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[Structural changes in the parenchymatous organs in animals in venous gas embolism of varying intensity and acute decompression disease].

Structural changes in tissues of liver, kidneys and lungs were studied in guinea pigs in post-decompressive gas venous embolism of high and low intensity. In moderate gas venous embolism cells of the organs studied display cytoplasm vacuolization due to the rupture of inner mitochondrial membrane and appearance of single rounded spheroidal structure with homogeneous contents situated near the cell nuclei that were thought to reflect formation of gas bubble within the cell. Possible pathogenetic mechanisms of formation of chronic decompressive disorders in asymptomatic gas formation are discussed.

Acute Disease↗

Phenytoin neuropathy: structural changes in the sural nerve.

Phenytoin has been implicated as a causative agent in peripheral neuropathy, although structural changes in nerve have not been characterized. A 47-year-old man was seen with clinical and electrophysiological signs of peripheral neuropathy after 30 years of phenytoin administration. Despite a modest dose of phenytoin (300 mg/day) blood levels were 31 to 38 micrograms/ml. A sural nerve biopsy showed a loss of large myelinated nerve fibers and a nonrandom clustered distribution of segmental demyelination and remyelination. The latter findings were accompanied by axonal shrinkage. Sixteen months after phenytoin was stopped, the patient's clinical and electrophysiological findings reflected improvement. These data indicate that long-term phenytoin administration can cause a reversible neuropathy characterized by axonal shrinkage and secondary demyelination.

Atrophy↗

Nuclease-induced DNA structural changes assessed by flow cytometry with the intercalating dye propidium iodide.

A flow cytometric analysis of DNA structural changes induced by cleavage with nucleases was performed on isolated HeLa nuclei by assessing changes in stainability with the DNA-specific fluorochrome propidium iodide (PI). After mild digestion with DNAse I, micrococcal nuclease, or with the single-strand-specific S1 and Neurospora crassa nucleases, fluorescence intensity of nuclei stained with PI increased by about 15-30% above the value of undigested control samples. No significant modifications were observed with the restriction enzymes Eco RI, Alu I, and Not I. The DNAse I-induced increase in fluorescence intensity was also observed with the non-intercalating dye Hoechst 33258, but not with mithramycin. Nuclease-induced fluorescence intensity changes as determined with PI were found to be dependent on the dye concentration. A constant increase (about 20%) was measured at dye/DNA-P ratios greater than 0.11. Below this value (2 micrograms/ml PI), the fluorescence intensity of digested samples was 15-30% lower than that of undigested controls. This behaviour towards intercalating dyes is similar to that of the relaxed (nicked) vs. the supercoiled (intact) form of circular DNA. These results suggest that conformation- but not sequence-specific nucleases induce a relaxation of DNA supercoils.

Coloring Agents↗

The effect of upper airway structural changes on central chemosensitivity in obstructive sleep apnea-hypopnea.

We examined the efficiency of upper airway structural changes in uvulopalatopharyngoplasty and/or tonsillectomy on central chemosensitivity, and whether the outcome of such surgeries can be predicted by the central chemosensitivity in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients. In 11 patients with OSAHS group, the average of the hypercapnic ventilatory response (HCVR) slope was 1.93 +/- 0.20 L/min/mm Hg preoperatively and 1.78 +/- 0.22 L/min/mm Hg postoperatively. The average of the mouth occlusion pressure at 0.1 second after the onset of inspiration (P (0.1)) slope was 0.47 +/- 0.06 cm H (2)O/mm Hg and 0.44 +/- 0.08 cm H (2)O/mm Hg, before and after surgery, respectively. There were no significant differences before and after treatment, although OSAHS was improved by these surgeries. In control group with 5 patients, the HCVR slope and P (0.1) slope also showed no significant difference before and after the procedure. When we divided the 11 OSAHS patients into 7 responders (apnea-hypopnea index < 20 events/h and > 50% reduction) and 4 poor responders, there was a significant difference between the average HCVR slope of responders (1.59 +/- 0.21 L/min/mm Hg) and that of poor responders (2.52 +/- 0.20 L/min/mm Hg). We saw no significant difference in physiologic (age, body mass index, one-piece tonsil weight), blood gas values, cephalometric, spirometric, or sleep parameters.

