient selection. Meaningful comparisons of different lithotriptors require multivariate analyses with adjustment for patient selection.

Female↗
PubMed1997

NFE, a new transcriptional activator that facilitates p50 and c-Rel-dependent IgH 3' enhancer activity.

The induction of immunoglobulin heavy chain (IgH) 3' enhancer activity has been coupled to ligand/receptor-dependent activation of resting B cells. To search for transcriptional target sites that account for this induction, extracts from lipopolysaccharide (LPS)-stimulated B cells and cell lines were used. Here we describe, by gel-retardation analysis, the identification of an NF-kappaB site and an adjacent nuclear factor ets-like (NFE) site in the 3' enhancer. The NFE motif binds four protein complexes in resting B cell extracts, of which two are down-regulated upon LPS stimulation. Gel shift-shift experiments of the NF-kappaB complexes with specific antibodies identified p50 and c-Rel proteins to be the predominant factors in primary LPS-stimulated cell extracts. Site-directed mutagenesis of these motifs demonstrates that they contribute to part of the enhancer activity in plasma cells. One copy of the NFkappaB/NFE motifs, linked to a heterologous reporter construct, displays lymphoid-restricted reporter gene activity in transient transfection assays. Mutation of either site abrogates all promoter activity. Complementation experiments demonstrate that although p50 and c-Rel expression vectors reconstitute transcription of an intact NF-kappaB/NFE reporter construct in a dose-dependent manner, mutation of the NFE site or the NF-kappaB site abrogates essentially all transcriptional activity in both plasma cells and in COS cells. Taken together, we provide evidence for the existence of an activator, NFE, which in combination with the p50 and c-Rel proteins, are part of the transcription factor machinery that regulates 3' enhancer activity, and thus the control of the IgH locus in late B lymphocyte development.

Animals↗
PubMed1997

Concomitant downregulation of IgH 3' enhancer activity and c-myc expression in a plasmacytoma x fibroblast environment: implications for dysregulation of translocated c-myc.

Regulation of immunoglobulin heavy chain (IgH) gene expression is controlled by a B cell-specific promoter, intronic enhancer and additional B cell-specific enhancer elements identified recently in the 3' end of the IgH locus. One of the latter elements, the IgH 3' enhancer, is of particular interest: (1) it is B cell-specific and active only in late B cell development; (2) in rodent plasmacytomas and in some human Burkitt's lymphomas it is part of a locus control region (LCR) that is involved in deregulation of the c-myc oncogene as a result of translocation into the IgH locus; and (3) it has been implicated in the mechanisms that control Ig gene class switch recombination. We have used a somatic cell hybridization approach to genetically analyse regulation of the activity of the IgH 3' enhancer. When mouse MPC11 plasmacytoma cells, in which the IgH 3' enhancer is active, are fused with fibroblasts, Ig expression is extinguished at the level of transcription. Here we show that in a MPC11 plasmacytoma x fibroblast environment, the IgH 3' enhancer is transcriptionally inactive. Furthermore, we demonstrate that binding of several B cell-specific transcription factors, essential for IgH 3' enhancer activity, is lacking, which may explain 3' enhancer inactivity, although the binding of repressors cannot be excluded. Moreover, the high expression level of c-myc, characteristic of the parental MPC11 cells carrying the t(12;15) translocation, is down-regulated in the hybrids to that in unfused fibroblasts. Therefore, inactivation of the IgH 3' enhancer is a multifactorial process affecting several transcription factors that control the cell-specific and developmental activity of the enhancer.

Animals↗
PubMed1997

The enhancer shift: a model to explain the developmental control of IgH gene expression in B-lineage cells.

The roles attributed to the E mu enhancer and the downstream 3' regions acting as locus control regions (LCRs) have allowed comparisons to be drawn between regulation of the IgH locus in early and late B-cell development and other systems governed by LCR activity. Here, the importance of the IgH 3'LCR and its putative functional role in the control of IgH gene expression is evaluated and compared with the 5'LCR regulatory region of the human beta-globin locus.

