Biomedical subjects

Akira Sasaki

Publications and source records attributed to Akira Sasaki.

At least 19 recordsLinked to original sources

PubMed2006

The role of trade-off shapes in the evolution of parasites in spatial host populations: an approximate analytical approach.

Given the substantial changes in mixing in many populations, there is considerable interest in the role that spatial structure can play in the evolution of disease. Here we examine the role of different trade-off shapes in the evolution of parasites in a spatially structured host population where infection can occur locally or globally. We develop an approximate adaptive dynamic analytical approach, to examine how the evolutionarily stable (ES) virulence depends not only on the fraction of global infection/transmission but also on the shape of the trade-off between transmission and virulence. Our analysis can successfully predict the ES virulence found previously by simulation of the full system. The analysis confirms that when there is a linear trade-off between transmission and virulence spatial structure may lead to an ES virulence that increases as the proportion of global transmission increases. However, we also show that the ESS disappears above a threshold level of global infection, leading to maximization. In addition just below this threshold, there is the possibility of evolutionary bi-stabilities. When we assume the realistic trade-off between transmission and virulence that results in an ESS in the classical mixed model, we find that spatial structure can increase or decrease the ES virulence. A relatively high proportion of local infection reduces virulence but intermediate levels can select for higher virulence. Our work not only emphasizes the importance of spatial structure to the evolution of parasites, but also makes it clear that situations between the local and the global need to be considered. We also emphasize the key role that the shape of trade-offs plays in evolutionary outcomes.

Adaptation, Physiological↗

PubMed2006

An immunohistochemical evaluation of BMP-2, -4, osteopontin, osteocalcin and PCNA between ossifying fibromas of the jaws and peripheral cemento-ossifying fibromas on the gingiva.

The present study examined histological difference between ossifying fibromas (OF, n=5) and peripheral cemento-ossifying fibromas (PCOF, n=7). Bone morphogenetic proteins (BMP)-2 and -4, osteopontin (OPN), osteocalcin (OCN) and proliferating cell nuclear antigen (PCNA) were used for the immunohistochemical examinations. Oxytalan fibers present at the periodontal tissue were stained to determine the tumor cell origin. Many OFs showed high immunohistochemical reactions for BMP-2, -4 and OPN compared to those of PCOFs. PCNA index (IP) of OFs was significantly higher than that of PCOFs. All the PCOFs showed a high expression of oxytalan fibers. Only two OFs exhibited a small number of oxytalan fibers. These results suggest that PCOF has only little ability to form hard tissue and seems to be a reactive lesion. The expression of oxytalan fibers reveals that OF does not only originate from periodontal tissue.

Adolescent↗

PubMed2006

The wave speed of intergradation zone in two-species lattice Müllerian mimicry model.

A spatially explicit model is studied to analyse the movement of coupled clines in two-species Müllerian mimicry system as exemplified by the comimicking helicoiine butterflies in Central-South America Heliconius erato and Heliconius melpomene. In this system, a pair of comimicking wing patterns of two species (mimicry ring) is found in a geographical region but another pair of wing patterns is found in a different geographical region. The distribution of mimicry rings thus forms a spatial mosaic in a large geographical scale, and the mechanism responsible for their stable maintenance has been a long-standing question in evolutionary biology. We here examine the speed of the movement of boundaries that divide the regions inhabited by different mimetic morphs in each comimicking species, by assuming coupled two-state stochastic cellular automatons where the flipping rate of the site occupied by a mimetic morph depends on the local density of the same morph and of the comimicking morph in the other species. The speed of cline movement shows a complex dependence on the coupling parameter between mimetic species--greater coupling of comimicking morphs between species slows down the cline movement only when the reduction in predation rate exhibits diminishing return to the increase of local mimetic morph density. The analytical predictions are confirmed by the results of Monte Carlo simulations. The speed of advance is quite different from that predicted from the conventional reaction-diffusion model, indicating that demographic stochasticity plays a critical role in determining the speed of cline movement. We also examine if the spatial heterogeneity in migration rate can stably maintain clines.

Animals↗

PubMed2006

Efficient method for the deprotection of tert-butyldimethylsilyl ethers with TiCl4-Lewis base complexes: application to the synthesis of 1beta-methylcarbapenems.

