T Paavonen

University of Tampere, Tammerfors, Province of Western Finland, Finland

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Publications (88)298.96 Total impact

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    ABSTRACT: The aim of the study was to evaluate the histopathology of neovascular tufts and vitreous samples collected from patients with diabetes. Vitreous samples and neovascular tufts were collected from patients with type 1 (n = 13) and (n = 17) type 2 diabetes with proliferative retinopathy, and from controls with a macular hole (n = 5). Neovessels were analysed using immunohistochemistry and vitreous samples with an enzyme-linked immunosorbent assay (ELISA). The main outcome measure was to examine differences in the levels of growth factors in patients with type 1 and type 2 diabetes with proliferative retinopathy. Vascular endothelial growth factor (VEGF)-A was most strongly present in the samples from patients with type 1 diabetes. In type 2 diabetes, VEGF-D was more abundantly present than in type 1 diabetes. Angiopoietin (ANG)-2 was also abundantly present. Macrophages and nuclear factor kappa B (NFkappaB) were found, indicating the presence of an inflammatory process in the neovascular tissues. VEGF-A and ANG-2 are equally important in the neovascular process in both type 1 and type 2 diabetes. VEGF-D is abundantly present in type 2 diabetes. In order to achieve better control of diabetic retinopathy, it might be beneficial to develop treatments that prevent the actions of ANG-2 and VEGF-D.
    The British journal of ophthalmology 04/2009; 93(8):1109-15. DOI:10.1136/bjo.2008.148841 · 2.81 Impact Factor
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    ABSTRACT: Previous work in type-I pollen allergies has mainly focused on lymphocytes and immune responses. Here, we begin to analyse with a systems biology view the differences in conjunctival epithelium obtained from healthy and allergic subjects. Transcriptomics analysis combined with light and electron microscopic analysis of birch pollen allergen Bet v 1 located within conjunctival epithelial cells and tissues from birch allergic subjects and healthy controls was carried out. Bet v 1 pollen allergen bound to conjunctival epithelial cells within minutes after the exposure even during the nonsymptomatic winter season only in allergic, but not in healthy individuals. Light- and electron microscopy showed that Bet v 1 was transported through the epithelium within lipid rafts/caveolae and reached mast cells only in allergic patients, but not in healthy individuals. Transcriptomics yielded 22 putative receptors expressed at higher levels in allergic epithelium compared with healthy specimens. A literature search indicated that out of these receptors, eight (i.e. 37%) were associated with lipid rafts/caveolae, which suggested again that Bet v 1 transport is lipid raft/caveola-dependent. We show a clear difference in the binding and uptake of Bet v 1 allergen by conjunctival epithelial cells in allergic vs healthy subjects and several putative lipid raft/caveolar receptors were identified, which could mediate or be co-transported with this entry. The application of discovery driven methodologies on human conjunctival epithelial cells and tissues can provide new hypotheses worth a further analysis to the molecular mechanisms of a complex multifactorial disease such as type-I birch pollen allergy.
    Allergy 02/2009; 64(6):868-75. DOI:10.1111/j.1398-9995.2008.01919.x · 6.00 Impact Factor
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    ABSTRACT: Neutrophil activation and tissue sequestration are crucial events in intestinal ischemia-reperfusion injury, but their role in the gut wall after clinical cardiopulmonary bypass (CPB) remains unclear. We tested whether local post-CPB inflammatory response in the gut wall would be associated with intestinal mucosal perfusion. Twenty pigs underwent 60 min of aortic clamping and 75 min of normothermic perfusion. Intestinal biopsies were taken after 120 min of reperfusion. Based on ileal myeloperoxidase activity (MPO), the animals were divided into 2 groups, CPB-induced increase in MPO (MPO+) versus no such increase (MPO-), for comparison of the parameters that measure gut mucosal perfusion. Ileal p(CO)((2)) and intramucosal pH were determined, and arterial gases were analyzed. Additionally, several hemodynamic parameters and blood thrombin-antithrombin complexes (TAT) were measured. Myocyte degeneration, endothelial activation and vasculitis were more pronounced in the MPO+ group (p < 0.05), while the MPO- group showed significantly increased pi(CO)((2)) and lower mucosal pH values during reperfusion. Hemodynamics and TAT levels did not differ between the groups. Tissue sequestration of neutrophils was poorly associated with perturbed mucosal perfusion after CPB. Mechanisms of gut wall injury after a low-flow/reperfusion setting can differ from those in reperfusion injury after total ischemia.