B-Lymphocytes↗
PubMed1997

Combined treatment with temporary short-term high dose rate iridium-192 brachytherapy and external beam radiotherapy for irradiation of localized prostatic carcinoma.

PURPOSE: To evaluate the treatment outcome after radical radiotherapy of localized prostate cancer in 50 patients (38 patients with stage T1-2 and 12 patients with stage T3) after a median follow-up time of 45 months (range 18-92 months). METHODS: The treatment was given by combination of external beam radiotherapy (50 Gy) and brachytherapy (2 x 10 Gy). The brachytherapy was given using TRUS-guided percutaneously inserted temporary needles with a high dose rate remote afterloading technique with Ir-192 as the radionuclide source. Three target definitions and dose levels inside the prostate gland were used. Local control was evaluated by digital rectal examination, TRUS-guided biopsies and serum PSA evaluations. RESULTS: Clinical and biopsy verified local control was achieved in 48 of the 50 (96%) patients; for stage T1-2 in 37 of 38 (97%) patients and for stage T3 in 11 of 12 (92%) patients. A posttreatment serum PSA level < or =1.0 ng/ml was seen in 42 (84%) patients, values from >1.0 to < or =2.0 ng/ml were seen in four (8%) patients and values exceeding 2.0 were seen in four (8%) patients. The late toxicity was minimal. CONCLUSION: The local control results and the minimal toxicity after the combined radiotherapy treatment are promising. However, long term results are necessary before general use.

Aged↗
PubMed1997

Predominant role of NF-kappa B p65 in the pathogenesis of chronic intestinal inflammation.

NF-kappa B is a key transcription factor of lymphocytes and macrophages with important regulatory functions in the immune system and inflammatory processes. These functions are at least partially based on its ability to regulate the promoters of a variety of genes whose products, such as cytokines, adhesion molecules and acute phase proteins, are critical for inflammatory processes. In the present study, we describe a method to treat established intestinal inflammation by local or systemic application of antisense phosphorothioate oligonucleotides targeting the translation start site of the p65 subunit of NF-kappa B. Specific downregulation of p65 by administration of antisense phosphorothioate oligonucleotides to mice with experimental colitis abrogated clinical and histological signs of mucosal inflammation. In contrast, control nonsense oligonucleotides were virtually inactive. Whereas systemic application of high doses (> 1500 micrograms) of p65 antisense oligonucleotides had striking toxic side effects, local application at all dosages tested did not result in toxic effects. The data provide direct evidence for the central importance of NF-kappa B p65 in experimental models of chronic intestinal inflammation and suggest the potential therapeutic utility of local p65 antisense treatment for patients with chronic intestinal inflammation.

Animals↗
PubMed1997

Temporal control of IgH gene expression in developing B cells by the 3' locus control region.

The suggested roles of the downstream 3' regions acting as a Locus Control Region (LCR), have allowed comparisons to be made between the regulation of the IgH locus with other model systems whose gene expression is governed by LCR activity. Here we summarize the importance of the IgH 3'LCR and its putative functional role in IgH gene expression and compare it with the 5'LCR regulatory region of the human beta-globin locus.

Animals↗
PubMed1997

Effects of pretreatment with an indeno-indole compound on lipid peroxidation in the cortex and medulla of rabbit kidneys after ischaemia-reperfusion.

The effects of 60 min of ischaemia with or without reoxygenation in vivo or in vitro on lipid peroxidation in cortical and medullary tissue from rabbit kidneys were measured as production of thiobarbituric acid-reactive substances (TBARS). Lipid peroxidation was more pronounced in medullary tissue compared with cortical tissue. The highest TBARS production was found in medullary slices subjected to reoxygenation in vitro immediately after 1 h of ischaemia. Reperfusion in vivo before reoxygenation in vitro attenuated the TBARS formation during subsequent in vitro incubation. Pretreatment of the rabbits with an indeno-indole compound (code name H 290/51) reduced the TBARS formation after 60 min of ischaemia and reoxygenation in vitro towards control values.

Animals↗
PubMed1997

Selective usage of VH genes in adult human B lymphocyte repertoires.