Adult↗

Comparative study of carbon dioxide and nitrogen atmospheric effects on the chemical structure changes during pyrolysis of phenol-formaldehyde spheres.

The effect of CO(2) atmosphere on the chemical structure changes of resol-type phenol-formaldehyde spheres during pyrolysis was investigated, in comparison with that of N(2) atmosphere, using FT-IR, TGA, and elemental analysis techniques. It was found that, in contrast to the expectation that CO(2) may act as an oxidizing agent at high temperature, it behaves very similar to N(2) during pyrolysis of PF spheres up to 700 degree C, but results in a somewhat different extent of some specific reactions. That is, although the reactions occurring up to 700 degree C were dominated by crosslinking and/or polyaromatization under both CO(2) and N(2) atmospheres, fewer alkyl-phenolic ether bonds were formed under CO(2) than under N(2). As a consequence, the samples carbonized under CO(2) at 700 degree C were found to have more pendant groups on the edge carbon atoms of carbon in the carbonized samples than those prepared under N(2) atmosphere.

Journal Article↗

Abnormalities of auditory evoked magnetic fields and structural changes in the left hemisphere of male schizophrenics--a magnetoencephalographic-magnetic resonance imaging study.

Functional and structural changes in 10 DSM-III-R male schizophrenics and 10 healthy volunteers were investigated using magnetoencephalographically (MEG) detected long-latency (N100 m) auditory evoked fields (AEFs) and magnetic resonance imaging (MRI). The AEFs were characterized by single moving equivalent dipoles, which were superimposed on MRIs. There were significant differences in dipole orientations and in AEF latencies in the left hemisphere of schizophrenics, when compared to the controls. The MEG-detected alterations were found to be associated with a bilateral volume reduction of the posterior superior temporal gyrus (pSTG), which was more pronounced in the left hemisphere. Separate analysis of white and gray matter has shown that the pSTG volume reduction resulted from decreased gray matter volumes without white matter changes. Both the functional and the morphological data indicate a left-hemispheric disturbance in our patients.

Adult↗

Probing the structural changes in the light chain of human coagulation factor VIIa due to tissue factor association.

The crystallographic structure of human coagulation factor VIIa/tissue factor complex bound with calcium ions was used to model the solution structure of the light chain of factor VIIa (residues 1-142) in the absence of tissue factor. The Amber force field in conjunction with the particle mesh Ewald summation method to accommodate long-range electrostatic interactions was used in the trajectory calculations. The estimated TF-free solution structure was then compared with the crystal structure of factor VIIa/tissue factor complex to estimate the restructuring of factor VIIa due to tissue factor binding. The solution structure of the light chain of factor VIIa in the absence of tissue factor is predicted to be an extended domain structure similar to that of the tissue factor-bound crystal. Removal of the EGF1-bound calcium ion is shown by simulation to lead to minor structural changes within the EGF1 domain, but also leads to substantial relative reorientation of the Gla and EGF1 domains.

Amino Acid Sequence↗

Acid-induced structural changes of a mouse IgG2a monoclonal antibody (MN12) studied by transient electric birefringence measurement.

Acid-induced structural changes of a mouse IgG2a monoclonal antibody (MN12) as indicated by Jiskoot et al. (Eur. J. Biochem. 201,223-232 (1991)) were studied by measuring the transient electric birefringence of MN12 in aqueous solution and in glycerol-water mixtures at different pH conditions. A multi-exponential analysis program, DISCRETE (Provencher,S.W., Biophys.J.16,27-41 (1976)), and a constrained inverse Laplace transform program, CONTIN (Provencher, S.W., Comp. Phys. Comm. 27, 213-227 (1982)) have been used to determine the number of exponentials needed to represent the data and their decay times. Measurement of the time-resolved electric field induced birefringence makes it possible to study rotational processes on a timescale from several tens of nanoseconds to microseconds. This enabled us to monitor the segmental flexibility and the rotational motion of single antibody molecules as well as the occurrence of aggregates. The results show an increase in hydrodynamic dimensions of MN12 upon lowering the pH from 6.6 to 2.7. Additionally, the original segmental flexibility, which could be monitored for the samples in glycerol-water mixtures, is altered at low pH. The results have been interpreted as swelling of MN12 followed by dimerization.

