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Biomedical subjects

Y Iwasa

Publications and source records attributed to Y Iwasa.

At least 127 records · Page 7Linked to original sources
PubMed1988

Free fitness that always increases in evolution.

I here introduce a free fitness function in population biology, which monotonically increases with time and takes its maximum at the evolutionary equilibrium. By suitably defining an "index" for each state, the free fitness is expressed as the average index plus an entropy term. In many cases, the index has a biologically clear meaning, such as the logarithmic population mean fitness. The technique is applicable to any Markov process model (either continuous or discrete) with a positive steady state. I discuss four examples from various branches of population biology: (1) one-locus-two-allele system of population genetics with mutation, selection, and random genetic drift; (2) evolutionary dynamics of quantitative characters; (3) a molecular evolution model; and (4) an ecological succession model. Introducing free fitness clarifies the balance between systematic forces (e.g. natural selection or successional trend toward the climax) and disturbing processes (e.g. random drift).

Animals↗
PubMed1988

The mechanism for the inhibitory action of N-(3',4'-dimethoxycinnamoyl)anthranilic acid (tranilast) on the release reaction in platelets.

The molecular basis for the inhibitory action of the antiatopic drug, N-(3',4'-dimethoxycinnamoyl)anthranilic acid (Tranilast), on the thrombin-induced release of a lysosomal enzyme, beta-N-acetylglucosaminidase, from washed rabbit platelets was investigated. Tranilast dose dependently increased cyclic AMP and cyclic GMP levels in thrombin-stimulated platelets, parallel with the inhibition of beta-N-acetylglucosaminidase release. There was no significant effect of Tranilast on adenylate or guanylate cyclase activity. Tranilast inhibited the activity of cyclic AMP and cyclic GMP phosphodiesterases in a cell-free system. The data suggest that the inhibitory action of Tranilast on the release reaction in platelets was due at least in part to inhibition of cyclic nucleotide phosphodiesterases followed by an elevation of cyclic AMP and cyclic GMP levels.

Acetylglucosaminidase↗
PubMed1988

Postmortem changes in the level of calcium pumping adenosine triphosphatase in rat heart sarcoplasmic reticulum.

The activity of calcium pumping adenosine triphosphatase (Ca2+-ATPase) in cardiac sarcoplasmic reticulum plays a pivotal role in myocardiac contraction-relaxation. The Ca2+-ATPase activity is controlled by phosphorylation and dephosphorylation of a sarcoplasmic reticulum protein "phospholamban" in response to neurotransmitters and drugs. To clarify the role of Ca2+-ATPase in the development of cardiac rigor mortis, we examined the changes of cardiac rigidity and cardiac sarcoplasmic reticulum Ca2+-ATPase activity up to 5 h after the decapitation of rats. Fifteen minutes after decapitation, the rats showed a cardiac rigidity on left ventricles. After 30 min, rigidity was obvious over the whole heart. After 1 h, the rigidity reached a high degree which was maintained for the rest of the observation period. On the other hand, the Ca2+-ATPase activity controlled by phosphorylation and dephosphorylation of phospholamban did not change for the whole observation period (5 h). Another Ca2+-ATPase activity representing the total amount of Ca2+-ATPase in sarcoplasmic reticulum gradually decreased. The data suggest that no significant phosphorylation or dephosphorylation of phospholamban occurs for a short time, at least for 5 h, after death and that the Ca2+-ATPase tends to relax the myocardium against the development of cardiac rigor mortis.

Animals↗
PubMed1987

Optimal recombination rate in fluctuating environments.

The optimal recombination rate which maximizes the long-term geometric average of the population fitness is studied for a two-locus haploid model, assuming that the fitnesses of genotypes AB, Ab, aB and ab are 1 + s(t), 1 - s(t), 1 - s(t), and 1 + s(t), respectively, where s(t) follows various stationary stochastic processes with the average zero. With positive recombination, the polymorphism is stably maintained at both loci. After an initial transient phase, the dynamics are reduced to one dimension, and are analyzed for weak selection limit, strong selection limit, and selection with two state Markovian jump. Results are: (1) If the environmental fluctuation has a predominant periodic component, ropt is approximately inversely proportional to the period irrespective of selection intensity. (2) If the fluctuation is a superposition of many periodic components, the one with the longest period is the most effective in determining ropt because the genetic dynamics cannot track very quick fluctuations (low pass filter effect). (3) If the power spectrum density is decreasing with the frequency, as in pink, or 1/f noises, ropt is small when selection is weak, and increases with the selection intensity. Numerical calculation of the genetic dynamics of a recombination modifier supports all these predictions for the evolutionarily stable recombination rate.

