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Biomedical subjects

Atsushi Takano

Publications and source records attributed to Atsushi Takano.

15 recordsLinked to original sources

Ligation of eustachian tube for intractable patulous eustachian tube: a preliminary report.

Pharyngeal orifice of the eustachian tube was ligated on ten patients, 15 ears with intractable patulous eustachian tube. While the eustachian tube orifice was observed by an endoscope inserted through the contralateral nostril, the orifice was ligated transnasally and/or transorally using instruments usually used in the endoscopic nasal surgery. Now 13-27 months after the surgery, the outcome was excellent (both symptoms and sonotubometry were normalized) in two ears, good (either symptoms or sonotubometry was improved) in seven ears, and unchanged in the remaining six ears. In one of the ears with an outcome of unchanged, the ligation was found to be spontaneously released soon after surgery, but the symptom was improved after the second operation 2.5 months after the first operation. Temporary otitis media with effusion was seen in one ear, mild inflammation around the ligated site also in one ear, but no other serious complication has been observed. Although further improvement in the surgical procedure and further discussion about its long-term outcome should be required, this procedure appeared to be one of the therapeutic options for intractable patulous eustachian tube.

Adult↗

The neuromedin U-growth hormone secretagogue receptor 1b/neurotensin receptor 1 oncogenic signaling pathway as a therapeutic target for lung cancer.

Using a genome-wide cDNA microarray to search for genes that were specifically up-regulated in non-small cell lung cancers (NSCLC), we identified an abundant expression of neuromedin U (NMU) in the great majority of lung cancers. Immunohistochemical analysis showed a significant association of NMU expression with poorer prognosis of patients with NSCLC. Treatment of NSCLC cells with short interfering RNA against NMU suppressed its expression and inhibited the growth of the cells; on the other hand, the induction of exogenous expression of NMU conferred growth-promoting activity and enhanced cell mobility in vitro. We found that two G protein-coupled receptors, growth hormone secretagogue receptor 1b and neurotensin receptor 1, were also overexpressed in NSCLC cells, and that a heterodimer complex of these receptors functioned as an NMU receptor. The NMU-receptor interaction subsequently induced the generation of a second messenger, cyclic AMP, to activate its downstream genes including transcription factors and cell cycle regulators. Treatment of NSCLC cells with short interfering RNAs for growth hormone secretagogue receptor or neurotensin receptor 1 suppressed the expression of those genes and the growth of NSCLC cells. These data strongly implied that targeting the NMU signaling pathway would be a promising therapeutic strategy for the treatment of lung cancers.

Animals↗

Nanophase-separated synchronizing structure with parallel double periodicity from an undecablock terpolymer.

A new nanophase-separated structure with parallel double periodicity has been identified for an undecablock terpolymer in bulk. The polymer includes two long poly(2-vinypyridine) (P) chains on each end, with five short polyisoprene (I) and four short polystyrene (S) chains at the center. This polymer exhibits a hierarchical lamellar structure with two crystallographic periods: 88 nm and 16 nm. The 88 nm period includes one thick P lamella and five thin I-S-I-S-I lamellae, of extremely high orientation.

Butadienes↗

Diblock-type supramacromolecule via biocomplementary hydrogen bonding.

Control of nanostructure formation by a diblock-type supramacromolecule via biocomplementary hydrogen bonding has been achieved. Two different homopolymers, poly(4-trimethylsilylstyrene) and poly(styrene-d8), that are end-decorated with complementary oligonucleotides, i.e., thymidine phosphates and deoxyadenosine phosphates, were prepared by using the phosphoramidite method and blended successively. Association behavior in a blend solution was examined with NMR, and a cast bulk film obtained from the solution has been confirmed to show a nanophase-separated structure by transmission electron microscopy and X-ray scattering. Suppression of this nanostructure formation of a block-type supramacromolecule was also attained by adding a smaller agent as an inhibitor.

Deoxyadenine Nucleotides↗

Characterization of SEZ6L2 cell-surface protein as a novel prognostic marker for lung cancer.

To identify molecules that might serve as biomarkers or targets for development of novel molecular therapies, we have been screening genes encoding transmembrane/secretory proteins that are up-regulated in lung cancers, using cDNA microarrays coupled with purification of tumor cells by laser microdissection. A gene encoding seizure-related 6 homolog (mouse)-like 2 (SEZ6L2) protein, was chosen as a candidate for such molecule. Semi-quantitative RT-PCR and western-blot analyses documented increased expression of SEZ6L2 in the majority of primary lung cancers and lung-cancer cell lines examined. SEZ6L2 protein was proven to be present on the surface of lung-cancer cells by flow cytometrical analysis using anti-SEZ6L2 antibody. Immunohistochemical staining for tumor tissue microarray consisting of 440 archived lung-cancer specimens detected positive SEZ6L2 staining in 327 (78%) of 420 non-small cell lung cancers (NSCLCs) and 13 (65%) of 20 small-cell lung cancers (SCLCs) examined. Moreover, NSCLC patients whose tumors revealed a higher level of SEZ6L2 expression suffered shorter tumor-specific survival compared to those with no SEZ6L2 expression. These results indicate that SEZ6L2 should be a useful prognostic marker of lung cancers.

