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T Ikonen

Publications and source records attributed to T Ikonen.

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

Acute rejection diagnosed with computed tomography in a porcine experimental lung transplantation model.

The role of computed tomography (CT) in the diagnosis of acute rejection was studied in an experimental lung transplantation model, with 15 left lung allotransplantations and six autotransplantations performed on piglets weighing 16-24 kg. There were 31 episodes of acute rejection. In the allotransplantation group the development of acute rejection was monitored 115 times with CT, transbronchial biopsy (TBB) and bronchoalveolar lavage (BAL). The stages of acute rejection were 1) ill-defined centrilobular micronodules or minimal patchy ground-glass opacities. 2) dense, small-nodular infiltration or extensive ground-glass opacities, and bronchial wall thickening. 3) lung volume loss and dense, patchy ground-glass opacities and 4) consolidation of the lung. In the autotransplantation group monitoring was done 42 times. After allotransplantation, TBB and BAL suggested rejection 60 times and infection 23 times. CT had 86.7% sensitivity and 85.6% specificity. During the first month these figures were, respectively, 71.4% and 84.2%. Rising histologic grade was associated with increasing stage of acute rejection on CT, which thus proved to be a sensitive and specific method for diagnosing acute rejection of lung transplant.

Acute Disease↗
PubMed1996

Mutual transcriptional interference between RelA and androgen receptor.

Cross-modulation between androgen receptor (AR) and NF-kappaB/Rel proteins was studied using various androgen- and NF-kappaB-regulated reporter genes under transient transfection conditions. In COS-1 cells, elevated expression of RelA (p65) repressed AR-mediated transactivation in a dose-dependent manner, whereas NFkappaB1 (p50), another major member of the NF-kappaB family, did not influence transactivation. The repression of AR appeared to involve the N-terminal region of the protein between residue 297 and the DNA-binding domain. RelA-mediated transrepression could not be overcome by increasing the amount of AR. Transcriptional interference between RelA and AR was mutual in that cotransfected AR was able to attenuate transactivation by RelA in a dose- and steroid-dependent fashion. An excess of RelA was able to rescue the repression to some extent. Immunological analyses of RelA and AR protein levels indicated that transrepression was not due to reciprocal decrease in their amounts. Neither did AR increase the concentration of IkappaBalpha, which can sequester and inactivate RelA. Electrophoretic mobility shift assays using extracts from cotransfected cells and purified recombinant proteins showed that AR and RelA did not significantly influence each other's DNA binding activity. Nevertheless, protein-protein interaction experiments demonstrated a weak association between AR and RelA. Collectively, these data suggest that the mutual repression in intact cells is due to formation of AR-RelA complexes that are held together by another partner or to competition for a coactivator required for transcription.

Animals↗
PubMed1996

Allele frequencies of the major milk proteins in the Finnish Ayrshire and detection of a new kappa-casein variant.

A total of 20990 Finnish Ayrshire cows were phenotyped for the major milk proteins by isoelectric focusing in polyacrylamide gels. The predominant alleles in the Finnish Ayrshire were alpha S1-casein B (0.999), alpha S2-casein A (0.991), beta-casein A1 (0.509) and alpha 2 (0.490), kappa-casein A (0.612) and beta-lactoglobulin B (0.716). The kappa-casein E allele (0.307) was also rather common in the Finnish Ayrshire. A new kappa-casein variant (kappa-casein F) was demonstrated in two Finnish Ayrshire cows, a dam and a daughter.

Alleles↗
PubMed1996

Molecular genetic characterization of new bovine kappa-casein alleles CSN3F and CSN3G and genotyping by PCR-RFLP.

In order to characterize the two new kappa-casein variants F and G (CSN3F and CSN3G) recently detected in Ayrshire and Pinzgauer cattle, exon IV of CSN3 from heterozygous animals was amplified by polymerase chain reaction (PCR), cloned and sequenced. The sequencing data revealed single point mutations at nucleotide positions 10530 (G-->A) for CSN3F and 10790 (C-->T) for CSN3G, corresponding to amino acid exchanges in positions 10 (Arg-->His) and 97 (Arg-->Cys) respectively. These mutations alter recognition sites for the restriction enzymes HhaI and MaeII, which were subsequently used to confirm these polymorphisms in cattle carrying CSN3F or CSN3G. A PCR-restriction fragment length polymorphism (RFLP) genotyping procedure for all currently known CSN3 alleles (CSN3A, CSN3B, CSN3C, CSN3E, CSN3F, CSN3G) was developed.

Alleles↗
PubMed1996

Selective assessment of single-lung graft function with 133Xe radiospirometry in acute rejection and infection.

