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Biomedical subjects

K Horimoto

Publications and source records attributed to K Horimoto.

At least 19 recordsLinked to original sources
PubMed2001

Statistical estimation of cluster boundaries in gene expression profile data.

MOTIVATION: Gene expression profile data are rapidly accumulating due to advances in microarray techniques. The abundant data are analyzed by clustering procedures to extract the useful information about the genes inherent in the data. In the clustering analyses, the systematic determination of the boundaries of gene clusters, instead of by visual inspection and biological knowledge, still remains challenging. RESULTS: We propose a statistical procedure to estimate the number of clusters in the hierarchical clustering of the expression profiles. Following the hierarchical clustering, the statistical property of the profiles at the node in the dendrogram is evaluated by a statistics-based value: the variance inflation factor in the multiple regression analysis. The evaluation leads to an automatic determination of the cluster boundaries without any additional analyses and any biological knowledge of the measured genes. The performance of the present procedure is demonstrated on the profiles of 2467 yeast genes, with very promising results. AVAILABILITY: A set of programs will be electronically sent upon request. CONTACT: horimoto@post.saga-med.ac.jp; toh@beri.co.jp

Analysis of Variance↗
PubMed2001

Comprehensive comparison between locations of orthologous genes on archaeal and bacterial genomes.

MOTIVATION: Following an extensive search for orthologous genes between the complete genomes from archaea and bacteria, the spatial association of the orthologs has been investigated in terms of synteny, the conservation of the order of neighboring genes. However, the relationships between the relative locations of remote orthologs over entire genomes have not been shown. RESULTS: Comprehensive comparisons between the locations of orthologs on nineteen archaeal and bacterial genomes are presented by the location to location correspondence based on the gene-location distance. When the two genomes are rotated such that a pair of orthologs with the shortest distance is set in the same angle, a statistically significant number of orthologs maintain their relative locations between the genomes. Even by the short distances at the 5% significance level, the rotations are restricted within a narrow range, suggesting an intrinsic angle for realizing similar locations between the orthologs in each genome pair. Furthermore, the rotations in the restricted range agree with the replication origin and terminus sites for the analyzed genomes where such sites are known. The relationship between location-maintained orthologs and gene function is also discussed.

Chromosome Mapping↗
PubMed2001

Local multiple alignment of numerical sequences: detection of subtle motifs from protein sequences and structures.

This paper presents a new method to find motifs from multiple protein sequences and multiple protein structures. The method consists of two parts: quantification and local multiple alignment. In the former part, protein sequences and protein structures are transformed into sequences of real numbers and real vectors respectively. In the latter part, fixed length regions having similar shapes are located. A Gibbs sampling algorithm for sequences of real numbers/vectors is newly developed for finding common regions. The results of the comparison with a standard Gibbs sampling program show that the method is particularly useful when structural information is available.

Algorithms↗
PubMed1999

[Observation of physiological change in the human ciliary body using an ultrasound biomicroscope during accommodation].

PURPOSE: To evaluate changes in the ciliary body during accommodation using an ultrasound biomicroscope (UBM). SUBJECTS AND METHODS: Eleven healthy persons, aged from 24 to 33 years, served as subjects. They were asked to lie in the supine position and to fixate a target placed on the ceiling 2 m above with the left eye. A concave lens with the power of -6 to -8 diopters was then placed before the fixating left eye. The thickness of the ciliary body in the right eye was measured by UBM in the nonaccommodative and accommodative states. FINDINGS: The anterior chamber in the right eye became significantly shallow during accommodation. The thickness of the ciliary body significantly increased during accommodation at 0.5 mm and 1.0 mm posterior to the scleral spur. It significantly decreased at 2.0 mm, 2.5 mm and 3.0 mm posterior to the scleral spur. CONCLUSION: During induced accommodation in the left eye, the anterior portion of the ciliary body in the right eye increased and the posterior portion decreased in thickness. The findings imply that the circular ciliary muscles are mainly involved in accommodation and not the longitudinal muscles.

Accommodation, Ocular↗
PubMed1998

A method for comparing circular genomes from gene locations: application to mitochondrial genomes.

