Biomedical subjects

P Rahkila

Publications and source records attributed to P Rahkila.

At least 19 recordsLinked to original sources

PubMed2006

Nuclear isomers in superheavy elements as stepping stones towards the island of stability.

A long-standing prediction of nuclear models is the emergence of a region of long-lived, or even stable, superheavy elements beyond the actinides. These nuclei owe their enhanced stability to closed shells in the structure of both protons and neutrons. However, theoretical approaches to date do not yield consistent predictions of the precise limits of the 'island of stability'; experimental studies are therefore crucial. The bulk of experimental effort so far has been focused on the direct creation of superheavy elements in heavy ion fusion reactions, leading to the production of elements up to proton number Z = 118 (refs 4, 5). Recently, it has become possible to make detailed spectroscopic studies of nuclei beyond fermium (Z = 100), with the aim of understanding the underlying single-particle structure of superheavy elements. Here we report such a study of the nobelium isotope 254No, with 102 protons and 152 neutrons--the heaviest nucleus studied in this manner to date. We find three excited structures, two of which are isomeric (metastable). One of these structures is firmly assigned to a two-proton excitation. These states are highly significant as their location is sensitive to single-particle levels above the gap in shell energies predicted at Z = 114, and thus provide a microscopic benchmark for nuclear models of the superheavy elements.

Journal Article↗

PubMed2006

Collectivity and configuration mixing in 186,188Pb and 194Po.

Lifetimes of prolate intruder states in 186Pb and oblate intruder states in 194Po have been determined by employing, for the first time, the recoil-decay tagging technique in recoil distance Doppler-shift lifetime measurements. In addition, lifetime measurements of prolate states in 188Pb up to the 8+ state were carried out using the recoil-gating method. The B(E2) values have been deduced from which deformation parameters |beta2|=0.29(5) and |beta2|=0.17(3) for the prolate and the oblate bands, respectively, have been extracted. The results also shed new light on the mixing between different shapes.

Journal Article↗

PubMed2003

New shape isomer in the self-conjugate nucleus 72Kr.

A new isomeric 0(+) state was identified as the first excited state in the self-conjugate (N=Z) nucleus 72Kr. By combining for the first time conversion-electron and gamma-ray spectroscopy with the production of metastable states in high-energy fragmentation, the electric-monopole decay of the new isomer to the ground state was established. The new 0(+) state is understood as the band head of the known prolate rotational structure, which strongly supports the interpretation that 72Kr is one of the rare nuclei having an oblate-deformed ground state. This observation gives in fact the first evidence for a shape isomer in a N=Z nucleus.

Journal Article↗

PubMed2002

Conversion electron cascades in 254(102)No.

The spectrum of prompt conversion electrons emitted by excited 254No nuclei has been measured, revealing discrete lines arising from transitions within the ground state band. A striking feature is a broad distribution that peaks near 100 keV and comprises high multiplicity electron cascades, probably originating from M1 transitions within rotational bands built on high K states.

Journal Article↗

PubMed2001

Isomer spectroscopy in (216)(90)Th(126) and the magicity of (218)(92)U(126).

Excited states in (216)Th were investigated via prompt and delayed gamma decays and the recoil-decay tagging method. The decay schemes of the I(pi) = (8+), t(1/2) = 128(8) micros, the I(pi) = (11-), t(1/2) = 615(55) ns, and the I(pi) = (14+), t(1/2) > or = 130 ns isomers were established. The configuration pi h(9/2)f(7/2) is assigned to the I(pi) = (8+) isomer, which implies that the h(9/2) and f(7/2) states are nearly degenerate. This is ascribed to increased binding of the f(7/2) orbital by its coupling to a low-lying I(pi) = (3-) state at E(x) = 1687 keV. The role of octupole and pairing correlations for a Z = 92 shell closure prediction is discussed on the basis of shell model calculations.

Journal Article↗

PubMed2001

Protein targeting to the plasma membrane of adult skeletal muscle fiber: an organized mosaic of functional domains.

