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1.
  • Guerova, G., et al. (author)
  • National Status Reports
  • 2020
  • In: Advanced GNSS Tropospheric Products for Monitoring Severe Weather Events and Climate. - Cham : Springer International Publishing. - 9783030139001 ; , s. 403-481
  • Book chapter (other academic/artistic)abstract
    • In this section a summary of the national progress reports is given. GNSS4SWEC Management Committee (MC) members provided outline of the work conducted in their countries combining input from different partners involved. In the COST Action paticipated member from 32 COST countries, 1 Near Neighbour Country and 8 Intrantional Partners from Australia, Canada, Hong Kong and USA. The text reflects the state as of 1 January 2018.
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  • Friberg, Britt, et al. (author)
  • Endometrial destruction by thermal coagulation : Evaluation of a new form of treatment for menorrhagia
  • 1998
  • In: Gynaecological Endoscopy. - : Wiley. - 0962-1091 .- 1365-2508. ; 7:2, s. 73-78
  • Journal article (peer-reviewed)abstract
    • Objective. To report the first clinical evaluation of a new balloon endometrial, thermal destruction system Cavaterm®, for outpatient treatment of menorrhagia. Design. To elucidate possible technical problems during treatment, to evaluate how the patients tolerated the treatment and to judge which patients were suitable for this form of treatment. Main outcome measures. Measurements of bleeding volumes in pads and tampons before and after treatment were performed as well as subjective evaluation by bleeding charts. Patients also estimated their degree of satisfaction. Setting. Gynaecology department at a university hospital. Subjects. 36 patients under 52 pears of age with menorrhagia, without suspicion of intracavitary pathology including malignancy. Results. No procedure-related complications occurred. The patients tolerated the treatment well. There was a significant reduction in measured bleeding volumes in pads and tampons, collected during one menstruation, 2-7 months after treatment compared with measurements before treatment. Four patients subsequently underwent hysterectomy and should not have been included in the study (two with pedunculated myoma and one with a septum; the fourth showed premalignant endometrial changes in the curettage preceding the treatment). At 18-28-month follow up, 29 of the suitable patients (91%) reported a significant reduction in bleeding and another three patients reported reduced but still profuse bleeding compared with pretreatment; 88% (28/32) rated the treatment results as excellent, and a further 9% (3/32) as good. Conclusions. We found the Cavaterm® system for endometrial destruction to be safe, efficient and easy to use.
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6.
  • Fritzell, Peter, et al. (author)
  • Cost-effectiveness of lumbar fusion and nonsurgical treatment for chronic low back pain in the Swedish lumbar spine study : A multicenter, randomized, controlled trial from the Swedish Lumbar Spine Study Group
  • 2004
  • In: Spine. - : Lippincott Williams & Wilkins. - 0362-2436 .- 1528-1159. ; 29:4, s. 421-434
  • Journal article (peer-reviewed)abstract
    • Study Design. A cost-effectiveness study was performed from the societal and health care perspectives. Objective. To evaluate the costs-effectiveness of lumbar fusion for chronic low back pain (CLBP) during a 2-year follow-up. Summary of Background Data. A full economic evaluation comparing costs related to treatment effects in patients with CLBP is lacking. Patients and Methods. A total of 284 of 294 patients with CLBP for at least 2 years were randomized to either lumbar fusion or a nonsurgical control group. Costs for the health care sector ( direct costs), and costs associated with production losses ( indirect costs) were calculated. Societal total costs were identified as the sum of direct and indirect costs. Treatment effects were measured using patient global assessment of improvement, back pain ( VAS), functional disability (Owestry), and return to work. Results. The societal total cost per patient ( standard deviations) in the surgical group was significantly higher than in the nonsurgical group: Swedish kroner (SEK) 704,000 ( 254,000) vs. SEK 636,000 ( 208,000). The cost per patient for the health care sector was significantly higher for the surgical group, SEK 123,000 ( 60,100) vs. 65,200 ( 38,400) for the control group. All treatment effects were significantly better after surgery. The incremental cost-effectiveness ratio ( ICER), illustrating the extra cost per extra effect unit gained by using fusion instead of nonsurgical treatment, were for improvement: SEK 2,600 ( 600 - 5,900), for back pain: SEK 5,200 ( 1,100 - 11,500), for Oswestry: SEK 11,300 ( 1,200 - 48,000), and for return to work: SEK 4,100 ( 100 21,400). Conclusion. For both the society and the health care sectors, the 2-year costs for lumbar fusion was significantly higher compared with nonsurgical treatment but all treatment effects were significantly in favor of surgery. The probability of lumbar fusion being cost-effective increased with the value put on extra effect units gained by using surgery.
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11.
  • Sjunnesson, Håkan, et al. (author)
  • Five month persistence of Helicobacter pylori infection in guinea pigs
  • 2003
  • In: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463. ; 111:6, s. 634-642
  • Journal article (peer-reviewed)abstract
    • Seven Dunkin-Hartley guinea pigs were infected with the Sydney strain of H. pylori (SS1). Gastric histopathology was evaluated and serum antibody response to H. pylori cell-surface proteins was analysed by enzyme immunoassay (EIA) and immunoblot. Tissue and faecal samples from five control animals were analysed for the presence of naturally occurring Helicobacter spp. infection by culture and Helicobacter genus-specific PCR. The H. pylori infection persisted for 5 months, in most animals accompanied by a histologically severe antral gastritis, exhibiting focal degeneration and necrosis of gastric crypt epithelium. Increased numbers of mitotic figures were observed in the gastric epithelium, indicating a regenerative process. Infected animals displayed specific antibodies towards H. pylori cell-surface proteins in immunoblot, whereas EIA was of dubious value creating false-positive results. Serum complement C3 and cholesterol levels appeared to be elevated in infected animals. Helicobacter spp. infection was not detected in the control animals. The persistent infection, accompanied by severe gastritis and a prominent serum antibody response, and the apparent absence of a natural Helicobacter spp. infection makes the guinea pig model useful in H. pylori research.
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12.