Biomarkers, Tumor↗

Response of temporomandibular joint intermittent closed lock to different treatment modalities: A multicenter survey.

This study investigated the clinical picture and different treatment methods and results at a number of institutions with the aim of establishing an effective method of treatment for intermittent closed lock (intermittent lock) of the temporomandibular joint (TMJ). The subjects were 104 patients (29 males, 65 females) diagnosed with intermittent lock among 1787 temporomandibular disorder patients. The cases were classified into two types based on the time and occasion when the intermittent lock occurred. The sudden onset type developed in 69.2%, and the habitually occurring type in 29.8%. The most common treatment was disk repositioning exercises alone (in 41 cases) followed by stabilization splints during sleeping. The highest efficacy rate (60.0%) was obtained with the combination of disk repositioning exercise and a repositioning splint followed by a rate of 52.6% with stabilization splints and 41.7% with disk repositioning exercise alone.

Adolescent↗

Gene expression profiles of small-cell lung cancers: molecular signatures of lung cancer.

To characterize the molecular mechanisms involved in the carcinogenesis and progression of small-cell lung cancer (SCLC) and identify molecules to be applied as novel diagnostic markers and/or for development of molecular-targeted drugs, we applied cDNA microarray profile analysis coupled with purification of cancer cells by laser-microbeam microdissection (LMM). Expression profiles of 32,256 genes in 15 SCLCs identified 252 genes that were commonly up-regulated and 851 transcripts that were down-regulated in SCLC cells compared with non-cancerous lung tissue cells. An unsupervised clustering algorithm applied to the expression data easily distinguished SCLC from the other major histological type of non-small cell lung cancer (NSCLC) and identified 475 genes that may represent distinct molecular features of each of the two histological types. In particular, SCLC was characterized by altered expression of genes related to neuroendocrine cell differentiation and/or growth such as ASCL1, NRCAM, and INSM1. We also identified 68 genes that were abundantly expressed both in advanced SCLCs and advanced adenocarcinomas (ADCs), both of which had been obtained from patients with extensive chemotherapy treatment. Some of them are known to be transcription factors and/or gene expression regulators such as TAF5L, TFCP2L4, PHF20, LMO4, TCF20, RFX2, and DKFZp547I048 as well as those encoding nucleotide-binding proteins such as C9orf76, EHD3, and GIMAP4. Our data provide valuable information for better understanding of lung carcinogenesis and chemoresistance.

Antineoplastic Agents↗

Increases of amphiregulin and transforming growth factor-alpha in serum as predictors of poor response to gefitinib among patients with advanced non-small cell lung cancers.

Serum levels of amphiregulin and transforming growth factor-alpha (TGF-alpha), which were identified previously to be expressed at high levels in non-small cell lung cancer (NSCLC) with poor response to gefitinib, were examined by ELISA using blood samples taken from 50 patients with advanced NSCLCs. Of 14 cases that revealed above the cutoff line for amphiregulin in serum, 12 responded poorly to gefitinib, whereas 18 of the 36 cases showing below the cutoff revealed partial response (PR) or stable disease (SD; P = 0.026). Thirteen of 15 patients who were positive for TGF-alpha responded poorly to gefitinib, whereas 18 of the 35 patients with negative TGF-alpha levels turned out to be relatively good responders (P = 0.014). Of 22 patients with positive values for either or both markers, 19 were poor responders. On the other hand, among 28 patients negative for both markers, 17 were classified into the PR or SD groups (P = 0.001). Gefitinib-treated NSCLC patients whose serum amphiregulin or TGF-alpha was positive showed a poorer tumor-specific survival (P = 0.037 and 0.002, respectively, by univariate analysis) compared with those whose serum amphiregulin or TGF-alpha concentrations were negative. Multivariate analysis showed an independent association between positivity for TGF-alpha and shorter survival times among NSCLC patients treated with gefitinib (P = 0.034). Amphiregulin or TGF-alpha positivity in NSCLC tissues was significantly higher in male, nonadenocarcinomas, and smokers. Our data suggest that the status of amphiregulin and TGF-alpha in serum can be an important predictor of the resistance to gefitinib among patients with advanced NSCLC.

Adult↗

Conductive metal nanowires templated by the nucleoprotein filaments, complex of DNA and RecA protein.

Development of preprogrammable conductive nanowires is a requisite for the future fabrication of nanoscale electronics based on molecular assembly. Here, we report the synthesis of conductive metal nanowires from nucleoprotein filaments, complexes of single- or double-stranded DNA and RecA protein. A genetically engineered RecA derivative possessing a reactive and surface accessible cysteine residue was reacted with functionalized gold particles, resulting in nucleoprotein filaments with gold particles attached. The template-based gold particles were enlarged by chemical deposition to form uniformly metallized nanowires. The programming information can be encoded in DNA sequences so that an intricate electrical circuit can be constructed through self-assembly of each component. As the RecA filament has higher degree of stiffness than double-stranded DNA, it provides a robust scaffold that allows us to fabricate more reliable and well-organized electrical circuitry at the nanoscale. Furthermore, the function of homologous pairing provides sequence-specific junction formation as well as sequence-specific patterning metallization.

