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Structural changes of mitochondria related to apoptosis.

The original concept of apoptosis stressed the morphological changes of the nucleus, condensation with the aggregation of chromatin, and the intactness of intracellular organelles including mitochondria. However, the application of molecular biology and flow-cytometric techniques to the research field of apoptosis has led to the proposal of the apoptotic processes which emphasizes the 'swelling of mitochondria' due to the opening of the 'permeability transition pores' of the mitochondrial membranes followed by a series of events including the collapse of the transmembrane potential of mitochondria and release of cytochrome c from mitochondria into the cytosol. Enlargement of mitochondria induced by various pathological conditions are classified into two categories: the swelling and the formation of megamitochondria (MG). Recently, we have found that free radical-induced formation of MG is succeeded by apoptotic changes of the cell. If the MG formation is actually related to apoptosis, this will be a new aspect of the structural changes of mitochondria involved in apoptosis besides the simple swelling of mitochondria. First, we will discuss the 'swelling of mitochondria' which characterizes the currently accepted hypothesis on the apoptotic processes of the cell, as described above, in the light of the literature. Second, the mechanisms controlling the size and distribution of mitochondria in the cell are dealt with paying special attention to the genetic regulation and cytoskeletons. Third, we have tried to characterize the MG formation to correlate apoptotic changes of the cell. Finally, we will discuss several problems to be solved in the future which involve mitochondria in apoptotic processes of the cell.

Apoptosis↗

Daily short-term head-up tilt can prevent structural changes in arteries of tail-suspended rats.

The aim of the present study was to investigate the effectiveness of daily 4-h head up tilt (HUT) in preventing the structural changes in arteries from rats induced by tail-suspension (TS). TS rat model was used to simulate the physiological effects of microgravity. Daily 4-h HUT was used to simulate the effect of intermittent artificial gravity (IAG). The results showed that TS alone induced an increase in the vessel media layer cross-sectional area (CSA), media wall thickness (T), mean number of smooth muscle cell layers (NCL) in basilar artery, and a decrease in these parameters in anterior tibial artery. Both the hypertrophic and atrophic changes in these arteries that might occur due to TS alone can be prevented by a 4h/d HUT treatment.

Journal Article↗

Comparative analysis of structural change in a free autovenous graft and in a transplant with spiral reinforcement after correction of experimental arterial defects.

In sixty-four dogs, a comparative analysis was made of structural changes produced in the wall of free autovenous graft and of a transplant strengthened by a spiral reinforcement (lavsan monothread) after transplantation of femoral vein segments into the common carotid artery. Histological and morphometric examinations made in an interval ranging from 3 days to 1 1/2 years after surgery showed that the strengthening of the venous graft by means of a reinforcement prevents its overextension when functioning as an artery, and keeps the endothelium intact. This reduces the danger of thrombotic complications in the operation area. The spiral reinforcement at the same time prevents compression of the vein by surrounding cicatricial tissue as well as an aneurysmatic extension of the transplant.

Animals↗

Structural changes of large conduit arteries in hypertension.

BACKGROUND: Structural alterations of large conduit arteries are a common pathway for any complication of hypertensive vascular disease. Whether increased arterial wall thickness occurs at an early phase in uncomplicated hypertension has remained largely ignored until recent years. METHODS: Sophisticated echo-Doppler techniques with a high degree of resolution and reproducibility have been developed to obtain reliable non-invasive determinations of intima-media thickness of superficial arteries such as the radial and the common carotid arteries. RESULTS: In uncomplicated hypertension, a significant increase in intima-media thickness is observed at the sites both of the radial and of the carotid arteries. The former is known to be constantly undamaged by atheroscierosis and is composed almost exclusively of arterial smooth muscle; operational arterial stiffness is found to be normal. The latter is strongly affected by atheroscierosis and predominantly composed of elastin and collagen fibres; operational arterial stiffness is found to be increased. In old subjects with systolic hypertension, radial artery hypertrophy is significantly reversed by drug therapy involving diuretics, converting enzyme inhibitors or both. This change occurs in parallel with the reduction in blood pressure. CONCLUSION: In sustained essential hypertension, arterial wall hypertrophy can be demonstrated in the absence of organ damage. Operational arterial elasticity is maintained in peripheral but not in central arteries. Structural changes of the large conduit arteries are substantially reversed by drug therapy together with a reduction in blood pressure.

Animals↗

Time-resolved resonance Raman analysis of chromophore structural changes in the formation and decay of rhodopsin's BSI intermediate.