Alleles↗
PubMed1986

Anti-platelet action of an anti-allergic agent, N-(3',4'-dimethoxycinnamoyl)anthranilic acid (tranilast).

The effects of N-(3',4'-dimethoxycinnamoyl)anthranilic acid (Tranilast), a blocker for histamine release from mast cells, on rabbit blood platelet functions were investigated. Tranilast inhibited dose dependently both the release of a lysozomal enzyme, beta-N-acetylglucosaminidase, and aggregation of washed rabbit platelets stimulated by thrombin and collagen. The IC50 was suspected to be 164 +/- 50 microM. The data suggest that Tranilast may be used as an anti-platelet agent in addition to an anti-allergic one.

Acetylglucosaminidase↗
PubMed1986

Influence of nonlinear incidence rates upon the behavior of SIRS epidemiological models.

When the traditional assumption that the incidence rate is proportional to the product of the numbers of infectives and susceptibles is dropped, the SIRS model can exhibit qualitatively different dynamical behaviors, including Hopf bifurcations, saddle-node bifurcations, and homoclinic loop bifurcations. These may be important epidemiologically in that they demonstrate the possibility of infection outbreak and collapse, or autonomous periodic coexistence of disease and host. The possible mechanisms leading to nonlinear incidence rates are discussed. Finally, a modified general criterion for supercritical or subcritical Hopf bifurcation of 2-dimensional systems is presented.

Humans↗
PubMed1985

Evolution in a metapopulation with space-limited subpopulations.

A model for the dynamics of a metapopulation with space-limited subpopulations (Roughgarden & Iwasa, 1985) is extended to include genetic variation for life-history traits. The traits include those expressed by the sessile adults in the space-limited subpopulations and traits expressed by the dispersing larvae. Conditions for increase of a new allele at a single locus are derived using two formulations, one that omits, and one that includes, age-structure among the sessile adults. From both formulations a criterion indicating the general direction of evolutionary change is derived: a new allele enters the population if it increases the average productivity of larvae from the subpopulations relative to the larval mortality rate, where the average is computed by weighting the productivity from each subpopulation by the amount of unoccupied space in it. This criterion may offer a start towards a theory for the evolution of life histories appropriate to the population structure of sessile marine invertebrates with pelagic larvae. In particular, the basal area of a sessile adult in a population with space-limited recruitment is a selectively neutral character.

Animals↗
PubMed1984

Phosphorylation of cardiac sarcolemma proteins by the calcium-activated phospholipid-dependent protein kinase.

Cardiac sarcolemma proteins were phosphorylated by exogenous Ca2+-activated phospholipid-dependent protein kinase (protein kinase C). The phosphorylation reactions were absolutely dependent on the simultaneous presence of Ca2+ and phosphatidylserine. Phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, sphingomyelin, and phosphatidic acid were ineffective in supporting protein kinase C-catalyzed membrane phosphorylation. The reactions were not stimulated by diolein. In contrast, diolein inhibited phosphatidylserine-stimulated phosphorylation at all calcium concentrations tested. The major substrates for protein kinase C in cardiac membranes were peptides of 88,000, 51,000, 42,000 daltons, and the peptide known as phospholamban (Mr = 27,000 or 11,000 depending on sample preparation). Phosphorylation of phospholamban by protein kinase C was additive with that catalyzed by membrane-bound or exogenous cyclic AMP-dependent protein kinase and with Ca2+-calmodulin-dependent protein kinase. The results suggest that protein kinase C might have a role in the regulation of cardiac membrane phosphorylation by beta-adrenergic and muscarinic cholinergic agonists.

Animals↗
PubMed1984

Theory of oviposition strategy of parasitoids. I. Effect of mortality and limited egg number.

The optimal oviposition strategies of parasitoids, the host range, and the number of eggs laid per host which result in the maximum lifetime performance of reproduction, are investigated. To study the effects of parasitoid mortality and of limiting total number of eggs laid by a parasitoid, a standard criterion used in previous theories of optimal diet and optimal patch use, the maximization of the foraging rate, is no longer suitable. The model is solved analytically by using dynamic programming. The results are as follows: The host preference of solitary parasitoids depends on the mortality during handling times; i.e., the forager tends to avoid hosts with high risk of foraging mortality. If the total number of eggs produced by a parasitoid is limited, and if the mortality during handling is negligible, the host range is wider when a larger number of eggs remains in the parasitoid's body. In general, however, the mortality-cost of forager and the egg-cost interplay, because the loss of future reproduction by mortality increases with the number of available eggs. In an example with two host types, host range is widest with an intermediate number of eggs available in the body. The optimal number of eggs per host laid by a gregarious parasitoid is also affected by the differential mortality of the forager, and by the number of available eggs.

