Timo Paavonen

Tampere University Hospital (TAUH), Tammerfors, Pirkanmaa, Finland

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Publications (179)586.41 Total impact

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    ABSTRACT: Cancerous inhibitor of protein phosphatase 2A (CIP2A) prevents proteolytic degradation of a universal transcription factor, c-Myc. Strong CIP2A expression associates with poor prognosis in early-stage tongue cancer and in other cancers. The aim of this study was to evaluate CIP2A and mucosal inflammation in tongue hyperplasia, in tongue cancer, and in its metastasis. Retrospective tongue and lymph node specimens (n = 105) were stained immunohistochemically with polyclonal antibody anti-CIP2A. CIP2A staining intensity and inflammation were assessed semi-quantitatively with light microscopy. CIP2A was similarly detected in tongue cancer and tongue hyperplasia, whereas local inflammation was stronger in cancer (p = 0.000). CIP2A expression was increased in metastasized cancer compared to non-metastasized (p = 0.019). Markers for poorer survival were tumor size of ≥20 mm, presence of metastasis and nodal CIP2A (p = 0.031, p = 0.000, p = 0.042). Cancer patients aged ≥60 with increased inflammation predicted poor survival (p = 0.037). CIP2A and inflammation might play a role in progression of tongue cancer.
    Apmis 11/2015; DOI:10.1111/apm.12462 · 2.04 Impact Factor
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    ABSTRACT: Epithelial-mesenchymal transition (EMT) has previously been linked to glioma invasion and progression. To determine whether EMT regulators, Twist and Zeb1, had clinical significance in astrocytic gliomas, the association of Twist and Zeb1 with clinicopathological and molecular factors was studied in 269 astrocytoma samples. Twist and Zeb1 were widely expressed in astrocytic gliomas, but the expression of the former did not correlate with that of the latter. Stronger Twist expression levels were associated with higher WHO grades (p=0.001), whereas Zeb1 did not correlate with WHO grades. We found no association between Twist and proliferation activity (Ki67/MIB-1), p53 status, epidermal growth factor receptor (EGFR) amplification or neural cell adhesion molecule (NCAM) expression. There was no significant difference in Twist or Zeb1 expression when primary and secondary gliomas were analysed. Tumours with high Twist expression were IDH1 negative (p=0.009). High hypoxia-inducible factor-1α expression correlated significantly with positive Twist expression (p<0.001), whereas it was not associated with Zeb1 expression. Zeb1 expression did not correlate with proliferation, EGFR or IDH1. Nevertheless, we did find a correlation between high Zeb1 expression and low p53 expression levels (p=0.027). Positive NCAM expression was significantly associated with Zeb1 positivity (p=0.022). Zeb1 had no association with patient survival, whereas positive Twist expression predicted poor survival for patients in both univariate (p<0.001) and multivariable analyses (p=0.027). EMT regulators, Twist and Zeb1, are common features of infiltrating astrocytomas, and Twist is upregulated in glioblastomas in particular. Twist may be a novel marker for poor prognosis in glioma patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Journal of clinical pathology 07/2015; DOI:10.1136/jclinpath-2015-202868 · 2.92 Impact Factor
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    ABSTRACT: Perioperative myocardial infarction (MI) with ischaemia-reperfusion injury (IRI) is a devastating entity occurring in 1-2% of patients after cardiac surgery. The molecular pathway leading to myocardial cellular destruction after MI may include monoamine oxidases. We experimentally investigated whether moclobemide, a monoamine oxidase inhibitor, enhances myocardial recovery after cardiac arrest and MI. Fifty-six syngeneic Fischer rats underwent heterotopic cardiac transplantation to induce reversible IRI after cardiac arrest. Twenty-eight rats also underwent permanent ligation of the left anterior descending coronary artery to induce MI after cardiac arrest. Twenty-eight rats with or without MI were treated with subcutaneous moclobemide 10 mg/kg/day. Methods used to study myocardial recovery were microdialysis for intramyocardial metabolism, histology and quantitative reverse-transcription polymerase chain reaction for high-mobility group box-1 (HMGB1), haeme