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Biomedical subjects

T Takasaka

Publications and source records attributed to T Takasaka.

At least 19 recordsLinked to original sources

Subtype IV of the BK polyomavirus is prevalent in East Asia.

BK polyomavirus (BKV) is ubiquitous in human populations, infecting children asymptomatically and then persisting in the kidney. Using either serological or genotyping methods, BKV isolates have been classified into four subtypes (I-IV), with subtype I mainly detected in all countries studied so far. To elucidate the subtype of BKV prevalent in East Asia, we examined BKV-positive urine samples collected from immunocompetent elderly patients in Mongolia, Northeast China, Northwest China, Southeast China, Southwest China, Vietnam and Japan. The 287-bp typing region of the viral genome in each of these samples was PCR-amplified and sequenced, and a phylogenetic tree was constructed. According to the tree, BKV isolates in East Asia were unambiguously classified into subtype I or IV (subtypes II and III were not detected). In Japan, subtype I was mainly detected and subtype IV was rare, whereas in the other regions subtype IV was detected frequently, at rates ranging from 24 to 100%. Thus, East Asia (excluding Japan) is a region in which subtype-IV BKV is prevalent, a finding that requires the view of the geographic distribution of BKV subtypes to be revised. Furthermore, we present evidence that the immunological states of urine donors do not affect the pattern of BKV subtypes.

BK Virus↗

Unambiguous identification of JC polyomavirus strains transmitted from parents to children.

JC polyomavirus (JCV), the etiological agent of progressive multifocal leukoencephalopathy, is ubiquitous in humans, infecting children asymptomatically, then persisting in renal tissue. It has been proposed that JCV is transmitted mainly from parents to children through long-term cohabitation. The objective of this study was to further elucidate the mode of JCV transmission. In 5 families, we selected parent/child pairs between whom JCV was probably transmitted (judged on the basis of the identity of a 610-bp JCV DNA sequence between the parent and child). We established 5 to 9 complete JCV DNA clones from the urine of each parent or child. The complete sequences of these clones were determined and compared in each family. Nucleotide substitutions were detected in 4 parents and 1 child, and sequence rearrangements (deletions or duplications) were found in 2 parents and 2 children. Phylogenetic comparison of the detected sequences indicated that the diversity of JCV DNA sequences was generated in each family (i.e. not caused by multiple infection). We found that in 4 of the 5 families, a sequence detected in the parent was completely identical to one in the child. These findings provided further support for the proposed mode of JCV transmission, i.e. parent-to-child transmission during cohabitation.

Adult↗

Asian domains of four major genotypes of JC virus, Af2, B1-b, CY and SC.

JC virus (JCV) strains worldwide can be classified into various genotypes based on DNA sequence variations. To define the domains of the four major JCV genotypes in Asia, we collected urine samples at six unstudied sites: three in southeastern Asia, two in the central highlands and one in central Asia. DNA was extracted from urine samples, and used to amplify a 610-bp region of the viral genome. For each geographical site, we determined 16 to 31 sequences, from which a phylogenetic tree was constructed to unambiguously classify detected JCV isolates into distinct genotypes. From JCV genotype profiles at the sites studied here and elsewhere, the following conclusions were drawn. Although Af2 is the major genotype in Africa, this genotype also occurs in western and central Asia. B1-b mainly occurs in western and central Asia, including the central highlands. CY occurs in northeastern Asia with the southern boundary between China and southeast Asian countries. Although SC predominates in southeastern Asia, it also occurs in northern and central Asia at lower frequencies. In addition, a few minor JCV genotypes (B1-a, B2 and B3) occur at many sites. We discuss here the anthropological and medical significance of the present findings.

Adult↗

The expression of apoptosis-related proteins in the aged cochlea of Mongolian gerbils.

