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PubMed2007

Human brain structural change related to acute single exposure to sarin.

OBJECTIVE: This study aimed to identify persistent morphological changes subsequent to an acute single-time exposure to sarin, a highly poisonous organophosphate, and the neurobiological basis of long-lasting somatic and cognitive symptoms in victims exposed to sarin. METHODS: Thirty-eight victims of the 1995 Tokyo subway sarin attack, all of whom had been treated in an emergency department for sarin intoxication, and 76 matched healthy control subjects underwent T1-weighted and diffusion tensor magnetic resonance imaging (DTI) in 2000 to 2001. Serum cholinesterase (ChE) levels measured immediately and longitudinally after the exposure and the current severity of chronic reports in the victims were also evaluated. RESULTS: The voxel-based morphometry exhibited smaller than normal regional brain volumes in the insular cortex and neighboring white matter, as well as in the hippocampus in the victims. The reduced regional white matter volume correlated with decreased serum cholinesterase levels and with the severity of chronic somatic complaints related to interoceptive awareness. Voxel-based analysis of diffusion tensor magnetic resonance imaging further demonstrated an extensively lower than normal fractional anisotropy in the victims. All these findings were statistically significant (corrected p < 0.05). INTERPRETATION: Sarin intoxication might be associated with structural changes in specific regions of the human brain, including those surrounding the insular cortex, which might be related to elevated subjective awareness of internal bodily status in exposed individuals.

Adult↗

PubMed1998

Structural changes in human tear lipocalins associated with lipid binding.

Structural and conformational changes in tear lipocalins were detected in association with ligand binding and release. Circular dichroism measurements demonstrated that ligand binding induces beta structure formation, aromatic side chain asymmetry, and a more rigid state in tear lipocalins (TL). The exposure of the tyrosyl component is less in apo-TL than in holo-TL. The sole tryptophan residue, Trp17, is buried in both holo- and apo-TL. The steady state exposure of Trp17 is the same in holo- and apo-TL, but the dynamic exposure is two-fold greater in apo-TL. Maneuvers to unfold the protein with urea or incubation in an acidic environment resulted in increased exposure of aromatic amino acids. Electron paramagnetic resonance studies verified that lipids are liberated from TL in an acidic environment. Acidic pH promotes conformational changes in TL involving aromatic residues, particularly the conserved residue Trp17. These changes are associated with lipid release. The liberation of lipid from the cavity of TL under acidic conditions involves a molten globule state of the protein. We postulate that TL, exposed to the steep surface pH gradient that exists at lipid-aqueous interfaces, would release lipid in association with a molten globule transition. The data suggest a plausible regulatory mechanism for lipid delivery from lipocalins at the tear film surface.

Anilino Naphthalenesulfonates↗

PubMed2002

Hyperhexosemia induced functional and structural changes in the kidneys: role of endothelins.

BACKGROUND/AIMS: Glomerular basement membrane (GBM) thickening and mesangial matrix expansion are characteristic features of diabetic nephropathy. The present study investigates the role of endothelins (ETs) in the pathogenesis of such changes in diabetic nephropathy. METHODS: Diabetic (streptozotocin-induced, 65 mg/kg), galactose-fed (30%) and control animals were followed up for 1 and 6 months. Animal groups also included diabetic and galactose fed animals on dual ET(A)/ET(B) receptor antagonist bosentan (100 mg/kg). A semi-quantitative reverse transcription polymerase chain reaction method was used to quantify mRNA expression of ET-1, ET-3, ET(A), ET(B), fibronectin and collagen alpha2(IV). Histological analyses of the kidneys and ET-1, ET-3 and fibronectin immunohistochemistry were performed. Morphometric assessment of the GBM after 6 months was performed. RESULTS: Diabetes increased mRNA expression of ET-1, ET-3, ET(A), ET(B), fibronectin and collagen alpha2(IV) after one and six months. In contrast, although increased ET(A) and ET(B) mRNAs were present following galactose feeding both at 1 and 6 months, ET-1, ET-3, fibronectin and collagen alpha2(IV)mRNAs were increased after 6 months. Both diabetes and galactose feeding caused increased GBM thickening. Furthermore, diabetes caused an increase in mesangial matrix production. Bosentan prevented increased fibronectin and collagen alpha2(IV) mRNA expression, increased mesangial matrix deposition and GBM thickening. CONCLUSION: This study has demonstrated that diabetes and galactose feeding induced functional and structural changes in the kidney are mediated via ETs.

