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Biomedical subjects

Atsushi Watanabe

Publications and source records attributed to Atsushi Watanabe.

At least 19 recordsLinked to original sources

Supradiaphragmatic thoracic duct clipping for chylothorax through left-sided video-assisted thoracoscopic surgery.

Chylothorax is a life-threatening clinical entity. Traditional surgical management for cases refractory to conservative treatment is thoracic duct ligation through a right open thoracotomy or closure of the site of duct laceration through an open thoracotomy. We report herein two patients with left chylothorax successfully treated by supradiaphragmatic thoracic duct (STD) ligation through left-sided video-assisted thoracoscopic surgery (VATS). This approach offers optimal exposure for the thoracic duct ligation and is useful for treatment of left chylothorax after left-sided thoracic surgery and idiopathic left chylothorax.

Aged↗

A BAC-based contig map of the cynomolgus macaque (Macaca fascicularis) major histocompatibility complex genomic region.

The construction of a cynomolgus macaque (Macaca fascicularis, Mafa) BAC library for genomic comparison between rhesus and cynomolgus macaques is necessary to promote the cynomolgus macaque as one of the important experimental animals for future medical and biological research. In this paper, we constructed a cynomolgus macaque BAC library and a map of the MHC (Mafa) genomic region for comparison of the genomic organization and nucleotide similarities between the human, the chimpanzee, and the rhesus macaque. The BAC library consists of 221,184 clones with an average insert size of 83 kb, providing a sixfold coverage of the haploid genome. A total of 114 BAC clones and 54 PCR primer sets were used to construct a 4.3-Mb contig of the MHC region. Diversity analysis of genomic sequence from selected subregions of the MHC revealed that the cynomolgus sequence varied compared to rhesus macaque, human, and chimpanzee sequences by 0.48, 4.15, and 4.10%, respectively. From these findings, we conclude that the BAC library and Mafa genomic map are useful tools for genome analysis and will have important applications for comparative genomics and identifying regions of consequence in medical research.

Animals↗

How to clamp the main pulmonary artery during video-assisted thoracoscopic surgery lobectomy.

We sometimes run across difficulty in dissection of the pulmonary arteries due to dense pleural adhesions and bleeding from the pulmonary artery during the video-assisted thoracoscopic surgery (VATS) lobectomy. In these cases, conversion of the VATS approach to open thoracotomy is a requisite. The presence of an easy and safe technique for pulmonary artery clamping will make the switch of the surgical procedure unnecessary. We developed the new technique for pulmonary artery clamping using 1-0 silk suture. This may become one of the standard techniques for pulmonary artery clamping not only in VATS but also in open thoracotomy, as well.

Constriction↗

Twisted flavors and tribimaximal neutrino mixing.

A new framework for handling flavor symmetry breaking in the neutrino sector is discussed where the source of symmetry breaking is traced to the global property of right-handed neutrinos in extra-dimensional space. Light neutrino phenomenology has rich and robust predictions such as the tribimaximal form of generation mixing, controlled mass spectrum, and no need of flavor mixing couplings in the theory.

Journal Article↗

Rapid evolution of major histocompatibility complex class I genes in primates generates new disease alleles in humans via hitchhiking diversity.

A plausible explanation for many MHC-linked diseases is lacking. Sequencing of the MHC class I region (coding units or full contigs) in several human and nonhuman primate haplotypes allowed an analysis of single nucleotide variations (SNV) across this entire segment. This diversity was not evenly distributed. It was rather concentrated within two gene-rich clusters. These were each centered, but importantly not limited to, the antigen-presenting HLA-A and HLA-B/-C loci. Rapid evolution of MHC-I alleles, as evidenced by an unusually high number of haplotype-specific (hs) and hypervariable (hv) (which could not be traced to a single species or haplotype) SNVs within the classical MHC-I, seems to have not only hitchhiked alleles within nearby genes, but also hitchhiked deleterious mutations in these same unrelated loci. The overrepresentation of a fraction of these hvSNV (hv1SNV) along with hsSNV, as compared to those that appear to have been maintained throughout primate evolution (trans-species diversity; tsSNV; included within hv2SNV) tends to establish that the majority of the MHC polymorphism is de novo (species specific). This is most likely reminiscent of the fact that these hsSNV and hv1SNV have been selected in adaptation to the constantly evolving microbial antigenic repertoire.

