The elasticity of motor-microtubule bundles and shape of the mitotic spindle.

In the process of cell division, chromosomes are segregated by mitotic spindles -- bipolar microtubule arrays that have a characteristic fusiform shape. Mitotic spindle function is based on motor-generated forces of hundreds of piconewtons. These forces have to deform the spindle, yet the role of microtubule elastic deformations in the spindle remains unclear. Here we solve equations of elasticity theory for spindle microtubules, compare the solutions with shapes of early Drosophila embryo spindles and discuss the biophysical and cell biological implications of this analysis. The model suggests that microtubule bundles in the spindle behave like effective compressed springs with stiffness of the order of tens of piconewtons per micron, that microtubule elasticity limits the motors' power, and that clamping and cross-linking of microtubules are needed to transduce the motors' forces in the spindle. Some data are hard to reconcile with the model predictions, suggesting that cytoskeletal structures laterally reinforce the spindle and/or that rapid microtubule turnover relieves the elastic stresses.

Stability of localized solutions in a subcritically unstable pattern-forming system under a global delayed control.

The formation of spatially localized patterns in a system with subcritical instability under feedback control with delay is investigated within the framework of globally controlled Ginzburg-Landau equation. It is shown that feedback control can stabilize spatially localized solutions. With the increase of delay, these solutions undergo oscillatory instability that, for large enough control strength, results in the formation of localized oscillating pulses. With further increase of the delay the solution blows up.

Functional analysis of conserved cysteine residues in the catalytic subunit of the yeast vacuolar H(+)-ATPase.

The A subunit of the yeast vacuolar ATPase contains three highly conserved cysteines: Cys-261, Cys-284, and Cys-538. Cys-261 is located within the nucleotide-binding P-loop. Each of the conserved cysteines, and one nonconserved cysteine, Cys-254, were altered to serine by site-directed mutagenesis, and the effects on growth at pH 7.5 were determined. The Cys-254-->Ser, Cys-261-->Ser and the double mutants all grew at pH 7.5 and contained nitrate- and bafilomycin-sensitive ATPase activity. However, the ATPase activities of the Cys-261-->Ser and the double mutants were insensitive to the sulfhydryl group inhibitor, N-ethylmaleimide, demonstrating that Cys-261 is the site of inhibition by N-ethylmaleimide. Changing either Cys-284 or Cys-538 to serine prevented growth at pH 7.5. Cys-284 and Cys-538 thus appear to be essential cysteine residues which are required either for assembly or catalysis.

Nonlinear rupture of thin liquid films on solid surfaces.

In this letter we investigate the rupture instability of thin liquid films by means of a bifurcation analysis in the vicinity of the short-scale instability threshold. The rupture time estimate obtained in closed form as a function of the relevant dimensionless groups is in striking agreement with the results of the numerical simulations of the original nonlinear evolution equations. This suggests that the weakly nonlinear theory adequately captures the underlying physics of the instability. When antagonistic (attractive/repulsive) molecular forces are considered, nonlinear saturation of the instability becomes possible. We show that the stability boundaries are determined by the van der Waals potential alone.

MULTISCALE TWO-DIMENSIONAL MODELING OF A MOTILE SIMPLE-SHAPED CELL.

Cell crawling is an important biological phenomenon underlying coordinated cell movement in morphogenesis, cancer, and wound healing. In recent decades the process of cell crawling has been experimentally and theoretically dissected into further subprocesses: protrusion of the cell at its leading edge, retraction of the cell body, and graded adhesion. A number of one-dimensional (1-D) models explain successfully a proximal-distal organization and movement of the motile cell. However, more adequate two-dimensional (2-D) models are lacking. We propose a multiscale 2-D computational model of the lamellipodium (motile appendage) of a simply shaped, rapidly crawling fish keratocyte cell. We couple submodels of (i) protrusion and adhesion at the leading edge, (ii) the elastic 2-D lamellipodial actin network, (iii) the actin-myosin contractile bundle at the rear edge, and (iv) the convection-reaction-diffusion actin transport on the free boundary lamellipodial domain. We simulate the combined model numerically using a finite element approach. The simulations reproduce observed cell shapes, forces, and movements and explain some experimental results on perturbations of the actin machinery. This novel 2-D model of the crawling cell makes testable predictions and posits questions to be answered by future modeling.

Organicity in child psychiatry. Signs, symptoms, and syndromes.