The authors have compared the VH gene utilization patterns among small resting immunocompetent B cells and large naturally activated B lymphocytes of healthy human adults. They employed a non-radioactive RNA in situ hybridization technique that allows detection of VH gene family expression at the single cell level. Pokeweed mitogen stimulated and unmanipulated mononuclear cells from peripheral blood and spleen of unrelated individuals were hybridized to digoxigenin-labelled antisense RNA probes specific for human VH families 1-6 and for the constant region genes C mu and C gamma. The observed VH gene family utilization patterns did not correlate with the genomic complexity of human VH genes. The VH3 gene family was most frequently used among resting B cells in both peripheral blood and spleen. Among naturally activated lymphocytes the VH6 gene was markedly over-represented, while expression of the VH1 and VH3 gene families was decreased. The data show that V-region mediated selection participates in shaping the peripheral antibody repertoire in healthy adults.

Adult↗
PubMed1997

High-energy transurethral microwave thermotherapy for large severely obstructing prostates and the use of biodegradable stents to avoid catheterization after treatment.

OBJECTIVE: To assess the use of high-energy transurethral microwave thermotherapy (TUMT) for large severely obstructing benign prostatic hyperplasia (BPH) and to compare the use of a biodegradable stent with that of a urethral Foley catheter after TUMT. PATIENTS AND METHODS: The study comprised 30 men (mean age 71 years, range 49-82) scheduled for prostatectomy for symptomatic BPH. Pre-operative investigations included the measurement of urinary free flow rate, residual urine volume (ultrasonographically), a digital rectal examination, transrectal ultrasonography, a symptom score, cystoscopy, cystometry and pressure-flow. The obstruction was graded according to the Schäfer nomogram. The patients were treated using the Prostatron (EDAP-Technorned, France) TUMT system; the software used provided a maximum power of 70 W. Patients were catheterised after treatment with either a Foley catheter or a biodegradable stent. After 3 months, the measurements and obstruction grading were repeated, and the effect of the stent assessed. RESULTS: In the entire group, the mean (SD) free flow increased from 7.7 (2.4) to 14.0 (3.3) mL/s, the residual urine decreased from 125 (86) to 23 (25) mL and the symptom score decreased from 16 (8) to 5 (4). The mean (SD) degree of obstruction decreased from 81.0 (16) to 62.6 (15). The biodegradable stent completely avoided post-treatment retention. CONCLUSION: High-energy TUMT can be used on large severely obstructing prostates with major subjective and objective improvements. The biodegradable stent is useful in relieving the problems of catheterization after treatment.

Aged↗
PubMed1997

Examination of intrarenal blood flow by Doppler ultrasound before and after extracorporeal shock wave lithotripsy for urolithiasis.

This study was aimed to test whether therapeutical extracorporeal shock wave lithotripsy (ESWL) may induce changes in renal parenchymatous blood flow, thereby indirectly indicating shock wave side effects on the renal parenchyma. In 18 patients, a Duplex ultrasound investigation of both kidneys was performed before and after ESWL. Pulsatility Index (PI), which is an estimation of renovascular resistance, increased in both treated and untreated kidney. However, the increase was confined to a subgroup of seven patients, who had received meperidine (a morphine analgetic) for analgesia. This increase is more likely to be due to a pharmacological effect of meperidine rather than a direct effect of ESWL on renal hemodynamics. In conclusion, we did not find any evidence of ESWL related affection of renal blood flow measured with duplex ultrasound, a technique sensitive enough to detect changes in renal hemodynamics due to morphine analgetics.

Adult↗
PubMed1996

A T cell controlled molecular pathway regulating the IgH locus: CD40-mediated activation of the IgH 3' enhancer.