MOTIVATION: Data on the entire structures of organelle and bacterial genomes, most of which are known to be circular, have accumulated at a rapid pace. This information enables us to utilize the locations of homologous gene pairs for measuring the dissimilarity between complete genomic structures. RESULTS: A macroscopic distance is presented for comparing circular genomes from their overall structures, on the basis of the locations of two pairs of homologous genes on the compared genomes. The novel aspect of our method is that the comparison between the genomes automatically reveals a relationship based on the information on all gene locations, by incorporating the mobility of each gene, which includes not only the gene order, but also the relative location between gene pairs. The plausibility of the newly defined distances is evaluated by means of 44 mitochondrial genomes. The genome distance shows high performance for quantitatively describing the differences between the gene organizations of the genomes. AVAILABILITY: Since the programs implementing these calculations require well-arranged gene organization data, they have not been released yet. However, one of the authors will analyze circular genomes upon request. Data on the gene organizations may be submitted electronically to the address below.

Animals↗
PubMed1996

Sodium hyaluronate eyedrops enhance tear film stability.

Sodium hyaluronate eyedrops can relieve various dry eye symptoms by prolonging the stability of the precorneal tear film. To determine the most effective concentration of sodium hyaluronate, we studied the concentration-dependent effects of sodium hyaluronate eyedrops on the precorneal tear film breakup time (BUT) in 12 volunteers. These subjects had a BUT of 10 seconds or less and a low tear volume determined with the phenol red thread test. They received four different concentrations of sodium hyaluronate eyedrops (0, 0.05, 0.1 and 0.3%). BUT was measured noninvasively using a non-contact specular microscope before the sodium hyaluronate eyedrop instillation and again after 5, 15, 30, 60, 120 and 180 minutes. The tear film stability period was prolonged significantly with 0.1% and 0.3% eyedrops at all measurement times (P < 0.05), while the eyes treated with 0% and 0.05% eyedrops showed no significant prolongation of tear film stability at any measurement times. The findings of this study confirm that sodium hyaluronate at a concentration of at least 0.1% is required to delay the breakup of the precorneal tear film.

Adult↗
PubMed1995

Prevalence of dry eye in Japanese eye centers.

BACKGROUND: The purpose of the investigation was to ascertain the prevalence of dry eye in new outpatients. METHODS: A total of 2127 consecutive new outpatients seen in eight Japanese centers from April 1992 to January 1993 underwent comprehensive examinations, including double vital staining and measurement of tear film break-up time, basal tear secretion, and tear clearance. Dry eye was diagnosed if patients had abnormalities of both the tear film and the ocular surface. RESULTS: Three hundred fifty-nine patients (17%) had dry eye. There was no seasonal pattern for dry eye. The condition was significantly more common in Tokyo than in suburban areas (P < 0.01). The prevalence of dry eye in visual display terminal (VDT) users and contact lens (CL) wearers was significantly higher than in non-VDT users and non-CL wearers (P < 0.05 and P < 0.02, respectively). CONCLUSION: Our findings suggest that dry eye is one of the most common ocular disorders encountered by physicians. Furthermore, if patients use VDTs or wear CLs, the likelihood of dry eye occurring is higher.

Adolescent↗
PubMed1994

A simple procedure for assigning a sequence motif with an obscure pattern: application to the basic/helix-loop-helix motif.

We have developed a simple method to assign a sequence motif with an obscure pattern. Given a multiple sequence alignment for a region of protein that is known or strongly believed to have the same secondary and tertiary structures, the quantification method by principal component analysis is designed to find the regions most likely to have the same structure in a protein outside of the original set. The potential of this newly developed method was evaluated with reference to the known basic/helix-loop-helix (bHLH) motifs, and its characteristics were discussed with four obscure but well-defined motifs and compared with the other methods for searching sequence motifs. The method was also applied to assign the bHLH motif in Epstein-Barr virus nuclear antigen 1 (EBNA-1). This application revealed one candidate for the basic/helix 1 region and two candidates for the helix 2 region in the bHLH motif, within the region from amino acid residues 460 to 600, which is in good agreement with our previous experimental studies on the DNA binding region of EBNA-1. The basic/helix-loop-helix-loop-helix structure thus assigned suggests a function of EBNA-1 which is associated with both replication and transcription.

Amino Acid Sequence↗
PubMed1994

Ocular surface damage and tear lactoferrin in dry eye syndrome.

We studied the relationship between the severity of ocular surface damage and the level of tear lactoferrin in primary and secondary Sjögren's syndrome and keratoconjunctivitis sicca not associated with Sjögren's syndrome. A significant negative correlation was found between Rose Bengal staining score and level of tear lactoferrin in all three groups. Analysis of covariance disclosed no significant differences in regression lines for Rose Bengal staining score vs tear lactoferrin level among the three groups. The three regression lines appeared to be identical to each other. These findings indicate that the severity of ocular surface damage due to dry eye largely depends on the tear secretory function of the lacrimal gland, and that the function of the lacrimal gland can be evaluated by determination of level of tear lactoferrin using the same standards regardless of differences in pathogenesis of underlying diseases.