The diagnosis of organicity in child psychiatry requires a high index of suspicion. For the beginning clinician, the idea that there are specific signs and symptoms associated with organicity has a certain appeal. However, a careful review of the literature reveals that except for a few instances, there are no specific signs, symptoms, or syndromes of organicity. Children with organic brain damage tend to exhibit the whole range of behavioral symptoms. The diagnosis of organicity can be supported with a thorough medical and psychiatric examination. The use of psychological testing to diagnose brain damage is unwise. Psychological tests can best be used as guides for the detection of associated learning problems and for the evaluation of outcome. The development of new laboratory techniques such as computerized EEGs and brain imaging seem promising aides for the future, but their exact role has not yet been established. There is suggestive evidence that children with organic brain disorders are more susceptible to environmental stresses, family disharmony, and toxicity from psychotropic medications. The attitude that the problems of the brain damaged child are fixed and untreatable seem unjustified. Psychotherapeutic and psychopharmacologic techniques are being developed to help the brain-damaged child and its family to cope with their handicaps.

Cardiac hypertrophy secondary to status epilepticus in the rat.

Status epilepticus was induced in rats by sequential injections of lithium and pilocarpine. Seizure activity was aborted by a combination of MK-801 and diazepam, with status duration ranging from 3 to 180 min. When the hearts were examined 8-12 days later, rats that had experienced an episode of status epilepticus had significantly heavier hearts than did controls. The nature of the cardiac tissue changes was not examined, and deserves further study.

Endothelial cell loss and corneal thickness after intracapsular extraction and iris clip lens implantation: a randomised controlled trial (interim report).

Patients in a randomised controlled trial were chosen either to have iris clip lens implantation after intracapsular cataract extraction or intracapsular extraction only. They were assessed in terms of corneal thickness, postoperative epithelial oedema, and endothelial cell counts. All patients had 1 eye submitted to operation, which was carried out by the same surgeon. There was significantly greater increase in corneal thickness (P less than 0.05) on the 5th postoperative day in eyes which had lens implants (23 patients with intracapsular extraction and 19 with implant), but the difference between the 2 groups became insignificant at 1 month (17 patients in each group). Daily corneal thickness measurements and observations of epithelial oedema in a subgroup (20 patients divided equally into 2 groups) showed that postoperatively there was greater and more widespread corneal oedema after implant surgery. When the operated eye was compared with the unoperated eye, endothelial cell loss was significantly greater in those with implants (P less than 0.01) than in those with simple intracapsular extraction.

Pathologic analysis of routine tonsillectomy and adenoidectomy specimens.

OBJECTIVES: Recent literature has suggested that histopathologic analysis of routine tonsillectomy and adenoidectomy (T&A) specimens may be unnecessary. This study investigates T&A specimen handling practices in the United States between 1989 and 1999. METHODS: Surveys were sent to 4715 members of the American Academy of Otolaryngology. Surveys assessed practice type, pathologic processing practices (full, gross, no pathology), and reasons for change. The authors also performed a retrospective analysis of 1583 pediatric T&A specimens for evidence of occult malignancy. RESULTS: Practice types were 80% private, 12% academic, 6% salaried, and 2% military. Chi squared analysis revealed a significant increase (P < 0.001) in respondents ordering "gross only" and "no pathology." The retrospective analysis found no occult malignancies. CONCLUSIONS: There is a statistically significant increase in the number of otolaryngologists sending routine T&A specimens for "gross only" and "no pathology." There was no correlation between the type of practice and changes in pathologic analysis performed.

Ripening of surface phases coupled with oscillatory dynamics and self-induced spatial chaos through surface roughening.

Some pattern formation processes on single-crystal catalytic surfaces involve transitions between alternative surface phases coupled with oscillatory reaction dynamics. We describe a two-tier symmetry-breaking model of this process, based on nanoscale boundary dynamics interacting with oscillations of adsorbate coverage on microscale. The surface phase distribution oscillates together with adsorbate coverage, and, in addition, undergoes a slow coarsening process due to the curvature dependence of the drift velocity of interphase boundaries. The coarsening is studied both statistically, assuming a circular shape of islands of the minority phase, and through detailed Lagrangian modeling of boundary dynamics. Direct simulation of boundary dynamics allows us to take into account processes of surface reconstruction, leading to self-induced surface roughening. As a result, the surface becomes inhomogeneous, and the coarsening process is arrested way before the thermodynamic limit is reached, leaving a chaotic distribution of surface phases. (c) 1999 American Institute of Physics.

Tinnitus and craniomandibular disorders--is there a link?

Associations between tinnitus and craniomandibular disorders (CMD) were investigated in an epidemiological sample, in tinnitus patients, and in patients attending a 'CMD-clinic'. Natural course of tinnitus was explored in a longitudinal epidemiological study of an elderly population. Several findings indicating a relatively strong relationship between CMD, tinnitus and subjective hearing loss were noted. This relationship seemed to be independent of objectively assessed degree of hearing loss, occupational noise exposure, general morbidity, medication or socioeconomic status. The prevalence of frequent headaches and fatigue or tenderness in jaw muscles was higher in tinnitus patients than would be expected if these conditions were unrelated. About one third of the individuals affected by tinnitus reported influence on tinnitus by jaw movements or pressure on the temporomandibular joint (TMJ). Diurnal bruxism and jaw fatigue appeared to be related to fluctuating tinnitus, vertigo, and hyperacusis. Stomatognathic and biofeedback treatment seemed to be able to reduce or eliminate tinnitus in some patients. Relatively low severity of tinnitus, normal hearing, fluctuating tinnitus, and some signs and symptoms of CMD are believed to constitute predictors of successful treatment outcome. Substantial longitudinal fluctuations with a high occurrence of spontaneous remissions of tinnitus were found in elderly people.