oxygenase-1 (HO-1), interleukin-6, hypoxia-inducible factor 1α and macrophages (CD68). Pyruvate increased in MI treated with moclobemide versus IRI with moclobemide (29.19 ± 7.64 vs 13.86 ± 8.49 µM, P = 0.028), reflecting metabolic activity after cardiac arrest and reperfusion. Myocardial inflammation increased in MI compared with IRI after 1 h (0.80 ± 0.56 vs 0, point score units [PSUs], P = 0.003), but decreased after 5 days in MI treated with moclobemide versus MI alone (0.80 ± 0.83 vs 2.00 ± 0.70, PSU, P = 0.033). Expressions of HMGB1, CD68 and HO-1 decreased in MI treated with moclobemide versus MI alone (1.33 ± 0.20 vs 1.75 ± 0.24, fold changes [FCs], P = 0.028; 5.15 ± 1.10 vs 9.59 ± 2.75, FC, P = 0.050; 10.41 ± 4.17 vs 21.28 ± 10.01, FC, P = 0.047), indicating myocardial recovery and increased cellularity of remote intramyocardial arteries. Moclobemide enhances myocardial recovery after cardiac arrest and MI; inhibition of remote myocardial changes may be achieved by targeting treatment against monoamine oxidase. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
    Interactive Cardiovascular and Thoracic Surgery 06/2015; 21(4). DOI:10.1093/icvts/ivv175 · 1.16 Impact Factor
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    ABSTRACT: Background: The diagnosis of regional myocardial infarction (MI) after cardiac arrest and ischemia-reperfusion injury (IRI) is a major clinical challenge. Objectives: We evaluated in a rat cardiac transplantation model whether IRI alone or with MI would induce complement C4d deposition. Material and Methods: Isogenic heterotopic cardiac transplantation was performed in 16 Fischer 344 rats to induce IRI, of which 9 rats also underwent ligation of the left anterior coronary artery (LAD) of the heart to yield MI. Histology and qRT-PCR for endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and transforming growth factor β (TGFβ) were performed after cessation of heart beat. C4d was evaluated by immunohistochemistry. Results: Myocardial inflammation and C4d deposition was increased in grafts with IRI+MI as compared with IRI (0.71 vs. 0.14, PSU, respectively, p < 0.04 and 80.13 vs. 20.29, PSU, respectively, p < 0.02). The expression of eNOS decreased in grafts with IRI + MI as compared with IRI (p < 0.05). Receiver operating characteristic (ROC) curve analysis showed that IRI + MI was associated with C4d deposition (AUC 0.837; S.E. 0.116; p = 0.035; 95% C.I. 0.610-1.000). Conclusions: Increased C4d deposition may be amenable to identify early MI after cardiac arrest. Early treatment aimed towards complement activation may provide a novel means for induced MI after cardiac arrest
    Advances in Clinical and Experimental Medicine 05/2015; 24(3):393-399. DOI:10.17219/acem/29181 · 1.10 Impact Factor

  • Oral Oncology 05/2015; 51(5):e40-e41. DOI:10.1016/j.oraloncology.2015.02.044 · 3.61 Impact Factor
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    ABSTRACT: Few data are available about the inflammatory cytokine profile of bronchoalveolar lavage (BAL) from young children with frequent wheeze. The first aim was to investigate the BAL cellular and cytokine profiles in infants with recurrent lower respiratory symptoms in whom bronchoscopy was indicated for clinical symptom evaluation. The second aim was to relate the BAL results with the histological findings of the endobronchial carina biopsies. Thirty-nine infants (median age 0.9 years) underwent lung function testing by whole-body plethysmography prior to the bronchoscopy. The BAL differential cell counts and cytokine levels were quantified. These findings were compared with the histological findings of the endobronchial carina biopsies. The differential cytology reflected mainly that described for healthy infants with lymphocyte counts at the upper range level. A positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement membrane was found. Detectable levels of pro-inflammatory cytokine proteins IL-1β, IL-17A, IL-18, IL-23, and IL-33 were found, whereas levels of Th2-type cytokine proteins were low. Frequent wheeze was the only clinical characteristic significantly related to detectable combined pro-inflammatory cytokine profile. Lung function did not correlate with any cytokine. A positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement thickness was found. Detectable production of pro-inflammatory cytokines associated positively with frequent wheeze.