Adolescent↗
PubMed1993

Divergence pattern and selective mode in protein evolution: the example of vertebrate myoglobins and hemoglobin chains.

The evolutionary relation of vertebrate myoglobin and the hemoglobin chains including the agnathan hemoglobin chain is investigated on the basis of a new view of amino acid changes that is developed by canonical discriminant analysis of amino acid residues at individual sites. In contrast to the clear discrimination of amino acid residues between myoglobin, hemoglobin alpha chain, and hemoglobin beta chain in warm-blood vertebrates, the three types of globins in the lower class of vertebrates show so much variation that they are not well discriminated. This is seen particularly at the sites that are ascertained in mammals to carry the amino acid residues participating in stabilizing the monomeric structure in myoglobin and the residues forming the subunit contacts in hemoglobin. At these sites, agnathan hemoglobin chains are evaluated to be intermediate between the myoglobin and hemoglobin chains of gnathostomes. The variation in the phylogenetically lower class of globins is also seen in the internal region; there the amino acid residues of myoglobin and hemoglobin chains in the phylogenetically higher class exhibit an example of parallel evolution at the molecular level. New quantities, the distance of sequence property between discriminated groups and the variation within each group, are derived from the values of discriminant functions along the peptide chain, and this set of quantities simply describes an overall feature of globins such that the distinction between the three types of globins has been clearer as the vertebrates have evolved to become jawed, landed, and warm-blooded. This result strongly suggests that the functional constraint on the amino acid sequence of a protein is changed by living conditions and that severe conditions constitute a driving force that creates a distinctive protein from a less-constrained protein.

Amino Acid Sequence↗
PubMed1993

[Evaluation of the effect of the sodium hyaluronate ophthalmic solution on tear film stability--non-contact specular microscopic evaluation].

Sodium hyaluronate solution is known to relieve various dry eye symptoms by suppressing the breakup of the preocular tear film. Using tear film stability as a parameter, we examined in 12 volunteers the time and concentration-dependent effects of sodium hyaluronate on their short precorneal tear film breakup time (BUT, 10 sec. or less) at a low tear volume (15 mm or less by using the phenol red thread test). Each subject underwent four separate study periods, receiving one of the following four ophthalmic solutions during each period: 0.05, 0.1, 0.3% w/v sodium hyaluronate (molecular weight, about 1,000,000) or the vehicle alone. BUT was measured non-invasively using a non-contact specular microscope before and 5, 15, 30, 60, 120, and 180 minutes after drug application. While BUT was not significantly prolonged after instilling either the vehicle or 0.05% solution, it was significantly increased at all times after applying either 0.1% or 0.3% solution, as compared to preinstillation. These results indicate that sodium hyaluronate solutions at concentrations of at least 0.1% can be effective in alleviating symptoms of dry eye.

Adult↗
PubMed1992

Structure model of core proteins in photosystem I inferred from the comparison with those in photosystem II and bacteria; an application of principal component analysis to detect the similar regions between distantly related families of proteins.

A principal component analysis based on the physico-chemical properties of amino acid residues is developed to assign similar regions between distantly related families of proteins, taking account of the species diversities in respective families. The most important advantage of this analysis should be that it reflects different physico-chemical properties and thus can predict more detailed structural properties, including the transmembrane helices, than the hydropathy analysis. Its first application reconfirms the similarity between the core proteins of photosynthetic reaction center in purple bacteria and those of photosystem II, indicating that the low percentage of identical amino acid residues estimated previously between them is due to much allowance for amino acid substitutions in purple bacteria. The application of this analysis to the core proteins of photosystem I reveals that any of these proteins includes two domains, each showing high similarity to the amino acid sequences of core proteins in photosystem II and purple bacteria. A core structure model of A1 and A2 proteins folded into four layers of sheets of transmembrane helices is proposed to provide a molecular basis for the electron pathway suggested by spectroscopic experiments as well as for the interaction sites with plastocyanin, 9 kDa protein and LHC proteins.

Amino Acid Sequence↗
PubMed1991

Principal component analysis to detect the similarity of distantly related proteins; its application to cytochromes c, c1 and f.

