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Structural changes in the heart and carotid arteries associated with hypertension in humans.

Hypertension is associated with structural changes in the vascular system and in the heart. This study has examined the relationships between carotid artery intima-media thickness and other risk factors in 52 untreated patients (20 hypertensive). Carotid intima-media thickness was measured bilaterally using a Duplex doppler ultrasonic scanner. In the hypertensive individuals the left ventricle was examined by echo-cardiography and the left ventricular mass index determined. There was a significant association between age and IMT, and both SBP and DBP and IMT. The IMT in the hypertensive group was significantly larger than in the normotensive group and in the hypertensive subjects there was a positive association between left ventricular mass index and IMT. There was no significant difference in calculated media stress between the normotensive and hypertensive groups, probably due to a small increase in carotid intima-media area combined with a small reduction in carotid lumen diameter. Hypertension is associated with a thickening of the intima-media of the carotid artery and an increase in left ventricular mass. Whether these changes in cardiac and arterial structure are in response to similar influences remains to be established.

Adolescent↗

[Structural changes in the brain in transient cerebral circulatory disorders detected in vivo by using computerized axial tomography and radioisotope cerebral scintigraphy].

Computer-aided axial tomography and radioisotopic (with 99mTc) scintigraphy of the brain were used for examining 54 patients with transient cerebral circulation disturbances, the clinical manifestations of which subsides within a period of less than 24 hours. In 28% of the patients, structural changes in the brain were revealed. The computer-aided tomography appeared to be more informative for their discovery, than the radioisotopic scintigraphy. On the basis of the data obtained the patients were divided into the following three groups: a) functional, i. e. having no lifetime structural changes in the brain detected at the moment of the examination (72% of all the patients), b) ischemic-infarctic one with a minor cerebral infarctions (13.5% of the patients), and c) hemorrhagic, with small-sized hemorrhagic foci in the brain (11.5% of the patients). The existence of the latter group should be regarded as a warning of dangers entailed by routine prevention and treatment of transient cerebral circulation disturbances with antiaggregants and anticoagulants. A new classification and terminology of the clinical symptoms caused by transient cerebral circulation disturbances are offered.

Cerebral Hemorrhage↗

Inducing rye 1R chromosome structural changes in common wheat cv. Chinese spring by the gametocidal chromosome 2C of Aegilops cylindrica.

To generate 1 R deletion and translocation lines, we introduced a 2C chromosome,which was derived from Aegilops cylindrica and was known to have a gametocidal function when added monosomically into common wheat cv. Chinese Spring (CS) and its derivative, into a wheat-rye 1R chromosome disomic addition line (CS-1R"). When the individuals with chromosome constitution 21" + 1R" + 2C' (2n = 45) were selfed, the 1R chromosome structural changes were found to be induced with high frequency (24.1%) among the progenies. By using C-banding and GISH analysis, we analyzed 1R structural changes in 46 F3 individuals, which came from 23 F2 plants. The rearranged 1R chromosomes could be characterized in about 85% of the F3 individuals. This included telosome 1RL (39.1%), iso-chromosome 1 RL (2.2%), whole arm translocation involving 1RL (32.6%), telosome 1RS (4.3%), iso-chromosome 1RS (4.3%), and 1R deletion mutant with break point in the long arm (2.2%). The mutant 1R lines obtained in this study will potentially be useful in mapping the chromosome locations of agronomically important genes located in 1R. This study also demonstrated that molecular markers might be used to identify wheat chromosome arm involved in translocation with 1R.

Chromosome Aberrations↗

Light microscopical investigations on structural changes of skeletal muscle as artifacts after postmortem stimulation.

Samples of skeletal muscle were taken from 20 human corpses where mechanical or electrical stimulation had been carried out up to 8h postmortem (hpm) in order to estimate the time since death. The stimulation had caused an idiomuscular bulge or tetanic contraction of the muscle tissue at this location. The muscle samples were examined for structural changes of the fibers by light microscopy. A comparison with control muscle samples taken contralaterally from the same corpse, showed that the findings previously interpreted as being of intravital origin, e.g. destruction of fiber integrity, invagination and contraction bands, could also be due to postmortem alterations. It is hypothesized that structural changes to the muscle fibers can, in general, be produced as long as the manifestation time is shorter than the supravital phase after the time of force impact.

Adult↗

Multiphoton polarization and generalized polarization microscopy reveal oleic-acid-induced structural changes in intercellular lipid layers of the skin.

