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Biomedical subjects

Y Iwasa

Publications and source records attributed to Y Iwasa.

At least 55 records · Page 3Linked to original sources
PubMed2000

Expression of stress-response and cell proliferation genes in renal cell carcinoma induced by oxidative stress.

Ferric nitrilotriacetate induces oxidative damage in renal proximal tubules that ultimately leads to a high incidence of renal cell carcinoma (RCC) in rats. In search of genes specifically involved in oxystress-induced carcinogenesis, we have applied a modified fluorescent differential display technique to the tumors and an established cell line as well as their non-neoplastic counterparts. We screened approximately 84,000 products. Reverse Northern blotting confirmed differential expression of 20 transcripts, which showed either significant increase, decrease or lack of expression in the RCCs. Five cDNA clones encoded novel products of unknown function. Fifteen cDNA clones were identified by homology search, which included annexin II, Y-box binding protein, ribosomal proteins, heat shock proteins, DNA polymerase, nonmuscle caldesmon (increased); protein tyrosine phosphatase (decreased); selenoprotein P, stromal cell-derived factor 1, intestinal trefoil protein, nicotinamide adenine dinucleotide, reduced form (NADH) dehydrogenase, and insulin-like growth factor binding protein 7 (deleted). Most of the identified genes were associated with stress-response or cellular proliferation. These results suggest that multiple, interactive genetic pathways are involved in carcinogenesis induced by oxidative stress.

Animals↗
PubMed2000

Effect of administration of nucleosides and nucleotides on protein turnover and the hypoxic myocardium.

Nucleotides and nucleosides have effects on improving energy metabolism and enhancing immune function. Under a surgical stress, requirement of nucleotides are increased as well as nitrogen. A well-balanced nucleoside solution (OG-VI) was developed for parenteral administration and its effect was examined in animals. The OG-VI solution contained 3.11% of nucleosides which was composed of inosine, guanosine monophosphate, cytidine, uridine and thymidine of 4:4:4:3:1 in molar ratio. The whole body protein turnover increased significantly in rats received total parenteral nutrition (TPN) with OG-VI after 70% hepatectomy and enhanced the fractional protein synthesis rates of the muscle and liver. Also myocardial contractility (%segment shortening, %SS) in dogs after occlusion of left anterior descending artery (LAD) was recovered to 70% after reperfusion in the OG-VI group. The creatine phosphate (PCr) / inorganic phosphate (Pi) was maintained the baseline level and did not decrease after hypoxia in the OG-VI group while PCr/ Pi was decreased after hypoxia in normal rat. These data suggested that the nucleoside-nucleotide (OG-VI) improved nitrogen metabolism and might stimulate synthesis of high-energy phosphate in recovery after severe surgical stress.

Animals↗
PubMed2000

The effect of high salt intake on the mandibular bone loss in Dahl-Iwai salt-sensitive rat.

The purpose of this study was to evaluate the effect of high salt intake on the mandibular bone in Dahl-Iwai salt-sensitive (DS) rats. Twenty-eight 11-week-old male DS rats were divided into four groups (n=7). The control groups received a normal (0.2% NaCl) diet while the experimental groups received a diet supplemented with 8.0% NaCl. The systolic blood pressure was significantly increased in the experimental groups compared to the control groups. The animals were sacrificed under ether anesthesia at the 8th week or the 22nd week of the experiment. The biochemical data in plasma and urine suggested negative calcium balance in the experimental groups compared to the control groups. The bone mineral density was significantly reduced at the 22nd week of high salt loading. The histomorphometric analysis suggested that the reduction of the mandibular bone volume had already started by the 8th week of high salt loading along with the increased bone resorption and the decreased bone formation, and that the improper bone remodeling balance became normalized by the 22nd week of high salt loading. In conclusion, these results indicate that a high salt intake causes not only severe hypertension but also a mandibular bone reduction in the DS rats.

Absorptiometry, Photon↗
PubMed1999

Formation of cone mosaic of zebrafish retina.