Time-resolved resonance Raman microchip flow experiments are performed to obtain the vibrational spectrum of the chromophore in rhodopsin's BSI intermediate and to probe structural changes in the bathorhodopsin-to-BSI and BSI-to-lumirhodopsin transitions. Kinetic Raman spectra from 250 ns to 3 micros identify the key vibrational features of BSI. BSI exhibits relatively intense HOOP modes at 886 and 945 cm(-1) that are assigned to C(14)H and C(11)H=C(12)H A(u) wags, respectively. This result suggests that in the bathorhodopsin-to-BSI transition the highly strained all-trans chromophore has relaxed in the C(10)-C(11)=C(12)-C(13) region, but is still distorted near C(14). The low frequency of the 11,12 A(u) HOOP mode in BSI compared with that of lumirhodopsin and metarhodopsin I indicates weaker coupling between the 11H and 12H wags due to residual distortion of the BSI chromophore near C(11)=C(12). The C=NH(+) stretching mode in BSI at 1653 cm(-1) exhibits a normal deuteriation induced downshift of 23 cm(-1), implying that there is no significant structural rearrangement of the Schiff base counterion region in the transition of bathorhodopsin to BSI. However, a dramatic Schiff base environment change occurs in the BSI-to-lumirhodopsin transition, because the 1638 cm(-1) C=NH(+) stretching mode in lumirhodopsin is unusually low and shifts only 7 cm(-1) in D(2)O, suggesting that it has essentially no H-bonding acceptor. With these data we can for the first time compare and discuss the room temperature resonance Raman vibrational structure of all the key intermediates in visual excitation.

Animals↗

Filamentous actin in paramecium cells: functional and structural changes correlated with phalloidin affinity labeling in vivo.

Rhodaminylated (R)-phalloidin microinjected into Paramecium tetraurelia cells at a final concentration of greater than or equal to 20 micrograms/ml produces considerable functional and structural changes. F-actin bundles (with 20 micrograms/ml phalloidin within 15 min) are formed, which subsequently (greater than 30 min) are sequestered into autophagic vacuoles; simultaneously, the originally intense fluorescence of a narrow cortical layer becomes more and more diminished. When such microinjected cells are processed for electron microscopy, they display concomitant ultrastructural alterations, namely, the formation of transcellular bundles of 5-7 nm-thick filaments, which subsequently appear in autophagosomes, as well as a considerable reduction of filamentous materials in the cortex. This, in turn, entails a considerable restructuring of the cortex, enabling free access of various structural components to the cortex. Higher doses of R-phalloidin abolish cytoplasmic streaming (e.g., 50 micrograms/ml after 20-30 min); although the cells may survive, new secretory organelles (trichocysts) are no longer docked to the cell membrane. In contrast, exocytosis of docked trichocysts (as well as subsequent membrane resealing and retrieval) is not impaired under any conditions. Cortical F-actin may account for the cytoplasmic streaming that may normally guarantee the delivery of new trichocysts to free docking sites at the cell membrane. When docking is inhibited by high R-phalloidin doses, excess free trichocysts are sequestered into autophagosomes (crinophagy). One of the most sensitive cell functions is food vacuole formation (assayed by prelabeling with India ink), which correlates with the presence of R-phalloidin labeling in the cytostomal region and around food vacuoles. The main conclusions from this work are that filamentous actin may be involved in structuring of the cortex and in cytoplasmic streaming, and may therefore influence the formation, and possibly the transcellular transport (cyclosis), of food vacuoles, as well as the docking of trichocysts, whereas it does not play a role in exocytosis per se or in the steps immediately following.

Actin Cytoskeleton↗

Fine structural changes in the superior cervical ganglion of adult rats after long-term administration of baclofen, a GABAB receptor agonist.

The aim of the present study was to examine the fine structural changes in the superior cervical ganglion of adult rats following baclofen treatment. On the addition of this GABAB receptor agonist there was a transient increase in the number of coated vesicles and pits in the dendrites of principal sympathetic neurons. As compared to the control ganglia, we found a significantly higher number of synapses which had coated pits attached to the postsynaptic densities. In interpreting these observations it is suggested that the GABAB receptors play some role in mediating the synaptogenetic action of GABA, although the formation of vacant postsynaptic densities and spines was not seen after baclofen treatment.

Action Potentials↗

Metabolic and structural changes in skeletal muscle during hypocaloric dieting.