OBJECTIVE: Apoptotic changes have been reported in the aged gerbil cochlea and are speculated to be one of the principal causes of presbyacusis. The objective of the study was to determine the underlying mechanism of apoptotic change in the aged gerbil cochlea. STUDY DESIGN: Prospective controlled animal study. METHODS: We examined the tissue distribution of bcl-2, bax, caspase-3p20, and caspase-3p32 using immunohistochemical techniques in the young and aged gerbil cochlea, together with the measurement of the distortion product of otoacoustic emission (DPOAE). RESULTS: Aged gerbils showed a significant reduction of the DPOAE amplitude as compared with that of the young gerbils, suggesting a disturbance of the auditory function in the aged cochlea. There was a significant decrease in the number of bcl-2-positive cells in the aged gerbils. The expression of bax in the aged group was slightly increased but did not significantly differ from that in the young gerbils. A significantly increased number of caspase-3p20-positive cells was observed in the organ of Corti, spiral ganglion, and lateral wall of cochlea in the aged gerbils as compared with those of the young gerbils. There was no significant difference in the expression levels of caspase-3p32 between the young and aged groups. In the aged cochlea, the degree of deterioration of DPOAE responses was compatible with those of both the reduction of bcl-2 and the activation of caspase-3p20. CONCLUSION: These data suggest that the suppression of bcl-2 protein expression may lead to apoptosis-induced presbyacusis through activation of caspase-3 in the aged gerbil cochlea.

Age Factors↗

Quantitative assessment of the pharyngeal airway by dynamic magnetic resonance imaging in obstructive sleep apnea syndrome.

Dynamic changes in the pharyngeal airway of patients with obstructive sleep apnea syndrome (OSAS) were evaluated by quantitating the findings of real-time imaging performed during wakefulness and spontaneous sleep by means of dynamic magnetic resonance imaging (MRI). Six patients with OSAS and 3 non-OSAS subjects, selected prospectively and randomly, underwent polysomnography and dynamic MRI. The cross-sectional areas of the soft palate and oropharynx and the anterior-posterior airway dimensions seen during wakefulness and spontaneous sleep were calculated by US National Institutes of Health imaging software. On the basis of a case control study, comparisons were made with age-matched and body mass index-matched obese non-OSAS snorers. Spontaneous sleep caused significant obstruction and narrowing of various sites of the pharyngeal airway in the OSAS patients, but not in the non-OSAS subjects. During wakefulness, the non-OSAS subjects showed no marked narrowing of the pharyngeal airways, whereas a transient but significant narrowing was observed in the OSAS patients. The mean values of both the cross-sectional area and the anterior-posterior diameter at the soft palate were significantly reduced by spontaneous sleep in the OSAS patients. Dynamic MRI in awake OSAS patients shows promise as a routine diagnostic tool for localizing the upper airway collapse for appropriate selection of surgical therapy.

Adult↗

Expression of the Sox10 gene during mouse inner ear development.

Mutations in the SOX10 gene, encoding a cell-lineage specific transcription factor, are associated with congenital deafness. We analyzed the expression of Sox10 mRNA in developing mouse inner ear by in situ hybridization. Sox10 mRNA is expressed in the entire epithelia of the otic vesicle at embryonic day 11.5 (E11.5) and in the developing cochlea and vestibule at E13.5. In postnatal day 8 and adult cochleas, Sox10 expression is restricted to the supporting cells of the organ of Corti. These expression profiles suggest that Sox10 is important for development of the cochlea.

Animals↗

Expression of connexin 31 in the developing mouse cochlea.

Connexin 31 (Cx31) mutations cause an autosomal dominant form of high-frequency hearing loss. The immunohistochemical localization of Cx31 in mouse cochlea was studied at different ages between 0 and 60 days after birth (DAB). Cx31-like immunoreactivity was detected in fibrocytes of spiral ligament and spiral limbus at 12 DAB, gradually enhanced with the increase of age and reached the adult pattern on 60 DAB. Immunoreactivity decreased gradually from the basal to apical turn in all developmental stages. The mRNA of Cx31 was also identified by RT-PCR. The distribution of Cx31 and connexin 26 were obviously different in the developing mouse cochlea. The expression and distribution of Cx31 in the development may explain the progressive hearing loss in human Cx31 mutations.

Age Factors↗

Characterization of novel and identified genes in guinea pig organ of corti.