Diet↗
PubMed1984

[Statistical analysis on 1,500 urinary calculi by using microcomputer].

In our laboratories, more than 1,500 urinary calculi have been analyzed by infrared spectroscopy. These data were statistically analyzed by microcomputer. The most frequent type was calcium oxalate combined with calcium phosphate, followed by pure calcium oxalate and magnesium ammonium phosphate combined with calcium phosphate. In particular, the composition of magnesium ammonium phosphate combined with calcium phosphate increased as compared with that four years earlier. Four years ago, we spent one month to statistically analyze 300 urinary calculi. But in this study, only sixteen days was required to analyze 1,500 urinary calculi by using a microcomputer.

Adolescent↗
PubMed1983

Acidic phospholipids stimulate the autophosphorylation of the catalytic subunit of cyclic AMP-dependent protein kinase.

The autophosphorylation of the catalytic subunit of cAMP-dependent protein kinase was stimulated by the acidic phospholipids phosphatidic acid, phosphatidylserine and phosphatidylinositol. Other phospholipids (phosphatidyl-ethanolamine, phosphatidylcholine, sphingomyelin), acidic compounds (dextran sulfate, polyglutamic acid, chondroitin sulfate, hyaluronic acid) and calcium-calmodulin were essentially inactive. Sodium dodecyl sulfate also stimulated the catalytic subunit autophosphorylation, but other detergents (Triton X-100 and deoxycholic acid) did not. The combination of phosphatidic acid and sodium dodecyl sulfate was as effective as each agent alone, suggesting similar stimulation mechanisms. The data suggest that acidic membrane phospholipids might have a role in regulating the autophosphorylation of the catalytic subunit of cAMP-dependent protein kinase.

Animals↗
PubMed1983

A high-affinity (Ca2+ + Mg2+)-ATPase in plasma membranes of rat ascites hepatoma AH109A cells.

The activity of calcium-stimulated and magnesium-dependent adenosinetriphosphatase which possesses a high affinity for free calcium (high-affinity (Ca2+ + Mg2+)-ATPase, EC 3.6.1.3) has been detected in rat ascites hepatoma AH109A cell plasma membranes. The high-affinity (Ca2+ + Mg2+)-ATPase had an apparent half saturation constant of 77 +/- 31 nM for free calcium, a maximum reaction velocity of 9.9 +/- 3.5 nmol ATP hydrolyzed/mg protein per min, and a Hill number of 0.8. Maximum activity was obtained at 0.2 microM free calcium. The high-affinity (Ca2+ + Mg2+)-ATPase was absolutely dependent on 3-10 mM magnesium and the pH optimum was within physiological range (pH 7.2-7.5). Among the nucleoside trisphosphates tested, ATP was the best substrate, with an apparent Km of 30 microM. The distribution pattern of this enzyme in the subcellular fractions of the ascites hepatoma cell homogenate (as shown by the linear sucrose density gradient ultracentrifugation method) was similar to that of the known plasma membrane marker enzyme alkaline phosphatase (EC 3.1.3.1), indicating that the ATPase was located in the plasma membrane. Various agents, such as K+, Na+, ouabain, KCN, dicyclohexylcarbodiimide and NaN3, had no significant effect on the activity of high-affinity (Ca2+ + Mg2+)-ATPase. Orthovanadate inhibited this enzyme activity with an apparent half-maximal inhibition constant of 40 microM. The high-affinity (Ca2+ + Mg2+)-ATPase was neither inhibited by trifluoperazine, a calmodulin-antagonist, nor stimulated by bovine brain calmodulin, whether the plasma membranes were prepared with or without ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetra-acetic acid. Since the kinetic properties of the high-affinity (Ca2+ + Mg2+)-ATPase showed a close resemblance to those of erythrocyte plasma membrane (Ca2+ + Mg2+)-ATPase, the high-affinity (Ca2+ + Mg2+)-ATPase of rat ascites hepatoma cell plasma membrane is proposed to be a calcium-pumping ATPase of these cells.

Animals↗
PubMed1983

Cholinergic antagonism of beta-adrenergic stimulation of cardiac membrane protein phosphorylation in situ.