The plasma membrane of differentiated skeletal muscle fibers comprises the sarcolemma, the transverse (T) tubule network, and the neuromuscular and muscle-tendon junctions. We analyzed the organization of these domains in relation to defined surface markers, beta-dystroglycan, dystrophin, and caveolin-3. These markers were shown to exhibit highly organized arrays along the length of the fiber. Caveolin-3 and beta-dystroglycan/dystrophin showed distinct, but to some extent overlapping, labeling patterns and both markers left transverse tubule openings clear. This labeling pattern revealed microdomains over the entire plasma membrane with the exception of the neuromuscular and muscle-tendon junctions which formed distinct demarcated macrodomains. Our results suggest that the entire plasma membrane of mature muscle comprises a mosaic of T tubule domains together with sareolemmal caveolae and beta-dystroglycan domains. The domains identified with these markers were examined with respect to targeting of viral proteins and other expresseddomain-specific markers. We found that each marker protein was targeted to distinct microdomains. The macrodomains were intensely labeled with all our markers. Replacing the cytoplasmic tail of the vesicular stomatitis virus glycoprotein with that of CD4 resulted in retargeting from one domain to another. The domain-specific protein distribution at the muscle cell surface may be generated by targeting pathways requiring specific sorting information but this trafficking is different from the conventional apical-basolateral division.

Animals↗

PubMed1999

Endocytosis in skeletal muscle fibers.

Defining the organization of endocytic pathway in multinucleated skeletal myofibers is crucial to understand the routing of membrane proteins, such as receptors and glucose transporters, through this system. Here we analyzed the organization of the endocytic trafficking pathways in isolated rat myofibers. We found that sarcolemmal-coated pits and transferrin receptors were concentrated in the I band areas. Fluid phase markers were taken up into vesicles in the same areas along the whole length of the fibers and were then delivered into structures around and between the nuclei. These markers also accumulated beneath the neuromuscular and myotendinous junctions. The recycling compartment, labeled with transferrin, appeared as perinuclear and interfibrillar dots that partially colocalized with the GLUT4 compartment. Low-density lipoprotein, a marker of the lysosome-directed pathway, was transported into sparsely distributed perinuclear and interfibrillar dots that contacted microtubules. A majority of these dots did not colocalize with internalized transferrin, indicating that the recycling and the lysosome-directed pathways were distinct. In conclusion, the I band areas were active in endocytosis along the whole length of the multinucleated myofibers. The sorting endosomes distributed in a cross-striated fashion while the recycling and late endosomal compartments showed perinuclear and interfibrillar localizations and followed the course of microtubules.

Animals↗

PubMed1999

Carbonic anhydrase III protects cells from hydrogen peroxide-induced apoptosis.

Carbonic anhydrase III (CA III; EC 4.2.1.1) is a cytoplasmic enzyme that exhibits a relatively low carbon dioxide hydratase activity. It is expressed at a very high level in skeletal muscle, where physical exercise has been shown to increase free radical production. In this work we show the effect of overexpression of CA III on cellular response to oxidative stress. Rat CA III cDNA was transfected to NIH/3T3 cells, which have no endogenous CA III expression. The isolated clones expressed CA III mRNA and protein. The protein was localized to cytoplasm and nuclei. Compared to parental cells, transfected cells showed lower basal oxidized state as judged by measurement of intracellular reactive oxygen species (ROS) using fluorescent dye and an image analysis system. Addition of exogenous H2O2 to cells induced a rapid increase of ROS in control but not in CA III overexpressing cells. Association of this phenomenon with CA III expression was further confirmed by showing that overexpression of CA II could not prevent H2O2-stimulated increase of ROS. In proliferation assays, CA III overexpressing cells grew faster and were more resistant to cytotoxic concentrations of H2O2 than control cells. After a 16 h exposure to oxidative stress, the number of apoptotic cells was also reduced in transfectants. Our results suggest that CA III functions as an oxyradical scavenger and thus protects cells from oxidative damage. A lower level of free radicals in CA III overexpressing cells may also affect growth signaling pathways.

3T3 Cells↗

PubMed1998

Differential targeting of vesicular stomatitis virus G protein and influenza virus hemagglutinin appears during myogenesis of L6 muscle cells.

