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Intracapsular implant rupture: MR findings of incomplete shell collapse.

The objective of this study was to determine the frequency and significance of the MR findings of incomplete shell collapse for detecting implant rupture in a series of surgically removed breast prostheses. MR images of 86 breast implants in 44 patients were studied retrospectively and correlated with surgical findings at explantation. MR findings included (a) complete shell collapse (linguine sign), 21 implants; (b) incomplete shell collapse (subcapsular line sign, teardrop sign, and keyhole sign), 33 implants; (c) radial folds, 31 implants; and (d) normal, 1 implant. The subcapsular line sign was seen in 26 implants, the teardrop sign was seen in 27 implants, and the keyhole sign was seen in 23 implants. At surgery, 48 implants were found to be ruptured and 38 were intact. The MR findings of ruptured implants showed signs of incomplete collapse in 52% (n = 25), linguine sign in 44% (n = 21), and radial folds in 4% (n = 2). The linguine sign perfectly predicted implant rupture, but sensitivity was low. Findings of incomplete shell collapse improved sensitivity and negative predictive values, and the subcapsular line sign produced a significant incremental increase in predictive ability. MRI signs of incomplete shell collapse were more common than the linguine sign in ruptured implants and are significant contributors to the high sensitivity and negative predictive values of MRI for evaluating implant integrity.

Breast↗

Effect of collapse on the stability of freeze-dried recombinant factor VIII and alpha-amylase.

Recombinant Factor VIII (rFVIII) and alpha-amylase were used as model proteins to examine the effect of freeze-drying process conditions on the long-term stability of these proteins as freeze-dried solids. The same sucrose/glycine formulation was used for all treatments. Three freeze-drying protocols were used-an "aggressive" and a "conservative" cycle that both produced pharmaceutically acceptable product, and a protocol that produced a collapsed matrix. For rFVIII, there was no difference in the biological activity versus the time profile for product freeze-dried under the three different conditions when stored at 5 or 25 degrees C. At 40 degrees C, however, the stability of the collapsed product appeared to be better than that of product freeze-dried with no collapse. Also, the level of residual moisture in the collapsed product was higher than that of the product with no collapse. For alpha-amylase, there was no significant difference in the stability profile at any of the temperatures over the time course of the study. The results support the conclusion that collapse is not necessarily detrimental to the long-term stability of freeze-dried proteins.

Animals↗

Molecular dynamics simulations of hydrophobic collapse of ubiquitin.

Nine nonnative conformations of ubiquitin, generated during two different thermal denaturation trajectories, were simulated under nearly native conditions (62 degrees C). The simulations included all protein and solvent atoms explicitly, and simulation times ranged from 1-2.4 ns. The starting structures had alpha-carbon root-mean-square deviations (RMSDs) from the crystal structure of 4-12 A and radii of gyration as high as 1.3 times that of the native state. In all but one case, the protein collapsed when the temperature was lowered and sampled conformations as compact as those reached in a control simulation beginning from the crystal structure. In contrast, the protein did not collapse when simulated in a 60% methanol:water mixture. The behavior of the protein depended on the starting structure: during simulation of the most native-like starting structures (<5 A RMSD to the crystal structure) the RMSD decreased, the number of native hydrogen bonds increased, and the secondary and tertiary structure increased. Intermediate starting structures (5-10 A RMSD) collapsed to the radius of gyration of the control simulation, hydrophobic residues were preferentially buried, and the protein acquired some native contacts. However, the protein did not refold. The least native starting structures (10-12 A RMSD) did not collapse as completely as the more native-like structures; instead, they experienced large fluctuations in radius of gyration and went through cycles of expansion and collapse, with improved burial of hydrophobic residues in successive collapsed states.

Computer Simulation↗

The role of the rate of vascular collapse in ischemia-induced acute contractile failure and decreased diastolic stiffness.