    10/2014; 4(1):35. DOI:10.1186/2045-7022-4-35
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    ABSTRACT: Background The aim of the study was to assess the localization of Polysialic acid (polySia) and Neural cell adhesion molecule (NCAM) in grade I–IV astrocytomas by confocal microscopy, and also to clarify and compare their relationship to conventional clinicopathological features in these tumors. Methods Study material was stained immunohistochemically for polySia, NCAM and IDH1-R132H point mutation. Confocal microscopy of polySia and NCAM staining was performed on tissue micro-array samples (TMA) of 242 diffusely infiltrating astrocytomas (grade II: 28; grade III: 33; grade IV: 181) and 82 pilocytic astrocytomas. The results were statistically correlated to clinicopathological factors and survival data. Results PolySia was observed in 45 cases (19%) and NCAM positivity in 92 cases (38%). All 45 tumors with polySia positivity were also positive for NCAM whereas there were 47 tumors which contained positive staining for NCAM but not for polySia. The simultaneous expression was concomitant and colocalized suggesting polysialyated NCAM (polySia-NCAM). PolySia expression was significantly stronger in IDH1 mutated tumors than in IDH1 non-mutated (p = 0.001, chi-square test). There were no significant differences in polySia-NCAM between primary tumors or recurrences (p = n.s., chi-square test). PolySia positivity was associated with longer patient survival in relation to total tumor material (p = 0.020, log-rank test). Furthermore, when only glioblastomas were assessed, patients with positive polySia had significantly better prognosis (p = 0.006, log-rank test). In multivariate survival analysis, polySia was found to be an independent prognostic factor. PolySia was nearly absent in grade I pilocytic astrocytomas (1 immunopositive tumor of 82). Conclusions Expression of polySia is common in adult grade II–IV astrocytomas, whereas it is nearly absent in pediatric grade I pilocytic astrocytomas. PolySia positivity is associated with longer survival rates in patients with a grade II–IV astrocytomas and also grade IV glioblastomas assessed separately. The results of this study suggest that IDH1 mutation may be associated with polySia expression pathways in malignant gliomas.
    BMC Cancer 08/2014; 14(1):623. DOI:10.1186/1471-2407-14-623 · 3.36 Impact Factor
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    ABSTRACT: Peptic ulcer bleeding (PUB) is a major cause of upper gastrointestinal bleeding. The effect of omeprazole on mucosal repair is unknown. We studied the effect of omeprazole, nonsteroidal anti-inflammatory agents, and smoking on PUB. There were 43 PUB patients who received regular or high dose of omeprazole for 72 h. Biopsies from antrum and corpus were taken before and after treatment. Biopsy samples from 20 celiac disease patients worked as controls. The expression of Ki-67, Bcl-2, COX-2, Hsp27, and Hsp70 was analyzed from patients and controls. Bcl-2 expression in PUB patients was lower than in controls. However, Bcl-2 increased significantly from 5.0 (SD 4.5) to 9.1 % (SD 6.7), p = 0.0004, in the antrum after omeprazole. In univariate analysis, a high omeprazole dose caused a more profound increase in Ki-67 expression in the corpus: 35.3 % (SD 54.8) than a regular dose: -10.1 % (SD 40.6), p = 0.022. In multivariate analysis, Ki-67 decreased significantly in the corpus between the pre- and posttreatment period (p = 0.011), while a high omeprazole dose (p = 0.0265), the use of NSAIDs (p = 0.0208), and smoking (p = 0.0296) significantly increased Ki-67 expression. Bcl-2 in the corpus increased significantly (p = 0.0003) after treatment. Our findings suggest that Bcl-2 may be an important factor in the pathogenesis of a peptic ulcer and PUB. In addition, high-dose omeprazole increased the expression of Ki-67, which may enhance the healing process of a peptic ulcer.