Exocytic organelles undergo profound reorganization during myoblast differentiation and fusion. Here, we analyzed whether glycoprotein processing and targeting changed during this process by using vesicular stomatitis virus (VSV) G protein and influenza virus hemagglutinin (HA) as models. After the induction of differentiation, the maturation and transport of the VSV G protein changed dramatically. Thus, only half of the G protein was processed and traveled through the Golgi, whereas the other half remained unprocessed. Experiments with the VSV tsO45 mutant indicated that the unprocessed form folded and trimerized normally and then exited the ER. It did not, however, travel through the Golgi since brefeldin A recalled it back to the ER. Influenza virus HA glycoprotein, on the contrary, acquired resistance to endoglycosidase H and insolubility in Triton X-100, indicating passage through the Golgi. Biochemical and morphological assays indicated that the HA appeared at the myotube surface. A major fraction of the Golgi-processed VSV G protein, however, did not appear at the myotube surface, but was found in intracellular vesicles that partially colocalized with the regulatable glucose transporter. Taken together, the results suggest that, during early myogenic differentiation, the VSV G protein was rerouted into developing, muscle-specific membrane compartments. Influenza virus HA, on the contrary, was targeted to the myotube surface.

Animals↗

PubMed1997

Endoplasmic reticulum to Golgi trafficking in multinucleated skeletal muscle fibers.

The organization of membrane trafficking between endoplasmic reticulum and Golgi within multinucleated muscle fibers was analyzed. We found that markers for the compartment involved in endoplasmic reticulum to Golgi trafficking exhibited perinuclear as well as interfibrillar localization. Furthermore, these markers showed prominent colocalization with microtubules. To analyze membrane trafficking, we followed the temperature-controlled transport of the G protein of the mutant vesicular stomatitis virus, tsO45, in isolated myofibers. Perinuclear and cross-striated staining were seen at 39 degrees C, while at 15 degrees C a diffuse staining component appeared along a subset of interfibrillar microtubules. At 20 degrees C, bright Golgi spots were seen to be associated with microtubules that appeared as circumnuclear rings and longitudinal bundles. Beneath the motor end plate, however, the organization of the Golgi elements and microtubules was found to be distinctive. Retrograde trafficking induced by brefeldin A resulted in the disappearance of the Golgi spots throughout the myofibers and the appearance of staining along microtubules. Thus, interfibrillar membranes seem to be active in protein export, and trafficking between endoplasmic reticulum and Golgi elements occurred throughout the myofibers. The results suggest that microtubules served as tracks for the two-way trafficking between the endoplasmic reticulum and the Golgi compartment.

Animals↗

PubMed1996

Down-regulation of transcription factors AP-1, Sp-1, and NF-kappa B precedes myocyte differentiation.

Terminal differentiation of myocytes involves withdrawal from the cell cycle, induction of myogenin expression, and finally formation of myotubes. To study the factors that regulate the initial phase of muscle differentiation, we analyzed the binding activities of transcription factors AP-1, Sp-1, and NF-kappa B in L6, C2C12, and rhabdomyosarcoma BA-Han-1C cells. Temporal changes in transcription factor binding activities were compared to the activation of myogenin promoter-driven CAT reporter gene and the expression level of myogenin, a master gene of myogenic differentiation. We observed a prominent decrease in the nuclear binding activities of AP-1, Sp-1, and NF-kappa B already 12 to 24 h after the transfer of cells to differentiation medium. The response was very similar in L6 and C2C12 myocytes and in BA-Han-1C rhabdomyosarcoma cells. The down-regulation clearly preceded the activation of myogenin promoter and the induction of myogenin and retinoblastoma expression, as well as the initiation of myocyte fusion. Cholera toxin and okadaic acid, established inhibitors of myogenin expression and muscle differentiation, strongly up-regulated the binding activities of AP-1, Sp-1, and NF-kappa B in differentiation medium. Myogenin expression and myocyte fusion were also inhibited. Levels of nuclear c-Fos and c-Jun proteins, components of the AP-1 complex, showed a prominent decrease already after 12 h in differentiation medium. These results show that the down-regulation of the proliferation-promoting transcription factors is a prerequisite to the initiation of myocyte differentiation.

Animals↗

PubMed1996

Down-regulation of nuclear binding activities of OXBOX-REBOX transcription factors during cellular senescence.