  • Tallini, G, et al. (author)
  • Correlation between clinicopathological features and karyotype in 100 cartilaginous and chordoid tumours. A report from the Chromosomes and Morphology (CHAMP) Collaborative Study Group
  • 2002
  • In: Journal of Pathology. - : Wiley. - 0022-3417. ; 196:2, s. 194-203
  • Journal article (peer-reviewed)abstract
    • The evaluation of chondroid lesions requires full integration of clinical, radiographic, and pathological data; tumour typing is often a challenge for the diagnostic pathologist. Although a variety of chromosomal abnormalities have been documented in chondroid lesions, the potential usefulness of cytogenetic analysis remains unclear. This study has critically reviewed and analysed 117 karyotyped samples from 100 patients with cartilaginous and chordoid tumours. Cases were selected based on successful chromosomal analysis and adequacy of clinical, radiographic, and pathological information. To ensure objective evaluation, the cytogenetic results were correlated in a double-blind setting with consensus diagnoses independently determined on each case, after complete review of the histological, radiographic, and clinical findings. Karyotypic aberrations were identified in 41/92 cartilaginous tumours (5/11 osteochondromas, 2/3 chondromyxoid fibromas, 0/4 chondroblastomas, 11/29 chondromas, 0/3 chondroid tumours of undetermined malignant potential, 22/40 chondrosarcomas and 1/2 miscellaneous cartilaginous lesions) and 5/8 chordomas. Complex karyotypic changes were a feature of malignant tumours (chondrosarcoma and chordoma) and of chondrosarcoma among cartilaginous tumours, where they correlated with high tumour grade. Among primary well-differentiated cartilaginous lesions of bone, the finding of an abnormal karyotype was consistently associated with a grade 1 chondrosarcoma diagnosis. Among karyotypically abnormal cartilaginous tumours, loss of distal 8q was associated with osteochondroma, +5 with synovial chondroma/chondromatosis and parosteal or soft tissue chondroma, alterations of chromosome arm 6q with chondromyxoid fibroma, +7 with bone chondrosarcoma, and 17pl alterations with grade 3 chondrosarcoma. Alterations involving 12q13 characterized synovial chondroma/chondromatosis in the chondroma group and myxoid chondrosarcoma of bone in the chondrosarcoma group. In conclusion, cytogenetic abnormalities in chondroid lesions are common and are not randomly distributed. They are associated with malignancy/tumour grade as well as with specific diagnoses in many cases, and can therefore be of potential value for tumour typing.
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13.
  • Wang, X, et al. (author)
  • Infection of BALB/c A mice by spiral and coccoid forms of Helicobacter pylori
  • 1997
  • In: Journal of Medical Microbiology. - 0022-2615. ; 46:8, s. 657-663
  • Journal article (peer-reviewed)abstract
    • Helicobacter pylori exists in two different morphological forms, spiral and coccoid. This study demonstrated that both forms can infect BALB/c A mice. The animals were inoculated orally three times at 2-day intervals with 10(8) cfu of both spiral and coccoid forms of strain CCUG 17874 (NCTC 11637), strain 25 and strain 553/93. Infection was followed over a 30-week period by histological scoring of the grade of inflammation in gastric biopsies. At each time point sera were collected for analysis in ELISA and immunoblot analysis. Both spiral and coccoid forms of all H. pylori strains gave significantly higher inflammation scores than a control group of animals 1 week after inoculation. The histological evidence persisted throughout the entire 30 weeks. The inflammation was most severe in the pylorus and duodenum. Infection with strain 553/93 displayed the most severe gastritis. The spiral form of strain CCUG 17874 gave an immune response after only 4 weeks, whereas its coccoid form as well as strains 25 and 553/93 (spiral and coccoid forms) gave a significant increase in antibody response in ELISA and immunoblot after 16 weeks. It is concluded that both spiral and coccoid forms of H. pylori can cause acute gastritis in BALB/c A mice.
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16.
  • Bengtsson, Jonas, 1961, et al. (author)
  • Can a failed ileal pouch anal anastomosis be left in situ?
  • 2007
  • In: Colorectal disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 9:6, s. 503-8
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Failure after ileal pouch-anal anastomosis (IPAA) is reported with a frequency of 10-20%. The failed IPAA can be excised or defunctioned. Indications for excision and further management of an indefinitely diverted pouch are poorly described. The aim of the present investigation was to investigate pouch-related problems and the histopathological pattern of the pouch mucosa in this group of patients. METHOD: In a cohort of 620 patients having IPAA with a median follow-up of 14 years, 56 patients with failure were identified. The patients with defunctioned pouches were assessed with regard to pouch-related problems and endoscopy with biopsies was performed. Biopsies were stained with haematoxylin-eosin, PAS for neutral mucins and Alcian blue/high iron diamine for sialomucins/sulphomucins. Morphological changes were grouped into three types modified according to Veress and assessed for dysplasia. RESULTS: Twenty-two patients with an indefinitely diverted pouch were found. The follow-up time after surgery for failure was 10 years. Thirteen patients completed the follow-up. Except for two patients with pelvic/perineal pain, there were no clinical problems. The majority of patients displayed mild to moderate macroscopic signs of inflammation. Morphologically, findings ranged from a preserved mucosal pattern to intense inflammatory reaction. No case of dysplasia or carcinoma was found. CONCLUSION: Most patients with an indefinitely diverted pouch had no complaints regarding the pouch. There was no case of dysplasia. Indefinite diversion may be preferable to pouch excision, especially given the associated morbidity.
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  • Borgfeldt, Christer, et al. (author)
  • High tumor tissue concentration of urokinase plasminogen activator receptor is associated with good prognosis in patients with ovarian cancer
  • 2003
  • In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 107:4, s. 658-665
  • Journal article (peer-reviewed)abstract
    • volved in tumor growth and metastasis. We assayed the components of the uPA system in homogenates of 64 primary epithelial ovarian tumors and 5 metastases and evaluated the association of these parameters to prognosis in the 51 malignant cases. The levels of uPA, PAI-2 and the uPA: PAI-I complex increased with progressive loss of histological differentiation (P-trend <0.001, <0.05 and <0.001). The level of PAI-I was higher in poorly than in well/moderately differentiated tumors (p = 0.03). The content of uPAR was lower in benign tumors as compared to borderline malignancies (p = 0.002), invasive primary tumors (p < 0.001), and metastases (p = 0.002). Surprisingly, the level of uPAR was lower in poorly differentiated as compared to both borderline (p = 0.01) and well differentiated malignant tumors (p = 0.005). Also, the level of uPAR was lower in advanced as compared to early stages of the disease (P-trend = 0.002). The median follow-up time for patients was 5.8 years. High tumor tissue levels of uPAR were associated with longer postoperative survival (HR = 0.4, 95% CI = 0.2-0.8, p = 0.01). In contrast, shorter survival was evident in patients with high tumor levels of uPA from 2 years on after operation (HR = 4.6, 95% CI = 1.2-17, p = 0.02). High tPA levels tended to be associated with shorter overall survival after 2 years (HR = 2.9, 95% 95% Cl = 0.9-9.8, p = 0.08). Although high tumor tissue content of uPAR was associated with a less aggressive phenotype characterized by well differentiated histology and longer survival, low content of uPAR in the poorly differentiated tumors and metastases presumably results from increased elimination of uPAR. (C) 2003 Wiley-Liss, Inc.