Hypocaloric dieting and fasting alter the contraction-relaxation characteristics of skeletal muscle and result in low frequency fatigue. We report the metabolic and structural changes in skeletal muscle in five morbidly obese female subjects who had biopsies of the gastrocnemius muscle on a base-line diet (2500 kcal/day) followed by a repeat biopsy after 2 wk of a 400-kcal/day carbohydrate diet. Hypocaloric dieting resulted in a significant increase in the intracellular muscle calcium content (p less than 0.05), which may account for the observed changes in muscle function. There were no significant changes in muscle glycogen, lactate, pyruvate, or free energy stores. There was a significant decrease in muscle enzymes [phosphofructokinase (p less than 0.05), succinate dehydrogenase (p less than 0.02)] and some muscle amino acid levels [glutamine (p less than 0.025), glycine (p less than 0.01), and alanine (p less than 0.02)], while muscle histochemistry showed type II fiber atrophy (p less than 0.025). However, these changes reflect a generalized response to hypocaloric dieting and probably do not explain the specific functional changes. Change in the muscle calcium content is probably an important mediator of the adverse functional effects of malnutrition.

Adolescent↗

Structural changes of the retina in retinal vein occlusion--imaging and quantification with optical coherence tomography.

BACKGROUND AND OBJECTIVE: To evaluate the potential of optical coherence tomography (OCT) for imaging and quantifying structural changes in the retinal architecture following venous occlusive disease. PATIENTS AND METHODS: We studied 20 patients with retinal venous occlusive disease: 5 patients suffered from branch retinal vein occlusion (BRVO), and 15 from central retinal vein occlusion (CRVO). Patients with CRVO were studied within 72 hours after the first onset of symptoms. Patients were examined by OCT after a complete ophthalmologic examination including fluorescein angiography. A standard set of linear scans through the center of fixation and individual scans over areas of special interest were performed. Scans were qualitatively evaluated and quantitative measurements were performed on single A-scans at 5 locations of linear scans. Measurements were taken in the center of fixation, at the foveal rim, and at the edge of the scan. We measured total retinal thickness, thickness of cystoid spaces, and thickness of the highly reflective outer band. RESULTS: OCT produced detailed images of retinal thickening, intra- and subretinal hemorrhage, intra- and subretinal fluid accumulation, and formation of intraretinal cystoid spaces. Quantitative evaluation revealed a mean central retinal thickness of 274 +/- 181 microm (72-760 microm) in patients with central retinal vein occlusion. Visual acuity did not correlate with central or extrafoveal retinal thickness. CONCLUSION: Optical coherence tomography is a useful imaging technique for studying changes of retinal architecture following venous occlusive disease. Even minor changes like localized subretinal fluid accumulation or beginning epiretinal membrane formation can be visualized in detail. In contrast to other diseases like diabetic maculopathy, quantitative assessment of macular thickness does not correlate to visual acuity. Nevertheless, because of detailed imaging, OCT might become a useful tool in the follow-up and treatment of individual patients.

Adult↗

Temporal and spatial dynamics of brain structure changes during extensive learning.

The current view regarding human long-term memory as an active process of encoding and retrieval includes a highly specific learning-induced functional plasticity in a network of multiple memory systems. Voxel-based morphometry was used to detect possible structural brain changes associated with learning. Magnetic resonance images were obtained at three different time points while medical students learned for their medical examination. During the learning period, the gray matter increased significantly in the posterior and lateral parietal cortex bilaterally. These structural changes did not change significantly toward the third scan during the semester break 3 months after the exam. The posterior hippocampus showed a different pattern over time: the initial increase in gray matter during the learning period was even more pronounced toward the third time point. These results indicate that the acquisition of a great amount of highly abstract information may be related to a particular pattern of structural gray matter changes in particular brain areas.

Adult↗

[Effects of land use structure change on regional ecological health--taking Shapingba County as an example].

Land resource is the carrier for the exchange of matter, energy and information flows, while the change velocity and the intensity of land use has strong effects on the ecological processes such as matter circulation, energy flow, and biologic diversity. Land use structure change will alter the type, area, and spatial distribution of ecosystem, and in the meantime, result in the changes of regional ecological health. Employing the principles and methods of landscape ecology, and through endowing relative ecological value to land use type, this paper analyzed the charaeteristics of recent 10 years land use change in Shapingba County of Chongqing, and discussed the effects of land use change on regional ecological health, aimed to provide scientific references for land use planning and sustainable land resource utilization. The results indicated that transformation often occurred among different land use types, and the land use structure in each transformation phase differed quite obviously. Under different land use structure, there was a great disparity in relative ecological value of sub-ecosystems, which played various roles in regional ecological health. In general, the regional relative ecological value embodied both increase and decrease. In the future, the relative ecological value of sub-ecosystem would represent three tendencies, i.e., increase first and decrease then, continuous decrease, and continuous increase. The situation of regional ecological health would gradually become better.