    Digestive Diseases and Sciences 08/2014; 59(11). DOI:10.1007/s10620-014-3242-z · 2.61 Impact Factor
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    ABSTRACT: Definitive treatment of extended thoracic aortic dilatation is a major surgical challenge. Histopathology of resected thoracic aortic wall may reveal undiagnosed aortitis affecting outcome. We sought to investigate the benefit of thorough histopathology after one-stage corrective surgery for the treatment of extended thoracic aortic dilatation. Five patients underwent one-stage corrective surgery using the hybrid open arch repair by the frozen elephant trunk together with endovascular aortic grafting. A representative sample of the resected aortic arch was procured for histology. T- and B-lymphocytes, plasma cells, macrophages, and immunoglobulin G4 (IgG4) positivity were evaluated by immunohistochemistry. The mean preoperative maximum aortic diameter was 54 mm (range, 41-79 mm). The mean follow-up was 18 months (range, 1-24 months). As confirmed by computed tomography (CT) upon follow-up, complete thrombosis of the false lumen at the level of the frozen elephant trunk was achieved in all patients with dissection. One patient was operated due to atherosclerotic dilatation of the thoracic aorta, and postoperative CT showed successful exclusion of the atherosclerotic dilatation; this 75-year-old man was diagnosed with IgG4-positive aortitis and experienced unexpected blindness after surgery without evidence of emboli or long-term neurological impairment upon repeated brain CT. The hybrid open arch repair by the frozen elephant trunk and simultaneous endovascular repair is a feasible choice for one-stage surgery through sternotomy aiming at definitive treatment of extended thoracic aortic pathology. However, systematic evaluation of inflammation may reveal concealed aortitis affecting postoperative outcome and need for long-term surveillance.
    International Journal of Angiology 06/2014; 23(2):101-6. DOI:10.1055/s-0034-1370887
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    ABSTRACT: Asthma and chronic rhinosinusitis with nasal polyps (CRSwNPs) are coexisting diseases that are multifactorial. The rural environment seems to protect from atopy, but its relation with nonatopic airway inflammations has been less investigated. Indoleamine 2,3-dioxygenase (IDO) is an enzyme involved in the catabolism of the essential amino acid tryptophan (Trp) to kynurenine (Kyn). Low IDO activity has been previously observed in atopy and asthma. The objective was to investigate the relationships of IDO activity, eosinophils, and cofactors during asthma and/or CRSwNPs. A Finnish population-based cohort of adult asthmatic patients (n = 245) and nonasthmatic patients (n = 405) was used. The presence of asthma and atopy were based on patient history and standardized diagnostic tests. The presence of acetyl salicylic acid intolerance, doctor-diagnosed NPs, and countryside environment during childhood were based on a questionnaire report. Serum IDO activity was evaluated by assessing the Kyn/Trp ratio by liquid chromatography. Low IDO activity was associated significantly with atopy, CRSwNPs, and an urban background. IDO activity did not correlate with pulmonary function. As expected, CRSwNPs was more frequent among asthmatic patients. A rural background has a protective effect from atopy and atopic asthma but it did not affect the prevalence of CRSwNPs or nonatopic asthma. Low IDO activity might result from the urban environment and influence the development of the atopic phenotype. On the other hand, low IDO activity, found in CRSwNPs, does not seem to be related to the urban background and thus may result from other, still unknown, factors.
