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Biomedical subjects

Y Iwasa

Publications and source records attributed to Y Iwasa.

At least 19 recordsLinked to original sources

The evolution of cooperation in a lattice-structured population.

The evolution of cooperation among unrelated individuals is studied in a lattice-structured habitat, where individuals interact locally only with their neighbors. The initial population includes Tit-for-Tat (abbreviated as TFT, indicating a cooperative strategy) and All Defect (AD, a selfish strategy) distributed randomly over the lattice points. Each individual plays the iterated Prisoner's Dilemma game with its nearest neighbors, and its total pay-off determines its instantaneous mortality. After the death of an individual, the site is replaced immediately by a copy of a randomly chosen neighbor. Mathematical analyses based on mean-field approximation, pair approximation, and computer simulation are applied. Models on one and two-dimensional regular square lattices are examined and compared with the complete mixing model. Results are: (1) In the one-dimensional model, TFT players come to form tight clusters. As the probability of iteration w increases, TFTs become more likely to spread. The condition for TFT to increase is predicted accurately by pair approximation but not by mean-field approximation. (2) If w is sufficiently large, TFT can invade and spread in an AD population, which is impossible in the complete mixing model where AD is always ESS. This is also confirmed by the invasion probability analysis. (3) The two-dimensional lattice model behaves somewhat in between the one-dimensional model and the complete mixing model. (4) The spatial structure modifies the condition for the evolution of cooperation in two different ways: it facilitates the evolution of cooperation due to spontaneously formed positive correlation between neighbors, but it also inhibits cooperation because of the advantage of being spiteful by killing neighbors and then replacing them.

Animals

Pollinator Foraging Strategies in Mixed Floral Arrays: Density Effects and Floral Constancy

The profitability of any foraging strategy may be in part dependent on the number of foragers adopting it, and so it can be viewed mathematically as a "game." We explore here the implications of a game-theoretic model of pollinators foraging on a mixed array of two flower species, with individual pollinators either specializing on one or the other, or else acting as generalists. We further allow for the possibility of specialist advantages in foraging efficiency. The predicted mixture of pollinator behavioral strategies depends on the overall floral density and the relative densities of the two flower species. Where floral resources are scarce, pollinators should behave as generalists whereas when resources are superabundant, specialization on the single most profitable flower type (all else being equal, the commonest one) is favored. At intermediate floral densities, a mix of floral specializations (floral constancy) is favored, so long as the rarer flower's density does not fall below some critical minimum level. Where the rarer flower is too rare, a mixture of generalists and common-species specialists is favored. Rare flowers are at a reproductive disadvantage in all cases, but their relative success is highest where their pollinators are flower constant.

Journal Article

Optimal Level of Chemical Defense Decreasing with Leaf Age

A recent study on a biennial plant demonstrated that pyrrolizidine alkaloids decrease with the age of leaves due to reallocation from old leaves to new leaves. Here we study the optimal age-specific pattern of defense chemical concentration in leaves that achieves the maximum growth rate of the plant. We consider a plant growing exponentially in a constant environment. Assumptions are the following: (1) The loss of leaves due to herbivory decreases with defense chemical concentration (2) The daily net photosynthesis of a leaf decreases with its age. (3) Using photosynthetic products, the plant produces new leaves that may contain defense chemicals. (4) Although there is a cost to producing new defense chemicals, such chemicals can be reallocated without cost. In the optimal schedule calculated using Pontryagin's maximum principle, the chemical defense level decreases with leaf age. The optimal level of chemical defense increases with the cost of leaf production and herbivory intensity but decreases with the cost of defense chemical production, effectiveness of the defense chemical, net productivity, and growth rate of the plant. If both generalist and specialist herbivores attack the same plant, the optimal defense level is dependent only on the generalists' abundance and sensitivity, but is independent of the specialists that are unaffected by the defense chemical.

Journal Article

Establishment probability in fluctuating environments: a branching process model.