Animals↗

PubMed2000

An examination of how structural changes can affect the rate of electron transfer in a mutated bacterial photoreaction centre.

A series of reaction centres bearing mutations at the (Phe) M197 position were constructed in the photosynthetic bacterium Rhodobacter sphaeroides. This residue is adjacent to the pair of bacteriochlorophyll molecules (P(L) and P(M)) that is the primary donor of electrons (P) in photosynthetic light-energy transduction. All of the mutations affected the optical and electrochemical properties of the P bacteriochlorophylls. A mutant reaction centre with the change Phe M197 to Arg (FM197R) was crystallized, and a structural model constructed at 2.3 A (1 A=0.1 nm) resolution. The mutation resulted in a change in the structure of the protein at the interface region between the P bacteriochlorophylls and the monomeric bacteriochlorophyll that is the first electron acceptor (B(L)). The new Arg residue at the M197 position undergoes a significant reorientation, creating a cavity at the interface region between P and B(L). The acetyl carbonyl substituent group of the P(M) bacteriochlorophyll undergoes an out-of-plane rotation, which decreases the edge-to-edge distance between the macrocycles of P(M) and B(L). In addition, two new buried water molecules partially filled the cavity that is created by the reorientation of the Arg residue. These waters are in a suitable position to connect the macrocycles of P and B(L) via three hydrogen bonds. Transient absorption measurements show that, despite an inferred decrease in the driving force for primary electron transfer in the FM197R reaction centre, there is little effect on the overall rate of the primary reaction in the bulk of the reaction-centre population. Examination of the X-ray crystal structure reveals a number of small changes in the structure of the reaction centre in the interface region between the P and B(L) bacteriochlorophylls that could account for this faster-than-predicted rate of primary electron transfer.

Crystallography, X-Ray↗

PubMed2001

Functional and structural changes in the kidney in the early stages of obesity.

The purpose of this study was to examine the histologic and functional changes that occur in the kidney in the early stages of obesity caused by a high-fat diet. Lean dogs (n = 8) were fed a standard kennel ration, and obese dogs (n = 8) were fed the standard kennel ration plus a supplement of cooked beef fat each day for 7 to 9 wk or 24 wk. Body weights were 58 +/- 5% greater and kidney weights were 31 +/- 7% greater in obese dogs, compared with the average values for lean dogs. Plasma renin activity and insulin concentrations were both 2.3-fold greater in obese dogs, compared with lean dogs. Obesity was associated with a mean arterial pressure increase of 12 +/- 3 mmHg, a 38 +/- 6% greater GFR, and a 61 +/- 7% higher renal plasma flow, compared with lean dogs. The glomerular Bowman's space area was significantly greater (+41 +/- 7%) in dogs fed the high-fat diet, compared with lean animals, mainly because of expansion of Bowman's capsule (+22 +/- 7%). There was also increased mesangial matrix and thickening of the glomerular and tubular basement membranes and the number of dividing cells (proliferating cell nuclear antigen-stained) per glomerulus was 36 +/- 8% greater in obese dogs, compared with lean dogs. There was also a trend for glomerular transforming growth factor-beta1 expression, as estimated by semiquantitative immunohistochemical analysis, to be elevated with the high-fat diet. Therefore, a high-fat diet caused increased arterial pressure, hyperinsulinemia, activation of the renin-angiotensin system, glomerular hyperfiltration, and structural changes in the kidney that may be the precursors of more severe glomerular injury associated with prolonged obesity.