    American Journal of Rhinology and Allergy 04/2014; 28(1):5-10. DOI:10.2500/ajra.2014.28.4013 · 1.81 Impact Factor
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    ABSTRACT: Aims: Heat shock protein 27 (Hsp27) is induced by cell stress conditions. In the presence of oxidative stress it functions as an antioxidant. To study the putative expression patterns and clinical significance of Hsp27, we assessed the associations between Hsp27, R132H mutation of Isocitrate dehydrogenase1 (IDH1-R132H), Hypoxia-inducible factor subunit alpha (HIF-1 alpha), Carbonic anhydrase IX (CA IX), and patient prognosis in astrocytic gliomas. Methods: Tissue micro-array samples of 295 grade II-IV astrocytomas were stained immunohistochemically for Hsp27, IDH1-R132H, HIF-1 alpha, and CA IX. We tested their relationship with clinicopathological features and patient survival. Results: There was a significant correlation between Hsp27 expression and increasing WHO grade (p<0.001). Hsp27 expression correlated significantly with IDH1 mutation when studied within the entire cohort (p<0.001) as well as separately in WHO grade II and III tumors (p=0.006 and 0.002, respectively). IDH1 mutation and HIF-1 alpha positive staining were detected simultaneously (p<0.001). In IDH1 mutated tumors, positive HIF-1 alpha staining correlated with CA IX expression (p=0.027), whereas no such correlation was found in IDH1 non-mutated tumors. IDH1 mutation was associated with a low cell proliferation index (p=0.001) and HIF-1 alpha with increasing proliferation (p = 0.003). Hsp27 expression was associated with a shorter rate of patient survival in univariate survival analysis (p=0.001). In multivariate survival analysis, patient age, IDH1 mutation and HIF-1 alpha appeared as independent prognostic factors (p<0.000, <0.000 and 0.011 respectively) Conclusions: Hsp27 expression is associated with increasing WHO grade and patient prognosis in astrocytic gliomas. The results suggest that IDH1 mutation may have an effect on the expression pathways of Hsp27 and CA IX.
    Histology and histopathology 03/2014; 29(9). · 2.10 Impact Factor
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    ABSTRACT: To evaluate the ability of an electronic nose (eNose) to discriminate prostatic cancer (PCa) from benign prostatic hyperplasia (BPH) from urine headspace potentially offering a clinically applicable noninvasive and rapid diagnostic method. ChemPro® 100 -eNose was used to discriminate PCa from BPH using urine sample headspace. Its performance was tested with 50 patients with confirmed PCa and 24 samples from 15 patients with BPH (15 patients provided urine preoperatively and 9 patients 3 months post-operatively) subjected to robotic-assisted laparoscopic radical prostatectomy or transurethral resection of prostate, respectively. The patients provided urine sample pre-operatively and BPH patients also 3 months post-operatively to be used as a pooled control sample population. A discrimination classifier was identified for eNose and subsequently, sensitivity and specificity values were determined. Leave-one-out cross-validation (LOOCV) was performed. Using LOOCV, eNose reached sensitivity of 78%, specificity of 67% and AUC of 0.77. Electronic nose is capable of rapidly and noninvasively discriminating PCa and BPH from urine headspace in patients subjected to surgery.
    The Journal of urology 02/2014; 192(1). DOI:10.1016/j.juro.2014.01.113 · 4.47 Impact Factor
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    ABSTRACT: The aim of this paper is to introduce an image source-independent automated method for segmentation and classification of prostate glands. This research focuses on light microscopic images of the samples from different laboratories using the same staining method. Color information in the image is highly dependent on the source and the conditions under which the image has been taken. The proposed method can be used to analyze images with color variations. Color information is used for the segmentation of tissue structures and Delaunay triangulation is used for gland segmentation. The proposed method uses triangulation to find the basic structure of any shaped and sized gland and to prevent misclassification of gland components. The proposed approach classifies the nuclei circumscribing the glands to single and multilayered. Other features used in the classification are the amount of nuclei and the area of the gland. The number of layers can be used for determining the malignancy of the tissue sample. In most cases, a single-layered gland is malignant and multilayered is benign. This segmentation approach is different than what has been previously used in the literature. In this paper, the glands are classified to four different categories: single layered, multilayered, rejected or nonclassified. This approach distinguishes majority of single and multilayered glands from each other.