TiCl4-Lewis base (AcOEt, CH3NO2) complexes smoothly deprotected tert-butyldimethylsilyl (TBDMS) ethers. The reaction velocity with these complexes, which seemed less reactive due to the influence of Lewis bases, was considerably greater than that with TiCl4 alone. Selective desilylations between aliphatic and aromatic TBDMS ethers (1 and 5), between 1 and benzyl, allyl, tosyl, methoxyphenyl, and chloroacetyl ethers (13, 14, 15, 16, and 17), and between TBDMS and TBDPS ethers (18 and 19) were successfully performed. Desilylation of TBDMS-aldol, acyloin, and beta-lactam analogues 9-12 proceeded smoothly due to anchimeric assistance by the neighboring carbonyl groups. The present method was successfully applied to the practical synthesis of 1beta-methylcarbapenems 20a'-f'.

Carbapenems↗

PubMed2006

The greater than twofold cost of integration for retroviruses.

Sexual reproduction, typically conceived of as a puzzling feature of eukaryotes, has posed an extraordinary evolutionary challenge in terms of the twofold replicative advantage of asexual over sexual organisms. Here we show mathematically that a greater than twofold cost is paid by retroviruses such as HIV during reverse transcription. For a retrovirus, replication is achieved through RNA reverse transcription and the effectively linear growth processes of DNA transcription during gene expression. Retroviruses are unique among viruses in that they show an alternation of generations between a diploid free living phase and a haploid integrated phase. Retroviruses engage in extensive recombination during the synthesis of the haploid DNA provirus. Whereas reverse transcription generates large amounts of sequence variation, DNA transcription is a high-fidelity process. Retroviruses come under strong selection pressures from immune systems to generate escape mutants, and reverse transcription into the haploid DNA phase serves to generate diversity followed by a phase of transcriptional clonal expansion during the restoration of diploidy from a stable, long lived, DNA encoded provirus.

Animals↗

PubMed2006

A mathematical model for apoptosome assembly: the optimal cytochrome c/Apaf-1 ratio.

Apoptosis, a highly conserved form of cell suicide, is regulated by apoptotic signals and their transduction with caspases, a family of cystein proteases. Caspases are constantly expressed in the normal cells as inactive pro-enzymes. The activity of caspase is regulated by the proteolysis. Sequential proteolytic reactions of caspases are needed to execute apoptosis. Mitochondrial pathway is one of these apoptotic signal pathways, in which caspases are oligomerized into characteristic heptamer structure, called apoptosome, with caspase-9 that activate the effector caspases for apoptosis. To investigate the dynamics of signal transduction pathway regulated by oligomerization, we construct a mathematical model for Apaf-1 heptamer assembly process. The model first reveals that intermediate products can remain unconverted even after all assemble reactions are completed. The second result of the model is that the conversion efficiency of Apaf-1 heptamer assembly is maximized when the initial concentration of cytochrome c is equal to that of Apaf-1. When the concentration of cytochrome c is sufficiently larger or smaller than that of Apaf-1, the final Apaf-1 heptamer production is decreased, because intermediate Apaf-1 oligomers (tetramers and bigger oligomers), which themselves are unable to form active heptamer, accumulate too fast in the cells, choking a smooth production of Apaf-1 heptamer. Slow activation of Apaf-1 monomers and small oligomers increase the conversion efficiency. We also study the optimal number of subunits comprising an active oligomer that maximize the conversion efficiency in assembly process, and found that the tetramer is the optimum.

Animals↗

PubMed2006

Shaping the phylogenetic tree of influenza by cross-immunity.

Cross-immunity among related strains can account for the selection producing the slender phylogenetic tree of influenza A and B in humans. Using a model of seasonal influenza epidemics with drift (Andreasen, 2003. Dynamics of annual influenza A epidemics with immuno-selection. J. Math. Biol. 46, 504-536), and assuming that two mutants arrive in the host population sequentially, we determine the threshold condition for the establishment of the second mutant in the presence of partial cross-protection caused by the first mutant and their common ancestors. For fixed levels of cross-protection, the chance that the second mutant establishes increases with rho the basic reproduction ratio and some temporary immunity may be necessary to explain the slenderness of flu's phylogenetic tree. In the presence of moderate levels of temporary immunity, an asymmetric situation can arise in the season after the two mutants were introduced and established: if the offspring of the new mutant arrives before the offspring of the resident type, then the mutant-line may produce a massive epidemic suppressing the original lineage. However, if the original lineage arrives first then both strains may establish and the phylogenetic tree may bifurcate.