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  • Börjesson, Lars, 1963, et al. (author)
  • The risk of dysplasia and cancer in the ileal pouch mucosa after restorative proctocolectomy for ulcerative proctocolitis is low: a long-term term follow-up study
  • 2004
  • In: Colorectal disease. - 1462-8910. ; 6:6, s. 494-8
  • Journal article (peer-reviewed)abstract
    • AIM: Some of the rare complications reported in patients with an ileopouch anal anastomosis (IPAA) after coloectomy for chronic ulcerative colitis are dysplasia and carcinoma. The supposed pathway is for the ileal pouch mucosa to go through adaptational changes then is to progress through the phases of chronic pouchitis, dysplasia and subsequently to adenocarcinoma. In many of these studies however, the dysplasia-cancer sequence is inconclusive since the carcinoma might have developed from the ileal mucosa itself or from residual viable rectal mucosa left behind. The purpose of this study was therefore to study the long-term ileal mucosal adaptation patterns and the incidence and grading of dysplasia in the ileal pouch mucosa in patients previously operated on for ulcerative proctocolitis. PATIENTS AND METHODS: Forty-five patients who had been operated on with an IPAA (25 males/20 females), with a median age of 54 years (range 34-76), were invited for clinical examination and pouch endoscopy including mucosal biopsies. The duration of their colitis until surgery was median 6 years (range 1-28) and the time median interval from start of disease until time of follow up 24.8 years (range 17-46). Three independent pathologists from two different centres reviewed sequential mucosal biopsies taken from separate sites of the pouch for dysplasia and mucosal adaptation patterns. RESULTS: The type C pattern with a severe inflammation in lamina propria together with severe atrophy of villi, sometimes with ulceration and granulation tissue, was observed by the two pathologists from one centre in 15 of 45 (33.3%) patients and in 11 (24.4%) of 45 by the third pathologist, respectively. As regards dysplasia one pathologist group evaluated 2/45 (4.4%) cases as low-grade dysplasia while the third pathologist considered one of these cases as indefinite for dysplasia and one as reactive. There was in this respect full agreement between the two centres in 43 (95.6%) of 45 cases. Neither high-grade dysplasia nor invasive carcinoma was diagnosed. CONCLUSION: Dysplastic transformation within the ileal pouch mucosa in patients operated for ulcerative proctocolitis is rare even after a long follow-up. These results are reassuring for both patients and surgeons. There seem to be no solid grounds to support routine surveillance for dysplasia in the ileal pouch mucosa in these patients. The surveillance for neoplastic changes in the remaining muscular/epithelial cuff is a separate issue however.
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  • Duff, S E, et al. (author)
  • Dysplasia in the ileoanal pouch.
  • 2002
  • In: Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. - 1462-8910. ; 4:6, s. 420-9
  • Journal article (peer-reviewed)abstract
    • Formation of an ileo-anal pouch is an accepted technique following colectomy in the surgical management of ulcerative colitis (UC) and familial adenomatous polyposis (FAP). The configuration of pouches and anastomotic techniques has varied over the last two decades. The increased use of stapling devices in formation of the pouch-anal anastomosis avoids the need for endoanal mucosal stripping and may contribute to improved functional results, but leaves a 'columnar cuff' of residual rectal mucosa in situ. Concerns regarding the long-term safety of the ileo-anal pouch have been raised by reports of the occurrence of dysplasia in the pouch mucosa and 15 cases of adenocarcinoma. In UC, persistence of underlying disease in the residual rectal mucosa, anal transition zone and columnar cuff provides the site for development of dysplasia and malignancy. Pouchitis is unlikely to be a major cause of dysplasia or malignancy, as long-term follow-up of patients with Koch pouches has demonstrated. In FAP, any persistent rectal mucosa and mucosa of the small intestine is at risk of adenomatous dysplasia due to the genetic alterations causing the disease. Long-term surveillance should focus on all FAP pouch patients, and in UC patients should be directed towards the diagnosis of residual rectal mucosa in the area distal to the pouch anastomosis. Specialist histopathological opinion is essential in the diagnosis of dysplasia in the ileo-anal pouch.
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20.
  • Edgar, James R, et al. (author)
  • ESCRTs regulate amyloid precursor protein sorting in multivesicular bodies and intracellular beta amyloid accumulation.
  • 2015
  • In: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 128:14, s. 2520-2528
  • Journal article (peer-reviewed)abstract
    • Intracellular beta amyloid (Aβ) accumulation is a key feature of early Alzheimer's disease (AD) and precedes the appearance of Aβ in extracellular plaques. Aβ is generated through proteolytic processing of amyloid precursor protein (APP), but the intracellular site of Aβ production is unclear. APP has been localized to multivesicular endosomes/bodies (MVBs) where sorting of APP onto ILVs could promote amyloidogenic processing or reduce Aβ production/accumulation by sorting APP and processing products to lysosomes for degradation. We show that APP localizes to the ILVs of a subset of MVBs that also traffic EGF receptor (EGFR), and is delivered to lysosomes for degradation. Depletion of the ESCRT components, Hrs or Tsg101, inhibited targeting of APP to ILVs and the subsequent delivery to lysosomes and lead to increased intracellular Aβ accumulation. This was accompanied by dramatically decreased Aβ secretion. Thus, the early ESCRT machinery has a dual role in limiting intracellular Aβ accumulation through targeting of APP and processing products to the lysosome for degradation and promoting Aβ secretion.
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21.
  • Fernö, Mårten, et al. (author)
  • Improved preparation technique of cervical carcinoma for flow cytometric DNA analysis with tissue disintegration in hydrochloric acid
  • 1990
  • In: In Vivo. - 0258-851X. ; 4:4, s. 225-229
  • Journal article (peer-reviewed)abstract
    • An one-step procedure using a nuclear isolation medium containing propidium iodide has been found to be a suitable preparation technique for flow cytometric DNA analysis in breast cancer samples. In the case of cervical squamous carcinoma, a pretreatment with HCl seems to be a methodological improvement. One advantage with the HCl modification is that some "false" near-diploid cell populations are abolished. These "false" G0/G1 peaks may represent diploid nuclei with a different stainability for propidium iodide compared to normal diploid nuclei. The HCl treatment has, furthermore, the advantage of increasing the elution of nuclei (mean factor of 4.0), especially non-diploid nuclei from higher differentiated squamous carcinomas.
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22.