We investigated the contribution of the rate of vascular collapse to the early contractile failure and decreased diastolic stiffness induced by ischemia. Isolated rat hearts (n = 8/group), perfused at 37 degrees C with blood through a roller pump and paced at 320 beats/min, were subjected to global ischemia either by switching off the roller pump (slow vascular collapse-group 1) or by reversing the direction of the roller pump for 5 s prior to switch-off (rapid vascular collapse-group 2). In group 1, residual coronary pressure declined progressively over the first 20 s of ischemia whereas in group 2 the pressure had fallen to zero within 2 s. The profile of ischemia-induced contractile failure was however, similar in both groups. Thus, after 2 s of ischemia, when residual perfusion pressure had declined by only 10% in group 1 (60.0 +/- 0.0 to 54.9 +/- 0.8 mmHg) but was virtually non-existent in group 2 (60.0 +/- 0.0 to 0.4 +/- 12.7 mmHg), left ventricular developed pressure had fallen to a similar extent in both groups (86 +/- 2% and 84 +/- 3%, respectively). Curve-fitting analysis for individual hearts showed that the profile of contractile failure was described by a double exponential process that was not significantly affected by the rapid vascular collapse. Left ventricular end-diastolic pressure in group 1 hearts progressively declined over the first 20 s of ischemia, the profile paralleling that of the dissipation of perfusion pressure. In contrast, in group 2 hearts, left ventricular end-diastolic pressure rose rapidly and leaked at 5 s, a period that coincided with the reversed direction of the perfusion pump. Similarly, in a separate study, the analysis of ventricular diastolic stiffness (n = 6/group) showed a rapid decline during the first 20 s of ischemia: this decline could be inhibited by the use of rapid vascular collapse. In additional experiments, hearts (n = 8/group) were paced at 220, 320 or 420 beats/min and ischemia was induced by reversing (5 s) and then stopping the perfusion pump. Myocardial oxygen consumption increased in parallel with heart rate and was matched by commensurate increases in the rate of contractile failure. Curve-fitting analysis showed that slow stimulation rates (220 beats/ min) significantly delayed contractile failure during the first 60 s of ischemia (first time constant = 14.5 +/- 4.1 s compared with 8.1 +/- 1.1 s at 320 beats/min and 6.3 +/- 1.1 s at 420 beats/min; P < 0.05 in both instances). In conclusion, vascular collapse associated with ischemia may contribute to the initial decrease in ventricular diastolic stiffness; however, it does not play a major role in determining the rate of acute contractile failure. Metabolic processes as reflected by oxygen consumption do however, appear to be important.

Animals↗

Pulse wave reflection at the collapsed segment of an artery in Riva-Rocci's method.

The contours of pressure and flow of a pulse wave arriving at the entrance of a collapsed segment of an elastic tube can be described by application of the basic laws of reflection. The collapsed segment acts like a valve. It is opened by the pressure of the pulse wave when the pressure within the tube becomes higher than the "collapse pressure", i.e. the pressure exerted on the segment from outside. This opening of the collapsed segment suddenly changes the sign of the pulse wave reflection from positive to negative; thus a typical contour change of the pulse proximal to the segment is observed. The most obvious effect is a reduction of the pulse pressure. The extent of this reduction is a function of the collapse pressure. A typical example of this phenomenon can be observed in an artery proximal to the segment which is collapsed due to pressure exerted by an inflated Riva-Rocci cuff. The effect is explained by the assumption that the sign of reflection changes when the pressure of the pulse wave crosses the level of the cuff pressure. This explanation is supported by the results of model experiments.

Blood Pressure Determination↗

Anterior versus posterior surgery for osteoporotic vertebral collapse with neurological deficit in the thoracolumbar spine.