We have demonstrated that both multiphoton polarization and generalized polarization (GP) microscopy may be combined to characterize the structural changes of intercellular lipids in skin. Both polarization and GP (at 440- and 490-nm emission) images obtained by analysis of Laurdan fluorescence suggest that the treatment of oleic acid results in a skin surface with a more random packing of lipid molecules, which allows easier water penetration. Our results show that combined polarization and GP microscopy can be used to characterize the physical and chemical changes in biological structures.

Culture Techniques↗

Dynamic structural change of the self-assembled lanthanum complex induced by lithium triflate for direct catalytic asymmetric aldol-Tishchenko reaction.

The development of a direct catalytic asymmetric aldol-Tishchenko reaction and the nature of its catalyst are described. An aldol-Tishchenko reaction of various propiophenone derivatives with aromatic aldehydes was promoted by [LaLi3(binol)3] (LLB), and reactivity and enantioselectivity were dramatically enhanced by the addition of lithium trifluoromethanesulfonate (LiOTf). First, we observed a dynamic structural change of LLB by the addition of LiOTf using 13C NMR spectroscopy, electronspray ionization mass spectrometry (ESI-MS), and cold-spray ionization mass spectrometry (CSI-MS). X-ray crystallography revealed that the structure of the newly generated self-assembled complex was a binuclear [La2Li4(binaphthoxide)5] complex 6. A reverse structural change of complex 6 to LLB by the addition of one equivalent of Li2(binol) was also confirmed by ESI-MS and experimental results. The drastic concentration effects on the direct catalytic asymmetric aldol-Tishchenko reaction suggested that the addition of LiOTf to LLB generated an active oligomeric catalyst species.

Catalysis↗

Presence of cardiovascular structural changes in essential hypertensive patients with coronary microvascular disease and effects of long-term treatment.

In asymptomatic essential hypertensive patients with angiographically normal coronary arteries and without left ventricular hypertrophy, dipyridamole-induced ischemic-like ST segment depression may be a marker of coronary microvascular disease. In this study we evaluated, first, whether this cardiac abnormality is linked to structural or functional vascular abnormalities, and second, the effect of antihypertensive treatment by 12-month administration of the angiotensin converting enzyme (ACE) inhibitor captopril (50 mg twice a day orally). In essential hypertensives with dipypridamole echocardiography stress test (DET) (DET+, n = 8) and without (DET-, n = 8) ST segment depression greater than 0.1 mV during intravenous dipyridamole infusion (0.84 mg/kg over 10 min), we studied the forearm blood flow (FBF, venous plethysmography, mL/100) modifications induced by intrabrachial acetylcholine (Ach) (0.15, 0.45, 1.5, 4.5, 15 micrograms/100 mL/min x 5 min each), an endothelium-dependent vasodilator, and by sodium nitroprusside (SNP) (1, 2, 4 micrograms/100 mL/min x 5 min each), a smooth muscle cell relaxant compound. Minimal forearm vascular resistances (MFVR), an index of arteriolar structural changes, were also calculated. Both Ach and SNP caused greater vasodilation in DET- as compared to DET+ while MFVRs were lower in DET- compared to DET+. After treatment, both DET+ and DET- patients showed a significant and similar reduction in blood pressure and left ventricular mass index, while vasodilation to acetylcholine and sodium nitroprusside was increased only in the DET+ group. In addition, forearm minimal vascular resistances were significantly reduced only in DET+ patients, who showed disappearance of dipyridamole-induced ischemic-like ST segment depression. In conclusion, these data confirm that essential hypertensive patients with microvascular coronary disease are characterized by the presence of structural changes in the forearm vascular bed. Our results also indicate that both cardiac and forearm vascular abnormalities can be reversed by antihypertensive treatment with an ACE inhibitor.

Acetylcholine↗

Efficacy of melatonin as protectant against oxidative stress and structural changes in liver tissue in pinealectomized rats.