We study the establishment probability of invaders in stochastically fluctuating environments and the related issue of extinction probability of small populations in such environments, by means of an inhomogeneous branching process model. In the model it is assumed that individuals reproduce asexually during discrete reproduction periods. Within each period, individuals have (independent) Poisson distributed numbers of offspring. The expected numbers of offspring per individual are independently identically distributed over the periods. It is shown that the establishment probability of an invader varies over the reproduction periods according to a stable distribution. We give a method for simulating the establishment probabilities and approximations for the expected establishment probability. Furthermore, we show that, due to the stochasticity of the establishment success over different periods, the expected success of sequential invasions is larger then that of simultaneous invasions and we study the effects of environmental fluctuations on the extinction probability of small populations and metapopulations. The results can easily be generalized to other offspring distributions than the Poisson.

Demography

The evolution of genomic imprinting.

In some mammalian genes, the paternally and maternally derived alleles are expressed differently: this phenomenon is called genomic imprinting. Here we study the evolution of imprinting using multivariate quantitative genetic models to examine the feasibility of the genetic conflict hypothesis. This hypothesis explains the observed imprinting patterns as an evolutionary outcome of the conflict between the paternal and maternal alleles. We consider the expression of a zygotic gene, which codes for an embryonic growth factor affecting the amount of maternal resources obtained through the placenta. We assume that the gene produces the growth factor in two different amounts depending on its parental origin. We show that genomic imprinting evolves easily if females have some probability of multiple partners. This is in conflict with the observation that not all genes controlling placental development are imprinted and that imprinting in some genes is not conserved between mice and humans. We show however that deleterious mutations in the coding region of the gene create selection against imprinting.

Animals

Sclerosing peritonitis associated with luteinized thecoma of the ovary.

A unique case of bilateral luteinized thecomas of the ovary associated with sclerosing peritonitis is reported and the clinical and pathological features of this and previously reported cases are reviewed. The patient, 52 years of age, presented with abdominal distension and diarrhea. Pelvic imaging studies revealed bilateral ovarian tumors with ascites. Total abdominal hysterectomy and bilateral salpingo-oophorectomy with adhesiotomy of the small bowel were performed. Histologically, the ovarian tumor was composed of closely packed spindle to round-shaped cells, and within the spindle cell population, lutein-like cells were scattered singly or in clusters. Mitotic counts of spindle cells revealed 12 mitotic figures (MF) per 10 high-power fields (HPF) in one part of the left ovarian tumor, but other areas of the tumor showed less than 3 MF/10 HPF on average. The lesion from the resected small bowel showed prominent fibrosis, confined to the serosa with no evidence of metastasis from the ovarian tumor. The patient has undergone adhesiotomy with partial resection of the small bowel seven times since the first laparotomy because of the recurrent small bowel obstruction. The patient has survived with complications due to short bowel syndrome for 7 years after the initial surgery and so far no recurrence or metastasis of the ovarian tumor has been identified. The case reported here also supports the idea that luteinized thecoma of the ovary associated with sclerosing peritonitis may be a distinct clinicopathologic entity, in terms of the unique association and of the unique features of thecoma; that is, bilateral, hormonally inactive and apparently benign in spite of its highly mitotic activity. Additional attention should be paid to the patient's quality of life, which is often degraded by peritoneal fibrosis and small bowel obstruction.

Female

Salivary duct carcinoma: a clinicopathologic study of three cases with a review of the literature.

Three cases of salivary duct carcinoma are presented. They occurred in a 60 year old man, a 66 year old man and a 57 year old woman. All of the lesions were located in the parotid gland. The tumor size ranged from 3 to 5 cm across the largest diameter. Facial paralysis was observed in two cases. Histologically, intraductal and invasive adenocarcinoma showing papillary, cribriform, and solid patterns with comedolike necrosis was observed. Immunohistochemically, the tumor cells were positive for keratin and epithelial membrane antigen. No myoepithelial cells were demonstrated within the tumor by staining for S-100 protein, alpha-smooth muscle actin or muscle specific actin. Ultrastructurally, intracytoplasmic lumina with microvilli, a moderate number of mitochrondria, lysosomes, and tight junctions were found. Regional lymph node metastasis was observed in one case, and distant metastasis developed in two cases. All of the patients were treated with adjuvant postoperative irradiation. One patient died of disease at 11 months after the initial diagnosis, another was alive with disease at 8 months, and the third patient was alive without disease at 2 years and 3 months. Salivary duct carcinoma should be differentiated from low-grade salivary gland carcinomas using morphologic and clinical criteria because of its poor prognosis even with aggressive therapy.