    European Surgical Research 12/2008; 42(1):59-69. DOI:10.1159/000169983 · 1.43 Impact Factor
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    ABSTRACT: Antithrombin (AT) may alleviate many cardiopulmonary bypass (CPB) and ischemia-reperfusion (I/R)-related adverse effects. Using a porcine model of clinical cardiac surgery on CPB, we tested the effects of supplementary AT on myocardial and lung I/R injury. Twenty pigs undergoing 60-min aortic clamping and 75-min normothermic perfusion were randomized in a blinded setting to receive an intravenous (i.v.) bolus of AT (250 IU/kg) (AT group, n = 10) or placebo (n = 10) 15 min before aortic declamping. An additional group of five animals received 500 IU/kg AT in an open-label setting (AT+). Thrombin-antithrombin complexes (TAT), activated clotting times (ACT), AT and myeloperoxidase (MPO) activities, troponin T, and several hemodynamic parameters were measured before CPB and after weaning from CPB up to 120 min after aortic declamping. After 120 min of reperfusion, myocardial and lung biopsies were taken for histological examination. AT effectively inhibited coagulation as assessed by ACT. In the AT and AT+ groups only, cardiac output (CO) and stroke volume (SV) showed a trend of post-ischemic recovery during the first 15 min after CPB. AT-attenuated reperfusion induced an increase in pulmonary arterial diastolic pressure (PAPD) but did not have significant effects on systemic or pulmonary vascular resistance. The effects of AT on SV, CO, and PAPD were fortified in the AT+ group. AT did not show effects on inflammatory changes in either myocardial or pulmonary tissue specimens. AT did not reduce post-ischemic troponin T release. Supplementary AT, in doses with significant anticoagulant effect, did not alleviate myocardial I/R injury in terms of histological inflammatory changes or post-ischemic troponin T release. Instead, however, AT-attenuated reperfusion induced an increase in pulmonary pressure after CPB. Mechanisms and clinical implications of these effects remain to be explored.
    Acta Anaesthesiologica Scandinavica 03/2007; 51(2):178-88. DOI:10.1111/j.1399-6576.2006.01185.x · 2.31 Impact Factor
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    ABSTRACT: Malignant progression, infiltrative growth pattern and recurrencies after surgery are characteristic features of diffuse gliomas. Ezrin is a membrane-cytoskeleton linker protein expressed in several types of neoplasms. In experimental models, increased ezrin expression correlates with invasion of malignant glioma cells. We studied ezrin expression and its correlation with patient survival in 229 primary and recurrent astrocytomas (WHO grades II-IV), oligodendrogliomas (II-III) and oligoastrocytomas (II-III) of 113 patients. Ezrin expression as evaluated by immunohistochemistry and immunoblotting was detected in all studied glioma types. Staining intensity and number of immunoreactive cells correlated with increasing malignancy of astrocytomas and oligoastrocytomas (P = 0.001). Ezrin expression was strongest in astrocytomas (P = 0.006). Also oligodendrogliomas were positive for ezrin. High ezrin expression in primary gliomas correlated with shorter time to recurrence (P < 0.05) and poor overall survival (P < 0.05) of the patients. Ezrin expression increased during progression of the tumours (P < 0.05). However, ezrin was not an independent prognostic factor. The results of this study show that ezrin expression is associated with progression of gliomas and correlates with histological cell type and WHO tumour grade.
    Neuropathology and Applied Neurobiology 11/2004; 30(5):472-7. DOI:10.1111/j.1365-2990.2004.00562.x · 4.97 Impact Factor
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    ABSTRACT: Following encouraging results from several single-center studies showing that early histological manifestations of chronic rejection are seen in the graft before a decline in transplant function, we tested this concept in a multicenter study and investigated whether protocol needle biopsy may be used as a surrogate to late graft survival in multicenter renal transplantation trials. During two mycophenolate mofetil trials, 621 representative protocol biopsies were obtained at baseline, 1 year, and 3 years. The samples were coded and evaluated blindly by two pathologists and a Chronic Allograft Damage Index (CADI) score was constructed. At 1 year only 20% of patients had elevated (>1.5 mg/100 mL) serum creatinine, whereas 60% of the biopsies demonstrated an elevated (>2.0) CADI score. The mean CADI score at baseline, 1.3 +/- 1.1, increased to 3.3 +/- 1.8 at 1 year and to 4.1 +/- 2.2 at 3 years. The patients at 1 year were divided into 3 groups, those with CADI <2, between 2 and 3.9, and >4.0, the first two groups having normal (1.4 +/- 0.3 and 1.5 +/- 0.6 mg/dL) and the third group pathological (1.9 +/- 0.8 mg/dL) levels of serum creatinine. At 3 years there were no lost grafts in the "low" CADI group, six lost grafts (4.6%) in the "elevated" CADI group, and 17 lost grafts (16.7%) in the "high" CADI group (P <.001). One-year histological CADI score predicts graft survival even when the graft function is still normal. This observation makes it possible to use CADI as a surrogate endpoint in prevention trials and to identify the patients at risk for intervention trials.