In the zebrafish retina, four types of cone photoreceptor cells (or cones) with different sensitive frequencies are arranged in a regular pattern, named "cone mosaic". A pair of small cones, one sensitive to red and the other sensitive to green, is in close contact and forms a "double cone". In addition, there are two kinds of single cones, sensitive to blue and to UV, respectively. We study characteristics of cell-differentiation rules that realize stable formation of cone mosaic. Assumptions are: undifferentiated cells are arranged in a regular square lattice, and they are one of the three types (B, U, and D cells). A D cell has two parts (G and R-parts) and takes one of the four directions. The cells change their cell type and orientation following a continuous-time Markovian chain. The state transtion occurs faster if it increases the stabilities of the focal cell, in which the stability is the sum of affinities with neighboring cells. After the transient period, the system may reach a stable pattern (pre-pattern). The pattern becomes fixed later when the cells are fully differentiated in which B cells, U cells, and D cells become blue-sensitive, UV-sensitive, and double cones, respectively. We search for the combinations of affinities between cell states that can generate the same cone mosaic patterns as in zerbrafish retina. Successful transition rules give (1) zero or small affinity with the pairs of cell states that are absent in the zebrafish cone mosaic (lambda(UR), lambda(BG)and the contact of two cells of the same type); (2) a large affinity between a part of D cells and a non-D cell (lambda(UG)and lambda(BR)); and (3) a positive affinity of an intermediate magnitude between two non-D cells (lambda(BU)) and between two parts of D cells (lambda(GR)). The latter should be of a magnitude of about 60-90% of the former. The time needed to form a regular pattern increases with the lattice size if all the cells start pre-pattern formation simultaneously. However, the convergence time is shortened considerably if the pre-pattern formation occurs only in a narrow band of morphogenetic cell layer that sweeps from one end of the lattice to the other.

Animals↗
PubMed1999

Good parent and good genes models of handicap evolution.

We previously studied a good genes handicap model in which male quality was heritable and improved offspring viability. We extend our analysis to species in which males provide direct benefits (e.g. parental care, better resources, the absence of contagious diseases). Male quality now affects female fitness by increasing female reproductive success. For this good parent handicap to work, the male signal must have condition-dependent expression. The equilibrium strength of female preference is controlled by the product of signal transmission efficiency, phenotypic variance of male quality and the effectiveness of male quality in improving female reproductive success. The equilibrium resulting from the good parent handicap has exactly the same form as with the good genes handicap. This allows us to compare the relative importance of these two forces in the evolution of female preferences. The handicap models (both good genes and good parent) also show cyclic evolution, as happens with the pure Fisherian model. However, we predict that the handicap process is often strong enough to lead to a stable equilibrium. This leads to the conclusion that cyclic evolution is less likely to occur for handicap than Fisherian traits.

Animals↗
PubMed1999

High incidence of allelic loss on chromosome 5 and inactivation of p15INK4B and p16INK4A tumor suppressor genes in oxystress-induced renal cell carcinoma of rats.

Ferric nitrilotriacetate induces oxidative damage in renal proximal tubules, a consequence of Fenton-like reaction, that ultimately leads to a high incidence of renal cell carcinoma (RCC) in rats. In order to find common genetic alterations in this oxystress-induced carcinogenesis model, RCCs were produced in F1 hybrid rats between Wistar and Long-Evans strains and genomes were screened for loss of heterozygosity (LOH) with microsatellite polymorphic markers by PCR. Five consecutive markers on chromosome 5 (D5Mgh5, D5Mit9, D5Mgh6, D5Mit11 and D5Mit6) showed LOH in >40% of the RCCs. As possible candidate tumor suppressor genes on chromosome 5, p15INK4B and p16INK4A were investigated for genetic alteration and aberrant methylation by Southern blot, PCR/SSCP/ sequencing and methylation-specific PCR. Genetic alteration (homozygous or hemizygous deletion with or without point mutation) or aberrant methylation were found in 30.7 and 53.8% of the RCC cases, respectively, which was proportionally associated with the histological nuclear grade and metastatic activity. Our data suggest that inactivation of p15 and p16 genes could be one of the major pathways responsible for oxystress-induced carcinogenesis.