Adenocarcinoma

Continual change in mate preferences.

Secondary sexual characters are highly variable both within and between species. Closely related species often differ markedly in sexual morphology but hardly at all in non-sexual traits. Here we show that Fisher's runaway process of sexual selection is intrinsically unstable and naturally leads to continual change in sexual traits. Runaway leads to semi-stable exaggeration of female preference for a male sexual character, followed by a slow decay of both traits until runaway is triggered again in a different direction. The process then repeats itself resulting in continual change in male sexual traits through time. Allopatric populations are thus expected to diverge without drift or substantial changes in selective pressures. If there is significant mutation bias acting on the male trait, continual change stops and a stable equilibrium appears. Such an outcome is more likely when exaggeration of the male sexual trait signals good genes.

Biological Evolution

Papillary serous carcinoma of the peritoneum in women. A clinicopathologic and immunohistochemical study.

BACKGROUND: Papillary serous carcinoma of the peritoneum (PSCP) is a primary peritoneal tumor in women that histologically resembles papillary serous carcinoma of the ovary (PSCO). Recognition of PSCP as an entity is controversial, as is the histogenesis, histopathologic differential diagnosis, and treatment. METHODS: Ten cases of PSCP retrieved from the pathology files of 4 hospitals in Kyoto and Nara, Japan, were studied clinicopathologically and immunohistochemically. RESULTS: Patient ages at presentation ranged from 40 to 74 years (median, 56 years). All patients were Asian (Japanese). None of the patients had a history of asbestos exposure. Most of the patients had abdominal swelling, ascites with positive cytology, and elevated serum CA125. At surgery, omental tumors with dissemination to the abdominal and pelvic peritoneum were found in all patients. The histology was similar to that of Grade 2 to 3 PSCO. Immunohistochemical studies using a panel of monoclonal antibodies against carbohydrates showed that Lewis Y is a good marker, in addition to S-100, placental alkaline phosphatase, CA125, and CD15 for separating PSCP from malignant mesothelioma (MM). With cytoreductive surgery and cisplatin-based combination chemotherapy and in some cases adoptive immunotherapy and radiation, a median survival of 27 months and a 5-year survival rate of 27% were attained. One patient with Grade 3 tumor has survived for more than 6 years after surgery. CONCLUSIONS: (1) Papillary serous carcinoma of the peritoneum is a definite clinicopathologic entity; (2) immunohistochemistry is a useful tool for distinguishing PSCP from MM; (3) cytoreductive surgery and cisplatin-based combination chemotherapy with other adjunct therapies such as immunotherapy and radiation may improve patient survival in PSCP.

Adult

Population persistence and spatially limited social interaction.

We investigate the persistence of a population composed of socially interacting individuals living in a lattice structured habitat and the effect of spatially limited social interaction, reproduction, and migration. Both cooperative interaction (enhancing the survivorship of neighboring individuals) and competitive interaction (reducing it) are examined. Mathematical analysis based on pair approximation (or doublet decoupling approximation) and computer simulation are used. Results are: If migration rate is not very large, the population tends to form clusters of individuals (clumped distribution) due to spatially limited reproduction. Although cooperative interaction is more effective in a spatially structured population, the population is more difficult to persist than in the corresponding population without spatial structure, because the shortage of nearest neighbor vacant sites reduces reproduction. Migration of individuals reduces the clumping of the spatial pattern. Pair approximation predicts the equilibrium density fairly accurately when the predicted density is sufficiently high (i.e., more than 40% sites are occupied). If the predicted density is low however, the pair approximation overestimates the equilibrium population level. To overcome this disagreement, we examined improved pair approximation.

Bias

[Operative indications and treatment in elderly patients with esophageal cancer].

A recent study indicates that infection of human papillomavirus (HPV) may cause esophageal cancer and that it takes several decades from infection of HPV to developing cancer. Even in early stage esophageal cancer, lymph node metastasis is usually observed in the mediastinum, abdomen and neck regions. As patients with esophageal cancer are potentially in a malnutritional state because of disturbance of intake before treatment, active nutritional support should be performed before and after surgery. An objective nutritional assessment is necessary for nutritional support. The nutritional assessment index (NAI) can be applied to elderly patients because there is no difference in nutritional parameters between elderly and young patients. From the point of view that surgical treatment has limitations concerning complete curability, we employed a remote after loading system (RALS) into a multidisciplinary treatment called the Kochi system, which consists of a combination of surgery, radiation therapy and chemotherapy. This multidisciplinary method of treatment greatly contributes to survival and quality of life of esophageal cancer patients especially in elderly cases.