Previous observations demonstrated that physiological levels of melatonin, the pineal secretory product, are important in protecting against oxidative stress-induced tissue damage. We investigated the effects of pinealectomy and administration of exogenous melatonin on liver tissue in rats. Pinealectomized (Px) and sham-operated (non-Px) rats were used. We evaluated structural changes, reduced glutathione (GSH) levels and malondialdehyde (MDA) levels. Rats were divided into three groups (10 rats in each group): control (non-Px), Px+vehicle and Px+melatonin (4 mg/kg given daily intraperitoneally for 10 days). Liver GSH levels were significantly lower in Px rats than in the control group. Melatonin administration significantly increased GSH levels (p < 0.05). Px caused a significant increase in MDA levels as compared with the control group and melatonin administration to Px rats significantly reduced MDA levels in the liver (p < 0.05). Sinusoidal dilatation to a varying degree developed in all Px rats. Severity of mononuclear cell infiltration and sinusoidal congestion were lower in Px+melatonin group than in the Px group. These findings suggest that a significant increase in oxidative and structural changes occur in rat livers after pinealectomy, which can be diminished by melatonin treatment.

Animals↗

Pertussis toxin induces structural changes in G alpha proteins independently of ADP-ribosylation.

Pertussis toxin catalyzes ADP-ribosylation of a family of GTP-binding proteins (G alpha proteins) involved in signal transduction. It is thought that this activity is responsible for the attenuating effects of the toxin on the actions of a number of hormones and neurotransmitters. By utilizing specific antisera for detecting on electrophoretic transfer blots (Western blots) alpha proteins that are subject to ADP-ribosylation, it was found that treatment of these proteins with pertussis toxin resulted in shifts in their electrophoretic mobility and marked enhancement of their immunoreactivity compared to untreated proteins. No changes in mobility or immunoreactivity with specific antisera were observed with beta subunits of G proteins. Both effects on alpha proteins required the same ingredients, including detergents, ATP, and sulfhydryl reducing agents, that other studies have shown are required for activation of the ADP-ribosylating activity of pertussis toxin. However, NAD+, the substrate for ADP-ribosylating activity, was not required. Moreover, inhibition of the ADP-ribosylating activity by 50 mM nicotinamide failed to block the NAD-independent effects of the toxin. These findings indicate that the toxin induces structural changes in alpha proteins independently of its ADP-ribosylating activity and raise the possibility that these structural changes are primary to ADP-ribosylation and causative of many of the biological effects of pertussis toxin.

Adenine Nucleotides↗

Structural changes in the tympanic membrane after repeated tympanostomy tube insertion.

In an animal model (rat) a polyethylene tympanostomy tube was repeatedly inserted (four periods lasting 2 weeks) into the upper rear quadrant of the right tympanic membrane (TM). The intervals between the different tubulation periods (TPs) lasted 3 weeks. The corresponding quadrant of the left TM was subjected to repeated myringotomies (four times). The structural changes in the TMs were evaluated otomicroscopically and by histological techniques 3 weeks and 3 months after the final TP. Repeated tympanostomy tube insertion caused a dramatically thickened pars tensa. The thickened areas were characterized by a scar tissue exhibiting sclerotic plaques and a dense connective tissue with bone-like formations. Occasionally, islands of keratinizing stratified squamous epithelium were noted within the thickened pars tensa as well as interrupting the epithelial lining facing the tympanic cavity. Similar structural changes occurred after myringotomy without tube insertion, but they were not so pronounced as after repeated tympanostomy tube insertion. The changes were not restricted to the manipulated quadrants, but also affected the untouched anterior quadrants. Throughout the observation period the anterior quadrants improved, while the rear quadrants remained severely affected.

Animals↗

Continuous nitric oxide inhalation reduces pulmonary arterial structural changes, right ventricular hypertrophy, and growth retardation in the hypoxic newborn rat.

Breathing low oxygen levels for several weeks produces progressive pulmonary artery hypertension and smooth muscle hypertrophy and hyperplasia in many species. Because nitric oxide (NO) is an important regulator of pulmonary vascular tone, we examined whether the continuous inhalation of low levels of NO gas would attenuate pulmonary arterial structural changes in hypoxic rat pups. Nine-day-old rat pups and their mothers continuously breathed at FIO2 0.21 or 0.10 with or without adding 20 ppm (by volume) NO for 2 weeks. Lung tissue was obtained for vascular morphometric analysis, and the hearts were dissected to measure right ventricular weight and levels of mRNA encoding rat atrial natriuretic factor (rANF). In addition, femur and skull length were radiographically determined. Breathing at FIO2 0.10 for 14 days increased pulmonary arterial wall thickness and the proportion of muscular arteries in the lung periphery. Right ventricular weight and right ventricular rANF gene expression increased, whereas body weight and skeletal growth were reduced (all P < .05). Continuous inhalation of 20 ppm NO at FIO2 0.10 for 2 weeks decreased hypoxic pulmonary vascular structural changes and somatic growth retardation and prevented the increase of right ventricular weight and right ventricular rANF mRNA levels. These observations suggest that chronically breathing NO attenuates pulmonary vascular smooth muscle hypertrophy and/or hyperplasia and extension into distal arterial walls, right ventricular hypertrophy, and growth retardation of newborns breathing at a low oxygen level.