In single-lung transplant recipients, the usefulness of spirometric indexes in detecting acute events involving the lung graft is limited due to the bias caused by the native lung. Selective functional monitoring is needed for the proper evaluation of complications after transplantation, but thus far, to our knowledge, no clinically feasible methods for selective graft-function assessment have been presented. In ten single-lung recipients, of whom six had a parenchymal lung disease and four had pulmonary hypertension, the relative ventilation (Vtx), perfusion (Qtx), and ventilation/perfusion ratio of the transplanted lung (V/Qtx) were determined with multidetector 133Xe radiospirometry. Additionally, the fractions of FEV1, FVC, and diffusing capacity for carbon monoxide (Dco) of the transplant (FEV1tx, FVCtx, Dcotx, respectively) were determined by using corresponding radiospirometric parameters for the calculation of their distribution between the lungs. The analysis included seven episodes of acute rejection and nine episodes of infection. The Qtx decreased during acute rejection but did not change during infection (p=0.001). Compared with the figures during infection, the V/Qtx increased during acute rejection significantly (p<0.05) in patients with underlying fibrosis or emphysema, but not in those with pulmonary hypertension. In detection of acute events, the sensitivity of the selective parameters, ie, FEV1tx (86%) and FVCtx (73%), was higher than that of the sum-function parameters, FEV1 (66%) and FVC (40%). Moreover, the sensitivity of Dcotx (80%) was higher than that of Dco (60%) in detecting acute rejection. The findings indicate that, in single-lung recipients with a parenchymal lung disease, the assessment of Qtx, V/Qtx, and Dcotx with a radioactive tracer can help to distinguish acute rejection from infection. The graft-selective parameters, ie, FEV1tx, FVCtx, and Dcotx, tended to be more sensitive than the corresponding sum-function parameters in detecting acute events, thus providing a more accurate functional profile of the single-lung graft.

Acute Disease↗
PubMed1996

Effect of physical training on exercise capacity and gas exchange in patients with chronic heart failure.

Decreased exercise capacity is the main factor restricting the daily life of patients with chronic congestive heart failure (CHF). We performed a controlled, randomized study to evaluate the effect of dynamic exercise training of moderate intensity on exercise capacity and gas exchange in patients with CHF. Twenty-seven patients with stable CHF, New York Heart Association (NYHA) functional class II and III, were randomized to training (n = 12) and control (n = 15) groups. During a 3-month period, the training group underwent a supervised physical training program using a bicycle ergometer for 30 min 3 times a week at a load corresponding to 50 to 60% of their peak oxygen consumption. Thereafter, they were advised to continue training at home for the next 3 months. The control group did not change their previous physical activity. A graded maximal exercise test with respiratory gas analysis and an endurance test with constant submaximal workload were performed at baseline and after 3 and 6 months. The exercise endurance increased from 14.7 +/- 2.0 to 27.8 +/- 2.7 min (p < 0.01) and the peak oxygen consumption tended to improve from 19.3 +/- 1.6 to 21.7 +/- 2.3 mL/kg/min (p = 0.09) during the supervised training period. At submaximal workloads, minute ventilation was reduced by 16% per se (p < 0.01) and by 7% in proportion to carbon dioxide production (p < 0.05). Oxygen consumption at the anaerobic threshold increased from 10.5 +/- 0.8 to 12.7 +/- 1.0 mL/kg/min (p < 0.05). The positive training effects were associated with an improvement in the NYHA functional class. The effects of supervised training were preserved during the home-based training period. The results indicate that physical training of moderate intensity significantly improves the exercise capacity and reduces the exaggerated ventilatory response to exercise, particularly at submaximal working levels in patients with CHF. This is associated with alleviation of symptoms.

Exercise↗
PubMed1996

Value of high-resolution computed tomography in routine evaluation of lung transplantation recipients during development of bronchiolitis obliterans syndrome.

BACKGROUND: Chronic rejection is a major long-term complication after lung transplantation. The purpose of our study was to evaluate the role of repeated high-resolution computed tomographic examinations in monitoring the development of bronchiolitis obliterans syndrome after lung transplantation. METHODS: A total of 126 high-resolution computed tomographic examination in 13 lung transplant recipients was analyzed. During a mean follow-up period of 23 months, bronchiolitis obliterans syndrome developed in eight of the patients. A scoring system from 0 to 10 based on the number of chronic changes on high-resolution computed tomography was developed, and the score of each patient was compared with decline in the forced expiratory volume in 1 second and maximal forced expiratory flow rate of 50% of the forced vital capacity. RESULTS: The score of chronic changes, measured at 1 year after transplantation, correlated inversely with the values of forced expiratory volume in 1 second and maximal forced expiratory flow rate at 50% of the forced vital capacity (p < 0.05). Stage I bronchiolitis obliterans syndrome was associated with scores of 4 to 6 (mean 5.0), stage 2 with scores of 6 to 9 (mean 7.0), and stage 3 with scores of 6 to 9 (mean 7.7). The sensitivity of high-resolution computed tomography was 93% and its specificity was 92% when five chronic changes were used as a cutoff level. CONCLUSIONS: The progress of chronic changes on high-resolution computed tomography occurs concurrently with the development of bronchiolitis obliterans syndrome. High-resolution computed tomography may provide additional morphologic information for noninvasive evaluation of chronic lung rejection.