Analysis of Variance↗

PubMed1980

[Structural changes of Hancock bioprostheses in children (author's transl)].

Conservative management is the treatment of choice for either congenital or acquired valvular disease in children. However, prosthetic valve replacement may sometimes be required and in this situation the surgeon is faced with the problem of which valvular substitute is the best for this particular patient. The glutaraldehyde-preserved Hancock porcine xenograft has been considered the safest one to use in the pediatric age group since the risks of thromboembolism as well as the mortality and morbidity related to anticoagulant treatment are reduced with this device. However durability of porcine bioprostheses at this time is still unknown, and it remains one of its major concerns. Recent reports have highlighted that porcine heterografts implanted in children undergo early and severe fibrocalcific degeneration. After having reviewed our pathological collection of explanted Hancock valves we have summarized our experience with pathology of porcine bioprostheses in young patients in the present report. Five Hancock heterografts were available for gross and histologic examination. They came from 3 children, 2 females and 1 male, who died or were reoperated upon because of prosthetic dysfunction. Both girls, aged 8 and 10 years, had undergone total correction of complete a-v canal which required mitral valve replacement in the first and mitrotricuspid valve replacement in the second. The first one was reoperated 2.10 years after surgery because of severe prosthetic stenosis and died in the 1st postoperative day of low output syndrome. The second, who developed the signs of mitral stenosis 3.4 years later, was successfully reoperated, but died in severe heart failure 2.9 years following mitral prosthetic re-replacement. The third patient, a 11-year-old boy, underwent mitral valve replacement because of mitral incompetence due to bacterial endocarditis; 5.4 years after surgery he necessitated reoperation because of mitral prosthetic stenosis. He is currently asymptomatic. Pathologic examination of the 5 explants (4 mitral, 1 tricuspid) which had been in place from 34 to 72 months (average 49 mos), showed a severe stenosis with impairment of the effective prosthetic orifice in all. The stenosis was due to coarse calcific deposits of the cusps and commissures and was worsened in 3 cases by fibrous tissue overgrowth on the inflow aspect of the leaflets. In 2 cases an atrial thrombosis was observed, as a consequence of prosthetic stenosis. Histologic examination together with microradiographic investigation showed in all cases the presence of diffuse calcifications of commissures and leaflets. Our pathological experience confirms that the Hancock bioprostheses, when implanted in children, undergoes structural changes early and severe enough so as to discourage their employment in this group of patients.

Bioprosthesis↗

PubMed1986

Cognitive structure changes with psychotherapy in neurosis.

This study investigated the relationship between improvement in psychotherapy and changes in cognitive complexity (structural organization and differentiation). Before undergoing 30 sessions of psychoanalytically oriented psychotherapy, 27 psychoneurotic subjects specified the target (major) complaints, described 15 figures (including themselves) and completed the repertory grid. After psychotherapy, subjects rated their improvement on the target complaints and again described the 15 figures and completed the repertory grid. The results showed that improvement in psychotherapy was associated with increased complexity in the patients' cognitive organization of the psychosocial world, but not with increased cognitive differentiation in interpersonal perception. Implications for the theory of neurosis and evaluation of change in the process of psychotherapy are discussed.

Adult↗

PubMed2006

[Isoflavone accumulation associated with cell structural changes in Maackia amurensis suspension cultures elicited by methyl jasmonate, salicylic acid and nitric oxide].

Comparison between changes in isoflavone accumulation and cell structure in Maackia amurensis suspension cultures elicited by methyl jasmonate (MeJA),salicylic acid (SA) and nitric oxide (NO) was studied. The results suggested that MeJA, SA and NO can all stimulate isoflavone production remarkably. After 9d treatment with 200 micromol/L MeJA,100 micromol/L SA and 50 micromol/L SNP, the isoflavone content was 417.18%, 185.45% and 222.45% of the control, respectively. At the same time, the electron-dense body (EDB) could be easily found in the cells, while its number achieved most after 9 d treatment,and the number of EDB and isoflavone content were positive correlated. It was deduced that elicitors stimulated plant secondary metabolites production associated with changes in cell structure.

