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PubMedDate not supplied

Structural changes of atrial myocardium during chronic atrial fibrillation.

Of all known arrhythmia's, atrial fibrillation (AF) is the most often met in the clinical setting and it is associated with an increase in mortality risk. Several risk factors for AF have been described and several mechanisms of induction and maintenance have been proposed. Studies in patients with AF have shown that structural changes occur in the atria, but the relationship between the structural remodelling and the chronicity of the arrhythmia are not well understood. The changes mainly concern adaptive (dedifferentiation of cardiomyocytes) and maladaptive (degeneration of cells with replacement fibrosis) features. In order to characterise the time course of the structural remodelling the need for animal models which adequately mimic chronic atrial fibrillation in humans is felt essential. In this review, the structural changes that are observed during prolonged sustained AF in patients and animal models, are described. Furthermore, the time course and potential mechanisms of structural remodelling are discussed and methods for elucidation of the underlying molecular mechanisms are presented.

Actins↗

PubMed1997

Structural changes in insulin-like growth factor (IGF) I mutant proteins affecting binding kinetic rates to IGF binding protein 1 and IGF-I receptor.

Ligand binding properties of five single amino acid substituted variants (V11A, D12A, Q15A, Q15E, and F16A) of human insulin-like growth factor I (IGF-I) were analyzed with respect to their binding affinities and binding kinetics to recombinant IGF binding protein 1 (IGFBP-1) and a soluble form of the IGF type I receptor (sIGF-I(R)), respectively. Side chains of the substituted residues are all predicted to be the most surface exposed in the alpha-helical portion of the B-region of the IGF-I molecule. The IGF-I variants were produced as fusion proteins to a IgG(Fc) binding protein domain, Z. Ligand binding kinetic rates were determined using BIAcore biosensor interaction analysis technology. All IGF-I variants showed altered binding affinities to both IGFBP- I and sIGF-I(R). Secondary structure content of the IGF-I variants was estimated using far-UV circular dichroism spectroscopy, followed by variable selection secondary structure calculations. The amount of calculated alpha-helicity is reduced for all the mutants, most predominantly for IGF-I(V11A) and IGF-I(F16A) proteins. Surprisingly, most of the effects of reduced binding affinities to both target proteins are attributed to lowered on-rates of binding, and these are correlated with the amount of alpha-helicity in each IGF-I variant. In addition, in some of the IGF-I variants, lowered off-rates of binding are observed. From the results, we propose that IGF-I is unusually sensitive to structural changes by surface amino acid substitutions in the B-region of the molecule. Therefore, biochemical or biological properties of amino acid substituted variants of IGF-I cannot be used in a straightforward way to dissect the direct involvement in binding of individual amino acid residues since structural changes may be involved.

Amino Acid Sequence↗

PubMed2003

Structure of DNA helicase RepA in complex with sulfate at 1.95 A resolution implicates structural changes to an "open" form.

The structure of a new crystal form (space group C2), grown at pH 8.0 and diffracting to 1.95 A resolution, of the replicative homo-hexameric DNA helicase RepA encoded by plasmid RSF1010 is reported. In contrast to previous crystals grown at pH 6.0 in space group P2(1) (Niedenzu et al., 2001), only one half (a trimer) of the RepA hexamer occupies the asymmetric unit of the space-group C2 crystals. The new crystal packing explains the pH-dependent hexamer-hexamer association mechanism of RepA. The C-terminus (264)VLERQRKSKGVPRGEA(279), which could not be modelled in the previous structure, is clearly defined in the present electron density except for the last four amino acids. Sulfate anions occupy the six ATPase active sites of RepA at positions where the product phosphates are supposed to bind. Binding of sulfate anions induces conformational changes both at the ATPase active sites and throughout the whole molecular structure. In agreement with electron microscopy, the above studies implicate structural changes to an "open" form that may occur upon binding and hydrolysis of nucleotide 5'-triphosphates and could be essential for DNA duplex-unwinding activity.