Biodiversity↗

Structural changes of actin-bound myosin heads after a quick length change in frog skeletal muscle.

Changes in the x-ray diffraction pattern from a frog skeletal muscle were recorded after a quick release or stretch, which was completed within one millisecond, at a time resolution of 0.53 ms using the high-flux beamline at the SPring-8 third-generation synchrotron radiation facility. Reversibility of the effects of the length changes was checked by quickly restoring the muscle length. Intensities of seven reflections were measured. A large, instantaneous intensity drop of a layer line at an axial spacing of 1/10.3 nm(-1) after a quick release and stretch, and its partial recovery by reversal of the length change, indicate a conformational change of myosin heads that are attached to actin. Intensity changes on the 14.5-nm myosin layer line suggest that the attached heads alter their radial mass distribution upon filament sliding. Intensity changes of the myosin reflections at 1/21.5 and 1/7.2 nm(-1) are not readily explained by a simple axial swing of cross-bridges. Intensity changes of the actin-based layer lines at 1/36 and 1/5.9 nm(-1) are not explained by it either, suggesting a structural change in actin molecules.

Actins↗

Stress-induced rearrangement of the myocardium: time course of structural changes in various types of stress.

Common morphological changes in the myocardium were revealed in rats exposed to three different types of stress. At the initial stages of stress, the structural changes were stereotypical (contractures) irrespective of the type of stress factor and differed only by their severity. At later stages contractures were gradually replaced by cytolytic injuries, which did not depend on the type of stress either. Early predominance of myocytolysis in combination with excessive contracture injuries led to rapid death, which is probably a manifestation of genetically determined low capacity to adapt to stress in some individuals.

Animals↗

Ca2+-induced structural changes in phosphorylase kinase detected by small-angle X-ray scattering.

Phosphorylase kinase (PhK), a 1.3-MDa (alphabetagammadelta)(4) hexadecameric complex, is a Ca(2+)-dependent regulatory enzyme in the cascade activation of glycogenolysis. PhK comprises two arched (alphabetagammadelta)(2) octameric lobes that are oriented back-to-back with overall D(2) symmetry and joined by connecting bridges. From chemical cross-linking and electron microscopy, it is known that the binding of Ca(2+) by PhK perturbs the structure of all its subunits and promotes redistribution of density throughout both its lobes and bridges; however, little is known concerning the interrelationship of these effects. To measure structural changes induced by Ca(2+) in the PhK complex in solution, small-angle X-ray scattering was performed on nonactivated and Ca(2+)-activated PhK. Although the overall dimensions of the complex were not affected by Ca(2+), the cation did promote a shift in the distribution of the scattering density within the hydrated volume occupied by the PhK molecule, indicating a Ca(2+)-induced conformational change. Computer-generated models, based on elements of the known structure of PhK from electron microscopy, were constructed to aid in the interpretation of the scattering data. Models containing two ellipsoids and four cylinders to represent, respectively, the lobes and bridges of the PhK complex provided theoretical scattering profiles that accurately fit the experimental data. Structural differences between the models representing the nonactivated and Ca(2+)-activated conformers of PhK are consistent with Ca(2+)-induced conformational changes in both the lobes and the interlobal bridges.

Animals↗

Light-induced structural changes in the active site of the BLUF domain in AppA by Raman spectroscopy.

The flavin-adenine-dinucleotide-binding BLUF domain constitutes a new class of blue-light receptors, and the N-terminal domain of AppA is a representative of this family. AppA functions as a transcriptional antirepressor, controlling the photosynthesis gene expression in the purple bacterium Rhodobacter sphaeroides. Upon light absorption, AppA undergoes a photocycle with a signaling state, which exhibits an approximately 10 nm red shift in the UV-vis absorption spectrum. We have characterized light-dependent changes in the active site of an AppA BLUF domain by Raman spectroscopy. The present study has found that altered chromophore-protein interactions, including a hydrogen bond at the C4=O position and structural changes around the N10-ribityl side chain, are key events in this activation process. These structural alterations are proposed to be responsible for the transmission of the light signal in the BLUF domain. This is the first report on a signaling-state Raman spectrum of a blue-light photoreceptor with a flavin chromophore.

Amino Acid Motifs↗

[Structural changes in spinal cord gray matter induced by gravitational overloads].