    Machine Vision and Applications 01/2014; 26(1):103-113. DOI:10.1007/s00138-014-0650-1 · 1.35 Impact Factor
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    ABSTRACT: Background: Confined ongoing ischemia after ischemia-reperfusion injury (IRI) may alter myocardial recovery. We evaluated in a rat cardiac transplantation model whether distal persistent myocardial ischemia (dMI) and remote preconditioning (RPreC) have a remote myocardial impact after IRI. Material and methods: Syngeneic heterotopic cardiac transplantation was performed on 29 Fischer344 rats to induce IRI, including nine rats which underwent distal ligation of the left anterior coronary artery (LAD) to yield distal MI (IRI+ dMI). RPreC was applied by occluding the left renal artery 5 min prior to reperfusion in six rats with IRI (IRI+ RPreC) as well as in seven with distal MI (IRI+ dMI+ RPreC). Microdialysis, histology and qRT-PCR for inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were performed after graft harvesting. Results: In contrast to IRI + dMI + RPreC (39 ± 7 μmol), glutamate decreased in IRI + RPreC and IRI + dMI as compared with IRI (26 ± 3 and 31 ± 8 vs 91 ± 20, μmol respectively, p < 0.007). The relative number of vacuolated intramyocardial artery nuclei decreased in IRI + dMI as compared with IRI (0.02 ± 0.01, range 0-12 vs. 0.42 ± 0.31, range 0-3.25 PSU respectively, p < 0.04). iNOS expression decreased in IRI + RPreC as compared with IRI (p < 0.04), and eNOS expression decreased in IRI + dMI + RPreC as compared with IRI + dMI (p < 0.006) along with increased glycerol release. Conclusions: dMI after IRI has a potentially beneficial myocardial impact after cardiac arrest, which is hampered by RPreC.
    Scandinavian journal of clinical and laboratory investigation 11/2013; 74(1). DOI:10.3109/00365513.2013.855944 · 1.90 Impact Factor
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    ABSTRACT: CIP2A is overexpressed in many cancers, including esophageal squamous cell carcinoma. The regulation of c-MYC and CIP2A expression is characterized by a positive feedback mechanism facilitating the expression of both of them and accelerating cancer cell proliferation in gastric cancer. Increased CIP2A expression is a predictor of poor survival in some cancers. The incidence of positive CIP2A immunostaining and its association with c-MYC and its predictive value in esophageal adenocarcinoma are unknown. All esophageal adenocarcinoma patients from 1990 to 2007 with sufficient material for analysis of CIP2A and c-MYC in two university hospitals were included in the study. In addition, biopsies from Barrett's epithelium from the cancer patients and control tissue from normal esophageal mucosa adjacent to the tumor were included. CIP2A was moderately or strongly positive in 77.9 %, and c-MYC in 93.8 % of the cancer specimens. These frequencies were statistically different from the expression in normal esophageal epithelium. In addition, there was a positive correlation between CIP2A and c-MYC expression (p = 0.018). According to adjusted Cox regression survival analysis, CIP2A and c-MYC had no effect on survival. However, among patients with stage IVA-IVB cancer, there was a trend toward poor prognosis in CIP2A-positive patients. The expression of CIP2A and c-MYC was associated with each other, and their overexpression was found in most cases of esophageal adenocarcinoma. However, CIP2A and c-MYC had no effect on survival.
    Medical Oncology 09/2013; 30(3):684. DOI:10.1007/s12032-013-0684-7 · 2.63 Impact Factor
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    Katri Mäkelä · Pauli Helén · Hannu Haapasalo · Timo Paavonen ·
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    ABSTRACT: Background C4d is a cleavage product of complement component C4 and is considered to serve as a marker for the site of complement activation. In this study C4d staining of grade I-IV astrocytic tumors was studied to explore if there is an association between complement activation and the grade of tumor, or patient survival. Methods Tissue micro-array samples of 102 astrocytomas were stained immunohistochemically. The material consisted of 9 pilocytic astrocytomas and 93 grade II-IV astrocytomas, of which 67 were primary resections and 26 recurrent tumors. The intensity of C4d staining as well as extent of C4d and CD34 staining were evaluated. The intensity of C4d staining was scored semiquantitatively. The extent of the staining was counted morphometrically with a point counting grid yielding a percent of C4d and CD34 positive area of the sample. Results The intensity and extent of C4d staining increased in grade II-IV diffusely infiltrating astrocytoma tumors in line with the malignancy grade (p = 0.034 and p = 0.016, respectively, Kruskal-Wallis test). However, C4d positive tumor area percentages were higher in grade I pilocytic astrocytomas than in grade II-IV diffusely infiltrating astrocytomas (p = 0.041, Mann–Whitney test). There was a significant correlation between CD34 positive and C4d positive endothelial area fraction in diffusely infiltrating astrocytomas (p < 0.001, Pearson correlation). In these tumors, the increasing intensity of C4d staining was also associated with worsened patient outcome (p = 0.014, log-rank test). Conclusion The worsening of patient outcome and malignant progression of tumor cells seem to be connected to microenvironmental changes evoked by chronically activated complement.