Cysteine↗

Identification of a 1.1-Mb region for a carcass weight QTL onbovine Chromosome 14.

We previously mapped a quantitative trait locus for carcass weight, designated Carcass Weight-1 (CW-1), to bovine Chromosome 14 using a purebred Wagyu pedigree based on progeny design analysis. To refine the critical region within 8.1 cM flanked by microsatellites BMS1941 and INRA094, we constructed a bacterial artificial chromosome (BAC) contig composed of 60 tiled BAC clones and prepared a high-density physical map including 80 microsatellites, of which 55 were developed in this study. We conducted linkage disequilibrium (LD) mapping in the CW-1 region with 47 microsatellites using paternal half-sib pedigrees whose sires exhibited homozygous CW-1 Q alleles in the region. The LD mapping study significantly narrowed the CW-1 locus to the 1.1-Mb region between microsatellites DIK7012 and DIK7020. Finally, we surveyed the 1.1-Mb-region genotypes of 1700 steers from 11 bulls having -/-, Q/-, or Q/Q alleles in the region, and we examined the effect of the CW-1 Q allele on carcass weight. The presence of the first Q increased carcass weight by 23.6 kg (95% confidence interval [CI], 17.6-29.5 kg), and the second Q increased carcass weight an additional 15.2 kg (95% CI, 10.7-19.7 kg). These results indicate the presence of a gene responsible for carcass weight within the 1.1-Mb region.

Animals↗

A huge primary peritoneal papillary adenocarcinoma which demonstrated imaging findings similar to those of extrahepatic-growing type hepatic tumor: report of a case.

We herein report a 69-year-old woman who presented with a huge intra-abdominal tumor which demonstrated imaging findings similar to those of extrahepatic-growing type hepatic tumor, but turned out to be primary peritoneal papillary adenocarcinoma. Computed tomography showed a well-demarcated mass, measuring 12.0 cm in diameter, which came in contact with the lateral segment of the liver and invaded the diaphragm and abdominal wall. Distant lymph node metastasis was also detected. A fine-needle aspiration biopsy of the tumor showed poorly differentiated adenocarcinoma of unknown origin. After chemotherapy with 5-fluorouracil and cisplatin, the maximal diameter of the tumor decreased to 6.0 cm. The patient then underwent a tumorectomy together with a lateral segmentectomy of the liver, a splenectomy, a partial resection of the diaphragm and abdominal wall, and a left oophorectomy. Histological and immunohistochemical examinations demonstrated the tumor to be primary peritoneal papillary adenocarcinoma.

Adenocarcinoma, Papillary↗

A randomized controlled trial of therapeutic exercise for clicking due to disk anterior displacement with reduction in the temporomandibular joint.

Therapeutic exercise is a new concept of treatment for patients with clicking due to anterior disk displacement with reduction (ADDWR). In order to investigate the efficacy of the exercise, we designed a randomized controlled clinical trial to compare with no-treatment controls. The subjects were patients who complained of painless unilateral reciprocal clicking and were diagnosed as having ADDWR by Magnetic Resonance Imaging (MRI). Forty-two patients were randomly assigned. Three months after the randomization, the success rate was 61.9% (13/21 joints) in the exercise group and 0% (0/21 joints) in the control group, with a significant difference between the two groups (p=0.0001). However, captured disks in the successful cases were seen in only 23.1% on MRI examination. In conclusion, the therapeutic exercise for clicking due to ADDWR is significantly effective in reducing the clicking, and thought to be much more conservative and cost-effective than splint therapy or surgery.

Adolescent↗

A new 9-lipoxygenase cDNA from developing rice seeds.

We isolated a novel C9 position specific lipoxygenase (r9-LOX1) cDNA from developing rice seeds. The enzymatic features of r9-LOX1 resembled those of rice LOX-L3 known to be contained in rice germ and to have C9-specific LOX activity. However, the expression level of the r9-LOX1 gene was higher in imbibed seeds rather than developing seeds. A homology search against the rice nucleotide database revealed the r9-LOX1 gene to be on rice chromosome 3 (accession number AC093017). The restriction enzyme map of the reported genomic sequence agreed with the result of the Southern blot analysis for the r9-LOX1. The enzyme could be useful for in vitro synthesis of 9,10-ketol-octadecadienoic acid.

Amino Acid Sequence↗

Novel synthesis and characterization of bioconjugate block copolymers having oligonucleotides.

Novel and efficient synthesis of polymers terminated with nucleotides via the phosphoramidite method has been developed. A hydroxyl-terminated polymer was converted into a polymer capped with a nucleotide in three steps, where the conversion of the reactions was very high, almost 100%. By repetition of this synthetic method, a block copolymer composed of a synthetic polymer, polystyrene, and biological oligonucleotides with thymidine units has been successfully synthesized. A microphase-separated structure of this block copolymer was observed by both transmission electron microscopy and small-angle X-ray scattering, and a cylindrical structure was confirmed.

Biopolymers↗