The problem of confirmation in clinical psychoanalysis.

The fact that a statement has scientific credibility only to the extent that it is confirmed makes it desirable to examine clinical confirmation of clinical hypotheses of the type that, when presented to patients in psychoanalysis or psychotherapy, commonly are referred to as interpretations. An attempt is made to show that clinical confirmation in significant ways resembles confirmation in natural science. Certain peculiarities of psychoanalytic prediction and postdiction are discussed.

[Torsion of an omental cyst. A rare cause of abdominal pain in children]. / Torkveret omentcyste. En sjaelden årsag til abdominalsmerter hos børn.

A case of torsion of an omental cyst in a boy aged three years is described. Operation was undertaken for suspected appendicitis. As a rule, the diagnosis is established during operation. If the condition is suspected clinically, the diagnosis may be established by ultrasonography, computed tomography or magnetic resonance. Treatment of omental or mesenteric cysts is always surgical.

Rupture of thin liquid films: generalization of weakly nonlinear theory.

In this paper, we investigate the rupture dynamics of thin liquid films driven by intermolecular forces via weakly nonlinear bifurcation analysis. The dynamic equations governing slow dynamics of the perturbation amplitude of the near-critical mode corresponding to several models describing the evolution of thin liquid films in different physical situations appear to have the same structure. When antagonistic (attractive and repulsive) molecular forces are considered, nonlinear saturation of the instability becomes possible, while the boundary of this supercritical bifurcation is determined solely by the form of the intermolecular potential. The rupture time estimate obtained in closed form shows an excellent agreement with the results of the previously reported numerical simulations of the strongly nonlinear coupled evolution equations upon fitting the amplitude of the small initial perturbation. We further extend the weakly nonlinear analysis of the film dynamics and apply the Galerkin approximation to derive the amplitude equation(s) governing the dynamics of the fastest growing linear mode far from the instability threshold. The comparison of the rupture time derived from this theory with the results of numerical simulations of the original nonlinear evolution equations shows a very good agreement without any adjustable parameters.

Mandibular distraction osteogenesis: at what age to proceed.

OBJECTIVE: To evaluate if there is a difference in mandibular distraction osteogenesis (MDO) treatment success rates and adverse outcomes in newborns, early infants, and older pediatric patients. DESIGN: Retrospective medical review spanning a nine-year period. Ten newborn (≤ 35 days old), five early infant (36 days-5 months) and eight older pediatric (> 5 months) patients underwent MDO for treatment of micrognathia with a severe tongue-based obstruction. Success was defined as avoidance of tracheostomy or CPAP, and decannulation of patients with tracheotomies. Postoperative complications were grouped into minor and major. RESULTS: MDO successfully treated 90% of newborns, 100% of early infants and 100% of older pediatric patients. There was no difference in the rates of success (p=0.48), minor (p=1.00) and major (p=1.00) postoperative complications between newborns and early infants. Older pediatric patients had no treatment failures, tended to have fewer minor (p=0.18) and significantly fewer major (p= 0.04) postoperative complications compared to younger patients. The distractor pin mobility (9%) and scar revisions (13%) were uncommon. CONCLUSIONS: Mandibular distraction osteogenesis is a reliable method for relieving severe tongue-based obstructions in pediatric patients. When comparing newborns and early infant patients, treatment success rates and the occurrence of complications were not found to be different. Older pediatric patients had no treatment failures, and tended to have fewer postoperative complications compared to younger patients.

Actin disassembly 'clock' and membrane tension determine cell shape and turning: a mathematical model.

Motile cells regulate their shape and movements largely by remodeling the actin cytoskeleton. Principles of this regulation are becoming clear for simple-shaped steadily crawling cells, such as fish keratocytes. In particular, the shape of the leading edge and sides of the lamellipodium-cell motile appendage-is determined by graded actin distribution at the cell boundary, so that the denser actin network at the front grows, while sparser actin filaments at the sides are stalled by membrane tension. Shaping of the cell rear is less understood. Here we theoretically examine the hypothesis that the cell rear is shaped by the disassembly clock: the front-to-rear lamellipodial width is defined by the time needed for the actin-adhesion network to disassemble to the point at which the membrane tension can crush this network. We demonstrate that the theory predicts the observed cell shapes. Furthermore, turning of the cells can be explained by biases in the actin distribution. We discuss experimental implications of this hypothesis.