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Biomedical subjects

A Nykänen

Publications and source records attributed to A Nykänen.

7 recordsLinked to original sources

The effect of platelet-derived growth factor ligands in rat cardiac allograft vasculopathy and fibrosis.

BACKGROUND: In chronic rejection, parenchymal fibrosis and cardiac allograft vasculopathy (CAV) characterized by neointimal growth are the leading causes of graft loss for heart transplant recipients. During alloimmune responses a variety of cytokines, adhesion proteins, and growth factors, such as platelet-derived growth factor (PDGF), are up-regulated. The PDGF family (AA, AB, BB, CC, DD), which acts mainly on connective tissue cells, is considered to be a potent mitogenic and chemotactic factor for fibroblasts and vascular smooth muscle cells. In this study, we evaluated the effects of PDGF ligands in chronic rejection. METHODS: Heterotopic heart transplantations were performed between fully major histocompatability complex-mismatched Dark Agouti to Wistar Furth rats receiving cyclosporine immunosuppression. Allograft coronary arteries were perfused with a recombinant adeno-associated virus (AAV) encoding enhanced green fluorescence protein (EGFP) as a control gene or PDGF-A, -B, -C, -D. Allografts were harvested at 100 days for morphometric analysis of CAV and fibrosis. RESULTS: AAV-mediated transgene expression was detected by EGFP immunoreactivity across the graft section (at 100 days) in AAV EGFP-perfused allografts. AAV PDGF-A, -C, and -D perfusion resulted in accelerated CAV and fibrosis. In contrast, AAV PDGF-B perfusion did not induce arteriosclerotic changes or fibrosis in cardiac allografts. CONCLUSIONS: AAV PDGF-A, -C, and -D overexpression accelerated the development of chronic rejection, whereas PDGF-B did not. Our results suggested that more targeted therapy with monoclonal antibodies blocking the active sites of PDGF-A, -C, and -D may produce beneficial effects on heart transplant survival.

Animals↗

ATP requirements and small interfering RNA structure in the RNA interference pathway.

We examined the role of ATP in the RNA interference (RNAi) pathway. Our data reveal two ATP-dependent steps and suggest that the RNAi reaction comprises at least four sequential steps: ATP-dependent processing of double-stranded RNA into small interfering RNAs (siRNAs), incorporation of siRNAs into an inactive approximately 360 kDa protein/RNA complex, ATP-dependent unwinding of the siRNA duplex to generate an active complex, and ATP-independent recognition and cleavage of the RNA target. Furthermore, ATP is used to maintain 5' phosphates on siRNAs. A 5' phosphate on the target-complementary strand of the siRNA duplex is required for siRNA function, suggesting that cells check the authenticity of siRNAs and license only bona fide siRNAs to direct target RNA destruction.

Adenosine Triphosphate↗

Synergistic inhibition of Listeria monocytogenes on cold-smoked rainbow trout by nisin and sodium lactate.

The inhibition of Listeria monocytogenes and mesophilic aerobic bacteria in cold-smoked rainbow trout by nisin, sodium lactate or their combination was studied. Nisin (4000-6000 IU/ml), sodium lactate (60%) or their combination (1:1) were injected into rainbow trout at an industrial scale before the smoking process, or injected into the finished smoked product. Both types of fish samples were smoked, sliced and vacuum-packed according to normal practice in the plant. Packages were opened and L. monocytogenes was inoculated (10(3)-10(4) log colony forming units (cfu)/g) onto the fish samples, which were then vacuum packed again. Samples were stored at 8 degrees C for 17 days or at 3 degrees C for 29 days. Listeria and mesophilic aerobic bacteria counts were measured once a week. The effects of treatments on sensory characteristics and storage stability were also analyzed. Both nisin and lactate inhibited the growth of L. monocytogenes in smoked fish, but the combination of the two compounds was even more effective. The combination of nisin and sodium lactate injected into smoked fish decreased the count of L. monocytogenes from 3.26 to 1.8 log cfu/g over 16 days of storage at 8 degrees C. The level of L. monocytogenes remained almost constant (4.66-4.92 log cfu/g) for 29 days at 3 degrees C in the samples injected before smoking and which contained both nisin and sodium lactate. The treatments did not affect the sensory characteristics of cold-smoked rainbow trout. Based on a triangle test, the sensory quality of all test samples remained unchanged for 23 days of storage at 3 degrees C, whereas the control fish prepared without additives or additional salt remained unchanged only for 16 days.