Despite the increasing number of reports on surgical treatments for thoracolumbar osteoporotic vertebral collapse with neurological deficits, the choice of surgery remains controversial. In this retrospective study, we compared the outcomes of posterior and anterior surgeries for single-level osteoporotic vertebral collapse with neurological deficit in the thoracolumbar spine. Both posterior and anterior surgical approaches were performed with a consistent procedure for a single surgical indication at one institution. Twenty-four patients treated with posterior surgery and 28 patients treated with anterior surgery were followed-up over an average of 5 years after surgery. Radiographic results (kyphotic angle, bony fusion, and instrumentation failure), neurological improvement, and surgical complications were compared between the two groups. The average correction angle after surgery was larger in the posterior group than in the anterior group (P = 0.013), but not at final follow-up (P = 0.755). The average loss of correction was also higher in the posterior group than in the anterior group (P = 0.037). There was no significant difference in neurological outcomes between anterior and posterior approaches (P = 0.080). Two-way analysis of variance (ANOVA) showed that the neurological outcome was better in wedge type than in flat type vertebral collapse, regardless of the type of surgical approach (P = 0.0093). In wedge type vertebral collapse, neurological improvement tended to be greater after anterior than after posterior surgery. In four of six cases with instrumentation failure in the anterior group, a titanium cage subsided more than 5 mm but bony fusion was eventually achieved without causing neurological problems. In the posterior group, six cases experienced instrumentation failure during the postoperative course (two cases with screws loosened from pedicles and bodies, and one case with breakage of a screw neck). None of the patients developed instrumentation-related neurological problems. Two cases in each group developed pseudoarthrosis. In single-level osteoporotic vertebral collapse with neurological deficit, anterior surgery tended to improve neurological deficit in wedge type, but not in flat type collapse, compared with posterior surgery.

Aged↗

X-ray diffraction studies on cation-collapsed DNA.

The polyamines spermidine, spermine and putrescine are now known to induce tertiary collapse of DNA. In this collapsed state DNA assumes a compact toroidal conformation. However, the structural details of DNA in these compact particles and the forces that stabilize the collapsed state are not clear. We show here that the structural arrangement of DNA in this tertiary conformation is determined by the chemical structure of the agent used to collapse. We have used aliphatic triamines (NH+3--(CH2)3--NH+2--(CH2)n--NH+3 with n = 3, 4, 5 and 8) and diamines (NH+3--(CH2)x--NH+3 with x = 2, 3, 4 and 6) to collapse DNA. We find that the Bragg spacing and the calculated interhelical spacing for a hexagonal packing model vary systematically with the length of the methylene bridge. We also find that the ionic strength of the solution has no effect on the Bragg spacing. This observation suggests that the arrangement of DNA strands in the complexes is determined by the structure of the polycation, and argues against suggestions that the structure of the collapsed state is maintained by the balance of long-range electrostatic repulsive and attractive forces. Instead we propose that DNA helices form a hexagonal array with counterions in the interstices between the helices resulting in a stable three-dimensional phase with high structural order. Arguments are presented favoring such a model in terms of stabilizing and destabilizing thermodynamic forces.

Animals↗

The enrichment of a neuronal growth cone collapsing activity from embryonic chick brain.

We have devised a simple bioassay for the identification of molecules that inhibit growth cone motility. Chick dorsal root ganglion (DRG) growth cones extending on laminin collapse when exposed to a suspension of embryonic brain membranes. Detergent-solubilized membranes from which the detergent has been removed collapse DRG growth cones extending on either laminin or chick L1. Collapse occurs over a time course of minutes and is fully reversible. Solubilized liver, primary fibroblast, or RN22 schwannoma cell membranes do not collapse DRG or retinal growth cones. Solubilized PC12 membranes cause retinal but not DRG growth cones to collapse. The collapsing activity from embryonic brain is heat-labile, is trypsin-sensitive, and behaves as a macromolecule on a sizing column. It can be enriched 100-fold by chromatography on heparin and hydroxylapatite. These results are consistent with the idea that growth cone motility is inhibited by specific membrane-associated proteins in the developing nervous system.

Animals↗

New insights into vascular collapse and growth dynamics in solid tumors.