Adenosine Triphosphatases↗

PubMed1999

A new concept of the pattern of structural changes with bone loss by histomorphometric analysis using bone slabs.

We examined naked bone slabs (1.2 mm thick) from iliac bone biopsied cores obtained from 33 women aged 33-89 years. The number, size, and shape of the pores in the bone slabs were analyzed. The results revealed that the % bone area (the percentage area occupied by bone in the slab) was linearly correlated with age and other parameters, such as the size of pores, irregularity of pores, and pore distance, but was not correlated to the number of pores. We found a second-degree polynomial relationship between the % bone area and the number of pores. Based on three parameters--% bone area, number of pores, and size of pores--cluster analysis was performed and the specimens divided into three groups. The group with sufficient bone mass showed few small round pores, and the group with severe bone loss revealed a few large pores that were caved in. The characteristics of these groups represented the relationship between bone mass and structural change. The remaining group with moderate bone loss was divided into two subgroups, one with an increased number of pores without expansion and one with expanded pores without an increase in number. We presumed that the variations between the groups were caused by differences between fine and rough structures in the trabeculae caused during the process of bone loss. We concluded that this analysis of bone slabs allowed the pattern of trabecular structural change that occurred with bone loss to be determined easily and visually.

Adult↗

PubMed2006

Structural changes in the vascular bundles of light-exposed and shaded spruce needles suffering from Mg deficiency and ozone pollution.

The correlation between structural changes of the vascular bundles and needle yellowing was examined for needles of damaged spruce (Picea abies (L.) Karst.) growing at a Mg-deficient and ozone polluted mountain site in the Central Black Forest (840m a.s.l.). In the previous year's sun-exposed needles, the following sequence of events was observed: (1) rapid needle yellowing, (2) hypertrophy and anomalous divisions of cambium cells, (3) phloem collapse, and, (4) production of atypical xylem tracheids. Under defined shade (reduction of the photosynthetically active photon flux density of the ambient light by 85-90%), the needles remained green, while the phloem collapsed completely within the first 6 weeks of shading; subsequently, a reversal of the collapse was observed. Under both light conditions, the content of Mg not bound to chlorophyll (Mg(free)) was in the range of 0.1 mg g(-1) needle dry matter, and hardly changed throughout the investigation period. After Mg fertilization, the Mg(free) level of the previous year's needles increased to 0.2 mg g(-1) dry matter, the light-exposed needles remained green, and the vascular bundles developed no anomalies. The data show that the rapid needle yellowing of ozone-exposed Mg-deficient needles did not depend on the collapse of the phloem. Mg deficiency played a key role in the development of anomalous vascular bundles under light, and also appears to explain the transient changes in sieve cell structure under shade. The role of Mg deficiency, rather than ozone pollution, in the damage of the sieve cells was confirmed in a long-term ozone exposure experiment with young clonal spruce growing under defined conditions.

Air Pollutants↗

PubMed1999

The staff's experience of structural changes in the health and medical service in western Sweden.

BACKGROUND: The structure and contents of the health and medical service have changed in recent years. The merger of Norra Alvsborgs and Uddevalla hospitals into one local district under one leadership (the NU medical service) is a Swedish example of a structural change. AIMS: This study intends to describe and analyse the staff's experience of a recently accomplished structural change in the local district NU medical service in the western part of Sweden. METHODS: This study has been carried out from a qualitative point of view inspired by grounded theory. From a theme guide with specific questions, 31 interviews were carried out with staff working in the NU medical service. FINDINGS: Four categories emerged from the body of interviews: 'participation', 'doubts', 'anxiety' and 'faith'. 'Participation' was defined as an overall core category, and was related to the other categories. The categories 'doubts', 'anxiety' and 'faith' were related to sub-categories and affected by the overall category 'participation'. CONCLUSIONS: The overall results point to the importance of participation of staff members concerned. The role of the leadership when undergoing structural changes is considered as a major factor to make other staff members participate.

Adaptation, Psychological↗

PubMed1996

Structural changes in the intramuscular connective tissue during development of bovine semitendinosus muscle.