After acute exposure of rats to gravitational overloads (GO) the reactive changes in neurons and interneuronal synapses of spinal cord were found. These are interpreted as morphologic signs of increased functional activity of neurons and activation of interneuronal impulse transmission. Chronic application of GO results in both reactive changes and damage of spinal cord structures. These changes were not seen after an acute exposure to GO, and thus they are associated with the repeated GO, indicating GO cumulative effect. Administration of "Vitavis" provides a membrane-protective effect, especially in respect to mitochondria of neurons and perineuronal glial cells in cervical and thoracic segments of spinal cord. The effect was less pronounced in spinal cord lumbar segments as a result of pericapillary edema, preventing the transport or drug from capillary bed to the neural structures.

Animals↗

Ultra-structural changes and developmental potential of porcine oocytes following vitrification.

This study evaluated the effects of exposure and/or vitrification of porcine metaphase II (MII) oocytes on their in vitro viability and ultra-structural changes with two experiments. Experiment 1 examined the effect of vitrified oocytes on microtubule localization, mitochondrial morphology, chromosome organization and the developmental rate in IVF control and vitrified oocytes. Oocytes matured for 44 h were subjected to IVF (IVF control). Oocytes matured for 42 h were exposed to cryoprotectants (CPA control), followed by 2h culture, and subjected to IVF. Oocytes vitrified at 42 h post-maturation were warmed, cultured for 2h, and subjected to IVF (vitrified). Experiment 2 evaluated the effect of oocytes freezing on development of ICSI with and without activation and parthenotes. Fresh and vitrified oocytes were subjected to ICSI with and without electrical activation. Cleavage and blastocyst rates were significantly (P<0.05) lower in vitrified IVF, parthenote and ICSI embryos than those in fresh counterparts. Between ICSI embryos from fresh oocytes and vitrified oocytes, the rates of blastocyst were significantly higher (P<0.05) in activated group than the group without activation. Significant differences (P<0.05) were observed in normal spindle configuration of vitrified (43.5%) compared to control (81.0%) oocytes, but no significant difference was observed between CPA exposed and control groups. In conclusion, porcine oocytes at MII stage are very sensitive to vitrification with altered microtubule localization and mitochondrial organization thus resulting in impaired fertilization and embryo development.

Animals↗

Personnel reductions and structural changes in health care: work-life experiences of medical secretaries.

OBJECTIVE: To explore the experiential aspects of 'psychosocial stressors and motivators' for medical secretaries, following a period of personnel reductions and structural changes in Swedish health care. The focus was to understand and describe work-life experiences for this specific group of women and how they managed in what can be presumed to be a more demanding work situation. METHOD: A descriptive qualitative study with repeated in-depth interviews of six medical secretaries (mean age: 45 years) in a large hospital in Sweden. The first interview took place in the autumn of 1997 (in connection with the last round of the 20% staff redundancies), 1998 and 2000. Thematic content analysis from audiotaped and transcribed interviews was used to obtain understanding. RESULTS: The study provided three main themes from the women's perceived stressors, motivators and coping options. The descriptions of their stressors provided the metaphor, 'energy thieves' with three underlying subthemes: 'too much work,' 'lack of recognition' and 'the dilemma of health, family and finances.' Experienced motivators, labeled as 'energy givers' had two subthemes: 'professional pride' and 'the comprehensive whole.' The women's descriptions about managing increasing demands were thematized as altering between 'being submissive and taking actions' with three subthemes: 'unequal communication,' 'resigned and passive reactions' versus 'cautious and solution-oriented coping.' Expressions concerned mainly 'energy thieves,' inclusively worries about 'lacking energy' (intrinsic stressor), combined with passive and cautious coping behavior. However, the descriptions became somewhat more varied and balanced with enriching and solution oriented factors in the follow-up interviews. CONCLUSIONS: There is an evident contrast between a demanding reality of work, described by medical secretaries in this study, and their expressed desire to have a more reasonable work environment that allowed them to be able to complete their work. They also wanted to be heard regarding their requests about work options and decent salaries. This study demonstrates the importance of making feelings of inferiority and injustice visible as well as to support professional pride and more assertive coping behavior. This is also valid for the need to enhance equal/congruent communication between interdependent workers. The study has implications for managers and health workers supporting and empowering women, providing administrative service in a clinical health care context. The subthemes being identified within the metaphor 'energy thieves,' in relation to resigned/passive reactions and cautious coping styles, could be used in stress prevention, while the understanding of 'energy givers' and the support of active and solution-oriented coping conducts could be used in health promotion work.

Adaptation, Psychological↗