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Biomedical subjects

Y Oono

Publications and source records attributed to Y Oono.

At least 19 recordsLinked to original sources

Relational patterns of gene expression via non-metric multidimensional scaling analysis.

MOTIVATION: Microarray experiments result in large-scale data sets that require extensive mining and refining to extract useful information. We demonstrate the usefulness of (non-metric) multidimensional scaling (MDS) method in analyzing a large number of genes. Applying MDS to the microarray data is certainly not new, but the existing works are all on small numbers (< 100) of points to be analyzed. We have been developing an efficient novel algorithm for non-metric MDS (nMDS) analysis for very large data sets as a maximally unsupervised data mining device. We wish to demonstrate its usefulness in the context of bioinformatics (unraveling relational patterns among genes from time series data in this paper). RESULTS: The Pearson correlation coefficient with its sign flipped is used to measure the dissimilarity of the gene activities in transcriptional response of cell-cycle-synchronized human fibroblasts to serum. These dissimilarity data have been analyzed with our nMDS algorithm to produce an almost circular relational pattern of the genes. The obtained pattern expresses a temporal order in the data in this example; the temporal expression pattern of the genes rotates along this circular arrangement and is related to the cell cycle. For the data we analyze in this paper we observe the following. If an appropriate preparation procedure is applied to the original data set, linear methods such as the principal component analysis (PCA) could achieve reasonable results, but without data preprocessing linear methods such as PCA cannot achieve a useful picture. Furthermore, even with an appropriate data preprocessing, the outcomes of linear procedures are not as clear-cut as those by nMDS without preprocessing.

Algorithms↗

Social inhibition and the regulation of temporal polyethism in honey bees.

Honey bee division of labor is characterized by temporal polyethism, in which young workers remain in the hive and perform tasks there, whereas old workers perform more risky outside tasks, mainly foraging. We present a model of honey bee division of labor based on (1) an intrinsic process of behavioral development and (2) inhibition of development through social interactions among the workers in a colony. The model shows that these two processes can explain the main features of honey bee temporal polyethism: the correlation between age and task performance; the age at which a worker first forages and how this age varies among hives; the balanced allocation of workers to hive tasks and foraging; the recovery of a colony from demographic perturbations; and the differentiation of workers into different behavioral roles. The model provides a baseline picture of individual and colony behavior that can serve as the basis for studies of more fine-grained regulation of division of labor.

Aging↗

Renormalization-group theoretical reduction.

It has been known for some time that singular perturbation and reductive perturbation can be unified from the renormalization-group (RG) theoretical point of view. However, renormalization-group approaches to singularly perturbed problems require explicit perturbation results, so they could be complicated practically. The approach proposed in this paper has considerably eliminated the need for explicit perturbation results, making the RG approach simpler than many conventional singular perturbation approaches. Consequently, we may assert that reductive extraction of global features of the problem is the essence of singular perturbation methods.

Journal Article↗

Yokonolide A, a new inhibitor of auxin signal transduction, from Streptomyces diastatochromogenes B59.

Bio-probes that inhibit the action of auxin are useful tools for the study of auxin signaling. To screen for specific inhibitors of auxin signaling, we used an Arabidopsis transgenic line harboring the auxin-inducible promoter derived from PS-IAA4/5 and the reporter gene, GUS (beta-glucuronidase). In this transgenic plant, the exogenous auxin specifically enhanced the expression of the GUS reporter gene. A novel 22-membered spiroketal-macrolide, yokonolide A (1), and related previously known compound, A82548A (2), were isolated from Streptomyces diastatochromogenes B59 as inhibitors of auxin inducible gene expression. The absolute structure of I was determined by detailed spectral analyses and chemical derivatization. 1 and 2 completely inhibited the auxin-induced transcription of the reporter gene at 5 and 1 microm, respectively. In contrast, 1 and 2 did not affect the translation of GUS reporter transcripts. In addition, 1 and 2 did not inhibit the gibberellin-induced alpha-amylase expression at 100 microM in barley aleurone cells. These results suggest that 1 and 2 specifically inhibit auxin signaling leading to auxin-mediated gene expression.

Anti-Bacterial Agents↗

[Less invasive surgery for the small size peripheral lung cancer: an indication and a review of VATS (video-assisted thoracic surgery) lobectomy].

According to increment of detection of the "small" size peripheral lung cancer measuring less than 20 mm in the greatest dimension, the "less" invasive VATS lobectomy has became widespread among the general thoracic surgeon. To decide on the indication of VATS lobectomy, the frequency of nodal metastasis and recurrence were examined in relation to size of the tumor. The diagnostic accuracy of nodal status in clinical and pathological examinations was 88% in the group with tumors less than 20 mm, 79% in the 21 to 30 mm group and 63% in the c-T2 group, respectively. Also, recurrencies were experienced more frequently in c-T2 (44%) than in c-T1 (19%). In our department, the VATS lobectomy was introduced under the condition as follows; the clinical stage should be limited to T1N0M0. Intraoperative histological examination of the locoregional lymph nodes is required to avoid the risk of local recurrence. In these limited conditions, the survival rate of VATS lobectomy is slightly superior to that of the standard thoracotomy in a same clinical stage. In the future, the application of this procedure should be investigated in older patients, and in more advanced cases.