Structural changes in the intramuscular connective tissue during development of bovine semitendinosus muscle were investigated using the cell-maceration method for scanning electron microscopy, by which cellular elements were eliminated and collagen fibrils and fibres were exposed. The endomysium was discontinuous and showed various shapes and sizes in the muscle of 7-month fetuses. The perimysium consisted of collagen fibres in loose contact with each other. In the muscle of neonatal calves, the endomysium consisted of cylindrical sheaths and displayed a honeycomb structure, and the perimysium was composed of several layers of collagen fibres. Collagen fibrils in the endomysium bound ever more closely with each other, and collagen fibres in the perimysium increased in thickness, and the wavy pattern of collagen fibres became more regular with growth of cattle. We have examined the mechanical strength of the intramuscular connective tissue by our new method, 'intramuscular connective tissue (IMCT) model'. The IMCT model is composed of collagen fibrils and fibres which maintains the organization in the endomysium and perimysium in situ. The shear-force value of the model increased rapidly from the 7th fetal month to the neonatal stage, and increased linearly with postnatal ageing thereafter. Changes in the arrangement of collagen fibrils and fibres seem to closely related to an increase in the mechanical strength of the intramuscular connective tissue during development of bovine skeletal muscle.

Animals↗

PubMed2006

Structural changes of oviduct of freshwater shrimp, Macrobrachium nipponense (Decapoda, Palaemonidae), during spawning.

The structural change of the oviduct of freshwater shrimp (Macrobrachium nipponense) during spawning was examined by electron microscopy. The oviduct wall structural characteristics seem to be influenced significantly by the spawning process. Before the parturition and ovulation, two types of epithelial cells (types I and II) are found in the epithelium. The free surfaces of type I and type II cells have very dense long microvilli. Under the type I and type II cells, are a relatively thick layer of secreting material and a layer of mostly dead cells. After ovulation, two other types of epithelial cells (types III and IV) are found in the oviduct wall epithelium. The free surface of type III cells only has short microvilli scattered on the surface. The thick layer with secreting material and the dead cell layer disappeared at this stage. In some type III cells, the leaking out of cytoplasm from broken cell membrane led to the death of these type III cells. The transformation of all four types of epithelial cells was in the order: IV-->I-->II-->III.

Adaptation, Physiological↗

PubMed2004

Binding of alpha1-acid glycoprotein to membrane results in a unique structural change and ligand release.

Alpha(1)-acid glycoprotein (AGP) consists of 183 amino acid residues and 5 carbohydrate chains and binds to basic and neutral drugs as well as steroid hormones. We investigated the structural properties and ligand-binding capacity of AGP under mild acidic conditions and its interactions with liposomes prepared from neutral or anionic lipids and the neutral drug, progesterone. Interestingly, AGP had a unique structure at pH 4.5, at which the tertiary structure changed, whereas the secondary structure remained intact. Furthermore, the binding capacity of AGP for progesterone did not significantly change under these conditions. It was also observed that AGP was strongly bound to the anionic membrane at pH 4.5, forming an alpha-helix-rich structure from the original beta-sheet-rich structure, which significantly decreased the binding capacity of AGP for progesterone. The structural transitions as well as the membrane binding were suppressed by adding NaCl. These results indicate that AGP has a unique structure on the membrane surface under mild acidic conditions. The conformational change induces binding to the membrane aided by electrostatic interaction, and AGP subsequently takes on a predominantly alpha-helical conformation.

Acids↗

PubMed1995

Structural changes in the water-oxidizing complex monitored via the pH dependence of the reduction rate of redox state S1 by hydrazine and hydroxylamine in isolated spinach thylakoids.