Functional capacity of mitochondria declines during aging and this impairment may have a major role in aging process. Several observations indicate that transcriptional efficiency is reduced during aging. Our purpose was to find out whether aging and cellular senescence affect the nuclear binding activities of transcription factors which bind to OXBOX-REBOX sequence present in promoter regions of numerous nuclear genes encoding mitochondrial proteins. These factors regulate and coordinate the expression of mitochondrial proteins. We observed a strong down-regulation in the nuclear binding activities of OXBOX-REBOX factors in replicatively senesced human WI-38 and IMR-90 fibroblasts. On the contrary, SV-40 immortalization highly increased the nuclear binding activities. A considerable down-regulation of OXBOX-REBOX factors was also observed in UVB-irradiated WI-38 fibroblasts. Irradiation induced photoaging in fibroblasts which involved cell cycle arrest and senescent morphology. Interestingly, the nuclear binding activities of OXBOX-REBOX factors were also prominently decreased in the liver of Wistar rats at the age of 30 months but not yet at the age of 18 months. Our results suggest that the down-regulation of OXBOX-REBOX factors could affect the expression level of mitochondrial proteins encoded in nucleus and hence induce disturbances in mitochondrial function and promote the cellular aging process.

Animals↗

PubMed1996

Transport pathway, maturation, and targetting of the vesicular stomatitis virus glycoprotein in skeletal muscle fibers.

We have infected isolated skeletal muscle fibers with the vesicular stomatitis virus or the mutant tsO45, whose glycoprotein is blocked in the endoplasmic reticulum at 39 degrees C. Immunofluorescence analysis for the viral glycoprotein indicated that the fibers were infected over their entire length at a virus dose of 10(9)/ml. When we infected the myofibers with the tsO45 mutant at 39 degrees C, the viral glycoprotein appeared to be localised to the terminal cisternae of the sarcoplasmic reticulum. Upon shifting the cultures to the permissive temperature, 32 degrees C, in the presence of dinitrophenol, which blocks vesicular transport, the viral glycoprotein proceeded to completely fill the sarcoplasmic reticulum. Thus, both the endoplasmic reticulum located at the terminal cisternae of the sarcoplasmic reticulum, and the entire endoplasmic and sarcoplasmic reticulum appeared to be continuous. Shifting the culture temperature from 39 degrees C to 20 degrees C, resulted in prominent perinuclear staining throughout the fibers, accompanied by the appearance of distinct bright dots between the nuclei. Electron microscopic immunoperoxidase labeling indicated that these bright structures represented the Golgi apparatus. When either the tsO45-infected or wild-type virus-infected fibers were incubated at 32 degrees C, the viral glycoprotein showed a staining pattern that consisted of double rows of punctate fluorescence. Immunogold labeling showed that the viral glycoprotein was present in both the transverse tubules as well as the endoplasmic/sarcoplasmic reticulum endomembranes. In addition, extensive viral budding was observed in the transverse tubules. Metabolic labeling experiments revealed that only half of the glycoprotein was processed in the Golgi, and this processed form had become incorporated into the budding viral particles. Thus, the processed viral glycoprotein was targeted to the transverse tubules. The other half of the glycoprotein remained endoglycosidase H-sensitive, suggesting its retention in the endoplasmic/sarcoplasmic reticulum endomembranes.

Animals↗

PubMed1993

Glutathione metabolism in skeletal muscle derived cells of the L6 line.

Skeletal muscle derived L6 myoblasts possess a considerably high resting total glutathione (TGSH) pool. Exposure to L-buthionine-[S,R]-sulphoximine resulted in a 90% depletion of the intracellular TGSH pool. All the key enzymes of glutathione metabolism, especially glutathione S-transferase, were observed to be considerably active in the undifferentiated cells. Se-dependent glutathione peroxidase activity appeared to account for most of the total GSH peroxidase activity of the cells. A significant contribution of gamma-glutamyl transpeptidase-independent (5 mM acivicin insensitive) mechanism to the extracellular GSH uptake capacity of the muscle cells was evident. Efflux of oxidized glutathione from the cells exposed to t-butyl hydroperoxide was rapid and appeared to be energy linked.

Activins↗

PubMed1992

Quantification of carbonic anhydrase III and myoglobin in different fiber types of human psoas muscle.

Carbonic anhydrase (CA III) and myoglobin contents from isolated human muscle fibers were quantified using a sensitive time-resolved fluoroimmunoassay. Human psoas muscle specimens were freeze-dried, and single fibers were dissected out and classified into type I, IIA and IIB by myosin ATPase staining. Fiber typing was further confirmed by SDS-PAGE. CA III and myoglobin were found in all fiber types. Type I fibers contained higher concentrations of CA III and myoglobin than type IIA and IIB fibers. The relative concentrations of CA III in type IIA and IIB fibers were respectively 24% and 10% of that in type I fibers. The relative concentrations of myoglobin in type IIA and IIB fibers were 60% and 28% of that in type I fibers. Anti-CA III immunoblotting results from fiber-specific pooled samples agreed well with quantitative measurements. The results indicate that CA III is a more specific marker than myoglobin for type I fibers.