    BMC Cancer 12/2012; 12(1):565. DOI:10.1186/1471-2407-12-565 · 3.36 Impact Factor
  • Henri Kajander · Timo Paavonen · Timo Valo · Matti Tarkka · Ari A Mennander ·
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    ABSTRACT: Objective: Immunoglobulin (Ig) G4-positive aortitis may determine outcome after surgery for ascending aorta. We evaluated IgG4 expression of dilated ascending aortic wall. Methods: The study consisted of 91 patients who underwent ascending aortic surgery. For histology, hematoxylin-eosin, elastase-van Gieson, and periodic acid-Schiff stainings were performed. The amount of T and B lymphocytes, plasma cells, macrophages, cell proliferation, and IgG4 positivity were determined by immunohistochemistry. Results: The aortic wall in 12 patients had IgG4 positivity that was always confined to the adventitia. Adventitial plasma cells were numerous in all but 2 of these patients (P < .0001). Aortitis was revealed in 2 patients (17%) with IgG4-positive staining of the aorta and in 6 patients (8%) with IgG4 negativity. IgG4 staining was significantly associated with total aortic wall inflammation (area under the curve, 0.865; standard error, 0.043; P = .000; 95% confidence interval, 0.779-0.950). The mean diameter of the ascending aorta was 69 ± 4.7 mm and 56 ± 1.1 mm in patients with IgG4 positivity and negativity, respectively (P < .004). Approximately half of the patients with IgG4 positivity had dissection (42%), compared with only 15 of 79 (19%) of the remaining patients (P = not significant). Two patients with IgG4 positivity had to undergo reoperation because of immediate postoperative dissection. Seven patients died, including 4 patients (33%) with IgG4 positivity; the remaining 3 patients (4%) were IgG4 negative (P < .005). Conclusions: IgG4-positive ascending aortic wall was frequent in our study cohort (13%) and revealed aortic inflammation associated with dilatation.
    The Journal of thoracic and cardiovascular surgery 10/2012; 146(6). DOI:10.1016/j.jtcvs.2012.09.039 · 4.17 Impact Factor
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    ABSTRACT: Objectives: Resuscitation after cardiac arrest may lead to ischemia-reperfusion injury and infarction. We evaluated whether sildenafil, a phosphodiesterase-5 inhibitor, has an impact on recovery after cardiac arrest in a rat cardiac transplantation model. Design: Sixty-one Fischer344 rats underwent syngeneic heterotopic cardiac transplantation after ischemia and ligation of the left anterior coronary artery of the heart to yield myocardial infarction (IRI + MI). Of these, 22 rats received subcutaneously injected sildenafil (1 mg/kg/day) (IRI +MI + S). Twenty-three additional grafted animals with transplantation only served as controls with ischemia reperfusion injury (IRI). After 2 days, immunohistochemistry for eNOS, and RT-PCR for iNOS and Aquaporin-7 were performed after graft harvesting and histology. Results: Two days after transplantation, remote intramyocardial arteries were more preserved in IRI + MI + S as compared with IRI +MI and IRI (0.74 ± 0.14, 0.56 ± 0.23 and 0.55 ± 0.22, PSU, p < 0.05, respectively). Decreased eNOS staining confirmed the presence of developing infarction in IRI + MI and IRI + MI + S. The expression of iNOS was significantly lower during IRI + MI +S as compared with IRI + MI (0.02 ± 0.01 and 1.02 ± 0.02, FC, p < 0.05). Conclusions: Administered at the onset of reperfusion and developing infarction, sildenafil has an impact on myocardial recovery after cardiac arrest and ischemia.