Humans↗

Anal canal squamous-cell carcinoma in situ, clearly demonstrated by indigo carmine dye spraying: report of a case.

To our knowledge, there has been no report of the use of indigo carmine dye spraying for the diagnosis of intraepithelial neoplasia. An asymptomatic 58-year-old female was referred to our hospital with a diagnosis of squamous-cell carcinoma in the anal canal. After indigo carmine dye spraying the margin and surface appearance of the lesion could be clearly defined. The lesion was completely removed by transanal resection. Final histologic diagnosis was squamous-cell carcinoma in situ with koilocytosis. Our case suggests that indigo carmine could be useful for the diagnosis of intraepithelia neoplasia.

Anus Neoplasms↗

Reductive use of renormalization group

It has been recognized that singular perturbation and reductive perturbation can be unified from the renormalization group (RG) theoretical point of view. However, the recognition has been only formal in the sense that it has not given us any new insight nor provided any new technical advantage over the usual RG approach. With our approach, the proto RG method proposed here, we can clearly show that system reduction is the key to singular perturbation methods. The approach also makes the calculation of singular perturbation results more transparent than the conventional RG approach. Consequently, for example, a consistent and easy RG derivation of the rotational covariant Newell-Whitehead-Segel equation is possible.

Journal Article↗

Factor XII Tenri, a novel cross-reacting material negative factor XII deficiency, occurs through a proteasome-mediated degradation.

A homozygous cross-reacting material negative factor XII-deficient patient with 3% antigen and activity levels of factor XII was screened for the identification of a mutation at the genomic level. Low-ionic strength single-stranded conformation polymorphism (SSCP) analysis and sequence analysis showed that the proband's gene for factor XII had an A-->G substitution at nucleotide position 7832 in exon 3, resulting in a Tyr34 to Cys substitution in the NH2-terminal type II domain of factor XII. We designated this mutation as factor XII Tenri. Mutagenic polymerase chain reaction (PCR), followed by KpnI digestion, showed a homozygous mutation in the proband's gene and heterozygous mutations in his parents and sister. Immunoprecipitation and Western blot analyses of plasma samples from the factor XII Tenri family indicated that the proband had a trace amount of variant factor XII with an apparent molecular mass of 115 kD, which was converted to the normal 80-kD form after reduction, suggesting that factor XII Tenri was secreted as a disulfide-linked heterodimer with a approximately 35-kD protein, which we identified as alpha1-microglobulin by immunoblotting. Pulse-chase experiments using baby hamster kidney (BHK) cells showed that Tenri-type factor XII was extensively degraded intracellularly, but the addition of cystine resulted in increased secretion of the mutant. Using membrane-permeable inhibitors, we observed that the degradation occurred in the pre-Golgi, nonlysosomal compartment and a proteasome appeared to play a major role in this process. On the basis of these in vitro results, we speculate that the majority of the factor XII Tenri is degraded intracellularly through a quality control mechanism in the endoplasmic reticulum (ER), and a small amount of factor XII Tenri that formed a disulfide-linked heterodimer with alpha1-microglobulin is secreted into the blood stream.

Adult↗

age Mutants of Arabidopsis exhibit altered auxin-regulated gene expression.

An Arabidopsis transgenic line was constructed expressing beta-glucuronidase (GUS) via the auxin-responsive domains (AuxRDs) A and B (BA-GUS) of the PS-IAA4/5 gene in an indoleacetic acid (IAA)-dependent fashion. GUS expression was preferentially enhanced in the root elongation zone after treatment of young seedlings with 10(-7) M IAA. Expression of the BA-GUS gene in the axr1, axr4, and aux1 mutants required 10- to 100-fold higher auxin concentration than that in the wild-type background. GUS expression was nil in the axr 2 and axr 3 mutants. The transgene was used to isolate mutants exhibiting altered auxin-responsive gene expression (age). Two mutants, age1 and age2, were isolated and characterized. age1 showed enhanced sensitivity to IAA, with strong GUS expression localized in the root elongation zone in the presence of 10(-8) M IAA. In contrast, age2 exhibited ectopic GUS expression associated with the root vascular tissue, even in the absence of exogenous IAA. Morphological and molecular analyses indicated that the age1 and age2 alleles are involved in the regulation of gene expression in response to IAA.

Arabidopsis↗

Reconstructing potential energy functions from simulated force-induced unbinding processes.