Administration, Inhalation↗

Transient versus persistent functional and structural changes associated with facilitation of Aplysia sensorimotor synapses are second messenger dependent.

Increases in activity of both protein kinase A (PKA) and protein kinase C (PKC) contribute to short-term facilitation of Aplysia sensorimotor synapses evoked by serotonin (5-HT). We report here that increasing levels of cAMP in sensory neurons evokes increases in both synaptic efficacy and in the number of sensory neuron varicosities contacting the major axons of motor cell L7 at intermediate times (3 hr) that persist for 24 hr. Treatment with phorbol esters results in a large transient increase in synaptic efficacy that is accompanied by a large transient increase in the number of sensory neuron varicosities with the newest varicosities most susceptible to elimination. The reversal of the synaptic facilitation and the structural changes does not appear to be the result of long-term inhibitory actions of persistent PKC activation by phorbol esters, since changes in synaptic efficacy can be evoked by additional applications of either phorbol esters or 5-HT. The short-lived changes in structure evoked by phorbol esters occur in preexisting sensory neurites and not by new growth, since increases in PKC activity with phorbol esters lead to reductions in neurite extension and to retractions by sensory neuron growth cones. The action of phorbol esters on growth cone extension is reversible with washout. The results suggest that increases in PKA and PKC activities by 5-HT contribute to short (minutes) and intermediate (hours) forms of facilitation of sensorimotor synapses while increases in PKA activity also mediate long-term (days) maintenance of synaptic facilitation.

Animals↗

Effect of structural change in viologen acceptors on the rate of single electron transfer from tributylphosphine.

The "flexible" 3 and "rigid" cyclic viologens 4, diquarternary salts of 2,2'-bipyridine and 1,10-phenanthroline, respectively, were treated with tributylphosphine (1) in acetonitrile containing a large amount of methanol under an argon atmosphere. A single electron transfer (SET) easily occurred from the latter to the former, the SET to 4 being 10(5)-10(6) times faster than the SET to 3. The reorganization energy lambda for the latter SET is thought to be larger than that for the former SET, because 3 undergoes a structural change upon the one-electron reduction to its radical cation, whereas the one-electron reduction of 4 takes place without a structural change. Taking into account the difference in lambda, and also taking into account the bond formation energy brought about by the follow-up reaction of the phosphine radical cation 1*(+) with methanol, the observed kinetics were well interpreted in terms of the Marcus theory.

Journal Article↗

Regression of cardiovascular structural changes--a preventive strategy.

Left ventricular hypertrophy is an independent "risk factor" for all kinds of cardiovascular disease. Structural vascular changes are of importance for the maintenance and progression of high blood pressure. To try to achieve regression of these structural changes seems a logical option as part of a preventive strategy in hypertension. The effect of antihypertensive therapy on structural cardiovascular changes in animal models and man is reviewed. A prolonged normalization of blood pressure without reflexogenic activation of trophic factors, if possible started early in the development of hypertension seems to be the optimal therapy to attain regression. There are some data indicating that regression of cardiac hypertrophy can improve cardiac function and reduce arrhythmias and furthermore that regression of structural vascular changes can positively affect the progression of hypertension. Although these preliminary result look promising there are still no data on how regression induced by antihypertensive therapy affects the mortality and morbidity associated with left ventricular hypertrophy.

Animals↗

[Structural changes in the microcirculatory bed and perivascular connective tissue in the myocardium during experimental hypercholesterolemia].

Light and electron microscopy were used in rabbits to study the effect of hypercholesterolemia (HC) on the microcirculatory bed (MCB), perivascular connective tissue and specialized cells of the myocardium. Within the first hours (1, 3, 6, 15, 24, 48 h) after cholesterol single administration to the animals, there were structural changes in the MCB, aggregation and superficial changes in red blood cells (echinocytes), stases, the presence of unusual ultrastructures in elastic membranes (EM) of the arterioles, in the amorphous substance of perivascular connective tissue, specifically near the venules, and focal dystrophy in cardiomyocytes. The ultrastructures detected in the EM of the arterioles and perivascular tissue seem likely to be the complexes of atherogenous lipoproteins and glycosaminoglycans. The transfer of the animals on the atherogenous diet entailed the reconstruction of small arteries of the myocardium and formation in them of so-called "Conti's pillows" as well as lipid deposition. A complex of structural changes revealed in the myocardium in the early stages of HC indicates the increased permeability of the microvessels, alterations in the blood rheological properties and circulatory disorders. A relationship was found between the intensity of the changes cited and blood cholesterol level. Injury to the MCB of an organ is likely to play an initial part in the mechanisms of atherogenesis.