The experimentally-observed phenomenon of vascular collapse in tumors represents a significant barrier to the delivery of blood-borne therapeutic drugs, and has been attributed to the elevated tissue stresses resulting from confined proliferation of tumor cells. This paper presents a mathematical framework which describes the evolution of growth-induced stresses in tumors and gives new insights into both vascular collapse and tumor growth dynamics. The linear-elastic description of anisotropic growth adopted here provides the mechanical model with a realistic constitutive basis, incorporating both the solid and stress-relaxation characteristics of soft biological tissues. A particular distribution of spatially non-uniform growth is proposed which is considered representative of a vascular tumor. The stress distribution associated with this growth pattern predicts the onset of vascular collapse, producing the well-defined regions observed in vascular collapse experiments: a peripheral layer with open blood vessels adjacent to a region of vascular collapse, enclosing an inner region where the vessels are open. The model also highlights the roles of various tissue properties in inducing vascular collapse. Moreover, the tumor growth rates predicted by this model reflect experimental observations, with exponential growth taking place immediately following vascularization, followed by a period of exponential retardation.

Animals↗

Nerve growth factor, glial cell line-derived neurotrophic factor and neurturin prevent semaphorin 3A-mediated growth cone collapse in adult sensory neurons.

Developmentally, semaphorin 3A (sema3A) is an important chemorepellent that guides centrally projecting axons of dorsal root ganglion (DRG) neurons. Sema3A-mediated growth cone collapse can be prevented by cyclic GMP (cGMP) and nerve growth factor (NGF) in embryonic neurons. Sema3A may also play a role in directing regrowth of injured axons in adults, and interactions with neurotrophic factors near the injury site may determine the extent and targeting of both regenerative and aberrant growth. The aim of this study was to determine whether NGF, glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) modulate sema3A-mediated growth cone collapse in cultured adult rat DRG neurons. Sema3A caused a significant increase in growth cone collapse, which was completely prevented by prior treatment with NGF, GDNF or NTN. Immunocytochemical experiments showed that sema3A-sensitive neurons were heterogeneous in their expression of neurotrophic factor receptors and responses to neurotrophic factors, raising the possibility of novel, convergent signaling mechanisms between these substances. Increasing cGMP levels caused growth cone collapse, whereas sema3A-mediated collapse was prevented by inhibition of guanylate cyclase or by increasing cyclic AMP levels. In conclusion, sema3A signaling pathways in adult neurons differ to those described in embryonic neurons. Three different neurotrophic factors each completely prevent sema3A-mediated collapse, raising the possibility of novel converging signaling pathways. These studies also show that there is considerable potential for neurotrophic factors to regulate sema3A actions in the adult nervous system. This may provide insights into the mechanisms underling misdirected growth and targeting of sensory fibers within the spinal cord after injury, that is thought to contribute to development of autonomic dysreflexia and neuropathic pain.

Animals↗

Numerical simulations of the aspherical collapse of laser and acoustically generated bubbles.

The details of nonlinear axisymmetric oscillations and collapse of bubbles subject to large internal or external pressure disturbances, are studied via a boundary integral method. Weak viscous effects on the liquid side are accounted for by integrating the equations of motion across the boundary layer that is formed adjacent to the interface. Simulations of single-cavitation bubble luminescence (SCBL) and single-bubble sonoluminescence (SBSL) are performed under conditions similar to reported experimental observations, aiming at capturing the details of bubble collapse. It is shown that any small initial deviation from sphericity, modeled through a small initial elongation along the axis of symmetry, may result in the formation and impact of two counter-propagating jets during collapse of the bubble, provided the amplitude of the initial disturbance is large enough and the viscosity of the surrounding fluid is small enough. Comparison between simulations and experimental observations show that this is the case for bubbles induced via a nano-second laser pulse (SCBL) during a luminescence event. In a similar fashion, simulations show that loss of sphericity accompanied with jet formation and impact during collapse is also possible with acoustically trapped bubbles in a standing pressure wave (SBSL), due to the many afterbounces of the bubble during its collapse phase. In both cases jet impact occurs as a result of P(2) growth in the form of an afterbounce instability. When the sound amplitude is decreased or liquid viscosity is increased the intensity of the afterbounce is decreased and jet impact is suppressed. When the sound amplitude is increased jet formation is superceded by Rayleigh-Taylor instability. In the same context stable luminescence is quenched in experimental observations. In both SCBL and SBSL simulations the severity of jet impact during collapse is quite large, and its local nature quite distinct. This attests to the fact that it is an energy focusing mechanism whose importance in generating the conditions under which a luminescence event is observed should be further investigated.