One-dimensional stochastic models demonstrate that molecular dynamics simulations of a few nanoseconds can be used to reconstruct the essential features of the binding potential of macromolecules. This can be accomplished by inducing the unbinding with the help of external forces applied to the molecules, and discounting the irreversible work performed on the system by these forces. The fluctuation-dissipation theorem sets a fundamental limit on the precision with which the binding potential can be reconstructed by this method. The uncertainty in the resulting potential is linearly proportional to the irreversible component of work performed on the system during the simulation. These results provide an a priori estimate of the energy barriers observable in molecular dynamics simulations.

Binding Sites↗

Molecular dynamics study of unbinding of the avidin-biotin complex.

We report molecular dynamics simulations that induce, over periods of 40-500 ps, the unbinding of biotin from avidin by means of external harmonic forces with force constants close to those of AFM cantilevers. The applied forces are sufficiently large to reduce the overall binding energy enough to yield unbinding within the measurement time. Our study complements earlier work on biotin-streptavidin that employed a much larger harmonic force constant. The simulations reveal a variety of unbinding pathways, the role of key residues contributing to adhesion as well as the spatial range over which avidin binds biotin. In contrast to the previous studies, the calculated rupture forces exceed by far those observed. We demonstrate, in the framework of models expressed in terms of one-dimensional Langevin equations with a schematic binding potential, the associated Smoluchowski equations, and the theory of first passage times, that picosecond to nanosecond simulation of ligand unbinding requires such strong forces that the resulting protein-ligand motion proceeds far from the thermally activated regime of millisecond AFM experiments, and that simulated unbinding cannot be readily extrapolated to the experimentally observed rupture.

Avidin↗

[Efficacy of sulbactam/cefoperazone in respiratory tract infections in elderly patients with underlying respiratory diseases].

We examined the clinical effect of sulbactam/cefoperazone (SBT/CPZ) on respiratory tract infections in elderly patients (from 65 to 91, average 70.8) with underlying respiratory diseases. Thirty (30) patients (25 men and 5 women) were registered and SBT/CPZ (2 g/day) divided into two doses, was administered intravenously through drip infusion. The efficacy rate was 63% (excellent in 1 patient and good in 18 patients). No significant difference in efficacy was found among patient's age groups (group 1: 65-69, group 2: 70-74, group 3: 75-79, group 4: > 80). Bacterial eradication rate was 50% (6 out of 12 strains). An adverse reaction occurred in one patient, who experienced uticaria. Laboratory abnormalities, which were increasing with their ages, were observed in 12 patients during the study. These results suggest that SBT/CPZ was effective, but we found it is important to use caution in the treatment of elderly patients on respiratory tract infections with underlying respiratory diseases.

Aged↗

Characterization of two members (ACS1 and ACS3) of the 1-aminocyclopropane-1-carboxylate synthase gene family of Arabidopsis thaliana.

The nucleotide sequences of two highly homologous 1-aminocyclopropane-1-carboxylate (ACC) synthase (ACS; EC 4.4.1.14)-encoding genes, ACS1 and ACS3, of Arabidopsis thaliana (At) have been determined. The sequence analysis shows that ACS3 is a pseudogene representing a truncated version of ACS1. The missing region of ACS3 corresponding to the fourth exon of ACS1 has been shown by Southern analysis to be absent in the At genome. The chromosomal locations of the five members of the At ACS multigene family have been determined. The results show that each family member resides on a different chromosome. This observation suggests that the ACS3 pseudogene originated by a partial inter-chromosomal gene duplication. The ACS1 polypeptide contains all the conserved and characteristic domains found in the ACC synthase isoenzymes from various plant species, but is unable to express ACS activity in Escherichia coli and yeast. The predicted amino-acid sequence of ACS1 is missing the highly conserved tripeptide, Thr-Asn-Pro (TNP), between Ile204 and Ser205. Introduction of TNP into ACS1 restores the ACS activity, whereas its removal from the enzymatically active ACS2 results in a loss of activity. The results suggest that TNP is crucial for expression of ACS activity in E. coli.

Amino Acid Sequence↗

[Evaluation of photon-counting X-ray radiography for the detection of pulmonary nodule: a preliminary report on experimental and clinical studies].

To evaluate the utility of photon counting X-ray radiography (quantum radiography: QR) for the detection of pulmonary nodules, experimental and clinical studies were performed in comparison with conventional X-ray (CXR). In the experimental study, spatial resolution was analyzed by using the micro-chart method. The simulated nodule detection study was performed by using a chest phantom. The results were evaluated by means of ROC analysis. In the clinical study, both images of CXR and QR were evaluated in a case of metastatic lung tumor. In the experimental study, the spatial resolution of QR was 200 microns. QR was superior to CXR in detecting simulated nodules in all areas. In clinical cases, QR was superior to CXR in depicting not only normal structures but also retrocardiac and retrodiaphragmatic pulmonary nodules.

Carcinoma, Renal Cell↗