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Vuokko Kinnula

Publications and source records attributed to Vuokko Kinnula.

13 recordsLinked to original sources
PubMed2006

ELMOD2 is a candidate gene for familial idiopathic pulmonary fibrosis.

We performed a genomewide scan in six multiplex families with familial idiopathic pulmonary fibrosis (IPF) who originated from southeastern Finland. The majority of the Finnish multiplex families were clustered in the region, and the population history suggested that the clustering might be explained by an ancestor shared among the patients. The genomewide scan identified five loci of interest. The hierarchical fine mapping in an extended data set with 24 families originating from the same geographic region revealed a shared 110 kb to 13 Mb haplotype on chromosome 4q31, which was significantly more frequent among the patients than in population-based controls (odds ratio 6.3; 95% CI 2.5-15.9; P = .0001). The shared haplotype harbored two functionally uncharacterized genes, ELMOD2 and LOC152586, of which only ELMOD2 was expressed in lung and showed significantly decreased messenger-RNA expression in IPF lung (n = 6) when compared with that of healthy lung (n = 7; P = .05). Our results suggest ELMOD2 as a novel candidate gene for susceptibility in familial IPF.

Chromosomes, Human, Pair 4↗
PubMed2006

Antioxidant enzymes in oligodendroglial brain tumors: association with proliferation, apoptotic activity and survival.

Purpose of the study was to investigate the relationship between antioxidant enzyme expression and clinicopathological features in oligodendroglial tumors. The expression of antioxidant enzymes and related proteins (AOEs), manganese superoxide dismutase (MnSOD), thioredoxin (Trx), thioredoxin reductase (TrxR) and gammaglutamylcysteine synthetase catalytic and regulatory subunits (GLCL-C and GLCL-R), was studied in 85 oligodendroglial tumors. The material included 71 primary (43 grade II and 28 grade III) and 14 recurrent (6 grade II and 8 grade III) tumors. Fifty-seven cases were pure oligodendrogliomas and 28 were mixed oligoastrocytomas. Immunoreactivity for MnSOD was found in 89%, Trx in 29%, TrxR in 76%, GLCL-C in 70% and GLCL-R in 68% of cases. Increased Trx expression was associated with higher tumor grade, cell proliferation and apoptosis (P=0.006, P=0.001 and P=0.003, Mann-Whitney test). Pure oligodendrogliomas showed more intense staining than oligoastrocytomas, especially for MnSOD (P=0.002, Mann-Whitney test). In the total series Trx was associated with poor prognosis in univariate survival analysis (P=0.0343, log-rank test) and furthermore in Cox multivariate analysis (P=0.009) along with age (P=0.002). The results suggest that the expression of Trx has a correlation to patient outcome and that there may be some association between AOEs, like MnSOD and Trx, and clinicopathological features of oligodendrogliomas.

Antioxidants↗
PubMed2006

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Journal Article↗
PubMed2006

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Journal Article↗
PubMed2005

Thoracoscopic lung biopsy is a safe procedure in diagnosing usual interstitial pneumonia.

OBJECTIVES: To evaluate the effect of lung biopsy on the survival of patients when histopathologic confirmation of usual interstitial pneumonia (UIP) is needed. BACKGROUND: Idiopathic pulmonary fibrosis is a distinct clinical entity with histopathologic features of UIP. Surgical biopsy is needed when clinical and radiologic findings are not typical. The safety of lung biopsy is a matter of debate, and the results of short-term mortality (< 30 days) after biopsy are variable. METHODS: Seventy-six patients with UIP, including 34 patients who underwent video-assisted thoracoscopic surgery (VATS) biopsy and 42 patients who underwent open-lung biopsy, were included in this retrospective study. All biopsies were reevaluated for UIP histopathology. Clinical data such as age at the time of biopsy, type of biopsy, preoperative pulmonary function, major postoperative complications, date and cause of death, and survival time after the biopsy were gathered. Median survival was used to compare the survival between different groups, and cumulative survival was estimated using Kaplan-Meyer method. RESULTS: Thoracoscopic biopsy was safe for diagnosing UIP, with no short-term mortality. In contrast, open-lung biopsy was followed by four deaths (5.3%) within 1 month after the procedure. All fatal cases were accompanied by a histopathologic pattern of diffuse alveolar damage. Age of the patient at the time of biopsy was a significant predicting factor for survival. Patients < 50 years old lived 181 months (range, 119 to 242 months), and patients > 50 years old lived 75 months (range, 55 to 95 months). CONCLUSIONS: VATS biopsy is a safe procedure in diagnosing UIP.

Biopsy↗
PubMed2003

High expression of nitric oxide synthases is a favorable prognostic sign in non-small cell lung carcinoma.

