Generic theory of active polar gels: a paradigm for cytoskeletal dynamics.

We develop a general theory for active viscoelastic materials made of polar filaments. This theory is motivated by the dynamics of the cytoskeleton. The continuous consumption of a fuel leads to a non equilibrium state characterized by the generation of flows and stresses. Our theory can be applied to experiments in which cytoskeletal patterns are set in motion by active processes such as those which are at work in cells.

Role of tensile stress in actin gels and a symmetry-breaking instability.

It has been observed experimentally that the actin gel grown from spherical beads coated with polymerization enzymes spontaneously breaks the symmetry of its spherical shape, and yields a "comet" pushing the bead forward. We propose a mechano-chemical coupling mechanism for the initialization of this symmetry breaking. Key assumptions are that the dissociation of the gel takes place mostly in the region of the external surface, and that the rates of the dissociation depend on the tensile stress in the gel. We analyze a simplified two-dimensional model with a circular substrate. Our analysis shows that the symmetric steady state is always unstable against the inhomogeneous modulation of the thickness of the gel layer, for any radius of the circular substrate. We argue that this model represents the essential feature of three-dimensional systems for a certain range of characteristic lengths of the modulation. The characteristic time of the symmetry-breaking process in our model depends linearly on the radius of curvature of the substrate surface, which is consistent with experimental results, using spherical latex beads as substrate. Our analysis of the symmetry-breaking phenomenon demonstrates aspects of mechano-chemical couplings that should be working in vivo as well as in vitro.

Asters, vortices, and rotating spirals in active gels of polar filaments.

We develop a general theory for active viscoelastic materials made of polar filaments. This theory is motivated by the dynamics of the cytoskeleton. The continuous consumption of a fuel generates a nonequilibrium state characterized by the generation of flows and stresses. Our theory applies to any polar system with internal energy consumption such as active chemical gels and cytoskeletal networks which are set in motion by active processes at work in cells.

The comparative effects of propofol versus thiopentone on left ventricular function during electroconvulsive therapy.

The purpose of this study was to compare the effect of propofol versus thiopentone on haemodynamics during electroconvulsive therapy (ECT), as estimated by echocardiography. Twenty-eight ASA 1 or 2 patients scheduled for ECT were randomly divided into two groups, to receive propofol 1 mg/kg (propofol group, n = 14) or thiopentone 2 mg/kg (thiopentone group, n = 14). Bilateral ECT was performed after the administration of propofol or thiopentone, succinylcholine and following assisted mask ventilation with 100% oxygen. Cardiac function was examined by transthoracic echocardiography, prior to induction of anaesthesia and throughout ECT until ten minutes after the seizure. In the propofol group, increased end-systolic area (ESA) and decreased fractional area change (FAC) were observed at one minute after the electrical shock compared with the awake condition. In the thiopentone group, increased ESA and decreased FAC were observed from one to three minutes after the electrical shock compared with the awake condition. There was no statistically significant change in afterload in the propofol group during the study. In contrast, increased afterload was observed from one to three minutes after the electrical shock in the thiopentone group (awake condition, 26 +/- 7 mmHg/cm2 [mean +/- SD]; one minute after ECT, 42 +/- 7*; two minutes after ECT, 44 +/- 6*; three minutes after ECT; 40 +/- 5*, respectively) (*P < 0.05). We concluded that a lesser haemodynamic change occurs after propofol anaesthesia (1 mg/kg) compared with thiopentone anaesthesia (2 mg/kg) during ECT.

Growth of fingerlike protrusions driven by molecular motors.

The actin cortex is an important part of the motile machinery of a eucaryotic cell. The cortex is steadily reorganized, for example, through the action of molecular motors forming active crosslinks between pairs of actin filaments. Here, the effect of correlations between molecular motors on the induced relative motion of two aligned filaments is investigated. It is found that the average relative velocity between filaments depends nonmonotonically on the motor concentration. Depending on the properties of the filaments' ends, the active interaction between filaments of the same orientation may lead either to a complete overlap or to separation. In addition to pure actin polymerization the active separation of filaments might be involved in the growth of long fingerlike protrusions (filopods).

[Diagnosis of the postoperative local recurrence of rectal cancer by FDG-PET--a case report].

Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) as the tracer of glucose metabolism was performed to identify a postoperative recurrent lesion of rectal cancer. A 66-year-old-man underwent trans-sacral local resection of the rectum for rectal cancer in 1992. A local recurrent mass was discovered, and abdomino-perineal resection of the rectum was performed in 1999. The serum CEA level increased gradually August in 2000, but there was no sign of recurrence on CT or MRI. FDG-PET was performed to reveal a presacral recurrent lesion. Total pelvic evisceration combined with resection of the sacrum, and a bilateral ureterostomy were performed in April 2001. The beneficial role of FDG-PET in the diagnosis of the postoperative local recurrence of rectal cancer is emphasized.

The suppressive mechanism of histamine release from rat peritoneal mast cells of iodine-enriched eggs.

We investigated the antiallergic activity of iodine-enriched egg by using rat peritoneal exudate cells. The effects were evaluated by the inhibition ratio of these compounds on histamine release from rat peritoneal exudate cells. Lipid and water-soluble fractions, which were separated from iodine-enriched egg yolk, were used for all experiments. Lipid fractionation of iodine-enriched eggs inhibited histamine release by compound-48/80 in a dose-dependent manner. Lipid fractionation of ordinary eggs had no effect. Neither the water-soluble fraction of iodine-enriched eggs nor ordinary eggs inhibited compound-48/80 induced histamine release. Neither lipid nor soluble fraction of iodine-enriched eggs inhibited histamine release in peritoneal exudate cells with Ca ionophore A23187 stimulation. The same fractions of ordinary eggs were also unable to inhibit histamine release. The lipid fraction, furthermore, was isolated to neutral and polar lipid fractionation. Although both neutral and polar lipid fractionation inhibited histamine release, the effect was dose-dependent in only neutral lipid fractionation. Neither fractions of ordinary egg inhibited histamine release. In conclusion, the components inhibiting histamine release in rat peritoneal exudate cells exist in the neutral lipid fraction of iodine-enriched eggs.

Fluctuations in sliding motion generated by independent and random actions of protein motors.

We consider theoretical fluctuations in the in vitro sliding movement of individual cytoskeletal filaments generated by an ensemble of protein motors whose actions are assumed to be statistically independent and random. We show that the mean square deviation of the sliding distances of a filament for a given period of time around their average is proportional to the inverse of the filament length. This result provides a basis for an experimental test of the general assumption on the independent and random actions of protein motors.

Unattainability of carnot efficiency in the brownian heat engine

We discuss the reversibility of the Brownian heat engine. We perform an asymptotic analysis of the Kramers equation on a Buttiker-Landauer system and show quantitatively that Carnot efficiency is unattainable even in the fully overdamped limit. The unattainability is attributed to inevitable irreversible heat flow over the temperature boundary.

Logarithmically slow expansion of hot bubbles in gases

We predict a logarithmically slow expansion of hot bubbles in gases in the process of cooling. A model problem is first solved, when the temperature has compact support. Then the temperature profile decaying exponentially at large distances is considered. The periphery of the bubble is shown to remain essentially static ("glassy") in the process of cooling until it is taken over by a logarithmically slowly expanding "core." An analytical solution to the problem is obtained by matched asymptotic expansion. This problem gives an example of how logarithmic corrections enter dynamic scaling.

Carnot's cycle for small systems: irreversibility and cost of operations

In the thermodynamic limit, the existence of a maximal efficiency of energy conversion attainable by a Carnot cycle consisting of quasistatic isothermal and adiabatic processes precludes the existence of a perpetual machine of the second kind, whose cycles yield positive work in an isothermal environment. We employ the recently developed framework of the energetics of stochastic processes (called "stochastic energetics") to reanalyze the Carnot cycle in detail, taking account of fluctuations, without taking the thermodynamic limit. We find that in this nonmacroscopic situation both processes of connection to and disconnection from heat baths and adiabatic processes that cause distortion of the energy distribution are sources of inevitable irreversibility within the cycle. Also, the so-called null-recurrence property of the cumulative efficiency of energy conversion over many cycles and the irreversible property of isolated, purely mechanical processes under external "macroscopic" operations are discussed in relation to the impossibility of a perpetual machine, or Maxwell's demon. This analysis may serve as the basis for the design and analysis of mesoscopic energy converters in the near future.

[A case of gastric cancer with multiple bone metastasis treated by nocturnal 5-fluorouracil infusion combined with pamidronate].