Acetates↗

PubMed2002

Protein structural changes induced by their uptake at interfaces.

For insertion into lipidic media, most hydrosoluble proteins must cross the lipid-water interface and thus undergo conformational transitions. According to their chemical sequences these transitions may be restricted to changes involving only the tertiary structure, while for other proteins this environment modification will induce drastic changes such as the unfolding of large domains. The structural transitions are mainly governed by the presence of hydrophobic domains and/or by the existence of induced amphipathic properties.

Adsorption↗

PubMedDate not supplied

[Direct proof of the existence of Ca2+-induced structural changes in miosin-containing thick filaments of vertebrate skeletal muscles].

Frog sartorius muscles were skinned with the help of detergent Triton X-100 in relaxing solution and then rigorized in the solution free of ATP and calcium (Ca2+-free rigor). Some of the X-ray diffraction patterns obtained from such muscles differed drastically from the patterns of usual "calcium" rigor state of the muscle. Analysis of the X-ray diffraction patterns of Ca2+-free rigor state of the muscle allows the following conclusions to be made. (1) It is proved that the so-called forbidden meridional reflections localised in groups at the successive orders of the repeat period of about 430 A are due to diffraction on the lattice formed by minor proteins of the thick filaments. This must be taken into account while interpreting the intensity changes of the meridional 143 and 215 A reflections in the contracting muscle. (2) The shafts of the myosin-containing filaments may exist in two different structural states; the transition between these states takes place on the change of calcium concentration. (3) The deflection of myosin cross-bridges from the shafts of the filaments is possible at either of two conformations of the myosin shafts. (4) The formation of actomyosin rigor-complexes does not necessarily leads to a structural change in the myosin filament. (5) Existence of Ca2+-induced structural changes in the thick filaments indicates possible myosin-linked regulations in the vertebrate skeletal muscle alongside with the actin-linked ones.

Animals↗

PubMed2004

Encapsulating chondrocytes in degrading PEG hydrogels with high modulus: engineering gel structural changes to facilitate cartilaginous tissue production.

A major challenge when designing cell scaffolds for chondrocyte delivery in vivo is creating scaffolds with sufficient mechanical properties to restore initial function while simultaneously controlling temporal changes in the gel structure to facilitate tissue formation. To address this design challenge, degradable photocrosslinked hydrogels based on poly(ethylene glycol) were investigated. To alter the gel's initial mechanical properties, hydrogels were fabricated by varying the initial macromer concentration from 10% to 15% to 20%. A twofold increase in macromer concentration resulted in an eightfold increase in the initial compressive modulus from 60 to 500 kPa. Gel degradation was tailored by incorporating fast-degrading crosslinks that enable maximal extracellular matrix (ECM) diffusion with time and a minimal number of nondegrading (or slowly degrading) crosslinks to maintain scaffold integrity and prevent complete gel erosion during tissue formation. Chondrocytes encapsulated in these gels produced cartilaginous tissue rich in glycosaminoglycans and collagen as seen biochemically and histologically. Interestingly, mass loss appeared to more closely match tissue secretion in gels fabricated from a 15% macromer concentration. However, the spatial ECM distribution was grossly similar in all three gels. By tailoring gel degradation and controlling network evolution during degradation, gels with optimal properties can be fabricated to support initially physiologic compressive loads while simultaneously supporting the formation of a neotissue.

Animals↗

PubMed1989

Catecholamine melanins. Structural changes induced by copper ions.

Melanins synthesized from adrenaline and dopamine in the presence or absence of copper ions were characterized by pyrolysis-gas chromatography-mass spectrometry and by IR and ESR methods. It was shown that Cu2+ are able to induce changes in the melanin structure. Melanins obtained from adrenaline-Cu2+ and dopamine-Cu2+ complexes are composed mainly from monomeric units of the indole type. Melanins synthesized from these catecholamines without Cu2+ contain additionally large amounts of unindolized monomeric units. The structure differences in both types of melanins are reflected in their sorptive abilities and spectroscopic characteristics.