Computer Simulation↗

[Lateral crural "J" flap repair to correct nasal valve collapse].

INTRODUCTION: Nasal valve collapse is a common cause of nasal airway obstruction. Although many techniques have been devised to treat this problem, the outcomes of most of them have been disappointing. The aim of this study is to report our experience using the lateral crural J-flap repair to correct the nasal valve collapse. This technique is based on a new view of the structural etiology of nasal valve collapse and it offers excellent functional and aesthetic outcomes. MATERIAL AND METHODS: We present a retrospective study of 19 patients diagnosed of nasal valve collapse that underwent lateral crural J-flap repair from 2003 to 2005. RESULTS: 28 lateral crural J-flap repairs were made. Six patients underwent concomitant nasal surgery. Mean follow-up was 428 days All the patients have reported improvement of the subjective sensation of inspiratory collapse and there has been no noticeable decrement in benefit over time. No complications due to the procedure were observed. CONCLUSION: The lateral crural J-flap repair is an efective treatment for nasal valve collapse with minimal morbidity and a high success rate.

Adult↗

Efficacy of selective intrabronchial air insufflation in acute lobar collapse.

Flexible fiberoptic bronchoscopy (FFB) to remove mucous plugs followed by selective intrabronchial air insufflation (SII) to expand the atelectatic lung was used in 17 surgical intensive care unit (SICU) patients with pulmonary lobar collapse. Thirteen patients were admitted for acute trauma, and the remainder were elderly postoperative patients. Lobar collapses occurred on SICU days 1 to 18 (mean +/- SEM: 5 +/- 1 days), and duration ranged from 4 to 258 hours (mean: 77 +/- 18 hours). Indications for FFB with SII included critical hypoxemia in 5 patients, worsening collapse in 2, and failure to respond to aggressive respiratory care in 10 (59%). FFB with SII was effective in 14 (82%) patients: 10 achieved full lung re-expansion, and 4 partial lung re-expansion. When lobar collapse was of less than 72 hours' duration, 92% (12 of 13) of patients had lungs re-expanded compared with 50% (2 of 4) whose collapse existed for more than 72 hours. The mean PaO2/FIO2 (fraction inspired oxygen) ratio was 135 +/- 18 prior to FFB with SII and increased to 205 +/- 21 after FFB with SII. Complications were minor and clinically insignificant. In conclusion, SII appears to be a simple, safe, effective adjunct to FFB in the treatment of SICU patients with pulmonary lobar collapse.

Acute Disease↗

The lateral crural J-flap repair of nasal valve collapse.

