Membrane Retraction Research Articles

Cytoplasm dynamics and cell motion: two-phase flow models

The motion of amoeboid cells is characterized by cytoplasmic streaming and by membrane protrusions and retractions which occur even in the absence of interactions with a substratum. Cell translocation requires, in addition, a transmission mechanism wherein the power produced by the cytoplasmic engine is applied to the substratum in a highly controlled fashion through specific adhesion proteins. Here we present a simple mechano-chemical model that tries to capture the physical essence of these complex biomolecular processes. Our model is based on the continuum equations for a viscous and reactive two-phase fluid model with moving boundaries, and on force balance equations that average the stochastic interactions between actin polymers and membrane proteins. In this paper we present a new derivation and analysis of these equations based on minimization of a power functional. This derivation also leads to a clear formulation and classification of the kinds of boundary conditions that should be specified at free surfaces and at the sites of interaction of the cell and the substratum. Numerical simulations of a one-dimensional lamella reveal that even this extremely simplified model is capable of producing several typical features of cell motility. These include periodic `ruffle' formation, protrusion–retraction cycles, centripetal flow and cell-substratum traction forces.

Deconstructing (and reconstructing) cell migration.

An overriding objective in cell biology is to be able to relate properties of particular molecular components to cell behavioral functions and even physiology. In the "traditional" mode of molecular cell biology, this objective has been tackled on a molecule-by-molecule basis, and in the "future" mode sometimes termed "functional genomics," it might be attacked in a high-throughput, parallel manner. Regardless of the manner of approach, the relationship between molecular-level properties and cell-level function is exceedingly difficult to elucidate because of the large number of relevant components involved, their high degree of interconnectedness, and the inescapable fact that they operate as physico-chemical entities-according to the laws of kinetics and mechanics-in space and time within the cell. Cell migration is a prominent representative example of such a cell behavioral function that requires increased understanding for both scientific and technological advance. This article presents a framework, derived from an engineering perspective regarding complex systems, intended to aid in developing improved understanding of how properties of molecular components influence the function of cell migration. That is, cell population migration behavior can be deconstructed as follows: first in terms of a mathematical model comprising cell population parameters (random motility, chemotaxis/haptotaxis, and chemokinesis/haptokinesis coefficients), which in turn depend on characteristics of individual cell paths that can be analyzed in terms of a mathematical model comprising individual cell parameters (translocation speed, directional persistence time, chemotactic/haptotactic index), which in turn depend on cell-level physical processes underlying motility (membrane extension and retraction, cell/substratum adhesion, cell contractile force, front-vs.-rear asymmetry), which in turn depend on molecular-level properties of the plethora of components involved in governance and regulation of these processes. Hence, the influence of any molecular component on cell population migration can be understood by reconstructing these relationships from the molecular level to the physical process level to the individual cell path level to the cell population distribution level. This approach requires combining experimental, theoretical, and computational methodologies from molecular biology, biochemistry, biophysics, and bioengineering.

Prospective study of tympanic membrane retraction, hearing loss and middle ear function

Prospective study of tympanic membrane retraction, hearing loss and middle ear function

Prospective Study of Tympanic Membrane Retraction, Hearing Loss and Middle Ear Function

Prospective Study of Tympanic Membrane Retraction, Hearing Loss and Middle Ear Function

Shrapnell Membrane and Mastoid Pneumatization

To assess whether a correlation exists between the degree of pars flaccida (PF) retraction and the degree of mastoid pneumatization. The degree of PF retraction was defined by means of an operating microscope and a pneumatic otoscope. Degree of mastoid pneumatization was assessed planimetrically, using mastoid x-rays. Private otologic clinic. A total of 595 ears, with intact pars tensa, of 332 adult patients. The degree of PF retraction was found to be inversely correlated to the level of mastoid pneumatization. Poorly pneumatized mastoids were associated with PF retractions. The poorer the pneumatization, the deeper the retraction. Well-pneumatized mastoids were associated with normal position of the PF. This study lends further support to the possibility that the mastoid pneumatic system functions as a middle ear pressure buffer. This possibility gives further explanation as to why ears with poorly pneumatized mastoids tend to develop tympanic membrane retractions and perforations, incus necrosis, or retraction pocket cholesteatoma, while ears with a large pneumatic system are rarely at such risk.