Animals↗

PubMed2006

Localization of dopamine receptor subtypes in the rat spiral ganglion.

Although dopaminergic neurons are thought to exist in the lateral olivocochlear efferent system and modulate the afferent nerve activity, the distribution of dopamine (DA) receptor subtypes is still obscure. In the present study, we investigated the localization of five subtypes of DA receptor (D1-5) by immunocytochemical analysis and the gene expression of D1-5 using RT-PCR procedure in the rat cochlea. Most, but not all, spiral ganglion neurons were immunolabeled with all the anti-DA receptor subunit antibodies and faint punctuate immunoreactivities were observed in inner hair cell regions. Gene expression for all receptors was detected. These results suggest that all DA receptor subtypes are present in spiral ganglion cells, and potentially regulate afferent neurotransmission.

Animals↗

PubMed2006

Endoscopic transtympanic tympanoplasty in the treatment of conductive hearing loss: early results.

OBJECTIVE: We describe our initial experience with endoscopic transtympanic tympanoplasty and evaluate whether this approach is adequate and minimally invasive in the treatment of conductive hearing loss. STUDY DESIGN: Prospective trial. SETTING: University hospital. PATIENTS: Nine patients underwent endoscopic transtympanic tympanoplasty, with an average follow-up period of 17 months. Presurgical diagnosis was made by transtympanic endoscopy through a perforation made by OtoScan laser-assisted myringotomy in the outpatient clinic. METHODS: With clean endoscopic visualization, ossiculoplasty was performed by inserting a trimmed tragal cartilage through the myringotomy perforation made by laser-assisted myringotomy. Two types of ossiculoplasty were performed: columella reconstruction and interposition. The tympanic membrane was covered with a chitin membrane or sealed with a small piece of perichondrium from the tragal cartilage. MAIN OUTCOME MEASURES: Perioperative and postoperative complications and preoperative and postoperative hearing. RESULTS: Endoscopic transtympanic tympanoplasty with columella and endoscopic transtympanic tympanoplasty with interposition were performed in seven and two patients, respectively. Insertion of the cartilage was performed without conversion to a conventional otomicroscopic technique. The average hearing level before the operation was 59 dB. After the endoscopic transtympanic tympanoplasty, the average improved to the level of 27 dB, with an average air-bone gap of 11 dB. The myringotomy perforation was closed within 2 to 3 weeks. CONCLUSION: As opposed to conventional methods, this procedure does not require surgical exposure such as otosclerosis drilling and skin incision, and avoids the substantial risk of unnecessary injury to the chorda tympani. Endoscopic transtympanic tympanoplasty for a disrupted ossicular chain is an adequate and minimally invasive procedure and should prove to be a useful surgical procedure in future endoscopic tympanoplasty.