  • Fredstorp-Lidebring, M, et al. (author)
  • Urokinase plasminogen activator and its inhibitor, PAI-1, in association with progression-free survival in early stage endometrial cancer
  • 2001
  • In: European Journal of Cancer. - 1879-0852. ; 37:18, s. 2339-2348
  • Journal article (peer-reviewed)abstract
    • Components of the urokinase plasminogen activator (u-PA) system are involved in the metastatic process, and have accordingly been associated with clinical outcome in a variety of malignant tumours. We investigated the prognostic importance of u-PA and plasminogen activator inhibitor type 1 (PAI-1) in endometrial cancer, analysed with luminometric immunoassay (LIA) and enzyme-linked immunosorbent assay (ELISA), respectively. Two different cut-off levels were used: the median and the 80th percentile-the latter because of the low progression rate for patients with early stage (I-II) endometrial cancer. After a median follow-up time of 6.8 years, univariate analysis of patients with stage I-II disease (n=188) showed that high u-PA and high PAI-1 content was associated with a shorter progression-free survival (PFS), but at different cut-off levels, uPA at the median (P=0.003), and PAI-1 at the 80th percentile (P<0.001). Among the other factors, DNA ploidy status was most strongly correlated to PFS, followed by age (continuous), International Federation of Gynaecology and Obstetrics (FIGO) grade of differentiation, S-phase fraction and progesterone receptor (PgR) status. Bivariate analyses, including ploidy and one of the factors u-PA or PAI-1, showed that both add significant prognostic information. We conclude that u-PA and PAI-1 are promising prognostic factors in early stage endometrial cancer.
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23.
  • Götlind, Yu-Yuan Chiu, 1964, et al. (author)
  • Interplay between Th1 and Th17 effector T cell pathways in the pathogenesis of spontaneous colitis and colon cancer in the Gai2-deficient mouse
  • 2013
  • In: International Immunology. - Oxford, United Kingdom : Oxford University Press. - 0953-8178 .- 1460-2377. ; 25:1, s. 35-44
  • Journal article (peer-reviewed)abstract
    • Gαi2-deficient mice spontaneously develop colitis. Using xMAP technology and RT-PCR, we investigated cytokine/chemokine profiles during histologically defined phases of disease: (i) no/mild, (ii) moderate, (iii) severe colitis without dysplasia/cancer and (iv) severe colitis with dysplasia/cancer, compared with age-matched wild-type (WT) littermates. Colonic dysplasia was observed in 4/11 mice and cancer in 1/11 mice with severe colitis. The histology correlated with progressive increases in colon weight/cm and spleen weight, and decreased thymus weight, all more advanced in mice with dysplasia/cancer. IL-1β, IL-6, IL-12p40, IL-17, TNF-α, CCL2 and CXCL1 protein levels in colons, but not small intestines increased with colitis progression and were significantly increased in mice with moderate and severe colitis compared with WT mice, irrespective of the absence/presence of dysplasia/cancer. CCL5 did not change during colitis progression. Colonic IL-17 transcription increased 40- to 70-fold in all stages of colitis, whereas IFN-γ mRNA was gradually up-regulated 12- to 55-fold with colitis progression, and further to 62-fold in mice with dysplasia/cancer. IL-27 mRNA increased 4- to 15-fold during the course of colitis, and colonic IL-21 transcription increased 3-fold in mice with severe colitis, both irrespective of the absence/presence of dysplasia/cancer. FoxP3 transcription was significantly enhanced (3.5-fold) in mice with moderate and severe colitis, but not in mice with dysplasia/cancer, compared with WT mice. Constrained correspondence analysis demonstrated an association between increased protein levels of TNF-α, CCL2, IL-1β, IL-6 and CXCL1 and dysplasia/cancer. In conclusion, colonic responses are dominated by a mixed T(h)1/T(h)17 phenotype, with increasing T(h)1 cytokine transcription with progression of colitis in Gαi2(-/-) mice.
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24.
  • Holgersson, Georg, et al. (author)
  • The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy
  • 2017
  • In: Neoplasma (Bratislava). - Bratislava : AEPress. - 0028-2685 .- 1338-4317. ; 64:6, s. 909-915
  • Journal article (peer-reviewed)abstract
    • Chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC). This treatment, however, offers only a small chance of cure and is associated with many side effects. Little research has been made concerning which patients benefit most/least from the treatment. The present study evaluates the prognostic value of anemia, leukocytosis and thrombocytosis at diagnosis in this treatment setting. In the present study, data were collected retrospectively for 222 patients from two different phase II studies conducted between 2002-2007 in Sweden with patients treated with chemoradiotherapy for stage IIIA-IIIB NSCLC. Clinical data and the serum values of hemoglobin (Hgb), White blood cells (WBC) and Platelets (Plt) at enrollment were collected for all patients and studied in relation to overall survival using Kaplan-Meier product-limit estimates and a multivariate Cox proportional hazards regression model. The results showed that patients with thrombocytosis (Plt > 350 x 109 /L) had a shorter median overall survival (14.5 months) than patients with normal Plt at baseline (23.7 months). Patients with leukocytosis (WBC > 9 x 109 /L) had a shorter median survival (14.9 months) than patients with a normal WBC at baseline (22.5 months). However, in a multivariate model including all lab parameters and clinical factors, only thrombocytosis and performance status displayed a prognostic significance. In Conclusion, thrombocytosis showed to be an independent prognostic marker associated with shorter overall survival in stage III NSCLC treated with curatively intended chemoradiotherapy. This knowledge can potentially be used together with established prognostic factors, such as performance status when choosing the optimal therapy for the individual patient in this clinical setting
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25.
  • Hultén, Leif, 1931, et al. (author)
  • Mucosal assessment for dysplasia and cancer in the ileal pouch mucosa in patients operated on for ulcerative colitis--a 30-year follow-up study.
  • 2002
  • In: Diseases of the colon and rectum. - 0012-3706. ; 45:4, s. 448-52
  • Journal article (peer-reviewed)abstract
    • Sporadic reports of epithelial dysplasia and the occasional development of adenocarcinoma in the ileal pouch mucosa have recently appeared in the literature, pointing toward yet another long-term complication of the continent ileostomy and the pelvic pouch. The incidence of dysplasia and the risk for developing cancer has not been critically evaluated, however, and the reports are contradictory, with most having short observation times. The purpose of this study was to report long-term mucosal adaptation patterns and the incidence of dysplasia in Kock pouches after a mean follow-up of 30 years for patients previously operated on for ulcerative proctocolitis.Two sets of two pathologists each (in Gothenburg, Sweden, and Manchester, United Kingdom) examined sequential, small-intestinal biopsy specimens from 40 patients with Kock pouch to observe long-term epithelial changes, with particular reference to the presence of dysplasia.There was full agreement between the two groups regarding the absence of high-grade dysplasia and invasive carcinoma (Categories 4 and 5 of the Vienna classification). There was, however, significant disagreement in reporting the frequency of low-grade and indefinite categories of dysplasia (Categories 2 and 3, of the Vienna classification). No attempt was made to report the differences within each set of pathologists.Because no case of high-grade dysplasia or invasive carcinoma was found in this study after a mean follow-up of 30 years, we conclude that it is very unlikely for invasive carcinoma to be a complication in ileal pouch mucosa.
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26.