    Transplantation Proceedings 01/2004; 36(1):89-91. DOI:10.1016/j.transproceed.2003.11.006 · 0.95 Impact Factor
  • Transplantation 01/2004; 78. DOI:10.1097/00007890-200407271-00298 · 3.78 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the predictive value of intratumoural microvessel density in breast cancer. We studied immunohistochemically primary tumours of 104 patients with metastasised breast cancer who took part in a randomised multicentre trial comparing docetaxel to sequential methotrexate and 5-fluorouracil. Vessels were highlighted with factor VIII staining and counted microscopically. Microvessel density was compared with clinical response to chemotherapy and patient survival. The microvessel density of the primary tumour was not significantly associated with patient's response to chemotherapy, time to progression or overall survival in the whole patient population or in the docetaxel or methotrexate and 5-fluorouracil groups. However, disease-free survival was longer in patients with low microvessel density (P=0.01). These findings suggest that microvessel density of the primary tumour cannot be used as a predictive marker for chemotherapy response in advanced breast cancer. British Journal of Cancer (2002) 86, 1905–1908. doi:10.1038/sj.bjc.6600325 www.bjcancer.com © 2002 Cancer Research UK
    British Journal of Cancer 07/2002; 86(12):1905-8. DOI:10.1038/sj.bjc.6600325 · 4.82 Impact Factor
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    ABSTRACT: We investigated the effects of jejunoileal denervation with or without ischemia-reperfusion on mucosal characteristics and small intestinal structure. Growing pigs underwent sham laparotomy, jejunal transection, or extrinsic jejunoileal denervation with or without in situ ischemia-reperfusion. Small intestinal morphology, crypt cell proliferation, enterocyte ultrastructure, and disaccharidase activities were analyzed from jejunum and ileum after eight weeks. Immunohistological analysis of the ileum showed no staining of catecholaminergic neurons after extrinsic denervation. Neural isolation of the jejunoileum with or without ischemia-reperfusion injury reduced weight gain and villous enterocyte density in the ileum, abolished the proximodistal gradient of sucrase activity, and increased mucosal thickness, villus height, and villus surface area in the ileum. However, gross jejunoileal morphology, crypt cell proliferation, and enterocyte ultrastructure remained unchanged. In conclusion, jejunoileal denervation in growing pigs selectively modulates constitutional mucosal characteristics in the ileum, presumably due to altered enterocyte turnover, without a decrease in small intestinal absorptive surface area. These changes are independent of short ischemia and subsequent reperfusion.
    Digestive Diseases and Sciences 04/2001; 46(3):476-85. DOI:10.1023/A:1005674426690 · 2.55 Impact Factor
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    ABSTRACT: Acute kidney allograft rejection is characterized by a lymphocyte infiltration. L-selectin on lymphocytes and its endothelial glycosylated ligands are instrumental in the initiation of lymphocyte extravasation to sites of inflammation. From more than 500 core biopsy specimens taken from kidneys after transplantation, 250 biopsies were graded to have signs of acute rejection. Of these, 52 biopsies with various grades of histologic signs of acute rejection were selected for the study. Controls were 15 biopsies taken within 30 min after revascularization and 10 specimens from well-functioning allografts showing no clinical or histologic evidence of rejection. Immunochemical stainings with monoclonal antibodies against functionally active decorated L-selectin ligands. i.e., sialyl-Lewis x (sLex, 2F3 and HECA-452) or sulfated lactosamine (MECA-79) were performed. Although no endothelial 2F3 and MECA-79 epitopes were detected in nonrejecting control specimens, the expression was induced at the onset and during acute allograft rejections. The level of expression (in semi-quantitative score) of 2F3 reactivity correlated with the severity of rejection (P<0.0001, grade I versus grade IIB), and the level of expression decreased as the rejection resolved. Kidney biopsies taken shortly after revascularization and thus undergoing reperfusion injury showed endothelial staining with another anti sLex antibody, HECA-452. This staining disappeared from well-functioning grafts and reappeared at the onset of an acute allograft rejection. These results suggest that expression of functionally active, properly glycosylated L-selectin ligands might have a role in reperfusion injury and in the initiation of acute rejections after human kidney allograft transplantation.