Animals↗

Fine-structural changes in the nucleus of primordial oocytes in immature hamsters.

This study reports observations on fine-structural changes in the nucleus of the oocyte in hamsters during the establishment of the primordial (unilaminar) follicle at 7 to 12 days after birth. Following pachytene, the nuclei at early diplotene contain simple chromosomal cores surrounding by a sheath of fibrillo-granular material symmetrically disposed in the form of lateral projections and loops. From 9 days onwards increasing numbers of the oocytes show nuclei lacking such chromosomal threads: instead, they contain randomly disposed, condensed fibrillar clumps with associated dense knots of material, and prominent aggregations of 25--30-nm granules. This second nuclear form is assumed by all oocytes examined at 11 and 12 days and appears to be the definitive diplotene phase. These changes in the appearance of the nuclear chromatin are discussed in the light of those found in oocytes of other species, and it is concluded that the hamster diplotene phase consists of a transitory 'compace' or uniform lampbrush stage, followed by a definitive dictyate condition like that in the rat, but with markedly differential condensation or extreme diffusion of lateral loops. This conclusion is examined in relation to findings which report a marked increase in the sensitivity of hamster oocytes to X-radiation at the time that the observed changes in nuclear configuration are taking place. The combined observations support the hypothesis that the dictyate stage in rodent oocytes represents a modified diplotene phase in which the high degree of spatial diffusion of components of chromosomes of the lampbrush type results in a reduced capacity for repair following exposure to ionizing radiations.

Animals↗

[Structural changes in the liposomes and the lamellar packing of liposomal lipids exposed to glycerin].

Glycerol-induced structural changes in multilamellar liposomes (ML) were studied by light and thin-section electron microscopy. It is shown that high concentrations of glycerol induce non-bilayer rearrangements of liposomal lipids in ML. The data obtained are discussed regarding the possible mechanisms of cryoprotector effects on natural (biological) and artificial (liposomal) membranes.

Animals↗

[Roentgen diagnosis of structural changes in the pubic area in children and adolescents. Personal case reports, differential diagnosis and literature review].

Structural changes in the pubic bone often are difficult to interpret. The radiologic appearance is very different. The differentiation between inflammatory and malignant processes is hardly to distinguish. We are reporting ten patients with osseous changes in the os pubic (4 Ewing's sarcoma, 1 osteosarcoma, 1 Morbus Hodgkin, 1 osteochondronecrosis, 2 osteochondritis, 1 subchronic osteomyelitis). Two patients with Ewing's sarcoma who were initially treated for osteomyelitis are described in detail. Differential diagnosis and previous literature are reviewed.

Adolescent↗

Chromatin structure changes suggest a compensatory response to c-myc gene amplification in malignant fibrous histiocytoma.

Changes in chromatin structure as determined from DNAse I hypersensitive site analysis are associated with c-myc amplification and increased transcript/protein levels in malignant fibrous histiocytoma (MFH) cell lines. A DNAse I hypersensitive site near the PO promoter region was observed in one MFH cell line (UR HCL 1), and in normal fibroblasts (HFF), but not in an MFH cell line with an amplified c-myc gene (P3C). A DNAse I hypersensitive site exclusive to P3C amplified c-myc was identified slightly 3' of exon one. No alterations in c-myc DNAse I hypersensitive site patterns were observed in HFF fibroblasts following serum release, when peak levels of c-myc transcript were induced. DNAse I hypersensitive site patterns associated with gene amplification may reflect a compensatory response by P3C cells to an abundance of c-myc transcript. Furthermore, elevated levels of protein in P3C cells provide additional evidence that amplified c-myc is an oncogene in MFHs.

Chromatin↗

Ligand-induced structural changes to maltodextrin-binding protein as studied by solution NMR spectroscopy.