A detailed kinetic analysis is presented for the pH dependence of the reduction of the water-oxidizing complex (WOC) in redox state S1 by hydrophilic amines NH2R (R = NH2, OH) in suspensions of isolated thylakoids. Measurements of patterns of the oxygen yield induced by a train of single-turnover flashes and evaluation of the data within the framework of an extended Kok model [Messinger, J., Wacker, U., & Renger, G. (1991) Biochemistry 30, 7852-7862] led to the following results: (a) the rate constants kS1(NH2R) exhibit strikingly similar pH dependencies for NH2OH and NH2NH2 with "titration waves" at pH 5.3-5.6; 6.2-6.5, and above a critical pH value of about 7.4; (b) the differences in the reaction mechanism between NH2OH (1-electron reduction) and NH2NH2 (2-electron reduction) are almost pH-independent; (c) the ratio of the rate constants, kS1(NH2OH)/kS1(NH2NH2), decreases by a factor of about 9 within the range 5 < pH < 8.5. A detailed analysis reveals that these data cannot be consistently explained by the assumption that the unprotonated forms NH2OH and NH2NH2 are the active species while the protonated cations [NH3OH]+ and [N2H5]+ are nonreactive. A quantitative description is achieved by the additional postulate that pH-dependent structural changes take place in the WOC, thereby modulating the reactivity toward exogenous redox active amines of the type NH2R. On the basis of the results of this study and a recent report [Messinger, J., & Renger, G. (1994) Biochemistry 33, 10896-10905], it is inferred that the WOC undergoes three specific structural changes, with characteristic pH values of 5.3-5.5, 6.2-6.5, and above 7.4.

Hydrazines↗

PubMed1996

Structural change in alpha-chymotrypsin induced by complexation with alpha 1-antichymotrypsin as seen by enhanced sensitivity to proteolysis.

Both human neutrophil elastase (HNE) and free chymotrypsin (Chtr) proteolyze Chtr within the complex that Chtr forms with antichymotrypsin (ACT). As free Chtr is stable both to self-digestion and to digestion by HNE, these results are indicative of a stability and/or conformational change in Chtr that accompanies complex formation. As determined by both N-terminal sequence analysis and matrix-assisted laser desorption ionization mass spectroscopy (MALDI-MS), the major initial sites of HNE cleavage of complexed Chtr are between gamma-chain residues A158/S159 and V188/S189. Significantly, this latter site is at the base of the S1 site that recognizes the P1 position of the serpin. A slower cleavage in the beta-chain between T139/G140 is also found. In addition, rACT is cleaved between residues V22/D23. The gamma-chain of complexed Chtr is also cleaved by free Chtr, but at different sites: L162/L163 and W172/G173. beta-Chain cleavages were also found between residues Q81/K82 and F114/S115. Cleavages similar to those described above were also found when Chtr was complexed with the L358F-rACT variant, but not for Chtr complexed with either of the smaller inhibitors bovine pancreatic trypsin inhibitor or turkey ovomucoid third domain, nor for the covalent adduct of Chtr with N-p-tosylphenylalanyl chloromethyl ketone. We conclude that the structural change in Chtr making it a proteinase substrate is coupled with the large conformational change in ACT following complex formation. Complexed Chtr is much less reactive toward proteolytic digestion in the presence of high salt than in its absence, in accord with the high-salt induced release of active enzyme from the Chtr.rACT complex and the suggestion that electrostatic interactions mediate the coupling of structural change between rACT and Chtr within the Chtr.rACT complex. Potential physiological consequences of this work are explored.

Amino Acid Sequence↗

PubMed2006

Raman spectroscopy determines structural changes associated with gelation properties of fish proteins recovered at alkaline pH.

Structural changes of alkali-treated rockfish protein isolate (AKPI) during frozen storage were elucidated using a Raman spectrometer and scanning electron microscope (SEM). The results were compared to conventional surimi (CS). No significant textural difference was noted between AKPI stored at pH 5.5 and 7.0. The strongest texture was found for AKPI frozen with cryoprotectants and CS, while the weakest texture was observed in AKPI frozen without cryoprotectants. SEM revealed the most discontinuity in gels of AKPI with no cryoprotectants and a more aggregated microstructure after storage at pH 5.5 than at neutral pH. Raman spectral analysis demonstrated refolding of AKPI by pH readjustment to 7.0, although the refolded structure was not identical to that before the pH shift. CS showed higher alpha-helix content (approximately 50%) than AKPI (approximately 20-30%). Frozen storage induced a decrease and an increase in the alpha-helix content of CS and AKPI samples, respectively. AKPIs were slightly less stable than CS during frozen storage.