The phosphorylation of cardiac membrane proteins has been studied in preparations of newborn chick hearts. Membranes were isolated from 32P-loaded tissue after treatment with or without the beta-adrenergic receptor agonist isoproterenol and/or the muscarinic cholinergic receptor agonist oxotremorine. The phosphorylation of a low molecular weight membrane protein was enhanced by isoproterenol as early as 10 s after adding the drug. This phosphoprotein had a molecular weight of approximately 26,000 or 14,000 depending on the conditions used to solubilize the membranes prior to electrophoresis. It is most probably phospholamban/calciductin. The apparent molecular weight of the protein observed at 26,000 increased by approximately 1,000 as phosphorylation increased. The phosphorylation of this protein was abolished by short term treatment of the isoproterenol-treated tissue with the muscarinic receptor agonist oxotremorine. Effects of oxotremorine were observed within 30 s and were maximal between 2-5 min. The oxotremorine-induced decrease in phosphorylation was accompanied by a decrease in molecular weight. This phosphoprotein was found in a membrane fraction enriched in cardiac sarcolemma as well as in another containing sarcolemma and sarcoplasmic reticulum. The phosphorylation of this membrane component may play a role in the effects of beta-adrenergic and muscarinic cholinergic agonists on cardiac contractile force.

Animals↗
PubMed1983

Comparison of high affinity Ca2+-ATPase and low affinity Ca2+-ATPase in rat liver plasma membranes.

Rat liver plasma membranes contained two types of calcium-dependent adenosine triphosphatase (Ca2+-ATPase, EC 3.6.1.3) activities. One of them had a high affinity for free calcium (Ca2+) with an apparent half maximal saturation constant (K0.5) of 0.2 microM (high affinity Ca2+-ATPase), and the other exhibited a low affinity with a K0.5 of 50 microM for Ca2+ (low affinity Ca2+-ATPase). The high affinity Ca2+-ATPase showed: independence from free magnesium (Mg2+), a wide range of optimum pH (7.2-7.5), inhibition by a large amount of calmodulin, and substrate preference for ATP, GTP and ITP. On the other hand, the low affinity Ca2+-ATPase showed: stimulation by Mg2+ as well as Ca2+, an optimum pH of 8, mild stimulation by calmodulin, reversible inhibition by calmodulin-antagonists, inhibition by dicyclohexylcarbodiimide, and substrate preference for UTP and GTP. Both Ca2+-ATPases were insensitive to Na+, K+, ouabain, NaN3 and KCN. Orthovanadate, a potent inhibitor for many ATPases, had no effect on both ATPases over a wide range of concentrations (7 nM-1.7 mM). The Ca2+-ATPases could be separated by gel filtration on a Sepharose 4B column after solubilization with Triton X-100. The high affinity Ca2+-ATPase showed a Stokes radius of about 49 A and a sedimentation coefficient of about 7.0 S with a molecular weight of 1.4 X 10(5). The frictional ratio was 1.4. The results suggest that the high affinity Ca2+-ATPase may be a possible candidate for an ATPase with Ca2+ pumping activity, and that the high affinity enzyme is distinct from the low affinity Ca2+-ATPase in the rat liver plasma membranes.

Animals↗
PubMed1983

[A double blind clinical trial of cefamandole and cefmetazole in complicated urinary tract infections].

We conducted a randomized double blind comparison of cefamandole (CMD) and cefmetazole (CMZ) in the treatment of 193 patients with complicated urinary tract infections. The patients received 1 gram of CMD or CMZ twice a day intravenously by drip infusion over 1 hour for 5 days. Pretreatment urinary leukocyte counts and urinary bacterial counts were at least 5 cells/hpf and 10(4) bacteria/ml, respectively. Each patient was randomly allocated either to CMD or CMZ group. There were 93 patients in CMD group and 100 patients in CMZ group. Clinical efficacy was evaluated based on the effect of treatment on bacteriuria and pyuria according to the criteria set by the UTI Committee, Japan. The response to CMD treatment was excellent in 18 cases (19.4%), moderate in 38 cases (40.9%) and poor in 37 cases (39.8%) with an overall effectiveness of 60.2%, whereas the response to CMZ was excellent in 19 cases (19.0%), moderate in 40 cases (40.0%) and poor in 41 cases (41.0%) with an overall effectiveness of 59.0%. No statistical significant difference was found between 2 treatment groups. Comparison of the bacteriological response between 2 groups showed that the eradication rate for strains of Gram-positive cocci were significantly higher in those patients treated with CMD. Gram-negative rods were eradicated from 68.4% of cases treated with CMD, and 78.0% of those with CMZ, but the difference was not significant. Adverse reactions were observed in 3 patients receiving CMD 1 case each of diarrhea, eruption and epigastric pain. Abnormality in laboratory tests was found in 6 patients in each treatment group. The results indicate that CMD is effective, safe and useful in the treatment of patients with complicated urinary tract infections, and its efficacy, safety and usefulness are comparable with those of CMZ.

Adolescent↗