Immunoglobulin heavy chain (IgH) class switch recombination and regulation of IgH expression levels are processes suggested to be controlled by the IgH 3' enhancer. Here we demonstrate that CD40 or IgM receptor stimulation of primary B cells results in transactivation of this enhancer. 4-Hydroxy-3-nitrophenylacetyl (NIP)-BSA induction of a K46 B cell line expressing a chimeric NIP-specific CD40 single chain receptor results in a ligand receptor-dependent response of a 3' enhancer ETS/AP-1 minimal promoter construct. Gel retardation analysis and genomic footprinting experiments reveal that CD40 or IgM induction recruits NFAB (nuclear factors of activated B cells) to the ETS/AP-1 motif. While IgM signalling recruits c-Fos, JunB and Elf-1 (NFAB-I), only JunB and Elf-1 were observed following CD40 signalling (NFAB-II). CD40 signalling, however, induces a Fos family-related partner for JunB, which may account for the transcriptional activity observed by NFAB-II in K46 cells. We propose a model whereby CD40 and IgM receptor-mediated signalling converge in the process of 3' enhancer activation in B lymphocytes. Our data provide a putative molecular explanation as to why CD40L-deficient mice, and possibly patients with hyper-IgM syndrome, are unable to undergo T cell-dependent class switch recombination but respond properly upon lipopolysaccharide-induced switch recombination.

Animals↗
PubMed1996

Physiological activation of the IgH 3' enhancer in B lineage cells is not blocked by Pax-5.

The mouse 3' enhancer contains a high-affinity binding site for the paired box protein Pax-5. Here, we demonstrate by genomic footprinting that the rat 3' enhancer contains a low-affinity binding site for Pax-5, which is occupied in activated splenic B cells. Thus, binding of Pax-5 to the IgH 3' enhancer appears to be evolutionarily conserved in rodents. Analysis of Pax-5 expression in primary B cells demonstrates that Pax-5 remains expressed after 4 days of lipopolysaccharide (LPS) induction, but is down-regulated in 5-day stimulated cells. Similarly, the expression of Pax-5 is down-regulated in vivo in activated large splenocytes, in contrast to small resting cells. Multimerization of the high-affinity Pax-5 binding site linked to a heterologous reporter gene demonstrates that Pax-5 can function as a transcriptional activator. In contrast, Pax-5 overexpressed in cell lines represses both the mouse and the rat 3' enhancer. Surprinsingly, cross-linking of the IgM receptor in BAL-17 cells containing a stably integrated 3' enhancer-dependent beta globin reporter gene demonstrates that induction of 3' enhancer activity is not blocked by Pax-5. Moreover, stimulation of 3' enhancer beta globin-transgenic splenocytes demonstrate that Pax-5 cannot repress-activation of the 3' enhancer upon LPS induction or CD40 receptor stimulation. Hence, activation of the IgH 3' enhancer occurs independently of changes in Pax-5 gene expression. This indicates that previous studies conducted in vitro may be an oversimplification of the function of Pax-5 and 3' enhancer activity.

Animals↗
PubMed1996

Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mice.

Chronic intestinal inflammation induced by 2,4,6,-trinitrobenzene sulfonic acid (TNBS) is characterized by a transmural granulomatous colitis that mimics some characteristics of human Crohn's disease. Here, we show that the transcription factor NF-kappa B p65 was strongly activated in TNBS-induced colitis and in colitis of interleukin-10-deficient mice. Local administration of p65 antisense phosphorothioate oligonucleotides abrogated clinical and histological signs of colitis and was more effective in treating TNBS-induced colitis than single or daily administration of glucocorticoids. The data provide direct evidence for the central importance of p65 in chronic intestinal inflammation and suggest a potential therapeutic utility of p65 antisense oligonucleotides as a novel molecular approach for the treatment of patients with Crohn's disease.

Adrenal Cortex Hormones↗
PubMed1996

Effect of a new inhibitor of lipid peroxidation on kidney function after ischaemia-reperfusion. A study on rat and rabbit kidneys.