Treatment of tympanic membrane retraction with the holmium laser

Politzerization, the Valsalva maneuver, and ventilation tube insertion are available treatments for tympanic membrane retraction. Ventilation of the middle ear cavity can correct tympanic membrane retraction in many cases, but not in all. Retraction may be localized or diffuse. This article describes experiments performed to evaluate a new method to "tighten" retracted or flaccid tympanic membranes with a holmium laser in a human temporal bone model. Ten temporal bones with mild-to-moderate retraction of the posterior superior quadrant or pars flaccida were treated with a series of laser pulses around and to the area of retraction. Umbo displacement before and after laser treatment was performed with a laser Doppler vibrometer to evaluate the effect on the acoustic function of the tympanic membrane. In all ears, the posterior superior quadrant retraction appeared to be completely corrected. Laser treatment of the posterior superior quadrant retraction produced improvement in umbo displacement below 1.0 kHz. After treatment of pars flaccida retraction, the configuration was improved a small amount; however, no increase in umbo displacement was found. (OTOLARYNGOL HEAD NECK SURG 1995;112:512-9.)

Treatment of tympanic membrane retraction with the holmium laser.

Politzerization, the Valsalva maneuver, and ventilation tube insertion are available treatments for tympanic membrane retraction. Ventilation of the middle ear cavity can correct tympanic membrane retraction in many cases, but not in all. Retraction may be localized or diffuse. This article describes experiments performed to evaluate a new method to "tighten" retracted or flaccid tympanic membranes with a holmium laser in a human temporal bone model. Ten temporal bones with mild-to-moderate retraction of the posterior superior quadrant or pars flaccida were treated with a series of laser pulses around and to the area of retraction. Umbo displacement before and after laser treatment was performed with a laser Doppler vibrometer to evaluate the effect on the acoustic function of the tympanic membrane. In all ears, the posterior superior quadrant retraction appeared to be completely corrected. Laser treatment of the posterior superior quadrant retraction produced improvement in umbo displacement below 1.0 kHz. After treatment of pars flaccida retraction, the configuration was improved a small amount; however, no increase in umbo displacement was found.

Cyclic remodelling of growth cone lamellae and the effect of target tissue

We report the existence of cyclical fluctuations in the total size of growth cone lamellae, represented by membrane protrusions and retractions, and show that aspects of this behavior can be regulated by the target tissue for the nerve fibers. The transition of the growth cone from a high to a less motile state, which occurs in the presence of the target tissue, has implications for the mechanisms that underlie nerve fiber elongation during development.

Comparison of polydioxanone and silicone plastic in the prevention of adhesive otitis media in the Mongolian gerbil

Adhesion of the tympanic membrane to the promontory may occur in chronic otitis media or in the postoperative ear. Silicone plastic sheets are commonly used to form a physical barrier to adhesion. These sheets are generally well tolerated, but they are subject to occasional extrusion, encapsulation, or foreign body reaction. The ideal barrier to adhesion formation would be a nonreactive, flexible, absorbable substance that would obviate long-term toxicity considerations. In this study polydioxanone sheets were compared with silicone plastic sheets in the middle ear of the Mongolian gerbil. The eustachian tube was cauterized to create severe tympanic membrane retraction. A fabricated sheet of polydioxanone was implanted in the middle ear of 30 Mongolian gerbils and compared with silicone plastic sheets implanted in another group of 30 animals. A sham operation was performed on the other ear to serve as a surgical control. Evaluation of the temporal bones at 5, 10, and 15 weeks showed no significant differences in the rate of adhesion formation, effusion formation, or polymorphonuclear infiltration by the Fisher exact test. There was histologic evidence that polydioxanone was still providing an effective barrier at 10 weeks. The results of this study demonstrate that polydioxanone sheets are as effective and as well tolerated as silicone plastic sheets in an animal model. Further study of polydioxanone in this role is warranted. (OTOLARYNGOL HEAD NECK SURG 1995;112:303-7.)

Inhibition of Listeria locomotion by mosquito oostatic factor, a natural oligoproline peptide uncoupler of profilin action

Mosquito oostatic factor, a naturally occurring decapeptide (YDPAPPPPPP), strikingly resembles the primary structure of oligoproline-rich regions within the protein ActA, a bacterial surface protein required for Listeria motility in host cells. When microinjected into Listeria-infected PtK2 cells, the insect oostatic factor rapidly blocks Listeria-induced actin rocket tail assembly as well as intracellular locomotion of this pathogen. At intracellular concentrations of about 90 nM, transient inhibition of rocket tail formation and bacterial locomotion occurs, followed by full recovery of tail length and motility. However, at 0.9 microM oostatic factor, both processes are permanently arrested. Introduction of oostatic factor by microinjection also causes PtK2 peripheral membrane retraction in both Listeria-infected and uninfected cells. Epifluorescence microscopy with bodipy-phallacidin reveals that cells microinjected with the insect factor lose all actin stress fibers and accumulate F-actin in regions of membrane retraction. When the insect peptide is combined with profilin as an equimolar binary solution (1 microM [final concentration] each), intracellular addition fails to inhibit Listeria rocket-tail formation, fails to block intracellular bacterial movement, and no longer causes marked membrane retraction. The ability of profilin to neutralize the inhibitory action of oostatic factor is consistent with complex formation, and this finding suggests that profilin may interact directly with ActA peptide as well as a host cell peripheral membrane component to promote actin filament assembly by locally generating ATP-actin. Dispersal of profilin from such sites by oligoproline-rich peptide inhibitors suggests that profilin is directly involved in intracellular pathogen locomotion and reorganization of actin cytoskeleton of the host cell peripheral membrane.