Carbonic Anhydrases↗

PubMed1992

Vertical jumping height and horizontal overhead throwing velocity in young male athletes.

The purpose of this study was to examine the effects of calendar and skeletal age, anthropometric dimensions, training history and their interactions on vertical jumping height and horizontal overhead throwing velocity in a cross-section of 318 young male athletes (age range 9-16 years) participating in cross-country skiing (n = 70), basketball (n = 40), apparatus gymnastics (n = 19), ice hockey (n = 50), track and field (n = 89) and wrestling (n = 50). Vertical jumping height was measured with four different loads held on the shoulders and then interpolated for loads representing 0 and 40% body mass. Horizontal overhead throwing velocity using both hands was determined for seven balls of different weights and then interpolated for weights representing 1 and 5% body mass. Both vertical jumping height and overhead throwing velocity were found to increase (P < 0.01) from the skeletally youngest to the oldest cohort when the effects of body height and mass were controlled. The inter-event comparisons did not reveal statistically significant differences in respect of vertical jumping height. Also in the overhead throwing tests, the inter-event differences were small, although the analysis of variance revealed statistically significant (P < 0.001) differences for the skeletal age cohorts of 13 and 14 years. While the quantity of training had no effect on vertical jumping height, it explained the results in the overhead throwing test. The effects of training on vertical jumping and horizontal overhead throwing among adolescent athletes were considered to be small, while maturational processes and anthropometric development followed by increase in calendar age were deemed to be of greater importance.

Adolescent↗

PubMed1992

Effect of oral contraceptives on plasma beta-endorphin and corticotropin at rest and during exercise.

Concentrations of immunoreactive beta-endorphin and corticotropin in plasma were studied in 27 healthy physically active women at rest and after the exercise test on a treadmill requiring 60% and 90% of the maximal oxygen consumption. Eleven of the subjects were on a combination-type of oral contraceptive pills, and the remaining 16 did not use any pills. Plasma immunoreactive beta-endorphin levels at rest were higher in pill non-users than in pill users. Corticotropin levels at rest did not differ between the pill users and non-users. After the 60% exercise test a slight increase was found in the concentrations of corticotropin and beta-endorphin in the pill non-users but not in the pill users. In the 90% exercise test, plasma beta-endorphin and corticotropin levels increased significantly in both groups. We conclude that the use of oral contraceptives may elevate the threshold of the intensity of exercise required to increase beta-endorphin and corticotropin secretion. Decreased resting concentration of beta-endorphin in pill users can be explained by suppression of normal cyclic ovarian function.

Adrenocorticotropic Hormone↗

PubMed1991

Bone mineral density of the calcaneus in 70- to 81-yr-old male athletes and a population sample.

Bone mineral content (BMC/W) and density (BMD) were studied in 70- to 81-yr-old active male endurance-trained (long-distance runners, cross-country skiers, N = 67), strength-trained (throwers, weight-lifters, N = 14), and speed-trained (sprinters, jumpers, N = 16) athletes. A population sample of similar age (N = 42) served as a control group. The measurements were performed at the calcaneus by single-energy photon absorption. The endurance-trained athletes had higher bone width and depth, and the strength and speed-trained athletes higher bone depth than the control subjects. The three groups of athletes showed 19-28% higher BMC (g.cm-1) and BMC/W (g.cm-2) than the control group (P less than 0.01-0.001). When the results were corrected for bone depth by assessing BMD (g.cm-3), the mean differences between the athletes and controls were 11-16% (P less than 0.05-0.01, not significant for the strength group). The highest BMD values were associated with moderate training for running and cross-country skiing. BMD did not correlate with serum total testosterone, but there was a negative correlation between BMD and sex hormone binding globulin and a positive correlation between BMD and the free androgen index in the endurance group. The results indicate that athletes having a long-term training history and being still active at over 70 yr of age preserve superior trabecular bone mass compared with the average male population of the same age.

Absorptiometry, Photon↗