Animals↗
PubMed1999

Sex specific X chromosome expression caused by genomic imprinting.

The conflict theory of genomic imprinting predicts that imprinted genes are growth enhancing when paternally expressed and growth suppressing when maternally expressed. The expression pattern of autosomal imprinted genes generally fits these predictions. However, the conflict theory cannot easily account for the pattern of X-linked imprinting in humans and mice. This has led us to propose a novel hypothesis that X-linked imprinting has evolved to control sex specific gene expression in early embryos. The hypothesis links paternal X-imprinting (i.e. paternal copy silencing) to random X-inactivation and the retention of Y-linked copies, and links maternal X-imprinting to escape from random X-inactivation and the loss of Y-linked copies. The hypothesis offers a good explanation of the existing data on X-imprinted genes.

Animals↗
PubMed1999

Fine-needle aspiration cytology of malignant hemangiopericytoma of the salivary gland: A case report.

A 79-yr-old woman presented with a 5-yr history of swelling of the left cheek. The fine-needle aspiration (FNA) smear showed a spindle-cell neoplasm with capillaries and benign endothelial cells. The spindle cells possessed pleomorphic, hyperchromatic elongated nuclei and a moderate amount of ill-defined cytoplasm. They also showed papillary arcades surrounded and encased by relatively small ovoid to short spindle cells. Subsequent surgical excision confirmed the presence of malignant hemangiopericytoma (HP). Immunohistochemical studies on the histologic section using vimentin were strongly positive, consistent with HP. To the best of our knowledge, this is the second published report of FNA cellular features of malignant HP of the salivary gland. Besides delineating the FNA cellular features of HP of the salivary gland, the present case illustrates the value of using immunohistochemical approaches. Diagn. Cytopathol. 1999;21:398-401.

Aged↗
PubMed1999

Clinical implications of mutations C-to-T1653 and T-to-C/A/G1753 of hepatitis B virus genotype C genome in chronic liver disease.

Among many mutational "hot spots" on hepatitis B virus (HBV) genome, A-to-T1762 and G-to-A1764 within the core promoter have been underscored in view of disease association as well as viral expression/replication. Although to a lesser extent, C-to-T1653 and T-to-V(C/A/G)1753 were also noteworthy in our previous study. To assess the clinical significance of these mutations, we determined the nucleotide sequence of an HBV DNA fragment covering these sites in HBsAg-positive blood donors (n = 160) and patients with chronic hepatitis (n = 66), liver cirrhosis (n = 45), and hepatocellular carcinoma (n = 58), most of whom were infected with genotype C HBV (subtype adr). In cases where HBe antigen was positive, the frequency of T1653 and/or V1753 showed a striking increment from chronic hepatitis patients (18%) to liver cirrhosis and/or hepatoma patients (82%), whereas that of T1762/A1764 was already high in chronic hepatitis patients (76%). In HBe antigen-negative cases, by contrast, significant difference in the frequency of T1653/V1753 mutants was found between blood donors (22%) and chronic hepatitis patients (67%). Our results suggest that T1653/V(particularly C)1753 mutants are more closely associated than T1762/A1764 with the progression of liver disease from chronic hepatitis to cirrhosis in HBe antigen-positive patients. A system of site-directed mutagenesis PCR RFLP was constructed to diagnose T1653 and C/A1753 more conveniently. Detecting T1653 and C/A1753 by this method would contribute to the differential diagnosis of HBV-associated liver disease.

Base Sequence↗
PubMed1999

Persistent oxidative stress in human colorectal carcinoma, but not in adenoma.