Aged

Overdispersed molecular evolution in constant environments.

According to recent data analysis of DNA sequences, the dispersion index, defined as the variance-to-mean ratio of the number of base substitutions in a lineage, is often much larger than unity, which is in conflict with simple Poisson processes assumed in the molecular clock hypothesis. In this paper, it will be shown that the dispersion index can be much larger than unity in a model in which the fitness of DNA sequences, mutation rate, and population size are all constant with time, and that moderately deleterious sequences are more abundant than the best fit sequences. Since the fixation probability of novel mutations depends on their fitness relative to the current sequence, the neutral mutation rate is enhanced once a deleterious mutation is fixed. In a simple case with two fitness classes, a large dispersion index can be produced by moderately deleterious mutations (3 < 4Ns < 6), but neither by nearly neutral (4Ns < 2) nor by strongly deleterious (4Ns > 7) mutations. Analysis of the case with 100 fitness classes shows that the dispersion index is insensitive to the population size, but greatly changes with the fitness distribution of DNA sequences. The model can explain why non-synonymous substitutions often have a larger dispersion index than synonymous substitutions.

Animals

Optimal growth schedule of pathogens within a host: switching between lytic and latent cycles.

We have studied the optimal growth schedule of a pathogen, which maximizes the total number of transmissions from an infected host to other individuals until host death or recovery. It is assumed that both transmission rate f(N) and host mortality increase with the number of pathogens, N. The model predicts that the optimal growth schedule of pathogens strongly depends on the curvature of f(N): If f(N) increases faster than linearly with N, the pathogens should always reproduce at the maximum speed. By contrast, if f(N) saturates with N, the optimal schedule is composed of (1) a brief initial stage of infection, in which the pathogens proliferate at the maximum speed (productive cycle), (2) followed by the long latent period with the "stationary infection level," N* (latent cycle), (3) which may end when the pathogens start rapid proliferation triggered either by the host's senescence ("programmed break") or by the sudden rise in the host's mortality ("incidental break"). The latter may be caused by the double infection of another strain. We also examine the Nash equilibrium schedule of pathogen growth in the presence of multiple infections.

Age Factors

Transcriptional regulation of ferritin messenger ribonucleic acid levels by insulin in cultured rat glioma cells.

Recent data have shown that ferritin, a ubiquitous protein, has a role as a regulator of cellular differentiation. In the present study we have investigated the expression of ferritin mRNAs in cultured C6 cells, a rat glioma cell line, in response to insulin, which has an important role in cellular growth and differentiation. Insulin stimulated steady state levels of both ferritin heavy chain and ferritin light chain mRNAs. An increase in the level of ferritin heavy or light chain mRNA was detected after 2 h of incubation with insulin, and a plateau was reached after 48 h for heavy chain mRNA and after 72 h for light chain mRNA. The responses were dose-dependent and were maximal at 100 nM for both mRNAs. Treatment of cells with actinomycin-D showed that insulin had no effect on the posttranscriptional stability of these mRNAs. Actinomycin-D inhibited insulin-induced accumulation of both mRNAs, suggesting transcriptional stimulation of ferritin genes by insulin. A nuclear run-on assay showed that the insulin-induced increase in ferritin heavy chain mRNA was due to an increase in the rate of gene transcription. We also demonstrated that insulin-like growth factor-I (IGF-I) increased ferritin heavy and light chain mRNA levels in a dose-dependent fashion, and that the maximum effect was obtained at a concentration of 10 nM on both mRNA levels. IGF-I was not only 10-fold more potent, but the absolute level of maximum stimulation was also about 2-fold greater than that for insulin. The combination of insulin (100 nM) and IGF-I (10 nM) showed no additive effect. The results suggested that the ferritin heavy and light chain genes are transcriptionally regulated by insulin and influenced by IGF-I.

Actins