  • Johansson, J, et al. (author)
  • Adenocarcinoma in the distal esophagus with and without Barrett esophagus. Differences in symptoms and survival rates
  • 1996
  • In: Archives of Surgery. - : American Medical Association (AMA). - 0004-0010. ; 131:7, s. 13-708
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To evaluate differences in clinical appearance and survival rates in patients operated on for adenocarcinoma in the distal esophagus with and without Barrett epithelium.DESIGN: Prospective clinical study.SETTING: University hospital, Sweden.PATIENTS: Fifty-four patients with adenocarcinoma in the distal esophagus with (n = 17) or without (n = 37) Barrett epithelium.INTERVENTION: Esophagectomy or total gastrectomy.MAIN OUTCOME MEASURES: Preoperative symptoms, endoscopic results, and histological findings; postoperative morbidity, mortality, and survival rates.RESULTS: The main indication for the endoscopic examination that revealed tumor in the group with Barrett esophagus was reflex-related symptoms in 6 patients (routine Barrett examination, n = 4; symptoms of reflux, n = 2), symptoms related to upper gastrointestinal tract bleeding in 6, and malignant symptoms in 5 (dysphagia, n = 4; weight loss, n = 1). In contrast, most patients in the cardia cancer group were admitted because of malignant symptoms (dysphagia, n = 26; epigastric pain, n = 9; and anemia, n = 2). Ten of 17 patients in the Barrett esophagus cancer group had tumors limited to the mucosa and submucosa only. In 1 patient the tumor grew into the muscular layer but not through it. In the remaining 6 patients the tumor did grow through the muscular layer and lymph node metastases were found. Wall penetration was found in 30 patients and metastases to lymph nodes in 29 patients in the cardia cancer group. The hospital mortality rate was 0 of 17 patients in the Barrett cancer group and 2 of 37 patients in the cardia cancer group. In the patients operated on for adenocarcinoma in the distal esophagus, a better long-term survival rate was seen in those with Barrett epithelium (50%) than in those without this metaplasia (10%) (log rank P = .005; X2 = 7.80).CONCLUSIONS: Concomitant Barrett epithelium improved the prognosis for patients with adenocarcinoma in the distal esophagus. Probably the reason for this was a higher rate of early-stage disease, because symptoms of gastroesophageal reflux and other benign disorders, not dysphagia, were most common in patients with adenocarcinoma without Barrett epithelium in the distal esophagus.
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27.
  • Järnerot, G, et al. (author)
  • Familial occurrence of microscopic colitis: a report on five families
  • 2001
  • In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 36:9, s. 959-962
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The etiology and pathogenesis of microscopic colitis is unknown. Whether genetic predisposition is of importance, as in many other gastrointestinal diseases, is unknown. Familial occurrence of collagenous colitis has earlier been reported only in two families. METHODS: Familial occurrence of microscopic colitis was searched for in a Swedish national microscopic colitis register. RESULTS: Familial occurrence of microscopic colitis was identified in five families. In all families a sister-sister relationship was found. Two sisters with collagenous colitis had been living apart in different Nordic countries for many years before developing the disease. In one pair, the smoking sister had collagenous colitis and the never smoking sister had lymphocytic colitis. CONCLUSIONS: Considering the relative rarity of microscopic colitis, these findings indicate that a genetic predisposition may be of importance.
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28.
  • Klementieva, O., et al. (author)
  • Nano-scale Infrared Imaging of β-sheet Structures in Synaptic Junctions of Primary Neurons Isolated from Transgenic Mice
  • 2018
  • In: 2018 43rd International Conference on Infrared Millimeter and Terahertz Waves, IRMMW-THz 2018. - 9781538638095 ; 2018-September
  • Conference paper (peer-reviewed)abstract
    • Aβ is a class of aggregation-prone proteins, which may misfold into stable, β-sheet rich fibrils. Aβ is linked to the development of synaptic pathology in Alzheimer's disease (AD). However, a main question in the AD field is how Aβ contributes to AD neuropathology? Up to now there is little evidence for protein structural changes in diseased neuron. Our aim is to study the distribution of β-sheet structures in AD transgenic neurons in order to uncover sub-cellular mechanism(s) by which amyloid β-sheet structures are involved in AD pathology.
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29.
  • Koul, A., et al. (author)
  • BRCA1 and BRCA2 mutations in ovarian cancer : Covariation with specific cytogenetic features
  • 2000
  • In: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X .- 1525-1438. ; 10:4, s. 289-295
  • Journal article (peer-reviewed)abstract
    • We analyzed 37 primary invasive carcinomas for BRCA1 and BRCA2 mutations by screening the entire coding regions of both genes. Seven predicted truncating mutations (four in BRCA1 and three in BRCA2) and one novel BRCA1 missense variant (S1542C) were identified (8/37, 22%). Two of the BRCA1 mutations were somatic changes, whereas the remaining three BRCA1 changes and all mutations of BRCA2 were found to be of germline origin. All eight BRCA-positive tumors were serous or seropapillary carcinomas (8/27 serous tumors, 30%), and all but one were poorly differentiated. The correlation between tumor karyotype and BRCA status showed that clonal chromosomal aberrations were present in all BRCA-positive tumors (8/8) compared with 20 of 29 BRCA-negative ones. The most consistently affected region in BRCA-positive tumors was the long arm of chromosome 6; alterations within this arm with a breakpoint in band 6q21 were seen in four of five BRCA1-positive and in two of three BRCA2-positive tumors, but only in four of 20 karyotypically abnormal tumors without BRCA mutations, suggesting that the genetic pathways of tumor progression differ in the two groups. The high frequency of germline BRCA mutations detected in this pilot study (16% of 37 invasive carcinomas) points to the need for more extended analyses of population-based series of patients to determine the true contribution of these predisposing genes to the overall incidence of ovarian cancer in this population.
  •  
30.