Arrest of Listeria movement in host cells by a bacterial ActA analogue: implications for actin-based motility.

Upon entering the host cell's cytoplasm, the pathogen Listeria monocytogenes can subvert the normal contractile system of the host cell; subsequent assembly of polar actin-filament structures is likely to provide the force for rapid intracellular bacterial movement and its cell-to-cell spread. We have now investigated the functional consequences of microinjecting Listeria-infected PtK2 cells with a synthetic peptide, CFEFPPPPTDE. This peptide represents one of four related oligoproline stretches in ActA, a bacterial surface protein necessary for Listeria-induced actin assembly. Over an estimated intracellular concentration range of 80 nM to 0.8 microM, this analogue rapidly blocks the formation of the actin-filament tails and arrests intracellular bacterial motility. Over the same time scale and concentration range, introduction of the ActA analogue also causes host cell membrane retraction. Bodipyphallacidin staining reveals that microinjection of the ActA analogue results in massive retraction of the actin cytoskeleton. Microinjection of 1-20 microM poly(L-proline) (intracellular concentration) fails to block Listeria intracellular movement or polar actin-filament assembly. As observed with ActA, however, poly(L-proline) does cause membrane retraction. Our findings demonstrate the efficacy of low molecular weight peptides in efforts to distinguish mechanistic features in Listeria motility and PtK2 host cell membrane reorganization. These observations also suggest that a cytoskeletal component sensitive to specific oligoproline peptides may participate in protein-protein interactions essential for both of these actin-associated processes.

鼓膜の異常陥凹と耳管障害

Tympanic membrane retraction is one of the important sequelae of otitis media with effusion (OME). In this study, the mechanism of atelectasis of the eardrums was investigated from the point of view of eustachian tube dysfunction.One hundred and six ears with refractory OME which were not cured by the age of 10 were examined, because many refractory OME cases exhibit various types of tubal dysfunction, including stenosis and excessive patency.When the relationship between passive tubal function and retraction of the eardrum was examined, the incidence of retraction was found to be significantly higher in ears with low opening pressure of the eustachian tube. Twenty five ears with tubal closing failure, evaluated by the sniffing test, showed a significantly higher incidence of tympanic membrane retraction than did those without evidence of closing failure.These results suggest that retraction of the eardrum is closely related to excessive patency or closing failure of the eustachian tube.

Advanced Cervical Dilatation: The Role of Cervical Cerclage

The patient who presents with advanced cervical dilatation and herniating membranes without clear signs of preterm labor prior to the time of fetal viability represents an obstetric dilemma. Nonintervention can be expected to result in inevitable preterm delivery and 20% fetal survival. This study represents the use of a McDonald cerclage in patients with advanced dilatation and herniation of membranes. The study population comprised 14 singleton pregnancies between 17 and 25 weeks gestation at 4 cm dilatation or greater. The operative technique included Foley catheter membrane retraction and McDonald cerclage with 5 mm mersilene tape. Results: The cervix was successfully closed in 13/14 patients (93%). Perioperative complication rate was 21%. Ten of 13 patients in whom the cerclage was successfully placed were delivered of healthy neonates who are alive and well (fetal survival rate 77%). The average duration of pregnancy after successful cerclage placement was 9.3 weeks (range 2 days-17 weeks). Conclusi...

Treatment of tympanic membrane retraction pockets by excision. A prospective study.

The treatment of tympanic membrane retraction pockets by simple excision is described in 66 ears in 50 patients. After one operation 65 per cent of the retraction pockets were successfully treated (mean follow up 14.1 months). Persisting perforations occurred in five patients after one excision. Retrotympanic cholesteatoma was found in one patient, after two retraction pocket excision operations. The number of myringotomies with grommet insertion and the presence of bilateral disease does not predict the outcome of the procedure. Simple excision should be considered in the first instance, rather than reinforcement tympanoplasty using temporalis fascia or cartilage graft, in the treatment of tympanic membrane retraction pockets.