Solution NMR studies on the physiologically relevant ligand-free and maltotriose-bound states of maltodextrin-binding protein (MBP) are presented. Together with existing data on MBP in complex with beta-cyclodextrin (non-physiological, inactive ligand), these new results provide valuable information on changes in local structure, dynamics and global fold that occur upon ligand binding to this two-domain protein. By measuring a large number of different one-bond residual dipolar couplings, the domain conformations, critical for biological function, were investigated for all three states of MBP. Structural models of the solution conformation of MBP in a number of different forms were generated from the experimental dipolar coupling data and X-ray crystal structures using a quasi-rigid-body domain orientation algorithm implemented in the structure calculation program CNS. Excellent agreement between relative domain orientations in ligand-free and maltotriose-bound solution conformations and the corresponding crystal structures is observed. These results are in contrast to those obtained for the MBP/beta-cyclodextrin complex where the solution state is found to be approximately 10 degrees more closed than the crystalline state. The present study highlights the utility of residual dipolar couplings for orienting protein domains or macromolecules with respect to each other.

Bacterial Proteins↗

Electrochemical Time-of-Flight in crosslinked collagen matrix solution: implications of structural changes for drug delivery systems.

Electrochemical Time-of-Flight (ETOF) method was used for the first time to measure the diffusion coefficient of 4-hydroxy-TEMPO, a molecular probe in collagen I matrix solution as a function of its concentration and the extent of crosslinking with glutaraldehyde (GA). The values of the diffusion coefficient were correlated with Circular Dichroism (CD) and viscosity data to assess the changes of the structure of a collagen matrix. The low value of probe diffusion coefficient indicates that the molecular collagen contributes to large diffusion hindrance of the medium. The combined Brinkman or effective medium model and the Carman-Kozeny model were used to estimate the average diameter of a matrix pore as a function of collagen solution composition. We show that 0.5% and 1% (w/w) collagen matrix crosslinked with the addition of GA above 0.1% (v/w) forms matrix with pores larger than in native collagen. This result suggests the existence of a micro-phase separation in the crosslinked collagen matrix. The implications of these findings for the design of small molecule drug delivery systems are discussed.

Circular Dichroism↗

Losartan ameliorates progression of glomerular structural changes in diabetic KKAy mice.

Pathological changes in glomerular structure are typically associated with the progression of diabetic nephropathy. The involvement of angiotensin II (AII) in pathogenesis of diabetic nephropathy has been extensively studied and the therapeutic advantages associated with blockade of renin-angiotensin system (RAS), primarily with angiotensin converting enzyme (ACE) inhibitors, has been well-documented. We studied the effect of RAS blockade with an AII receptor antagonist (losartan) vs. an ACE inhibitor (enalapril) on glomerular lesions in KKAy mice, a model of type 2 diabetes mellitus. Losartan was administered at 3 and 10 mg/kg/day and enalapril at 3 mg/kg/day for 14 weeks in the drinking water. The doses of losartan at 10 mg/kg/day was expected to be equivalent to 3 mg/kg/day of enalapril when considering clinical doses for lowering blood pressure. The dose of 3 mg/kg/day of losartan was selected to compare the efficacy at equivalent dose of enalapril. Histologic observation demonstrated suppression of glomerular mesangial expansion and glomerulosclerosis with exudative lesion in the 10 mg/kg/day losartan group when compared to the untreated diabetic controls. A lesser degree of glomerulosclerosis was also observed with losartan and enalapril treatment at 3 mg/kg/day. Ultrastructural examination of renal glomeruli from the high dose losartan group revealed a decreased degree of effacement and/or irregular arrangement of glomerular podocytic foot process. The beneficial effect of RAS inhibition with the AII receptor antagonist losartan on diabetic glomerular lesions was clearly demonstrated in this study. These findings, therefore, provide mechanistic explanation for the clinical utility of losartan for use in the treatment of diabetic nephropathy in man.

Administration, Oral↗

Metabolic and structural changes in newly synthesized proteoglycans induced by implantation of a polyethylene sheet in the rabbit knee joint.