A number of proteins are expressed in the organ of Corti and are considered to be responsible for hearing. However, most of them have not been identified. Therefore, to achieve a better understanding of the genetic factors influencing these traits, the first step is to characterize the genes expressed in the organ of Corti. In the present study, a cDNA library was constructed from the guinea pig organ of Corti. After sequencing isolated clones, 196 expressed sequence tags (ESTs) were identified with FASTA analysis: 65 ESTs showed significant sequence homology to previously identified genes in guinea pig, human or other species, and 131 ESTs showed no significant matches to sequences already present in the DNA database DDBJ/GenBank/EMBL. A variety of matching sequences, some of which were known to be cochlea-specific, were found through FASTA analysis of the 65 clones. RT-PCR with a panel of 10 different tissue mRNA revealed the restricted expression of 13 unknown clones. The results of our analysis allowed the establishment of a list of genes expressed in the guinea pig organ of Corti.

Animals↗

Novel mutations in the connexin 26 gene (GJB2) responsible for childhood deafness in the Japanese population.

Mutations in the connexin 26 gene (GJB2), which encodes a gap-junction protein and is expressed in the inner ear, have been shown to be responsible for a major part of nonsyndromic hereditary prelingual (early-childhood) deafness in Caucasians. We have sequenced the GJB2 gene in 39 Japanese patients with prelingual deafness (group 1), 39 Japanese patients with postlingual progressive sensorineural hearing loss (group 2), and 63 Japanese individuals with normal hearing (group 3). Three novel mutations were identified in group 1: a single nucleotide deletion (235delC), a 16-bp deletion (176-191 del (16)), and a nonsense mutation (Y136X) in five unrelated patients. The 235delC mutation was most frequently observed, accounting for seven alleles in 10 mutant alleles. Screening of 203 unrelated normal individuals for the three mutations indicated that the carrier frequency of the 235delC mutation was 2/203 in the Japanese population. No mutation was found in group-2 patients. We also identified two novel polymorphisms (E114G and I203T) as well as two previously reported polymorphisms (V27I andV37I). Genotyping with these four polymorphisms allowed normal Japanese alleles to be classified into seven haplotypes. All 235delC mutant alleles identified in four patients resided only on haplotype type 1. These findings indicate that GJB2 mutations are also responsible for prelingual deafness in Japan.

Adolescent↗

Identification of carp proopiomelanocortin-related peptides and their effects on phagocytes.

We report the immunomodulating effects of proopiomelanocortin (POMC)-related peptides on phagocytic cells in carp. The complete amino acid sequences of two carp POMCs (I and II) were deduced from the nucleotide sequences after cDNA cloning. Both POMCs consist of 194 amino acids (91% sequence identity) including identical alpha-melanotropin (MSH) and beta-endorphin (EP). All hormonal peptides derived from two POMCs were identified by mass spectrometry after separation by high-performance liquid chromatography of an acid-acetone extract from a single pituitary. These peptides were alpha-MSH, N-Des-Ac-alpha-MSH, di-Ac-alpha-MSH, beta-MSH I, beta-MSH-II, N-Ac-beta-EP(1-29), corticotropin-like intermediate lobe peptide I and II and N-terminal peptide of POMC I and II. The immunomodulating effects of synthetic MSHs and EPs on phagocytic cells from carp head kidney were examined. Di-Ac-alpha-MSH, beta-MSH I, N-Ac-beta-EP(1-29) and beta-EP(1-29) increased the production of superoxide anion at 0.1-100 ng ml-1 for these MSHs and 1-100 ng ml-1 for EPs in RPMI 1640 medium.

Amino Acid Sequence↗

Gap junction systems in the mammalian cochlea.

Recent findings that a high proportion of non-syndromic hereditary sensorineural hearing loss is due to mutations in the gene for connexin 26 indicate the crucial role that the gene product plays for normal functioning of the cochlea. Excluding sensory cells, most cells in the cochlea are connected via gap junctions and these gap junctions appear to play critical roles in cochlear ion homeostasis. Connexin 26 occurs in gap junctions connecting all cell classes in the cochlea. There are two independent systems of cells, which are defined by interconnecting gap junctions. The first system, the epithelial cell gap junction system, is mainly composed of all organ of Corti supporting cells, and also includes interdental cells in the spiral limbus and root cells within the spiral ligament. The second system, the connective tissue cell gap junction system, consists of strial intermediate cells, strial basal cells, fibrocytes in the spiral ligament, mesenchymal cells lining the bony otic capsule facing the scala vestibuli, mesenchymal dark cells in the supralimbal zone, and fibrocytes in the spiral limbus. One function of these gap junctional systems is the recirculation of K(+) ions from hair cells to the strial marginal cells. Interruption of this recirculation, which may be caused by the mutation in connexin 26 gene, would deprive the stria vascularis of K(+) and result in hearing loss.