Animals↗

PubMed2003

Age and sex differences in hip joint space among asymptomatic subjects without structural change: implications for epidemiologic studies.

OBJECTIVE: The prevalence of hip osteoarthritis (OA) increases significantly with age. Although it is not clear whether joint space loss at the hip is a feature of normal aging or a reflection of the OA process, epidemiologic criteria for OA are based on narrowing alone. The aim of this study was to determine whether changes in joint space width occur with age, and whether there are sex differences, in asymptomatic subjects without hip OA. METHODS: We identified a total of 1,806 subjects who had undergone intravenous urography between 1994 and 1996 and sent a questionnaire to the 1,527 of these subjects who were alive in 1998; 1,031 replies (68%) were received. All radiographs were read by an observer blinded to age, sex, and pain status. Individual radiographic features of OA (narrowing, osteophyte, sclerosis, and cysts) were graded, and an overall qualitative grade was allocated, according to a standard atlas. Minimum joint space width (JSW) was measured by metered caliper to within 0.1 mm. A total of 276 women (mean age 63 years) and 257 men (mean age 64 years) were identified who had never had hip pain (defined as having ever had pain on most days for at least 1 month) and who had no evidence of either joint space narrowing or osteophyte (grade 0, no structural changes). The minimum JSW in either hip was tabulated according to age. RESULTS: JSW measurement was reproducible (95% confidence limits of agreement) to within +/-0.5 mm. At all ages, men had larger JSW than women (3.85 mm in women, 4.19 mm in men, mean difference 0.34 mm; 95% confidence interval [95% CI] 0.24, 0.44). A significant decline in JSW with age was seen in women, with a mean difference between ages 45-54 and 75-84 years of 0.36 mm (95% CI 0.15, 0.58; P = 0.001). No significant change in JSW with age was seen in men (mean difference 0.16 mm; 95% CI -0.11, 0.43). Analysis of an additional 64 women and 61 men who were without hip pain and had overall qualitative grade 1-2 changes gave similar results. Implementing these results to alter the threshold for definition of hip OA in women from < or =2.5 mm to < or =2.2 mm reduced the prevalence of hip OA from 10.6% to 5.6%. CONCLUSION: These sex differences in joint space have significant implications in terms of the major emphasis on joint space narrowing in definitions of hip OA. Women also have a significant progressive decline in joint space with age that is not seen in men. This suggests that in women, loss of cartilage may be an age-related phenomenon that is independent of other aspects of structural change. Consideration should be given to the development of sex-specific definitions of hip "OA."

Age Factors↗

PubMedDate not supplied

Age-related structural changes in the human midbrain: an MR image study.

We measured midbrain structures of 194 subjects without neurological disorders, using T2-weighted MR imaging. Age was negatively correlated with the maximum anteroposterior distance of the midbrain through the substantia nigra (MD), and the average distance from the substantia nigra to the red nucleus (SNRND), while a positive correlation was found between aging and the maximum distance of the substantia nigra (SND). Significant left-right differences were revealed in MD, SND, SNRND and the area of the red nucleus (RNA), which was possibly responsible for cerebral hemispheric dominance or handedness. There were gender differences in MD and the maximum interpeduncular distance (IPD) in age-matched groups. Age-related structural changes of the midbrain may have a close relation to a decline in motor performance with aging. These findings provide essential information to evaluate the MR images of neurodegenerative disorders.

Age Distribution↗

PubMed1981

Structural changes after transmitter release at the frog neuromuscular junction.