Lipid peroxidation of mitochondrial and cell membrane structures is the final step in the oxygen radical-induced damage observed at reperfusion of kidneys after ischaemia. We compared the ability of an indeno-indol compound (code name H290/51) with that of alpha-tocopherol to inhibit lipid peroxidation in reoxygenated isolated rat renal tissue in vitro measured as production of TBARS (thiobarbituric acid reactive substances). H290/51 was 100 times more efficient than alpha-tocopherol. Treatment of rats in vivo with H290/51 in a dosage giving a plasma concentration of 500 nmol L-1 inhibited TBARS production measured in vitro by 80%. Treatment of rabbits with H290/51 almost completely inhibited radical production at reperfusion after 60 min of ischaemia measured with spin trap technique using OXANOH (2-ethyl-3-hydroxy-2,4,4-trimethyloxazolidine) as a spin trap. Furthermore, such pretreatment significantly improved kidney function and survival of rabbits subjected to 60 min of ischaemia to the left kidney and contralateral nephrectomy. These studies stress the importance of inhibiting lipid peroxidation to prevent the ischaemia-reperfusion damage and furthermore suggest a role for treatment with antioxidants like H290/51 in clinical practice, e.g. at reconstructive renal surgery and transplantation.

Animals↗
PubMed1996

Concrement formation and urease-induced crystallization in urine from patients with continent ileal reservoirs.

OBJECTIVES: To study the relationship between urinary tract infection, urine composition and concrement formation in patients with continent ileal reservoirs for urinary diversion. PATIENTS AND METHODS: The study comprised 27 patients (seven men and 20 women, mean age 47 years, range 23-76) with continent ileal reservoirs who were followed for a mean of 67 months (range 13-146) by annual reservoiroscopy, intravenous urography and urine culture; at the final follow-up, a sample of their morning urine was analysed for a range of compounds and the number and size of any particles present or produced in response to incubation with urease. RESULTS: The presence of urease-producing bacteria was associated with the formation of concrement. However, a few patients in whom an infection with urease-producing organisms was not detected also formed concrement. Urine from those patients forming stones tended to have a high calcium and a low citrate concentration. After incubation with urease, significantly more and larger particles were formed in the urine from stone formers. There was a strong correlation (r = 0.8) between urinary calcium content and urinary pH when the urease-induced precipitation commenced, and between urinary calcium and the size and volume of the crystals developed (r = 0.9) after 4 h of incubation. CONCLUSIONS: There are many factors which might influence the formation of concrement, e.g. outflow conditions, the presence of staples or infection in the reservoir, and the composition of the urine is also important. It thus appears appropriate to determine if measures to reduce urinary calcium and increase urinary citrate can decrease the episodes of stone formation in those patients with continent ileal reservoirs for urinary diversion who frequently form stones.

Adult↗
PubMed1996

Elevated expression levels of an Ig transgene in mice links the IgH 3' enhancer to the regulation of IgH expression.

To delineate the role of the IgH 3' enhancer in the regulation of Ig heavy (IgH) chain gene expression, mice harbouring rearranged IgH transgenes, with (PSVmu3) and without (PSVmu1) this element, were produced. RNA and protein analysis from the different transgenic lines revealed a 5- to 7-fold increase in the expression level of the transgene containing the IgH 3' enhancer. This difference is also reflected at the protein level in hybridomas generated from the two transgenic lines. The elevation of transgene Ig expression in the PSVmu3 lines is restricted to activated B lymphocytes, an observation which is further supported by the ability of this transgene to be reactivated upon immunization. Interestingly, although the up-regulation of transgene expression in PSVmu3 animals is considerably higher in comparison to the PSVmu1 animals, a significant response is still observed in the PSVmu1 mice. We speculate therefore that the IgH locus is subject to transcriptional modification in late B cell development. Our data suggest that both the Emu enhancer and the IgH 3' enhancer can up-regulate transgene Ig expression, but the presence of the 3' enhancer results in elevated levels of transgene Ig production. It therefore appears that the expression level of IgH genes is subject to transcriptional modification during B cell development. Additional control elements are most likely required for optimal Ig expression, since our expression data from the transgene in PSVmu3 animals are incompatible with endogenous Ig levels. The recent identification of additional enhancer elements in the far 3' end of the IgH locus supports this possibility. The data presented here provides a sound basis for the production of high levels of mAb, possibly tailored to suit the needs of the researcher.

Animals↗