    Journal of the American Society of Nephrology 12/2000; 11(12):2358-65. · 9.47 Impact Factor
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    ABSTRACT: In this retrospective study we describe the immunohistochemical expression pattern of sLe(x) epitopes in endothelial and epithelial cells of 59 squamous carcinomas of the tongue, and relate this to the relative survival rates of the patients. Endothelial sLe(x) expression was significantly elevated in malignant lesions compared to normal tissues, but did not have any prognostic value for the relative survival rate. In contrast, epithelial sLe(x) expression was decreased in carcinomas compared to normal tongue. The patients whose carcinoma showed only moderate epithelial HECA-452 reactivity had a significantly better relative survival rate than the patients with tumor specimens with neglible or very high HECA-452 reactivity. The epithelial staining with the two other anti-sLe(x) antibodies (CSLEX-1 and 2F3) did not correlate with the survival rates of tongue carcinoma patients.
    Apmis 11/2000; 108(10):705-12. · 1.92 Impact Factor
  • Transplantation Proceedings 10/2000; 32(6):1299-300. DOI:10.1016/S0041-1345(00)01233-1 · 0.95 Impact Factor
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    ABSTRACT: Lymphocyte infiltrate is a hallmark of inflammatory responses. We have previously shown that de novo-induced endothelial sialyl Lewis x (sLex) expression guides lymphocytes in an L-selectin-dependent manner to sites of acute organ transplant rejections. In this research, we have analyzed five groups of chronic lung inflammations to determine the presence of properly glycosylated, i.e., sulfated, sLex-decorated, L-selectin ligands. Two anti-sLex (2F3 and HECA-452) and one anti-6- and/or 6'-sulfated and/or 6,6'-bisulfated (MECA-79) monoclonal antibodies (mAbs) were used. The control lung specimens did not express L-selectin ligands on endothelium. In contrast, the endothelial staining intensity and the number of positive peribronchial venules and capillaries with mAbs 2F3, HECA-452, and MECA-79 were significantly greater in bronchial biopsies from patients with asthma compared with normal specimens (P<0.003). However, no significant increase of peribronchial endothelial reactivity with these antibodies was observed in adult respiratory distress syndrome, chronic bronchitis, fibrosing alveolitis, and granulomatous inflammation compared with controls. These data suggest that sulfated sLex glycans, acting putatively as ligands for L-selectin, could be instrumental in lymphocyte extravasation into human peribronchial lung tissue during asthma, but not so important in several other inflammatory lung diseases.
    American Journal of Respiratory Cell and Molecular Biology 10/2000; 23(4):492-8. DOI:10.1165/ajrcmb.23.4.4113 · 4.11 Impact Factor
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    ABSTRACT: This study was conducted to illustrate and classify the abnormalities found on high-resolution MR imaging of symptomatic Achilles tendons in athletic adult patients. One hundred patients with 118 painful Achilles tendons were imaged with a 1.5-T magnet. The tendon, peritendinous tissues, tendon insertion, and musculotendinous junction were examined on MR imaging. Twenty-eight patients underwent surgery, and histopathologic samples were taken in 13. Long-term follow-up was performed, on average, 3.4 years after MR imaging. Of 118 painful Achilles tendons, abnormalities were detected in 111. These were in the tendon (n = 90), surrounding structures, or both. Fifty-four tendons had a focal area of increased intratendinous signal, best detected on axial high-resolution T1-weighted gradient-echo MR imaging. Histopathology confirmed abnormal tendon structure. Of the 21 surgically proven foci of tendinosis, 20 were revealed on MR imaging. At the level of the insertion, changes were found in the tendon in 15%, in the retrocalcaneal bursa in 19%, and in the calcaneal bone marrow in 8% of the studies. Abnormalities in peritendinous soft tissues were detected in 67%. More than one type of abnormality was found in 64% of the studies. Lesions in the Achilles tendon and in the peritendinous structures can have similar clinical presentation. MR imaging detects and characterizes these changes. A more specific diagnosis and prognosis can be made with the use of MR imaging than with clinical examination alone.