A new method has been developed for detecting the similarity between distantly related families of proteins. The amino acid sequences of each family of proteins are vertically aligned by a homologous alignment method and the physico-chemical properties of the amino acid residues at the corresponding site are evaluated simultaneously, by method of the principal component analysis. Taking into account the species diversity of each family of proteins, we assign the similar regions between the different families of proteins by the overlapping degree of the standard deviations around the mean values of the first principal component. To investigate the homologous relationship between the electron transport proteins in photosynthetic and O2 respiratory systems, this method has been applied to 70 species of mitochondrial cytochrome c, 4 species of cytochrome c1 and 7 species of cytochrome f. This analysis reveals that both cytochrome f and cytochrome c1 have large regions which are similar to those of cytochrome c. Assuming that these similar regions have the same stereochemical structures as those in cytochrome c, we can predict the outlines of the tertiary structures of cytochrome c1 and cytochrome f, respectively, each able to interact with its electron acceptor, cytochrome c and plastocyanin.

Amino Acid Sequence↗
PubMed1990

Discrimination between adaptive and neutral amino acid substitutions in vertebrate hemoglobins.

A discriminant analysis on the basis of the physicochemical properties of amino acid residues is developed to investigate the accumulation pattern of amino acid substitutions in a family of proteins. The application of this analysis to vertebrate hemoglobins reveals the following new results. (1) The major components of teleost fish and amphibian hemoglobins showing the Root effect are sharply discriminated from mammalian hemoglobins in several regions of the alpha and beta chains, whereas shark, minor components of teleost fish and amphibian, reptile, and bird hemoglobins showing no Root effect exhibit a gradual change to mammalian hemoglobin in a straightforward way. This result suggests at least two lines of molecular evolution in vertebrate hemoglobins. (2) The nonadult hemoglobin chains are allocated to the latter line, i.e., tadpole, zeta, and pi chains are similar to shark and trout I chains, and epsilon and gamma chains are similar to some of the reptile chains. (3) In any case, most of the amino acid residues causing the discrimination are located near the sites that carry the amino acid residues conserved well throughout all classes of vertebrates, suggesting that modifications adapting to the respective living conditions or respiratory organs have taken place effectively near the amino acid residues essential for the manifestation of cooperative oxygen binding. (4) The amino acid residues at other sites are changed from one to another species even within the same class, showing a constant substitution rate as a whole. These amino acid substitutions may be nearly neutral, being under a weak functional constraint. The number of sites allowing such neutral substitutions is rather small, less than one-half of all the sites in the adult hemoglobins of bird and mammal, whereas it amounts to two-thirds in teleost fish hemoglobins.

Amino Acid Sequence↗
PubMed1989

Rapid evolutionary repair of base mispairings in stem regions of eukaryotic 5S rRNA.

An extensive set of 216 eukaryotic 5S rRNA sequences are compared and the previous observations, that (i) invariable base positions are located primarily in loop regions and (ii) stem regions are more variable but the number of mispairings is kept small, are confirmed. On the basis of a comparison of the contemporary sequences, evolutionary processes of base substitutions in stem regions are discussed. It is found that there is no evident selective pressure to keep a particular kind of base pair in stem regions and individual bases may change freely as long as mispairings are kept few. It is also found that the secondary structure of 5S rRNA has been maintained stable by an equilibrium between base pair formation- and destruction-substitutions and that the low occurrence of mispairings in stem regions is attributable to a high value (ca. 90) of the equilibrium constant. The present analyses suggest a structure-function relationship of the eukaryotic 5S rRNA; stem regions structurally help loop regions to interact well with other ribosomal components and therefore, there is a marked selection pressure to maintain the secondary structure under the evolutionary noise of mutation.

Animals↗
PubMed1987

Accumulation pattern of amino acid substitutions in protein evolution.

A simple method for the evolutionary analysis of amino acid sequence data is presented and used to examine whether the number of variable sites (NVS) of a protein is constant during its evolution. The NVSs for hemoglobin and for mitochondrial cytochrome c are each found to be almost constant, and the ratio between the NVSs is close to the ratio between the unit evolutionary periods. This indicates that the substitution rate per variable site is almost uniform for these proteins, as the neutral theory claims. An advantage of the present analysis is that it can be done without knowledge of paleontological divergence times and can be extended to bacterial proteins such as bacterial c-type cytochromes. It is suggested that the NVS of cytochrome c has been almost constant even over the long period (ca. 3.0 billion years) of bacterial evolution but that at least two different substitution rates are necessary to describe the accumulated changes in the sequence. This "two clock" interpretation is consistent with fossil evidence for the appearance times of photosynthetic bacteria and eukaryotes.

Amino Acid Sequence↗