Adolescent↗

PubMed2006

Comparison of intratympanic and intravenous dexamethasone treatment on sudden sensorineural hearing loss with diabetes.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of intratympanic administration of dexamethasone (IT-DEX) treatment on sudden sensorineural hearing loss (SSNHL) patients with diabetes by comparing the results with intravenous administration of dexamethasone (IV-DEX) treatment. STUDY DESIGN: Comparative study. SETTING: University hospital and affiliated hospital. PATIENTS: Ten sequential SSNHL patients with diabetes receiving IT-DEX and 21 sequential SSNHL patients with diabetes receiving IV-DEX. Patients with low tone hearing loss were excluded. INTERVENTION: In the IT-DEX group, two methods were applied to deliver DEX (4 mg/ml): injection through a perforation made by laser-assisted myringotomy or through a tympanostomy tube. IT-DEX administration was performed on 8 sequential days. In the IV-DEX group, DEX was administrated intravenously starting from an amount of 8 mg/d followed by taped doses for 10 days. MAIN OUTCOME MEASURES: Preprocedure and postprocedure hearing levels and complications. RESULTS: In the IT-DEX group, the average hearing level before the treatment was 79 dB. Overall, all 10 patients showed improvement of more than 10 dB in the pure-tone audiogram, with a mean improvement of 41 dB. Seven patients (70%) demonstrated successful results, and four recovered completely. In the IV-DEX group, 14 (67%) of the 21 patients showed improvement of more than 10 dB with a mean improvement of 25 dB. Thirteen patients (62%) demonstrated successful results. Free blood sugar during and after the IT-DEX treatment remained below the pretreatment levels, whereas four patients in the IV-DEX group demonstrated worsening of the hyperglycemia. CONCLUSION: IT-DEX treatment is at least as effective as IV-DEX treatment for SSNHL patients with diabetes.

Adult↗

PubMed2006

Pathogenic role of connective tissue growth factor (CTGF/CCN2) in osteolytic metastasis of breast cancer.

UNLABELLED: The role of CTGF/CCN2 in osteolytic metastasis by breast cancer cells and its mechanism of action were studied. Osteolytic metastasis accompanied by CCN2 and PTHrP overproduction was efficiently inhibited by an anti-CCN2 antibody. Furthermore, we found that CCN2 was induced by PTHrP through PKA-, PKC-, and ERK-mediated pathways therein. INTRODUCTION: Connective tissue growth factor (CTGF/CCN2) is a mediator of local angiogenesis induced by breast cancer, but its role in osteolytic metastasis has not been evaluated. PTH-related peptide (PTHrP) is another critical factor in the development of the osteolytic metastasis. Using both in vivo and in vitro approaches, we studied whether/how neutralization of CCN2 prevented bone metastasis and how PTHrP signaling is related. MATERIALS AND METHODS: A mouse model of bone metastasis by human breast cancer cell line MDA231 was treated with a CCN2-neutralizing antibody, and osteolytic bone metastases were assessed on radiographs and immunohistochemistry. Ccn2 gene expression and transcription were examined by Northern blot and luciferase analysis. Immunoblot analysis and kinase inhibitors were used to identify the signaling pathways implicated. Anti-angiogenic/osteoclastogenic effects of ccn2 downregulation were also evaluated. RESULTS: Treatment of mice with a CCN2-neutralizing antibody greatly decreased osteolytic bone metastasis, microvasculature, and osteoclasts involved. The antibody also suppressed the growth of subcutaneous tumor in vivo and proliferation and migration of human umbilical vein endothelial cells (HUVECs) in vitro. Downregulation of ccn2 also repressed osteoclastogenesis. CCN2 expression was specifically observed in cancer cells producing PTHrP and type I PTH/PTHrP receptor (PTH1R) invaded the bone marrow, and PTHrP strongly upregulated ccn2 in MDA231 cells in vitro. Activation of protein kinase C (PKC) and protein kinase A (PKA) was necessary and sufficient for the stimulation of ccn2 by PTHrP. Indeed, inhibition of the extracellular signal-regulated kinase (ERK1/2), PKC, or PKA by specific inhibitors counteracted the stimulation of ccn2 expression. Incubation of MDA231 cells with PTHrP induced the activation of ERK1/2. Consistent with these findings, inhibition of PKC prevented PTHrP-induced ERK1/2 activation, whereas 12-O-tetradecanoylphorbol13-acetate (TPA), a stimulator of PKC, upregulated it. CONCLUSIONS: CCN2 was critically involved in osteolytic metastasis and was induced by PKA- and PKC-dependent activation of ERK1/2 signaling by PTHrP. Thus, CCN2 may be a new molecular target for anti-osteolytic therapy to shut off the PTHrP-CCN2 signaling pathway.

Animals↗

PubMed2006

[Simultaneous determination of pesticides in agricultural products by LC/MS/MS using clean-up with ultrafiltration].