Nocturnal infusion of 5-fluorouracil (5-FU) combined with pamidronate was performed in a 62-year-old male gastric cancer patient with multiple bone metastasis. The patient was administered 500 mg of 5-FU five days a week continuously for 10 hours per day from 21 o'clock to 7 o'clock for 5 months. In addition to 5-FU, 45 mg of pamidronate was administered intravenously every two weeks. Remarkable sclerotic changes were shown during the treatment in the bone metastatic foci, and the range of motion was enlarged. Serum levels of CEA and CA19-9 were decreased to the normal levels. There were no serious side effects such as myelosuppression, diarrhea or palmo-plantar dermatitis. This combination therapy of nocturnal infusion of 5-FU with pamidronate was considered effective for gastric cancer in patients with multiple bone metastasis without serious side effects.

Protein friction exerted by motor enzymes through a weak-binding interaction.

Recently Vale et al. (1989, Cell 59, 915-925.) reported an observation of the one-dimensional Brownian movement of microtubules bound to flagellar dynein through a weak-binding interaction. In this study, we propose a theoretical model of this phenomenon. Our model consists of a rigid microtubule associated with a number of elastic dynein heads through a weak-binding interaction at equilibrium. The model implies that (1) the Brownian motion of the microtubule is not directly driven by the atomic collision of the solvent particles, but is driven by the thermally-generated structural fluctuations of the dynein heads which interact with the microtubule; (2) dynein heads through a weak-binding interaction exert a frictional drag force on the sliding motion of the microtubule and the drag force is proportional to the sliding velocity the same as in hydrodynamic viscous friction. This protein friction, with such viscous-like characteristics, may well play a role as a velocity-limiting factor in the normal ATP-induced sliding movement of motile proteins.

A physical model of ATP-induced actin-myosin movement in vitro.

The nature of the mechanism limiting the velocity of ATP-induced unidirectional movements of actin-myosin filaments in vitro is considered. In the sliding process two types of "cyclic" interactions between myosin heads and actin are involved, i.e., productive and nonproductive. In the productive interaction, myosin heads split ATP and generate a force which produces sliding between actin and myosin. In the nonproductive interaction "cycle," on the other hand, myosin heads rapidly attach to and detach from actin "reversibly," i.e., without splitting ATP or generating an active force. Such a nonproductive interaction "cycle" causes irreversible dissipation of sliding energy into heat, because the myosin cross-bridges during this interaction are passive elastic structures. This consideration has led us to postulate that such cross-bridges, in effect, exert viscous-like frictional drag on moving elements. Energetic considerations suggest that this frictional drag is much greater than the hydrodynamic viscous drag. We present a model in which the sliding velocity is limited by the balance between the force generated by myosin cross-bridges in the productive interaction and the frictional drag exerted by other myosin cross-bridges in the nonproductive interaction. The model is consistent with experimental findings of in vitro sliding, including the dependence of velocity on ATP concentration, as well as the sliding velocity of co-polymers of skeletal muscle myosin and phosphorylated and unphosphorylated smooth muscle myosins.

Acute decrease in vitellogenin synthesis by deprivation of food and water in laying hens.

Vitellogenin synthesis during a decrease in egg production caused by depriving food and water was investigated in Single Comb White Leghorn hens. They were transferred from long days of 14L: 10D to short days of 10L: 14D 5 days before food and water deprivation. Then food was deprived for 5 days and water for 2 days. The body weight was markedly decreased by the treatment and reached its minimum after 5 days. The egg production rate which was 85% before the treatment was nil after 4 days. On day 3 the circulating vitellogenin concentrations, measured by a newly established RIA system, was markedly decreased by deprivation of food and water to 22% of the pretreatment level. The concentrations remained less than 10% during cessation of egg laying. Serum luteinizing hormone (LH) and progesterone concentrations decreased gradually, but estradiol 17 beta (E2) decreased abruptly. This acute decrease closely coincided with the decrease in egg production and the weight of the oviduct and ovary. These concentrations were gradually increased after day 16 and returned to the normal level after 46 days. Circulating thyroxine (T4) and triiodothyronine (T3) concentrations gradually increased from the beginning of the change in the day length and peaked on day 7 or 9, whereas reverse (r)T3 rapidly increased. The concentrations again decreased at the beginning of molting which occurred later due to the deprivation of food and water. Thus, these results demonstrated for the first time that the decrease in egg production induced by deprivation of food and water closely related to the decrease in vitellogenin synthesis as well as gonadal and pituitary functions. Further, recovery of egg production was coupled with the increase in the ovary and oviduct weight, and circulating LH, E2, progesterone, and vitellogenin.