    Scandinavian cardiovascular journal: SCJ 09/2012; 47(1). DOI:10.3109/14017431.2012.732235 · 1.03 Impact Factor
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    ABSTRACT: Indoleamine 2,3-dioxygenase (IDO) is an enzyme involved in the catabolism of tryptophan, suppressing T-cell activity. IDO activity and expression are increased in many malignant diseases, including hematological malignancies. IDO expression can mediate immunotolerance to tumors. IDO activity and expression have not previously been studied in chronic lymphocytic leukemia (CLL). We measured IDO activity by calculating the kynurenine-tryptophan (kyn-trp) ratio. IDO and IDO2 gene expression was determined by using real-time polymerase chain reaction (PCR). In patients with CLL, the serum kyn-trp ratio-reflecting increased IDO activity-was significantly higher compared with controls, but in peripheral blood mononuclear cells (PBMCs)-mainly representing malignant B cells-the expression of genes encoding IDO and IDO2 enzymes was reduced. Increased IDO activity in patients with CLL may affect disease progression, although it originates from cells other than malignant B cells.
    Clinical lymphoma, myeloma & leukemia 09/2012; 12(5):363-5. DOI:10.1016/j.clml.2012.06.001 · 2.02 Impact Factor
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    ABSTRACT: Aim: To determine whether an electronic nose can differentiate cultured nonmalignant and malignant prostatic cells from each other and whether the smell print is secreted to the surrounding medium. Materials & methods: Prostatic nonmalignant (EP-156T and controls) and malignant (LNCaP) cell lines, as well as conditioned and unconditioned media, were collected. The smell prints of the samples were analyzed by a ChemPro(®) 100 electronic nose device. The data were normalized and dimension reduction was conducted. The samples were classified and misclassification rates were calculated. Results: The electronic nose differentiated the nonmalignant and malignant cell lines from each other, achieving misclassification rates of 2.9-3.6%. Cells did not differ from the conditioned medium but differed from the unconditioned medium (misclassification rates: 0.0-25.6%). Conclusion: Malignant and nonmalignant prostatic cell lines have distinct smell prints. Prostatic cancer cells seem to modify the smell print of their medium.
    Future Oncology 09/2012; 8(9):1157-65. DOI:10.2217/fon.12.93 · 2.48 Impact Factor

Publication Stats

3k Citations
586.41 Total Impact Points


  • 2011-2015
    • Tampere University Hospital (TAUH)
      Tammerfors, Pirkanmaa, Finland
  • 2007-2015
    • University of Tampere
      • • Medical School
      • • Department of Pathology
      Tammerfors, Pirkanmaa, Finland
  • 1980-2009
    • University of Helsinki
      • • Department of Bacteriology and Immunology
      • • Department of Pathology
      • • Transplantation Laboratory
      • • Department of Ophthalmology
      Helsinki, Province of Southern Finland, Finland
  • 2004-2007
    • University of Oulu
      • Department of Pathology
      Uleoborg, Oulu, Finland
  • 2000-2003
    • The University of Calgary
      • Department of Surgery
      Calgary, Alberta, Canada
    • Finnish Cancer Registry, Helsinki
      Helsinki, Uusimaa, Finland
  • 1988-2002
    • Helsinki University Central Hospital
      • • Department of Pathology
      • • Department of Surgery
      Helsinki, Uusimaa, Finland
  • 1992
    • Finnish Institute of Occupational Health
      Helsinki, Uusimaa, Finland
    • Gazi University
      • Department of Surgery
      Ankara, Ankara, Turkey
  • 1991
    • Royal National Hospital For Rheumatic Diseases NHS Foundation Trust
      Bath, England, United Kingdom
  • 1990
    • Middlesex University, UK
      Londinium, England, United Kingdom