  • Koul, Anjila, et al. (author)
  • Distinct sets of gene alterations in endometrial carcinoma implicate alternate modes of tumorigenesis
  • 2002
  • In: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 94:9, s. 2369-2379
  • Journal article (peer-reviewed)abstract
    • BACKGROUND. Endometrial carcinomas seem to carry a different prognosis depending on the presence or absence of concomitant complex atypical hyperplasia (hyperplasia). The molecular genetic profile of these two pathogenetic types, based on the genes reportedly mutated in these cancers, remains to be defined. Although microsatellite inability is reported in approximately 25% of endometrial carcinomas, its relation with the 2 pathogenetic types is not investigated. METHODS. To elucidate their underlying genetic changes, we analyzed 53 sporadic endometrial tumors, including 19 with and 34 without hyperplasia, for microsatellite instability (MSI), DNA ploidy (by flow cytometry), and for mutations in different genes. RESULTS. Microsatellite instability was present in 21%, DNA nondiploidy in 15%, and mutations in the PTEN, KRAS, CTNNB1/beta-catenin, TP53, and CDKN2A genes were detected in 32, 11, 13, 17, and 0% of the tumors, respectively. Microsatellite instability and mutations in these genes were present in tumors both with and without complex atypical hyperplasia. All cases with complex atypical hyperplasia were early stage (I-II) endometrioid tumors and associated with long progression free disease (P = 0.0004). Furthermore, most tumors with hyperplasia had low World Health Organization or International Federation of Gynecology and Obstetrics grade, had less myometrial invasion, and showed expression of estrogen receptors. All MSI tumors were diploid and had a significantly higher rate of PTEN mutations, but similar rates of KRAS, beta-catenin, and TP53 mutations compared with microsatellite stable tumors. TP53 mutations more often were found in nondiploid tumors but never in tumors with PTEN, KRAS, or beta-catenin mutations, and all PTEN mutations occurred in diploid tumors. CONCLUSIONS. Thus, PTEN, KRAS, beta-catenin, and TP53 mutations occurred in tumors both with and without hyperplasia, but PTEN and TP53 mutations were more common in tumors without hyperplasia. However, none of these genes seems to clearly distinguish tumors with and without hyperplasia, suggesting that other factors may be involved. Conversely, alterations in the PTEN and TP53 genes seem to define distinct subgroups of endometrial carcinoma, the former associated with diploidy and MSI, the latter with macroscopic chromosomal instability.
  •  
31.
  • Koul, Anjila, et al. (author)
  • TP53 protein expression analysis by luminometric immunoassay in comparison with gene mutation status and prognostic factors in early stage endometrial cancer
  • 2002
  • In: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X .- 1525-1438. ; 12:4, s. 362-371
  • Journal article (peer-reviewed)abstract
    • Mutations in the TP53 tumor suppressor gene have been shown to significantly correlate with poor prognosis in endometrial cancer. In the present study we have evaluated a luminometric immunoassay (LIA) for quantitative estimation of TP53 protein expression in 65 cytosol preparations from endometrial cancer, previously analyzed for mutations in TP53 exons 4-10. LIA showed high (greater than or equal to 0.6 ng/mg protein) expression of TP53 protein in all eight tumors with missense mutation, but high protein levels were also detected in 15 tumors with normal TP53 sequence. All four tumors with nonsense or frameshift mutations had low or no TP53 protein expression. LIA was further evaluated in a retrospective study of 201 cytosol samples from endometrial cancer. TP53 overexpression (>= 0.6 ng/mg protein) was observed in 22% of the tumors and correlated with nonendometrioid histology types (P = 0.005), poorly differentiated tumors (P = 0.001), higher FIGO grade (P = 0.001), DNA nondiploidy (P = 0.002), and high S-phase fraction (P = 0.03). After a median follow-up time of 6.8 years (range 0.7-9.9 years), 22 (13%) progressions were observed in the 175 patients with early stage (I-II) disease. TP53 overexpression (P = 0.04), FIGO grade 3 vs. 1 + 2 (P = 0.01), higher age (P = 0.02), and DNA nondiploidy (P < 0.001) showed significant correlation to shorter progression-free survival in these patients. We conclude that TP53 protein analysis by LIA provides an incomplete correlation to mutation status and cannot substitute for mutation analysis in assessment of prognosis in endometrial carcinoma. In comparison to TP53 overexpression and higher FIGO grades, DNA nonploidy status seems to be a better prognostic indicator to define a subset of early stage endometrial cancer patients who may benefit by adjuvant chemotherapy/radiotherapy.
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32.
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33.
  • Lindahl, Bengt, et al. (author)
  • Prospective malignancy grading of invasive squamous carcinoma of the uterine cervix. Prognostic significance in a long-term follow-up.
  • 2007
  • In: Anticancer research. - 1791-7530 .- 0250-7005. ; 27:4C, s. 2829-2832
  • Journal article (peer-reviewed)abstract
    • A multifactorial grading score (MGS) for invasive squamous cell carcinoma of the uterine cervix has demonstrated its capacity to predict survival in a 5-10 year perspective and metastasis frequencies, and is a valuable tool for treatment schedules. In this study it was shown that the power of prognosis is valid even up to 20 years. In this material from 619 cervical carcinoma patients the MGS scores turned out to remain as strong as earlier proven. Earlier studies have shown that MGS is superior to other mono- and multifactorial grading systems, histological differentiation into cell types, age, clinical stage, irradiation and DNA-analysis. Treatment of cervical squamous cell carcinoma is more specific today to meet the patients' need for instance to preserve fertility or to minimize operation and eventually radiotherapy. The MGS score is a strong prognostic tool in patients with cervical carcinoma.
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34.
  •  
35.
  • Löfberg, Robert, et al. (author)
  • Oral budesonide versus prednisolone in patients with extensive and left sided ulcerative colitis
  • 1996
  • In: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 110:6, s. 1713-1718
  • Journal article (peer-reviewed)abstract
    • BACKGROUND & AIMS: Systemic glucocorticosteroids (GCSs) have proven efficacy in active ulcerative colitis but cause undesired systemic side effects. Therefore, new GCSs with high topical activity and a high rate of metabolism may be of clinical value in this condition. The aim of this study was to explore the efficacy and safety of the topically acting GCS budesonide in an oral controlled-release formulation in extensive or left-sided, mild to moderately active ulcerative colitis. METHODS: A 9-week, randomized, double-blind, controlled trial was performed, and treatments with 10 mg budesonide or 40 mg prednisolone daily, both gradually tapered, were compared. Endoscopic improvement and effect on endogenous plasma cortisol were assessed. RESULTS: Thirty-four patients were administered budesonide, and 38 patients were administered prednisolone. Mean endoscopic scores improved significantly in both groups but without difference between the groups. Five patients in the budesonide group and 7 patients in the prednisolone group deteriorated and were withdrawn from the study. Morning plasma cortisol levels were suppressed in the prednisolone group (entry, 449 nmol/L; 2 weeks, 116 nmol/L; 4 weeks, 195 nmol/L) but were unchanged in the budesonide group. CONCLUSIONS: The GCS budesonide administered in an oral controlled-release formulation seems to give an overall treatment result in active ulcerative colitis approaching that of prednisolone but without suppression of plasma cortisol levels. This concept merits further evaluation.
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36.
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37.
  • Marthinsen, L, et al. (author)
  • Intestinal spirochetosis in eight pediatric patients from Southern Sweden - A clinical, histopathological and ultrastructural study
  • 2002
  • In: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463. ; 110:7-8, s. 571-579
  • Journal article (peer-reviewed)abstract
    • Intestinal spirochetes in humans have been recognized for more than a century, but it is still a matter of debate whether they are just commensal organisms or whether they cause colorectal disease. Most descriptions to date are of adult patients, while reports in the pediatric literature have been scarce. In a retrospective study we found eight children with intestinal spirochetosis. The findings, clinical as well as pathological, with light- and electron microscopy, are presented. In all patients, a 3 pm-thick layer of spirochetes was visualised on the luminal aspect of the epithelial cells covering the enterocytes and part of the gland openings. In five of the eight cases an inflammatory cell reaction was seen by light microscopy and in one patient a picture suggesting intracytoplasmatically located spirochetes was seen by electron microscopy. Despite partial or complete destruction of microvilli, spirochetes were still able to adhere to the enterocyte membranes. In three children there was a clear correlation between treatment and relief of symptoms. In four there was partial improvement and in one child no change in bowel-related symptoms. We believe that intestinal spirochetes may cause colorectal disease in children. Possible pathogenic mechanisms are discussed.