Chloroquine↗

PubMed2002

Structural changes in the brain in depression and relationship to symptom recurrence.

Depression is an important public health problem affecting about 15% of the general population; however, little is known about possible changes in the brain that might underlie the disorder. Neuroimaging has been a powerful tool to map actual changes in the brain structure of depressed patients that might be directly related to their symptoms of depression. Some imaging studies of brain structure have shown smaller hippocampal volume with the chronicity of depression correlating to a reduction in volume. Although the meaning of these findings is unclear, other studies have shown increased amygdala volume. Studies have found reductions in volume of the frontal cortex, with some studies showing specific reductions in subregions of the frontal cortex, including the orbitofrontal cortex. Findings of an increase in white matter lesions in elderly patients with depression have been replicated and correlated with late-onset depression, as well as impairments in social and cognitive function. These findings point to alterations in a circuit of brain regions hypothesized to include the frontal cortex, hippocampus, amygdala, striatum, and thalamus, that underlie symptoms of depression.

Journal Article↗

PubMed2003

Light- and pH-dependent structural changes in the PsbS subunit of photosystem II.

In higher plants, the PsbS subunit of photosystem II (PSII) plays a crucial role in pH- and xanthophyll-dependent nonphotochemical quenching of excess absorbed light energy, thus contributing to the defense mechanism against photoinhibition. We determined the amino acid sequence of Zea mays PsbS and produced an antibody that recognizes with high specificity a region of the protein located in the stroma-exposed loop between the second and third putative helices. By means of this antiserum, the thylakoid membranes of various higher plant species revealed the presence of a 42-kDa protein band, indicating the formation of a dimer of the 21-kDa PsbS protein. Crosslinking experiments and immunoblotting with other antisera seem to exclude the formation of a heterodimer with other PSII protein components. The PsbS monomer/dimer ratio in isolated thylakoid membranes was found to vary with luminal pH in a reversible manner, the monomer being the prevalent form at acidic and the dimer at alkaline pH. In intact chloroplasts and whole plants, dimer-to-monomer conversion is reversibly induced by light, known to cause luminal acidification. Sucrose-gradient centrifugation revealed a prevalent association of the PsbS monomer and dimer with light-harvesting complex and PSII core complexes, respectively. The finding of the existence of a light-induced change in the quaternary structure of the PsbS subunit may contribute to understanding the mechanism of PsbS action during nonphotochemical quenching.

Amino Acids↗

PubMed1989

The effects of near-UV radiation on human lens beta-crystallins: protein structural changes and the production of O2- and H2O2.

beta-Crystallins (beta 1-, beta 2- and beta 3-crystallin) comprise nearly half the protein of the human lens. The effect of near-UV radiation, which is one of the possible risk factors in cataract formation, on the beta-crystallins is investigated in this study. Protein intersubunit crosslinking, change in charge of the protein subunits to more acidic species and changes in protein tertiary structure (conformation) by 300 nm irradiation are reported. The fluorescence yield of protein tryptophan residues decreases by 300 nm irradiation. There is an increase in nontryptophan fluorescence (lambda cx 340 nm, lambda cm 400-600 nm), and in protein absorption at 340 nm, due to the formation of tryptophan photooxidation products. Both tryptophan and its oxidation products can be photoexcited by 300 nm irradiation and the latter are known to be good photosensitizers. The results provide evidence for the generation of H2O2 in the irradiated human beta-crystallin solutions by the Type I photosensitizing action of the chromophores absorbing at 300 nm. The H2O2 is generated via the intermediate production of O2 anion; the latter spontaneously dismutates to H2O2, presumably via O2- protein interactions. The amount of H2O2 generated per absorbed photon is compared for various solutions of beta 1-, beta 2- and beta 3-crystallins from human lenses of different age.