Animals↗

A structural change in the Neurospora plasma membrane [H+]ATPase induced by N-ethylmaleimide.

The reaction of N-ethylmaleimide (NEM) with Cys-532 of the Neurospora plasma membrane [H+]ATPase results in inhibition of ATP hydrolysis which is protected by MgADP (Pardo, J. P., and Slayman, C. W. (1989) J. Biol. Chem. 264, 9373-9379). To examine the conformational state of the ATPase upon NEM modification, we have used limited trypsinolysis and domain-specific antibodies. The NEM-reacted ATPase shows increased sensitivity to trypsin, particularly in the central hydrophilic region of the polypeptide thought to contain the ATP binding and phosphorylation sites. In addition, competitive enzyme-linked immunosorbent assays indicate that the C-terminal domain of the ATPase becomes more accessible to antibody binding while the N-terminal region becomes more protected. The NEM-induced structural change is accompanied by loss of the ability to form a phosphoenzyme intermediate. The change in tertiary conformation occurs specifically upon NEM reaction with Cys-532 since neither NEM modification of Cys-545 nor fluorescein 5'-isothiocyanate modification of Lys-474 alters the tryptic digestion pattern of the ATPase. Furthermore, modification of Cys-532 with the less bulky sulfhydryl reagent methyl methanethiosulfonate does not result in a detectable structural change or loss of enzymatic activity. Thus, the introduction of a relatively bulky maleimide group at Cys-532 has specific and far-reaching effects upon the structure and function of the ATPase.

Adenosine Triphosphate↗

Three-dimensional structural changes in living hippocampal neurons imaged using magnetic AC mode atomic force microscopy.

We developed the magnetic AC (MAC) mode atomic force microscopy (AFM) to image the 3D ultrastructure of living hippocampal neurons under physiological conditions. Initially, the soma, the dendrites and the growth cones of hippocampal neurons were imaged. The imaging force was adjusted to a small value for the long-term observation. The neural spines were damaged when the tip produced a large force; the spines regenerated after the force was reduced. Subsequently, we explored the relationship between structural changes in hippocampal neurons and Alzheimer's disease by employing the new imaging technique. Time-lapse image acquisition (10 min intervals) showed that the growth cone collapsed after the addition amyloid peptide fragment beta(25-35), which is thought to initiate Alzheimer's disease. In addition, we found substantial changes in mechanical properties and in the volume of individual growth cone. This study suggested that MAC mode AFM may be a powerful tool for observing long-term structural changes in living neural cells under physiological conditions.

Amyloid beta-Peptides↗

FINE STRUCTURAL CHANGES IN THE INTESTINAL EPITHELIUM OF THE BULLFROG DURING METAMORPHOSIS.

The fine structural changes occurring in the columnar absorbing cells of the intestinal epithelium during metamorphosis of the bullfrog, Rana catesbeiana, have been examined by phase contrast and electron microscopy. Tissue samples taken just posterior to the entrance of the hepatopancreatic duct were fixed in veronal acetate-buffered osmium tetroxide and embedded in methacrylate. Under the action of the metamorphic stimulus (thyroid hormone), specific and characteristic responses were given by differentiated larval cells and undifferentiated basal cells within the same epithelium. The functional larval cells underwent degenerative changes and were retained for a time within the metamorphosing epithelium. Dense bodies appeared and increased in number in association with the loss of normal cell structure. Because of their morphology and time of formation, these bodies have been tentatively identified as lysosomes. Early in metamorphosis the basal cells did not change, but they subsequently proliferated to form a new cell layer beneath the remaining degenerating cells that lined the lumen. After the dying cells were sloughed into the gut, the new epithelium differentiated to form the adult tissue. The columnar epithelial cells of the mature animal differed in their fine structural organization from their larval precursors. Therefore, their adult configuration was molded by the action of the metamorphic stimulus.

Animals↗