  •  
38.
  • Nejdfors, P, et al. (author)
  • Intestinal permeability in humans is increased after radiation therapy
  • 2000
  • In: Diseases of the Colon & Rectum. - 0012-3706. ; 43:11, s. 1582-1587
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Irradiation inflicts acute injuries to the intestinal mucosa with rapid apoptosis induction and subsequent reduction in epithelial surface area. It may therefore be assumed that the intestinal barrier function is affected. The aim of this study was to compare the mucosal permeability in irradiated rectum and nonirradiated sigmoid colon from patients subjected to radiation therapy before surgical treatment for rectal cancer. METHODS: Segments from sigmoid colon and rectum obtained from irradiated and nonirradiated patients were stripped from the serosa-muscle layer and mounted in Ussing diffusion chambers. The mucosa-to-serosa passage of the marker molecules 14C-mannitol, fluorescein isothiocyanate-dextran 4,400, and ovalbumin was followed for 120 minutes. RESULTS: The permeability to the markers was size-dependent and increased linearly across time in all specimens. The passage of all markers was increased in irradiated rectum compared with nonirradiated sigmoid colon, whereas in specimens from nonirradiated patients there were no differences between rectum and sigmoid colon. Histologic signs of crypt and mucosal atrophy were found in the irradiated rectal specimens. CONCLUSIONS: Early gastrointestinal complications after radiation therapy may be the result of mucosal atrophy in addition to mucosal damage, with a loss of barrier integrity.
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39.
  •  
40.
  • Nilsson, J, et al. (author)
  • Screening for oesophageal adenocarcinoma : an evaluation of a surveillance program for columnar metaplasia of the oesophagus
  • 2000
  • In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 35:1, s. 6-10
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Screening patients with columnar metaplasia of the oesophagus for adenocarcinoma is controversial owing to the low cancer incidence and diverging opinions as to whether screening improves the prognosis of these patients. Our aim was to evaluate a screening program for adenocarcinoma in patients with columnar metaplasia in the oesophagus, with focus on cancer incidence and costs.METHODS: One hundred and ninety-nine patients with columnar metaplasia of the oesophagus were identified through an endoscopy database, and the original patient records were reviewed.RESULTS: The patients were followed up for 797 years in total and during this time were subjected to 1071 upper gastrointestinal endoscopies. During the screening period 5 patients presented with adenocarcinoma; thus the cancer-incidence was 1 in 159 patient-years. The cost of detecting one cancer was 294,950 SEK (US$ 37,815). However, only four of the five patients were suitable for oesophagectomy, and of these, one patient turned out to have an advanced cancer. All patients developing cancer had columnar metaplasia of the oesophagus longer than 3 cm and specialized columnar epithelium (intestinal metaplasia/Barrett oesophagus).CONCLUSIONS: Low cancer incidence, high costs, and the doubtful prognosis for the patients with identified cancer question the benefits and cost-effectiveness of cancer screening among patients with columnar metaplasia in the oesophagus.
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41.
  •  
42.
  • Rangel, Ignacio, 1969-, et al. (author)
  • Degree of colitis correlates with microbial composition and cytokine responses in colon and caecum of G alpha i2-deficient mice
  • 2016
  • In: Fems Microbiology Ecology. - Oxford, United Kingdom : Oxford University Press (OUP). - 0168-6496 .- 1574-6941. ; 92:7
  • Journal article (peer-reviewed)abstract
    • An altered immune response and gut microbiota have been associated with the pathology of inflammatory bowel diseases (IBDs). However, there is limited knowledge of how inflammation is associated with changes in the microbiota. We studied the microbiota in the intestine and faeces as well as the cytokine gene expressions in caecum and colon of a mouse model (G alpha i2(-/-)) of colitis, and analysed them in relation to the degrees of inflammation in the colon. The degree of colitis was associated with general changes in the complexity of the microbiota and was corroborated by quantitative analyses of the Bacteroides and Lactobacillus. High gene expression levels of IL-17 and IFN-gamma in colon and caecum were detected in G alpha i2(-/-) mice with moderate and severe colitis. High IL-27 gene expression in the colon of mice with moderate and severe colitis and in the caecum of mice with moderate colitis was also detected. Negative correlations between IL-27 and Bacteroides and Lactobacillus and between IFN-gamma and Lactobacillus were detected in caecum. This research indicates that the degree of colitis in IBD correlates with the gene expression of cytokines and with disturbances in the gut microbiota. Furthermore, the caecum could have an important role in the pathology of IBD.
  •  
43.
  • Rauvala, M, et al. (author)
  • Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor progression.
  • 2006
  • In: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. - : BMJ. - 1048-891X .- 1525-1438. ; 16:3, s. 1297-302
  • Journal article (peer-reviewed)abstract
    • The incidence of uterine cervical cancer has increased slightly in Western countries, with an increase in relatively young women. Overexpression of matrix metalloproteinases (MMPs)-2 and -9 has turned out as a prognostic factor in many cancers. We compared the expression of the proteins MMP-2 and MMP-9 in cervical primary tumors with clinical outcome and risk factors of cervical cancer. One hundred sixty-one patients with cervical cancer treated in Umeå University Hospital or Sahlgrenska University Hospital, Sweden, between 1991 and 1995 were included in the study. Paraffin-embedded tissue samples obtained prior to treatment were examined immunohistochemically by specific antibodies for MMP-2 and MMP-9. Forty-two percent of the tumors were intensively positive for MMP-2 and 31% for MMP-9. Nineteen percent of the samples were intensively positive for both proteinases and 47% negative or weak for both. Overexpression of MMP-2 seemed to predict unfavorable survival under Kaplan-Meier analysis and in the multivariate analysis. Early sexual activity and low parity seemed to correlate to overexpression of MMP-2. MMP-9 was not associated with survival or sexual behavior. Intensive MMP-9 was noted in grade 1 tumors. We conclude that MMP-2 and MMP-9 have different roles in uterine cervical cancer. MMP-2 could be associated with aggressive behavior, but MMP-9 expression diminishes in high-grade tumors.
  •  
44.