Circular Dichroism↗

PubMed2000

Ultrasonographic study of carotid artery structural changes with natural longevity.

The changes in carotid artery structure during the natural longevity of the Uighurs people were compared with other ethnic groups. The 419 subjects were divided into (1) longevity and (2) older groups as follows: Uighurs longevity group in Hotan (ULH); and Uighurs, Hans and Kazaks older groups in Hotan or Balikun (UOH, HOH, HOB and KOB). The wall thickness of the common carotid artery (CCA) was measured by ultrasonography. Risk factors were evaluated by measuring total cholesterol (T-C), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and fasting glucose, and by 24-h ambulatory blood pressure monitoring. Wall thickness and blood pressure were greater in the Balikun groups than in the Hotan groups. The CCA wall was thicker in Uighurs and Kazaks than in Hans, in the ULH than in the UOH. There was no significant difference in blood pressure among the Hotan groups. LDL-C and glucose were higher and HDL-C was lower in the Hotan groups than in the Balikun groups. T-C, LDL-C, TG and glucose were higher in the HOH than in the ULH and UOH. Systolic blood pressure and LDL-C were higher and TG was lower in the KOB than in the HOB. These results suggest that an increased CCA wall thickness can be attributed to age in Hotan, and to a higher blood pressure level in Balikun, and that the higher blood pressure affected the Balikun groups more than the Hotan groups.

Aged↗

PubMed2006

Microbial population structure changes in a suspended carrier biofilm reactor.

The changes of microbial population structure in biofilm caused by variations of COD/NHNH4(+)-N ratio in influent were investigated in a suspended carrier biofilm reactor (SCBR). When COD/NHNH4(+)-N was 10, the highest COD removal reached was about 73.8 per cent, whereas the highest NH4(+)-N removal, about 55.9 per cent, was reached when COD/NH4(+)-N was 5. By using fluorescence in situ hybridization (FISH) and confocal laser scanning microscopy (CLSM) observation, it was found that the thickness of the biofilm formed on the carrier was about 80 to 120 microm, and ammonia-oxidizing bacteria (AOB) and nitrifying bacteria existed mainly in the upper layer about 20 to 30 microm. The results of the quinone profile analysis showed that when the COD/NH4(+)-N increased, the microbial diversity (DQ) increased, while the proportions of AOB and nitrifying bacteria in the biofilm communities decreased.

Ammonia↗

PubMed2003

[Expression of type II collagen gene and structural change in bone tissues of rats with experimental fluorosis].

OBJECTIVE: To investigate the effects of excessive intake of fluoride on the expression of type II collagen gene and types and morphological change of collagen fiber in the bone tissues of rats. METHODS: A rat model with fluorosis was established by adding 221 mg/L of sodium fluoride (NaF) to drinking water for the rats for 15 days, 30 days and two months, respectively. Type II collagen alpha1 (II) cDNA probe was prepared, and cDNA-mRNA in-situ hybridization was employed to detect change in expression of type II collagen mRNA in the bone tissues of rats with excessive intake of fluoride (221 mg/L NaF). Picrosirius-polarization method was used to observe types of collagen and morphology of collagen fiber in the bone tissues. RESULTS: Chondroblasts were found in the femur and other bone tissues of the rats after exposure to fluoride. cDNA-mRNA in-situ hybridization showed that expression of type II collagen gene could be observed in the cytoplasm of chondrocytic lacuna and chondrified bone tissues. mRNA in collagen of chondrocytes of the rib cartilage reached the peak level 15 days after exposure to fluoride, and decreased gradually one month and two months after exposure. Polychromatic type II collagen, breakage of collagen fiber, disorder array and reduced content of type II collagen could be found in the bone tissues with picrosirius-polarization method. CONCLUSIONS: Excessive intake of fluoride could lead to changes in types and structure of collagen (cross-linkage) of bone tissues, which caused expression of type II collagen gene in the chondrified bone tissues and enhanced its expression in the rib cartilage tissues.

Animals↗