Adult↗
PubMed1994

Stimulation of androgen-regulated transactivation by modulators of protein phosphorylation.

The effect of modulators of protein phosphorylation on the transcriptional activity of the androgen receptor (AR) was studied under transient expression conditions. Activators of protein kinase-A [8-bromo-cAMP (8-Br-cAMP)] and protein kinase-C (phorbol 12-myristate 13-acetate) or an inhibitor of protein phosphatase-1 and -2A (okadaic acid) influenced minimally pMMTV-chloramphenicol acetyl-transferase (CAT) activity in CV-1 cells cotransfected with an AR expression plasmid in the absence of androgen. In the presence of testosterone, however, all compounds enhanced AR-mediated transactivation by 2- to 4-fold. A nonsteroidal antiandrogen, Casodex, behaved as a pure antagonist; it blunted the action of testosterone and was not rendered agonistic by activators of protein kinase-A. A reporter plasmid containing two androgen response elements (AREs) in front of the thymidine kinase promoter (pARE2tk-CAT) was also used to examine promoter specificity. It was activated by 8-Br-cAMP, forskolin, or okadaic acid even without AR or androgen. However, when forskolin or okadaic acid was used together with androgen and AR, the resulting AR-dependent transactivation of pARE2tk-CAT was more than additive. Intact DNA- and ligand-binding domains, but not the N-terminal amino acid residues 40-147, of the receptor were mandatory for the synergism between protein kinase-A activators and androgen. Immunoreactive AR content in transfected COS-1 cells was not influenced by exposure to 8-Br-cAMP. Similar results were obtained by ligand binding assays. Quantitative or qualitative differences were not observed in DNA-binding characteristics between receptors extracted from cells treated with testosterone with or without protein kinase-A activator. Collectively, the synergistic stimulation of AR-dependent transactivation by androgen and protein kinase activators is not due to changes in cellular AR content or affinity of the receptor for the cognate DNA element; rather, this phenomenon seems to result from altered interaction of ligand-activated AR with other proteins in the transcription machinery.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

Dominant negative regulation of trans-activation by the rat androgen receptor: roles of the N-terminal domain and heterodimer formation.

A series of deletion mutants was constructed for the rat androgen receptor (AR) to delineate sequences involved in transcriptional activation. Using transient expression conditions in CV-1 cells and in vitro DNA-binding studies, the amino-terminal domain of the receptor was shown to contain a region (residues 147-296) that is mandatory for trans-activation. Receptors with deletions (residues 147-408) in the N-terminal domain, but with intact DNA- and ligand-binding domains, interacted in vitro with androgen-responsive elements albeit with affinities lower than that of the wild type receptor. Coexpression of N-terminal deletion mutants (delta 46-408 and delta 38-296) with the wild type AR blunted trans-activation by the latter protein in a dominant fashion. By contrast, a hormone-binding-deficient receptor (delta 788-902) that had poor intrinsic activity potentiated the trans-activation by the native receptor. Mechanisms by which deletion mutants in the N-terminal region abolish the function of the wild type protein appear to involve heterodimer formation during interaction with DNA and direct competition for available binding sites on DNA, rather than squelching of accessory proteins. In contrast to impaired trans-activation, binding of the ligand to N-terminal deletion mutants brought about conformational changes that were comparable in wild type and mutant forms, as judged by electrophoretic mobility shift assays. Taken together, these data have specified a region in the N-terminal domain of the AR that plays a decisive role in transcriptional regulation.

Animals↗
PubMed1993

Thoracoscopic fundoplication.

Thoracoscopic fundoplication and hiatoplasty were performed by a videoassisted technique in a patient with longstanding pathologic gastro-oesophageal reflux, reflux oesophagitis and hiatal hernia. Ten months later the patient was asymptomatic and had normal findings by oesophageal endoscopy and 24-hour pH-monitoring. Thoracoscopic fundoplication may be useful in patients with intra-abdominal adhesions due to previous abdominal surgery. Also obese patients with large hiatal hernias and perioesophageal adhesions may benefit from the thoracoscopic approach.

Adult↗