Animals↗

Adapting atomic force microscopy for cell biology.

We present details of our AFM modifications to produce an adaptable imaging system for the cell biologist. We have designed and validated a new inverted microscope interface and a scan head with increased Z-range, based upon the TopoMetrix Explorer AFM. We have utilised these changes, together with home-made glass ball cantilevers, to obtain topographical information over cells with large Z-dimension (over 15 microm high), and mapped calcitonin-calcitonin receptor binding forces in living bone cells. We conclude that modified AFM can be used to evaluate intermolecular events in living cells and that this approach will ensure general application to the study of receptor-ligand interactions under truly physiological conditions.

Animals↗

Adenoids provide a microenvironment for the generation of CD4(+), CD45RO(+), L-selectin(-), CXCR4(+), CCR5(+) T lymphocytes, a lymphocyte phenotype found in the middle ear effusion.

Adenoidectomy in children with otitis media with effusion reduces inflammation in the middle ear by an unknown mechanism. Potentially, the adenoids of these children may serve as a site for the differentiation of lymphocytes, which after entering blood circulation eventually extravasate in the middle ear mucosa and thereby contribute to excessive inflammation. During lymphocyte extravasation various adhesion molecules and chemokines play a crucial role. To evaluate possible connections between the adenoids and middle ear inflammation, the expression of the chemokine receptors CXCR4 and CCR5 and the lymphocyte homing receptor L-selectin were analyzed in adenoidal and middle ear lymphocytes. It was found that most CD4(+) T lymphocytes in the middle ear effusion express the memory phenotype marker CD45RO and the chemokine receptors CXCR4 and CCR5, but are negative for the lymphocyte homing receptor L-selectin. This cell phenotype was rare in peripheral blood but was found much more frequently in the adenoids. The results suggest that the adenoids provide a microenvironment for the generation for CD4(+), CD45RO(+), L-selectin(-), CXCR4(+) and CCR5(+) T lymphocytes. Further, these cells may include cells that have the capacity to home to the middle ear mucosa. As the adenoidal CD4(+) memory phenotype CD45RO(+) T cells expressed the activation antigen CD69 and included cells expressing the HIV co-receptors CXCR4 and CCR5 at a high level, they may be permissive for HIV infection.

Adenoids↗

Synergistic antimicrobial effect of nisin whey permeate and lactic acid on microbes isolated from fish.

The antimicrobial activity of a combination of lactic acid and whey permeate fermented by a nisin-producing Lactococcus lactis strain was tested by the agar diffusion method using bacteria isolated from fish as test organisms. Lactic acid inhibited all bacterial strains studied, but nisin whey permeate inhibited Gram-positive bacteria only. The combination was more effective than lactic acid alone against Pseudomonas fluorescens and Staphylococcus hominis isolated from fish, and Pseudomonas aeruginosa ATCC9721 and Micrococcus luteus ATCC9341.

Animals↗

Molecular epidemiology of HIV-1 based on phylogenetic analysis of in vivo gag p7/p9 direct sequences.

Viruses of different geographical origin are circulating in Finland. We wanted to test whether phylogenetic analysis of patient lymphocyte proviral quasispecies sequences could be used to group different strains into genetic lineages. The gag p7/p9 coding region was analyzed using solid-phase direct sequencing from 30 patients in Finland and Estonia. Proviral sequences were found to represent at least four, possibly even five, different, highly diverged major lineages. Different methods of phylogenetic analysis resulted in the same conclusion. Serial samples from the same patients, taken over a period of several years showed limited variation over time. Cases of potential patient-to-patient transmission or common source of infection were identified based on the sequence analysis. Compared to similar analyses of longer genome segments, the gag p7/p9 nucleic acid binding protein coding region produces analogous results in phylogenetic analysis. The method can be used as a rapid way of determining the genetic subtype of HIV-1 strains circulating in populations.

Capsid Proteins↗