OBJECTIVES: Nasal valve collapse is a common cause of nasal airway obstruction. Although many techniques have been devised to correct both the functional and aesthetic aspects of this problem, none is uniformly successful. I propose that the true locus and solution to the problem lies lateral to the nasal valve angle in the fibroareolar tissue that connects the lateral aspect of the lateral crus to the bony pyriform aperture. Age-related or surgically induced weakening and loosening of these structurally important, fibroareolar connections result in a prolapse of the lateral aspect of the lateral crura away from the pyriform margin and toward the septum with a consequent narrowing of the nasal valve region. A new method of repair is described. METHODS: Bilateral marginal incisions are made following the curvature of the palpated caudal edge of the lower lateral cartilage starting at the dome region medially. The incision is extended laterally until the entire lateralmost aspect of the lateral crus is freed, generating a J-shaped chondrocutaneous flap that is medially and superiorly based. Following this, supraperichondrial dissection of the lateral crus is carried out, exposing the dome region and the upper lateral cartilage. The J-flap is then pulled caudally and laterally, and the excess overlapping tissue is evaluated. Two composite strips of vestibular skin and cartilage are resected: one parallel to the marginal incision and the second at the lateral edge of the J-flap. The flap is transposed and sutured into position, pulling open the nasal valve angle. RESULTS: Preliminary results are presented for 18 patients who underwent 19 lateral crural J-flap repairs of nasal valve collapse. Nine patients underwent concomitant septal, sinus, or turbinate procedures. Two patients underwent unilateral J-flap repair. One patient required revision. Eighty-nine percent of patients reported markedly improved nasal airway patency and elimination of the subjective sensation of inspiratory collapse. Mean time to follow-up was 257 days. There has thus far been no noticeable decrement in benefit over time. CONCLUSION: This new technique for the treatment of nasal valve collapse may offer a simple and effective approach to the problem of nasal valve collapse with minimal morbidity and a high rate of success. The technique is based on a new view of the structural etiology of nasal valve collapse.

Adult↗

Characteristics and outcome among patients suffering from in hospital cardiac arrest in relation to the interval between collapse and start of CPR.

AIM: To describe survival after in-hospital cardiac arrest in relation to the interval between collapse and start of cardiopulmonary resuscitation (CPR). PATIENTS: All patients suffering in-hospital cardiac arrest in Sahlgrenska University Hospital in Göteborg, Sweden between 1994 and 1999 in whom resuscitative efforts were attempted and for whom the interval between collapse and start of CPR was known. METHODS: Prospective recording of various factors at resuscitation including the interval between collapse and start of CPR. Retrospective evaluation via medical records of patients' previous history, clinical situation prior to cardiac arrest and final outcome. RESULTS: Survival to discharge was 33% among the 344 patients in whom CPR was started within the first minute as compared with 14% among the 88 patients in whom CPR started more than 1 min after collapse (P=0.008). The corresponding figures for patients found in ventricular fibrillation was 50 versus 32% (NS); for patients found in pulseless electrical activity 9 versus 3% (NS) and for patients found in asystole 19 versus 0% (NS). Correcting for dissimililarties in the previous history and factors at resuscitation, the adjusted odds ratio and 95% confidence limits for being discharged from hospital when CPR was started within 1 min compared with a later start was 3.06 with 95% confidence limits of 1.59-6.31. CONCLUSION: Among patients with in-hospital cardiac arrest in whom the interval between collapse and start of CPR was known, we found that in 80% of the cases CPR was started within the first minute after collapse. Among these patients, survival to discharge was twice that of patients in whom CPR was started later. These results highlight the importance of immediate CPR after in-hospital cardiac arrest.

Aged↗

Evaluation of debonding characteristics of a new collapsible ceramic bracket.