A method for simultaneous determination of multiple pesticide residues in agricultural products was developed by using a pretreatment with ultrafiltration, followed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The pretreatment process (extraction of pesticides from agricultural products with methanol, dilution of the extract with water, and ultrafiltration) gave recoveries in the range of 50-150% for 63 of 83 pesticides spiked at 0.25 microg/ g into 6 agricultural products. The detection limits of pesticides by LC/MS/MS were below 0.0005-0.05 micro/g. This method is useful for screening purposes and for multiresidue analysis of pesticides in agricultural products. Pesticide residues in 50 domestic crops were investigated by this method, and residues of 14 pesticides were detected in 30 crops.

Chromatography, Liquid↗

PubMed2006

[Preliminary report: observation by video laryngoscope of glottal narrowing due to cricoid pressure].

BACKGROUND: When the applied cricoid pressure is too strong, or the place or direction of the pressure application is not appropriate, glottal closure may occur, but its details are unclear. METHODS: We evaluated possible changes in the size of the rima glottides due to backward pressure on the cricoid cartilage or backward pressure or backward, upward, and rightward pressure (BURP) on the thyroid cartilage using a video laryngoscope (Fine View' Laryngoscope, Tray Medical, Tokyo) in 6 adult males and 6 females with Cormack and Lehane grade 1. RESULTS: The right-to-left distance of the rima glottides was 5.1 +/- 1.2 mm without pressure application but was reduced to 3.8 +/- 1.7, 3.5 +/- 1.8, 2.8 +/- 1.9, 2.4 +/- 1.8, and 2.6 +/- 1.2 mm by 20 N and 30 N backward pressure on the cricoid cartilage and 20 N and 30 N backward pressure and BURP on the thyroid cartilage, respectively. Compared with the absence of pressure application, 20 N and 30 N backward pressure and BURP on the thyroid cartilage significantly reduced it. It was reduced to 1 mm by 30 N backward cricoid pressure in 1 patient while glottal closure occurred due to 30 backward thyroid pressure in 1 patient. CONCLUSIONS: The right-to-left distance of the rima glottides was significantly reduced by backward pressure or BURP on the thyroid cartilage, and was also markedly reduced by cricoid pressure in 1 of the 12 patients.

Adult↗

PubMed2006

[A novel approach to loco-regional cancer chemotherapy with a chitosan-CDDP solution].

The authors applied 70% deacetylated chitin (DAC 70, chitosan) as a vehicle of cis-platinum (CDDP) to achieve loco-regional cancer chemotherapy, in an attempt to hold the drug in the target region with a locally sustained release. The DAC-70 powder was dissolved in a 0.1 M HCI solution into where CDDP solution and glycerol phosphate solution were added. The resulting product, DAC-70/CDDP became a muco-adhesive solution. The adhesiveness between the solution and human colonic mucosa was measured ex vivo by our own method, and a release profile of the CDDP was examined in vitro using an atomic absorption method. The adhesive force was stronger at 37 degrees C than that of at 25 degrees C. Ten percent of the CDDP was gradually delivered for 6 hours, while the release was maintained at the same levels for the following 72 hours. The release rate increased by 10-20% when lysozyme was added in the incubation systems. However, the release profile of the drug showed no remarkable changes. The DAC-70/CDDP solution provided a favorable adhesiveness with human colonic mucosa, while in situ degradability of the solution should be improved further more.

Adhesiveness↗

PubMed2005

Opacity effect on extreme ultraviolet radiation from laser-produced tin plasmas.

Opacity effects on extreme ultraviolet (EUV) emission from laser-produced tin (Sn) plasma have been experimentally investigated. An absorption spectrum of a uniform Sn plasma generated by thermal x rays has been measured in the EUV range (9-19 nm wavelength) for the first time. Experimental results indicate that control of the optical depth of the laser-produced Sn plasma is essential for obtaining high conversion to 13.5 nm-wavelength EUV radiation; 1.8% of the conversion efficiency was attained with the use of 2.2 ns laser pulses.

Journal Article↗

PubMed2005

Epidemiology and disease-control under gene-for-gene plant-pathogen interaction.