Immunohistochemical expression of neuronal (n), endothelial (e), and inducible (i) NOS and their association with the type, grade, apoptotic index, proliferation of tumors and the survival of patients were investigated in 89 biopsies of non-small cell lung carcinoma (NSCLC). In tumor cells, expression of iNOS was detected in 35/89 (40%) cases, while 79/89 (89%) and 72/89 (81%) cases showed weak to intense positivity for eNOS and nNOS, respectively. Strong eNOS staining was seen significantly more often in adenocarcinomas than in squamous cells carcinomas (p=0.016), and iNOS immunoreactivity was seen more often in grade I-II tumors than in grade III tumors (p=0.024). There was no significant difference between the low and high apoptotic indexes or between the low and high proliferation rates of tumors in any instance of NOS staining. The patients with tumors showing high nNOS expression tended to have better survival than the others (p=0.06, log-rank; p=0.04, Bresow; p=0.048, Tarone-Ware). Similarly, the patients with tumors showing high expression of iNOS, eNOS and nNOS, as determined by a combined sum index, had a better survival than those with a low sum index for these enzymes (p<0.05). The results show intense expression of eNOS and nNOS, and moderate expression of iNOS in tumor cells of non-small cell carcinoma. Intense NOSs expression seems to be a favorable prognostic sign in non-small cell lung carcinoma.

Apoptosis↗
PubMed2002

Soluble syndecan-1 and serum basic fibroblast growth factor are new prognostic factors in lung cancer.

Syndecan-1 is a ubiquitous and multifunctional extracellular matrix proteoglycan,which mediates basic fibroblast growth factor (bFGF) binding and activity. Shedding of syndecan-1 ectodomain from the plasma membrane is highly regulated. We evaluated the influence of soluble syndecan-1 and serum bFGF determined by ELISA on outcome in 184 lung cancer patients (non-small cell lung cancer, n = 138; small cell lung cancer, n = 46). Serum syndecan-1 and bFGF levels were determined from sera taken before treatment. The median follow-up of the patients alive (n = 21) was 8.1 years (range, 6.6-8.9 years). High serum syndecan-1 and bFGF levels tended to occur in the same patients (P = 0.044). When the serum values corresponding to the highest tertile were used as the cutoff value, the median survival time of the patients with a high serum syndecan-1 level (>59 ng/ml) was 4 months [95% confidence interval (CI), 3-6 months] as compared with 11 months (9-16 months) among those with lower serum levels (P = 0.0001), and the median survival time of the patients with a high bFGF level (>3.4 pg/ml) was 5 months (3-8 months) versus 11 months (8-14 months) in those with a lower level (P = 0.023). In general, the prognostic influence of both factors was independent of the histological subtype. Both serum syndecan-1 level (relative risk, 1.8; 95% CI, 1.1-3.1) and serum bFGF level (relative risk, 1.6; 95% CI, 1.0-2.7) had independent influence on survival in a multivariate survival analysis in non-small cell lung cancer. We conclude that high serum syndecan-1 and bFGF levels at diagnosis are associated with poor outcome in lung cancer.

Adult↗
PubMed2002

Manganese superoxide dismutase genotypes and asbestos-associated pulmonary disorders.

Manganese superoxide dismutase (MnSOD) activity is highly elevated in the biopsies of human asbestos-associated malignant mesothelioma. We therefore examined if polymorphism in the mitochondrial targeting sequence of the MnSOD gene modified individual susceptibility to this malignancy or related asbestos-associated pulmonary disorders. The study population consisted of 124 male Finnish asbestos insulators who were all classified as having been exposed to high levels of asbestos; 63 of the workers had no pulmonary disorders and 61 either had malignant mesothelioma or the non-malignant pulmonary disorders asbestosis and/or pleural plaques. No significant associations were found between the MnSOD genotypes and these ill-health. This study therefore suggest no major modifying role for the MnSOD polymorphism in development of asbestos-associated pulmonary disorders.

Asbestos↗
PubMed2002

VEGF and bFGF are highly expressed in intraluminal fibromyxoid lesions in bronchiolitis obliterans organizing pneumonia.

Bronchiolitis obliterans organizing pneumonia (BOOP) and usual interstitial pneumonia (UIP) are fibrous pulmonary disorders in which new fibromyxoid connective tissue is formed in distal air spaces. In BOOP this tissue is susceptible to even complete reversal, but in UIP it participates in the remodelling of the interstitium. Our previous study showed that in BOOP this newly formed intraluminal tissue is more capillarized than in UIP. This paper studies the immunohistochemical expression of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and Flk-1, and basic fibroblast growth factor (bFGF) in BOOP and UIP. It was hypothesized that there would be a difference in the expression of these angiogenic growth factors paralleling the difference in their capillarization. The results show that both VEGF and bFGF are widely expressed in BOOP and in UIP. It was shown with two different VEGF antibodies that its expression was more pronounced in the intraluminal fibromyxoid lesions in BOOP than in UIP (p<0.001 and 0.004, respectively). Similarly, bFGF also showed stronger espression in BOOP than in UIP (p<0.02) in these areas. The expression of Flt-1 and Flk-1 was in agreement with the expression of VEGF. It is concluded that the growth factors VEGF and bFGF may have an important role in the pathogenesis of BOOP and UIP; furthermore, their expression correlates with the angiogenic activity of the newly formed intraluminal fibromyxoid connective tissue in BOOP. Angiogenesis mediated by these growth factors may be one reason for the reversal of intraluminal fibromyxoid connective tissue in BOOP and for its good clinical outcome.

Cryptogenic Organizing Pneumonia↗