Few studies have been conducted focusing on a potential role of reactive oxygen species in tumor cell metabolism. Here we studied human colorectal adenocarcinomas and adenomas to determine whether oxidative stress is imposed on cancer cells in vivo and used specific antibodies against 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (HNE)-modified proteins, and 3-nitro-L-tyrosine (3-NT) to determine whether there is an association between oxidative stress and cellular proliferation. Higher levels of oxidative modifications in DNA and proteins were observed in carcinoma cells, but not in adenoma cells, than in the corresponding nontumorous epithelial cells by immunohistochemistry as well as high-performance liquid chromatography (HPLC)-based 8-OHdG determination. The fraction of proliferating cell nuclear antigen-positive cells was proportionally associated in adenocarcinomas with the staining intensities of 8-OHdG and 3-NT. Furthermore, Western blot analysis of the proteins extracted from carcinoma cells revealed several specific proteins modified by HNE or peroxynitrite. Thus we concluded that colorectal carcinoma, but not adenoma cells, are exposed to more oxidative stress than their corresponding nontumorous epithelial cells, regardless of clinical stage and histology, and further that the oxidative stress in carcinoma cells might stimulate cellular proliferation.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Crossover accelerates evolution in GAs with a Babel-like fitness landscape: mathematical analyses.

The effectiveness of crossover in accelerating evolution in genetic algorithms (GAs) is studied with a haploid finite population of bit sequences. A Babel-like fitness landscape is assumed. There is a single bit sequence (schema) that is significantly more advantageous than all the others. We study the time until domination of the advantageous schema (Τ&subd;). Evolution proceeds with appearance, spread, and domination of the advantageous schema. The most important process determining Τ&subd; is the appearance (creation) of the advantageous schema. Crossover helps this creation process and enhances the rate of evolution. To study this effect, we first establish an analytical method to estimate Τ&subd; with or without crossover. Then, we conduct a numerical analysis using the frequency vector representation of the population with the recurrence relations formulated after GA operations. Finally, we carry out direct computer simulations with simple GAs operating on a population of binary strings directly prepared in the computer memory to examine the performance of the two analytical methods. It is shown that Τ&subd; is reduced greatly by crossover with a mildly high rate when the mutation rate is adjusted to a moderate value and that an advantageous schema has a fairly larger order (the number of bits). From these observations, we can determine implementation criteria for GAs, which are useful when we are applying GAs to engineering problems having a conspicuously discontinuous fitness landscape.

Algorithms↗
PubMed1999

Intranuclear distribution of 8-hydroxy-2'-deoxyguanosine. An immunocytochemical study.

We used immunofluorescence staining (monoclonal antibody N45.1) with cytological imprinting to study changes in the intranuclear distribution of 8-hydroxy-2'-deoxyguanosine in renal cells of male Wistar rats after oxidative stress by ferric nitrilotriacetate. In the control proximal tubule cells, small spherical signals were uniformly distributed throughout the nuclei. Under oxidative stress, immunofluorescence intensity was increased, especially near nuclear membrane. In cells with nuclear shrinkage or deformity, intense, diffuse signals throughout the nuclei were observed. Our results suggest that specific nuclear sites are vulnerable to oxidative DNA damage and that diffuse intense signals precede cell death after oxidative stress.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

[Distinct genotypes of TTV infection in non A-non C hepatitis].

TTV DNA was tested by polymerase chain reaction with two set primers(NG061/NG063, T801/T935) in patients with nonA-nonC acute and chronic hepatitis. TTV DNA was detected in 75.9-100% by T801/T935, 47.1-48.3% by NG061/NG063 of 46 patients. The nucleotide sequences including 185 bp in the N22 region of 22 TTV DNA isolates from patients with acute and chronic nonA-nonC hepatitis, were classified into various TTV genotypes such as 1a, 1b and non-1. Our results demonstrate that genotype 1b may induce hepatic injury.