Animals↗

Effects of contralateral noise on measurement of the psychophysical tuning curve.

The effects of the addition of contralateral noise on the psychophysical tuning curve (PTC) were examined in subjects with normal hearing. The masking threshold of the tail part of the PTC tended to decrease with the addition of contralateral noise, although the threshold reduction was usually less than 5 dB. On the other hand, the effects of contralateral noise were relatively small around the tip of the PTC contour. Focusing on the effects of contralateral noise on the masking threshold at the tail part of the PTC, the effects of changing the time between initiation of masking the tone and the presentation of the masked probe tone on the threshold reduction at the tail part of the PTC were also observed. The results indicate that the reduction of the masking threshold by the addition of contralateral noise tended to be larger when the presentation of the signal tone was delayed after the onset of the masker. Usually, when the signal tone was presented under conditions of the forward masking paradigm, the reduction of the threshold was most remarkable. Results obtained in the present study are discussed based on the known characteristics of the olivocochlear (OC)-efferent fibers activated by contralateral noise.

Adult↗

Measurement of stapedius contraction during vocalization effort in patients after laryngectomy or tracheostomy.

The contraction of the stapedius muscle during the effort of vocalization was examined by measurement of acoustic compliance in subjects who had undergone laryngectomy or tracheostomy. No significant level of persistent compliance change was recorded in any of the subjects, indicating the absence of effective contraction of the stapedius during the vocalization effort. In two subjects who use an electrolarynx, although no significant compliance change resulted from the simple vocalization effort without the electrolarynx (no actual vocalized sound), a remarkable level of persistent compliance change was observed during the vocalization using the electrolarynx. These results seem to indicate that a simple vocalization effort without actual voice cannot elicit effective contraction of the middle ear muscles, and that sound generation during vocalization is essential for effective contraction of the middle ear muscles during vocalization, at least in some human subjects.

Aged↗

Cisplatin-induced apoptotic cell death in Mongolian gerbil cochlea.

Cisplatin is well known to cause cochleotoxicity. In order to determine the underlying mechanisms of cisplatin-induced cell death in the cochlea, we investigated the apoptotic changes and the expression of bcl-2 family proteins controlling apoptosis. Mongolian gerbils were administered 4 mg/kg/day cisplatin consecutively for 5 days. The cisplatin-treated animals showed a significant deterioration in the responses of both distortion product otoacoustic emissions and the endocochlear potential as compared with those of the age-matched controls, suggesting outer hair cell and stria vascularis dysfunction. The presence of DNA fragmentation revealed by a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling method was recognized in the organ of Corti, the spiral ganglion, and the stria vascularis in the cisplatin-treated animals whereas almost negative results were obtained in the control animals. The nuclear morphology obtained by Hoechst 33342 staining revealed pyknotic and condensed nuclei, confirming the presence of the characteristic features of apoptosis. A significant increase and reduction in the number of bax- and bcl-2-positive cells, respectively, following cisplatin treatment was observed in the cells of the organ of Corti, the spiral ganglion, and the lateral wall. These findings suggest a critical role for bcl-2 family proteins in the regulation of apoptotic cell death induced by cisplatin. The underlying mechanisms of the cisplatin-induced cell death are discussed.

Animals↗

Apparent change of masking functions with compression-type digital hearing aid.

Signal perception ability under conditions of a narrow band masker in subjects with hearing aids was examined using a theoretical model of the auditory nerve fibre (ANF) with a deteriorated tuning curve in addition to measurements of actual masking function in subjects wearing hearing aids. The results obtained indicate that the apparent masking function could be affected by the frequency-gain character as well as by the degree of compression. Usually, the compression-type of amplification with flat and/or high-frequency weighted characteristics improves not only the apparent thresholds but also the apparent masked thresholds under conditions of lower frequency masking. On the other hand, a low-frequency masker amplified by a higher gain with low-frequency weighted amplification could cause larger upward-masking effects on the signal perception of the higher frequency signal in some conditions. The present study may contribute to our understanding of the underlying mechanisms of the effects of different amplification by the aid.

Acoustic Stimulation↗