A sheet of polyethylene was surgically implanted in a rabbit right patello-femoral joint and changes in the structure and chemical composition of newly synthesized articular cartilage proteoglycans (PGs) were studied 1 month after surgery. The articular cartilage from implanted and sham-operated control knee joints was labeled in vitro with 3H-glycine and 35S-SO4 and then extracted with 4 M guanidinium chloride (GuHCl) solution. Labeled extracts were analyzed by dissociative CsCl gradient centrifugation and by Sepharose CL-2B column chromatography. The labeled glycosaminoglycan side chains were analyzed by Sephadex G-200 column chromatography and specific enzymatic digestions. Compared with sham-operation, the trochlear articular cartilage of operated joints incorporated more 35S-SO4 and 3H-glycine into newly synthesized PGs and proteins. It also synthesized a higher proportion of extractable, hydrodynamically large and high density 35S-PG monomers with increased proportion of molecules, able to interact with exogeneous hyaluronan (HA). The fibro-cartilagenous 'osteo-chondrophytic' spurs, compared with trochlear hyaline articular cartilages, incorporated less 35S-SO4 and 3H-glycine and synthesized less extractable high density 35S-PG monomers able to interact with exogenous HA. Their 35S-GAG side chains were more heterogeneous and segregated into three distinct peaks as shown by Sephadex G-200 column chromatography. The results of the present studies demonstrate that, in response to the implant, there was an increase in the biosynthetic capacity of chondrocytes which synthetized larger PG monomers able to interact wih HA.

Animals↗

Structural changes in membranes of large unilamellar vesicles after binding of sodium cholate.

The interaction of the bile salt cholate with unilamellar vesicles was studied. At low cholate content, equilibrium binding measurements with egg yolk lecithin membranes suggest that cholate binds to the outer vesicle leaflet. At increasing concentrations, further bile salt binding to the membrane is hampered. Before the onset of membrane solubilization, diphenylhexatriene fluorescence anisotropy decreases to a shallow minimum. It then increases to the initial value in the cholate concentration range of membrane solubilization. At still higher cholate concentrations, a drop in fluorescence anisotropy indicates the transformation of mixed disk micelles into spherical micelles. Perturbation of the vesicle membranes at molar ratios of bound cholate/lecithin exceeding 0.15 leads to a transient release of oligosaccharides from intravesicular space. The cholate concentrations required to induce the release depend on the size of the entrapped sugars. Cholesterol stabilizes the membrane, whereas, in spite of enhanced membrane order, sphingomyelin destabilizes the membrane against cholate. Freeze-fracture electron microscopy and phosphorus-31 nuclear magnetic resonance (31P NMR) also reflect a change in membrane structure at maximal cholate binding to the vesicles. In 31P NMR spectra, superimposed on the anisotropic line typically found in phospholipid bilayers, an isotropic peak was found. This signal is most probably due to the formation of smaller vesicles after addition of cholate. The results were discussed with respect to bile salt/membrane interactions in the liver cell. It is concluded that vesicular bile salt transport in the cytoplasm is unlikely and that cholate binding is restricted to the outer leaflet of the canalicular part of the plasma membrane.

1,2-Dipalmitoylphosphatidylcholine↗

Myocardial force development and structural changes associated with monocrotaline induced cardiac hypertrophy and heart failure.

In this study alterations are characterized which occur, in myocardial force development morphological appearance and protein composition, during the development of cardiac hypertrophy and heart failure in monocrotaline (MCT) treated rats. The transition from cardiac hypertrophy to heart failure was studied by comparing the results from control (CON) and two MCT groups (40 and 44 mg/kg body weight). The three experimental groups consisted of at least five animals each. Parameters studied were: body weight (measured daily), lung/body weight ratio, right ventricular wall volume and thickness, and force development in thin right ventricular trabeculae at 27 degrees C, using different extracellular calcium concentrations and pacing frequencies. MCT injection resulted in marked right ventricular hypertrophy and heart failure as evidenced by an up to 2-fold increase in lung/body weight ratio and a 1.7-fold increase in wall volume. The MCT groups showed a negative force-frequency relation and maximum force was up to 2-fold less than in the CON group. Protein analysis by means of one- and two-dimensional gel electrophoresis revealed a marked (7-fold) up-regulation of the slow myosin heavy chain isoform as well as a 4.5-fold increase in the content of the cytoskeletal protein desmin, whereas the mitochondrial protein ATP-synthase content was reduced. Hence MCT-induced cardiac hypertrophy and heart failure result in altered cellular calcium handling, depression of maximum force output, an increase in the economy of myocardial contraction and changes in cytoskeletal structure and energy supply.

Animals↗