Amino Acid Sequence↗
PubMed1998

Noise-induced regularity of spatial wave patterns in subalpine abies forests

In subalpine forests dominated by Abies species in Japan and northeastern United States, trees show traveling wave of regeneration with many striped zones of tree dieback, moving downwind at a constant rate. Previous theoretical studies have demonstrated that a very simple model can generate wave-like spatio-temporal patterns of tree regeneration in a lattice-structured habitat with each site occupied by a cohort of trees. A cohort taller than the average height of its windward neighbor experiences stand-level dieback in the next time step and the height becomes zero. Otherwise the cohort increases its height at a constant rate. Starting from a random initial pattern, this simple deterministic model can generate a saw-toothed pattern that moves downwind at a constant rate, but the distance between adjacent dieback zones has a large variance. In this paper, we study the effects of "noises" in tree dieback rules in two forms which help to generate more regular patterns: (1) additional random disturbances at a low rate, which change the size of "clusters" (defined as a group of cohorts between adjacent dieback zones) by splitting a large cluster into two or by merging a small one with a neighbor, and (2) the stochastic rule of tree dieback, represented by the probability of dieback in unit time being a sigmoidal function of the difference in the tree height between the site and the windward neighbors. These noises are effective both for one-dimensional and two-dimensional models, but spatial patterns are much more regular in the two-dimensional model than in the one-dimensional model. Copyright 1998 Academic Press

Journal Article↗
PubMed1998

Cell-differentiation rules that generate regular mosaic patterns: modelling motivated by cone mosaic formation in fish retina.

We study characteristics of cell-differentiation rules that realize stable formation of regularly arranged checker-board patterns, exemplified by cone "mosaic" zebrafish retina, or the regular arrangement of cone photoreceptor cells. We consider the situation in which cells are arranged on a square lattice and are initially undifferentiated. Later each cell becomes one of the two differentiated states, affected by the state of the neighboring cells. The cells that undergo differentiation form a "morphogenetic cell row" which sweeps from one end to the other end of the lattice through time. This models an outward sweep of the margin of expanding mosaic region of the retina which occurs as undifferentiated photoreceptor cells become differentiated in concentric circles, joining the mosaic. We introduce an index to measure the ability of cell-differentiation rules to generate regular checker-board patterns from irregular initial patterns, and attempt to characterize the successful rules. We first show the importance of six "preservation conditions" which guarantee perfectly regular photoreceptor arrangement for all the rows after a regular row. Then we select an additional six "optimizing conditions" for responses to configuration that are consistently shown by the rules of high average scores. We also examine the effect of interaction between responses to different configurations. Finally we examine the concept of morphogenetic row precedence, i.e. that the successful rules generating a high score tend to treat the consistency with neighbors in the newly differentiated cells (those in the morphogenetic cell row) as more important that the consistency with previously differentiated neighbors.

Animals↗
PubMed1998

On rugged shape of skin tumor (basal cell carcinoma).

Basal cell carcinoma (BCC) is the most common cancer of the skin that is made of transformed basal cells of the human epidermis, and spreads along the epidermis--dermis junction. It often forms tumor cell mass that protrudes towards the dermal connective tissue with many branches. Histopathological examination of the cancer demonstrates the cell mass of a rugged shape appearing as many regular spaced islands in a two-dimensional section. We study the process of cell proliferation and spatial pattern formation of the skin tumor by a pair of partial differential equations of tumor cells and nutrients. The assumptions are: (1) proliferation rate of tumor cells depends on the availability of nutrients, which simply diffuse out of capillaries through connective tissue; (2) nutrients are consumed by active tumor cells; (3) cell diffusion coefficient expressing tumor cell movements increase with the cell density and the nutrient availability. Starting from the initial condition with a single layer of tumor cells. the model develops a smooth colony if n'0 is large, but a characteristic rugged spatial pattern of tumor cell mass if n'0 is small, in which n'0 is nutrient concentration multiplied by square root of growth efficiency divided by diffusion coefficient of nutrients. The proportion of the area occupied by tumor cells increases with n'0. The coefficient of variation in the width of "islands" of tumor cell mass is rather small (0.2 reverse similar0.6), implying the regularity of the spatial pattern. We also analyses the photographs of a two-dimensional section of tumor cell mass and compare the spatial patterns generated by the model.

Aged↗