    American Journal of Roentgenology 08/2000; 175(1):251-60. DOI:10.2214/ajr.175.1.1750251 · 2.74 Impact Factor
  • S Yilmaz, E Taskinen, T Paavonen, P Häyry
    Transplantation Proceedings 03/2000; 32(1A Suppl):12S. · 0.95 Impact Factor
  • Annals of transplantation: quarterly of the Polish Transplantation Society 02/2000; 5(2):37-43. · 1.43 Impact Factor
  • S Yilmaz, E Taskinen, T Paavonen, P Häyry
    Transplantation Proceedings 02/2000; 32(1):12-12. DOI:10.1016/S0041-1345(00)00809-5 · 0.95 Impact Factor
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    ABSTRACT: This study investigates the effects of ileal autotransplantation on morphology, crypt cell proliferation, and brush border disaccharidases of the remaining jejunoileum and colon in growing pigs with 75% proximal small bowel resection. Resection was performed on 30 pigs, of which 15 underwent an autotransplantation of the remaining ileum. The autotransplanted pigs showed reduced weight gain and remnant ileal length when compared to the resected controls. In the autotransplanted pigs, small bowel diameter and weight, mucosal weight and protein content, villus height and surface area, crypt depth, and the number of proliferating crypt cells were reduced similarly both in the intact jejunum and in the autotransplanted ileal remnant. Autotransplantation also decreased the number of proliferative crypt cells of the colon. Specific activities of maltase and sucrase tended to increase in the autotransplanted ileal remnant, whereas the total enzyme activities decreased. These results suggest that ileal autotransplantation disturbs postresectional adaptation of the remaining gut.
    Digestive Diseases and Sciences 12/1999; 44(11):2187-95. DOI:10.1023/A:1026636216324 · 2.55 Impact Factor
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    ABSTRACT: E- and P-selectins, expressed on vascular endothelium, and their sialyl-Lewis(x )(sLe(x))- and/or sialyl-Lewis(a) (sLe(a))-containing ligands have a crucial role in extravasation and metastasis of circulating cells. We wanted to analyse the role of selectins and their ligands in head and neck tumours. A total of 40 consecutive biopsy specimens were collected from surgery performed at the Helsinki University Central Hospital between September 1995 and November 1996. The series of specimens contained both benign and malignant head and neck tumours of epithelial, lymphoid or mesenchymal origin. All these were analysed with immunohistochemistry for epithelial and endothelial expression of sLe(x) and sLe(a) glycans and E- and P-selectins. Epithelial expression of sLe(x) and sLe(a) glycans was higher in benign than in malignant lesions in both epithelial and lymphoid tumours. On the other hand, endothelial expression of sLe(x), sLe(a), E- and P-selectin was lower in benign than in malignant lesions in both epithelial and lymphoid tumours. These data suggest that altered epithelial and endothelial expression of sLe(x) and sLe(a )glycans acting on selectin ligands is linked to the development of head and neck tumours.
    Journal of Cancer Research and Clinical Oncology 11/1999; 125(10):569-76. DOI:10.1007/s004320050318 · 3.01 Impact Factor

Publication Stats

2k Citations
298.96 Total Impact Points

Institutions

  • 2009
    • University of Tampere
      • Department of Pathology
      Tammerfors, Province of Western Finland, Finland
  • 2007
    • University of Oulu
      • Department of Pathology
      Uleoborg, Oulu, Finland
  • 1980–2004
    • University of Helsinki
      • • Department of Pathology
      • • Department of Bacteriology and Immunology
      • • Transplantation Laboratory
      Helsinki, Southern Finland Province, Finland
  • 2000
    • The University of Calgary
      • Department of Surgery
      Calgary, Alberta, Canada
  • 1988–1997
    • Helsinki University Central Hospital
      • • Department of Surgery
      • • Department of Oncology
      • • Department of Pathology
      Helsinki, Province of Southern Finland, Finland
  • 1992
    • Gazi University
      • Department of Surgery
      Ankara, Ankara, Turkey