Composite autograft for tympanoplasty and tympanomastoid surgery

In 1982, 40 composite cartilage perichondrial autografts performed to prevent recurrent cholesteatoma secondary to canal wall defects were reviewed. A follow-up of those cases, plus 62 new cases, as well as the composite autografts for severe tympanic membrane retractions (55 cases) and selected tympanoplasties (22 cases) is presented. No recurrent cholesteatomas or retraction pockets developed at the graft sites, with one graft failure in the latter group.

Pathology and pathogenesis of tympanic membrane retraction

Temporal bones without evidence of otitis media, as well as temporal bones with various types of otitis media, were examined for the presence of retractions of the tympanic membrane and their related histopathologic progression to the formation of cholesteatoma. Retractions were not present in non-otitis media, purulent, or mucoid otitis media. Retractions were observed in 2.1% of temporal bones with serous otitis media and 19.5% of temporal bones with chronic otitis media. All temporal bones with retractions demonstrated evidence of current or previous otitis media. Histopathologic changes of the middle ear cleft were associated with the type and degree of retraction. This study supports the continuum theory according to which otitis media with effusion eventually leads to a variety of sequelae and/or to chronic otitis media. The tympanic membrane appears to follow progressive changes, from simple retraction to retraction pockets and finally to cholesteatoma.

Grommets and cholesteatoma in children.

Cholesteatoma in children may be a sequel to chronic exudative otitis media with tympanic membrane retraction but the role of grommets in the possible facilitation of squamous epithelial invasion into the middle ear is not yet clear. A retrospective study was made of the history and prior treatment in 25 children who underwent mastoidectomy for cholesteatoma at St. Mary's Hospital between 1975 and 1986. Thirteen patients had undergone previous middle ear aeration procedures which included myringotomy, cortical mastoidectomy and grommets. There was no difference in the site or severity of cholesteatoma in the operated and non-operated cases. Of the seven patients with a history of multiple grommets three had primarily attic, and three had primarily mesotympanic disease. The latter had greater ossicular erosion. One patient with an intact tympanic membrane had grommet insertion subsequently developed a cholesteatoma. While cholesteatoma due directly to the presence of grommets is rare, it appears that children who require multiple grommet insertions constitute a high risk group and should be very closely monitored.

Tympanometry.

The basic principles essential for interpreting two-component, multiple frequency tympanograms first are reviewed. These principles then are applied to an analysis of tympanometric shape (conductance, susceptance, and admittance tympanograms) as a function of probe frequency in subjects with normal middle ear transmission systems. The final section presents tympanometric data from patients with confirmed middle ear pathologies that produce an increase in resonant frequency (e.g., middle ear effusion, otosclerosis, ossicular adhesions, and tympanic membrane retraction) or a decrease in resonant frequency (e.g., otitis externa, serous otitis media, tympanic membrane pathology, and ossicular discontinuity). The advantages and disadvantages of a particular probe frequency and/or admittance component are illustrated with individual cases. The cases further demonstrate that the same tympanometric pattern can be recorded from ears with different pathologies (e.g., tympanic membrane perforation with cholesteatoma, tympanic membrane retraction, ossicular adhesions, and middle ear effusion), and conversely, that the same pathology can result in different tympanometric shapes (e.g., tympanic membrane perforation, middle ear effusion, and otosclerosis). Caution, therefore, must be exercised in ascribing a tympanometric abnormality to a specific middle ear lesion.

Model of Epithelial Downgrowth

We present a cat model of prolific epithelial downgrowth reviewing the scanning and transmission electron microscopy data. The cat model of posterior corneal epithelialization closely mimics the human clinical condition in the following areas: uneven epithelial spread over the endothelial surface on scanning electron microscopy, prominence of intercellular desmosomes and hemidesmosomes, and attachment of the latter to a basement membrane overlying a newly formed posterior collagenous layer. Cell layering is attenuated during the centripetal spread of cells down the center of the cornea. Adjacent endothelial cells show signs of cytotoxicity by increased microvilli and eventual plasma membrane retraction. Endothelial cells are covered by the advancing epithelium with subsequent endothelial cell death. The density of subepithelial collagen attachments would suggest that removal of Descemet's membrane would be required to guarantee total epithelial cell removal.

High-resolution computed tomography of the middle ear and mastoid. Part II: Tubotympanic disease.

Of more than 200 patients who underwent high-resolution computed tomography (CT) of the middle ear, the vast majority had tubotympanic disease in one of its forms: middle ear effusion, tympanosclerosis, granulation tissue, tympanic membrane retractions, or acquired cholesteatoma. The CT appearance of each of these conditions is discussed and illustrated. Emphasis is placed on the differential diagnosis of tubotympanic disease by determining dependent from nondependent soft-tissue opacity using two CT projections.