An introduction of disease-resistant variety of a crop plant often leads to the development of a virulent race in pathogen species that restores the pathogenicity to the resistant crop. This often makes disease control of crop plants extremely difficult. In this paper, we theoretically explore the optimal 'multiline' control, which makes use of several different resistant varieties, that minimizes the expected degree of crop damages caused by epidemic outbreaks of the pathogen. We examine both single-locus and two-locus gene-for-gene (GFG) systems for the compatibility relationship between host genotypes and pathogen genotypes, in which host haplotype has either susceptible or resistant allele in each resistance locus, and the pathogen haplotype has either avirulent or virulent allele in the corresponding virulence locus. We then study the optimal planting strategy of host resistant genotypes based on standard epidemiological dynamics with pathogen spore stages. The most striking result of our single-locus GFG model is that there exists an intermediate optimum mixing ratio for the susceptible and resistant crops that maximizes the final yield, in spite of the fact that the susceptible crop has no use to fight against either avirulent or virulent race of the pathogen. The intermediate mixture is optimum except when the initial pathogen spore population in the season consists exclusively of the virulent race. The optimal proportion of resistant crops is approximately 1/R(0), where R(0) is the basic reproductive ratio of pathogen--the rest (the vast majority if R(0) is large) of crops should be the susceptible genotype. By mixing susceptible and resistant crops, we can force the pathogen races to compete with each other for their available hosts. This competition between avirulent and virulent races prevents the fatal outbreak of the virulent race (the super-race) that can infect all the host genotypes. In the two-locus GFG control, there again exists the optimal mixing ratio for the fraction of universally susceptible genotype and the total fraction of various resistant genotypes, with the ratio close to 1/R(0).

Crops, Agricultural↗

PubMed2005

Overexpression of heat shock proteins in pallido-nigral axonal spheroids of nonhuman aged primates.

The occurrence of spheroids has been described in the globus pallidus (GP) and substantia nigra pars reticulata (SNr) of aged rhesus monkeys. Opinions vary as to the origin of spheroids. Ultrastructural and immunohistochemical analysis suggested that spheroids originate from degenerating axons or astroglia. In the present study, we have investigated the GP and SNr of aged monkeys (Macaca fascicularis and Macaca mulatta). Although immunoreactive for microtubule-associated protein (MAP) 1A, tau, amyloid precursor protein, synaptophysin and phosphorylated neurofilament, spheroids were not immunoreactive for MAP1B and MAP2. We confirmed the axonal nature of pallido-nigral spheroids in aged rhesus monkeys. Pallido-nigral spheroids have been reported to overexpress stress proteins, such as ubiquitin, alphaB-crystallin, and heat shock protein (Hsp) 27. We further evaluated the expression of Hsps in pallido-nigral spheroids. As well as being intensely immunoreactive for ubiquitin, alphaB-crystallin, Hsp27, and Hsp70, spheroids were immunoreactive for Hsp32 (heme oxygenase-1), Hsp40, Hsp60, and Hsp90. On the basis of these findings, we speculate that Hsp32-immunoreactive spheroids might be expressed as an oxidative stress response. Induction of other Hsps might play a role in protection of axons from the aggregation of neurofilament, MAPs and other proteins, and failure to protect degenerating axons might result in their proteolysis by the ubiquitin-proteasome system.

Age Factors↗

PubMed2005

Heparanase gene and protein expression in ameloblastoma: possible role in local invasion of tumor cells.

Ameloblastoma is the most common odontogenic neoplasm, particularized by its local invasiveness. Heparanase is the endo-glucuronidase enzyme that specifically cleaves heparan sulfate, the important modulator of extracellular matrix, and related to invasion of tumor cells. In this study, we addressed to show the gene expression and localization of heparanase in ameloblastoma. Immunohistochemistry and in situ hybridization of heparanase were carried out in 23 ameloblastomas. Strong expression of heparanase at both mRNA and protein levels was detected in all ameloblastomas studied. Small tumor nests and budding epithelial branches showed stronger staining pattern and the stromal tissues at the immediate vicinity of the tumor nests with strong heparanase expression were loose and edematous. Cystic areas and squamous metaplastic areas of the tumor showed intense staining with heparanase antibody proposing the implication of heparanase in these processes. These results suggest the possible contribution of heparanase in the local invasiveness and secondary morphologic changes of ameloblastoma.

Ameloblastoma↗