  • Rohrer, Julia M., et al. (author)
  • Putting the Self in Self-Correction : Findings From the Loss-of-Confidence Project
  • 2021
  • In: Perspectives on Psychological Science. - : Sage Publications. - 1745-6916 .- 1745-6924. ; 16:6, s. 1255-1269
  • Journal article (peer-reviewed)abstract
    • Science is often perceived to be a self-correcting enterprise. In principle, the assessment of scientific claims is supposed to proceed in a cumulative fashion, with the reigning theories of the day progressively approximating truth more accurately over time. In practice, however, cumulative self-correction tends to proceed less efficiently than one might naively suppose. Far from evaluating new evidence dispassionately and infallibly, individual scientists often cling stubbornly to prior findings. Here we explore the dynamics of scientific self-correction at an individual rather than collective level. In 13 written statements, researchers from diverse branches of psychology share why and how they have lost confidence in one of their own published findings. We qualitatively characterize these disclosures and explore their implications. A cross-disciplinary survey suggests that such loss-of-confidence sentiments are surprisingly common among members of the broader scientific population yet rarely become part of the public record. We argue that removing barriers to self-correction at the individual level is imperative if the scientific community as a whole is to achieve the ideal of efficient self-correction.
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45.
  •  
46.
  •  
47.
  • Sjunnesson, Håkan, et al. (author)
  • High intake of selenium, beta-carotene, and vitamins A, C, and E reduces growth of Helicobacter pylori in the guinea pig
  • 2001
  • In: Comparative Medicine. - 1532-0820. ; 51:5, s. 418-423
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Helicobacter pylori is a human gastroduodenal pathogen associated with type-B gastritis and gastric cancer. Low gastric tissue antioxidant levels are believed to increase the risk of developing gastric cancer. We investigated whether dietary antioxidant levels protect against infection and type-B gastritis in H. pylori-infected guinea pigs. METHODS: Dunkin-Hartley guinea pigs infected for 6 weeks with H. pylori were fed diets with various antioxidant levels. Stomach specimens were cultured, and gastritis was graded from 0 to 3. RESULTS: Supplementation with vitamins A, C, and E and with selenium yielded H. pylori recovery from 17% of challenged animals, compared with 43% of those fed a control diet. Gastritis was scored at 0.33 and 0.93, respectively. Supplementation with only vitamin C or astaxanthin had less effect on gastritis and recovery rate. In a second experiment, gastritis score in a group given vitamins A, C, E, and selenium and beta-carotene was 2.25 and in a control group, it was 2.57. The H. pylori recovery rate was 75 and 100%, respectively, with fewer colonies from animals given antioxidant supplementation (P < 0.05). CONCLUSIONS: A combination of antioxidants can protect against H. pylori infection in guinea pigs. In animal studies, antioxidant intake should be low to optimize development of H. pylori-associated disease. Furthermore we established that H. pylori causes severe gastritis in guinea pigs.
  •  
48.
  • Sturegård, Erik, et al. (author)
  • Severe gastritis in guinea-pigs infected with Helicobacter pylori
  • 1998
  • In: Journal of Medical Microbiology. - 0022-2615. ; 47:12, s. 1123-1129
  • Journal article (peer-reviewed)abstract
    • An appropriate animal model is essential to study Helicobacter pylori infection. The aim of this study was to investigate if H. pylori can colonise the guinea-pig stomach and whether the infection causes gastritis and a serological response similar to that observed in man. Guinea-pigs were infected either with fresh H. pylori isolates from human gastric biopsies or with a guinea-pig passaged strain. When the animals were killed, 3 and 7 weeks after inoculation, samples were taken for culture, histopathology and serology. H. pylori was cultured from 22 of 29 challenged animals. All culture-positive animals exhibited a specific immune response against H. pylori antigens in Western blotting and gastritis in histopathological examination. Antibody titres in enzyme immunoassay were elevated among animals challenged with H. pylori. The inflammatory response was graded as severe in most animals and consisted of both polymorphonuclear leucocytes and lymphocytes. Erosion of the gastric epithelium was found in infected animals. These results suggest that the guinea-pig is suitable for studying H. pylori-associated diseases. Moreover, guinea-pigs are probably more similar to man than any other small laboratory animal as regards gastric anatomy and physiology.
  •  
49.
  • Tennvall, Jan, et al. (author)
  • DNA analysis as a predictor of the outcome of induction chemotherapy in advanced head and neck carcinomas
  • 1993
  • In: Archives of Otolaryngology - Head and Neck Surgery. - 1538-361X. ; 119:8, s. 867-870
  • Journal article (peer-reviewed)abstract
    • We investigated whether flow cytometric DNA index and/or ploidy status are predictors of response to chemotherapy and survival. Fifty consecutive patients with previously untreated locally advanced squamous cell carcinomas of the head and neck received induction chemotherapy consisting of three courses of cisplatin (100 mg/m2) and a subsequent 120-hour infusion of fluorouracil (1000 mg/m2 per 24 hours) repeated every 3 weeks. Chemotherapy was followed by radiotherapy to a median target dose of 65 Gy and subsequent surgery for residual tumor. The median observation time was 27 months (range, 24 to 57 months). Flow cytometric DNA analysis was based on formalin-fixed and paraffin-embedded tissue from pretreatment tumor biopsy specimens. Complete response after induction chemotherapy was achieved in only 12% (2/17) of patients with diploid tumors compared with 39% (13/33) of those with nondiploid tumors. Among patients with nondiploid tumors, DNA index was higher for those responding to chemotherapy compared with the nonresponders. Complete response to chemotherapy was apparently a prerequisite for survival in the nondiploid group. Of the patients not responding to chemotherapy but responding to subsequent radiotherapy, survival was better among those with diploid tumors than among those with nondiploid tumors.
  •  
50.
  • Tennvall, Jan, et al. (author)
  • T3N0 glottic carcinoma: DNA S-phase as a predictor of the outcome after radiotherapy
  • 1993
  • In: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 113:1, s. 220-224
  • Journal article (peer-reviewed)abstract
    • In consecutive series of 326 laryngeal cancer patients, of 29 (9%) with stage T3N0 glottic carcinomas, 23 achieved complete local remission after curative radiotherapy and form the basis of the present investigation. Flow cytometry determinations of DNA-ploidy status and the S-phase fraction, and a "histopathological malignancy grading system" were evaluated as possible patient- and/or tumor-related predictors of local recurrence. Twelve patients (52%) were continuously disease-free after radiotherapy, whereas 10 (43%) manifested local recurrence, and one distant metastasis. The radiotherapy delivered to patients who later suffered from a local recurrence did not differ from those being continuously disease-free. The frequency of local recurrence was significantly correlated to patients whose primary tumours manifested a low S-phase fraction (p < 0.05). A low S-phase fraction may indicate slowly proliferating tumour-cells, which become more radioresistant on exposure to a series of fractionated doses, as their reassortment into sensitive phases will be proportionately slower.
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