A new collapsible ceramic bracket designed with a metal-lined arch wire slot has been recently introduced. The bracket also incorporates a vertical slot designed to help create a consistent bracket failure mode during debonding. The new bracket is thought to combine the esthetic advantages of ceramics and the functional advantages of debonding metal brackets. The purpose of this study was to compare (1) the shear bond strength of the new collapsible bracket with a traditional ceramic bracket, (2) the compressive force required to debond the new bracket from the enamel surface with that needed to debond a traditional metal bracket, and (3) the bond failure location when debonding the new bracket and a traditional ceramic bracket when pliers are used. Sixty-one Clarity collapsible ceramic brackets, 41 Transcend 6000 brackets, and 21 Victory Series metal brackets were bonded to the teeth with the same bonding system. The Zwick Universal Test Machine was used to determine the shear bond strength of 21 teeth bonded with the new bracket and 20 teeth bonded with the Transcend brackets. The same testing device was used to determine the compression force levels needed to debond 20 collapsible brackets and 21 metal brackets. Pliers were used to debond both the new ceramic brackets and Transcend brackets to determine the mode of bond failure. After debonding, all teeth and brackets were examined under 10x magnification. Any adhesive remaining after bracket removal was assessed according to the Adhesive Remnant Index (ARI). The findings indicated that the shear bond strength of the new Clarity ceramic bracket was comparable to that of a conventional ceramic bracket. Similarly, there were no significant differences in the results of the compression tests comparing the magnitude of forces needed to deform and debond both the new ceramic and metal brackets. The ARI scores for both the shear and compression tests indicated a similar bond failure pattern when the new collapsible brackets were compared with either the conventional ceramic or metal brackets. On the other hand, the chi-square test results indicated that, when debonding pliers were used, there was a significantly greater incidence of an ARI score of 1 with the collapsible brackets. This indicated that, when debonding the new brackets with the Weingart pliers, there was a greater tendency for most of the adhesive to remain on the enamel surface. In conclusion, the main advantage of the Clarity ceramic brackets is that they can be debonded in the same manner as metal brackets. When the new ceramic brackets are debonded with the Weingart pliers, most of the residual adhesive remained on the enamel surface, a pattern that is similar to the one observed with metal brackets. The failure at the bracket-adhesive interface decreases the probability of enamel damage but necessitates the removal of more residual adhesive after debonding.

Adhesives↗

Modulation of the incidence of hamster pulmonary endocrine cell hyperplasia by unilateral collapse of the lung.

We evaluated the effects of the unilateral collapse of the left lung on the formation of pulmonary endocrine cell hyperplasia (PECH) induced by 4-nitroquinoline 1-oxide (4NQO) in Syrian golden hamsters. Ten hamsters were injected subcutaneously with 20 mg/kg body weight of 4NQO, once a week for 4 weeks and treated with injection of silicone rubber into the left thorax at the 8th experimental week. Another 30 animals were divided into three groups: treated with 4NQO only, left lung collapse only, and vehicle only. All animals were sacrificed at the 30th week. The lung tissues were embedded in paraffin; 50 serial sections were made from the tissues of each animal and were studied histologically and immunohistochemically. PECH showed a positive immunostain for calcitonin and/or serotonin. In the uncollapsed right lungs of the animals treated with both 4NQO and unilateral collapse, the mean incidence of PECH was 12.2 x 10(-2)/mm3 lung volume; the incidences of PECH in the animals treated with 4NQO only, collapse only, and vehicle only were 4.1, 3.8, and 1.4 x 10(-2)/mm3, respectively. In the collapsed left lungs, PECH did not form, regardless of 4NQO treatment. This study demonstrates that unilateral collapse of the lung modulates the incidence of PECH induced by 4NQO in hamsters.

4-Nitroquinoline-1-oxide↗

Structural basis for the self-chaperoning function of an RNA collapsed state.

Prior to folding to a native functional structure, many large RNAs form conformationally collapsed states. Formation of the near-native collapsed state for the bI5 group I intron RNA plays an obligatory role in self-chaperoning assembly with its CBP2 protein cofactor by preventing formation of stable, misassembled complexes. We show that the collapsed state is essential because CBP2 assembles indiscriminately with the bI5 RNA in any folding state to form long-lived complexes. The most stable protein interaction site in the expanded state-CBP2 complex overlaps, but is not identical to, the native site. Folding to the collapsed state circumvents two distinct misassembly events: inhibitory binding by multiple equivalents of CBP2 and formation of bridged complexes in which CBP2 straddles cognate and noncognate RNAs. Strikingly, protein-bound sites in the expanded state RNA complex are almost the inverse of native RNA-RNA and RNA-protein interactions, indicating that folding to the collapsed state significantly reduces the fraction of RNA surfaces accessible for misassembly. The self-chaperoning function for the bI5 collapsed state is likely to be conserved in other ribonucleoproteins where a protein cofactor binds tightly at a simple RNA substructure or has an RNA binding surface composed of multiple functional sites.

Base Sequence↗