The sequence of structural changes that occur during synaptic vesicle exocytosis was studied by quick-freezing muscles at different intervals after stimulating their nerves, in the presence of 4-aminopyridine to increase the number of transmitter quanta released by each stimulus. Vesicle openings began to appear at the active zones of the intramuscular nerves within 3-4 ms after a single stimulus. The concentration of these openings peaked at 5-6 ms, and then declined to zero 50-100 ms late. At the later times, vesicle openings tended to be larger. Left behind at the active zones, after the vesicle openings disappeared, were clusters of large intramembrane particles. The larger particles in these clusters were the same size as intramembrane particles in undischarged vesicles, and were slightly larger than the particles which form the rows delineating active zones. Because previous tracer work had shown that new vesicles do not pinch off from the plasma membrane at these early times, we concluded that the particle clusters originate from membranes of discharged vesicles which collapse into the plasmalemma after exocytosis. The rate of vesicle collapse appeared to be variable because different stages occurred simultaneously at most times after stimulation; this asynchrony was taken to indicate that the collapse of each exocytotic vesicle is slowed by previous nearby collapses. The ultimate fate of synaptic vesicle membrane after collapse appeared to be coalescence with the plasma membrane, as the clusters of particles gradually dispersed into surrounding areas during the first second after a stimulus. The membrane retrieval and recycling that reverse this exocytotic sequence have a slower onset, as has been described in previous reports.

Animals↗

PubMed1988

Cardiovascular structural changes induced by isolation-stress hypertension in the rat.

The cardiovascular structural remodelling associated with psychogenic hypertension was investigated in genetically normotensive rats subjected to isolation stress. Male Wistar rats were stressed by intermittent social isolation and compared to control rats living in groups. The stressed rats had higher systolic blood pressures than the control rats throughout the study. After 1 week of isolation, ornithine decarboxylase activity, a marker for hypertrophy, was increased in the right ventricle of the stressed rats. After 6 weeks of intermittent isolation, the myocardium of the stressed rats was hypertrophied, involving both right and left ventricles. The aorta was also hypertrophied, whereas the tail artery remained unaffected. Later, after 12 weeks of isolation, the left ventricular hypertrophy persisted whereas the right ventricle and aorta returned to normal. It seems, therefore, that social stress hypertension is accompanied by very early structural changes, which affect at least the heart and the aorta, and cannot be directly linked to the severity or duration of hypertension.

Animals↗

PubMed1989

[Structural changes of the heart in craniocerebral trauma].

A study is presented of structural changes in the myocardium due to head injuries. General histological, histochemical, histoenzymological methods and electron microscopy were used. The authors revealed a complex of dystrophic and adaptative changes in the contractile myocardium, interstitial connective tissue and blood circulatory bed. These changes depended directly on the character of the craniocerebral injury and time from the beginning of the trauma.

Brain Injuries↗

PubMed1986

[Structural changes in the sugar chains of gamma-glutamyltranspeptidase by malignant transformation].

Structures of the sugar moieties of gamma-glutamyl transpeptidases purified from the kidney and the liver of rat, mouse, and cattle were studied after being chemically released as oligosaccharides. The results indicated that both organ-specific and species-specific differences exist in the sugar chains of the enzyme. Comparative studies of sugar chains of the heavy and light subunits of the rat kidney enzyme revealed that high mannose-type sugar chains are found only in the heavy subunit. By the same analysis of the oligosaccharide fractions obtained from four isozymic forms of the rat kidney enzyme, it was found that all these enzymes contain 2 mole of neutral sugar chains but different numbers of acidic sugar chains in one molecule. Comparative studies of oligosaccharides obtained from the enzymes purified from rat AH-66 hepatoma and from normal rat liver revealed that more than 40% of the sugar chains of the hepatoma enzyme contain bisecting N-acetylglucosamine residues which are not found in those of the liver enzyme. By making use of the structural changes associated with malignant transformation, a new diagnostic method or hepatoma was developed. In principle, the method consists of affinity chromatography of the desialylated serum enzyme using an erythroagglutinating lectin agarose column.

Animals↗