Alleles↗

Transient cardiomyopathy in a patient with congenital contractural arachnodactyly (Beals syndrome).

We report on an infant with Beals syndrome (congenital contractural arachnodactyly [CCA], MIM 121050) with transient cardiomyopathy showing ballon-like dilatation of the left ventricle that was similar to noncompaction. The patients father and two of his brothers were also found to have CCA without cardiovascular complications. CCA, which is caused by a mutation of the gene for fibrillin 2 protein is similar to Marfan syndrome (MIM 154700), which is caused by a mutation of fibrillin 1 but produces a life-threatening cardiovascular complications. This is the first report of CCA with transient cardiomyopathy. We discuss the mechanism of the spontaneous improvement of cardiomyopathy in this case on the basis of expression of the responsible gene.

Cardiomyopathies↗

Mutations in p53 cDNA sequence introduced by retroviral vector.

The high mutation rates of retroviruses are a potential problem with retroviral vectors. We studied the mutation rates and spectra of p53 sequences transduced with a retroviral vector in a cancer gene therapy model. When p53-deficient H358 non-small cell lung cancer cells were treated with a retroviral vector carrying normal p53 cDNA, most of transduced cells were killed by apoptosis. However, a small number of clones escaped p53-mediated apoptosis. We examined the p53 cDNA structure in these resistant clones. PCR-based analysis showed that 88/102 clones had detectable mutations in p53, including gross rearrangements, deletions/insertions, and base substitutions. To study the mutation rate of the p53 sequence in all transduced clones, the retroviral vector containing the non-functional p53 gene and the Neo-resistant marker gene was introduced into H358 cells. Only one of 95 isolated clones showed a base substitution. These results indicate that the mutation rate of p53 is not particularly high, but there is a significant risk that cancer cells will resist p53 gene therapy as a result of retroviral replication errors.

Animals↗

Bovine hepatocyte growth factor and its receptor c-Met: cDNA cloning and expression analysis in the mammary gland.

Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic cytokine that plays a crucial role in the embryonic and postnatal development of various organs including the mammary gland. We cloned bovine HGF and its c-Met receptor cDNAs, and examined their expression during mammary gland development in dairy cows. The 2.5-kbp HGF cDNA clone contained a 2190 bp open reading frame coding a 730 amino acid protein, while the 4.8-kbp c-Met cDNA clone contained a 4152 bp open reading frame coding a 1384 amino acid protein. The bovine HGF and c-Met sequences exhibited more than 87% identity with those of other mammals. RT-PCR analysis revealed ubiquitous expression of both HGF and c-Met mRNAs in various bovine tissues tested. HGF mRNA was detected only in the inactive stage of bovine mammary gland development and not in the developing, lactating, and involuting stages, while c-Met mRNA was detected in the inactive and involuting stages. Immunohistochemical analysis demonstrated that the c-Met protein was found on mammary epithelial cells in the inactive, developing, and involuting stages, and on myoepithelial cells in all stages. These results suggest pivotal roles of HGF and c-Met in the development of bovine mammary gland.

Animals↗

Sequence effect of docetaxel and carboplatin on toxicity, tumor response and pharmacokinetics in non-small-cell lung cancer patients: a phase I study of two sequences.

PURPOSE: To investigate sequence effects on toxicity, tumor response and pharmacokinetics of docetaxel and carboplatin, together with a determination of the maximum-tolerated dose (MTD) and recommended dose for each schedule. PATIENTS AND METHODS: A total of 46 chemotherapy-naive patients with advanced non-small-cell lung cancer were randomized to receive docetaxel before (schedule A) or after (schedule B) carboplatin. The dose levels studied were [docetaxel (mg/m(2))/carboplatin (mg x min/ml)] 50/5, 60/5, 60/6, 60/7, and 70/6. Treatment cycles were repeated every 3 or 4 weeks unless disease progression or undue toxicity occurred. RESULTS: Of the 46 patients, 44 were assessable for toxicity and received a total of 84 cycles. The major dose-limiting toxicity was neutropenia. When the docetaxel dose was 60 mg/m(2), the carboplatin MTD was deemed to be AUC 7 in both schedules. When the docetaxel dose was escalated to 70 mg/m(2), the carboplatin MTD was reached in schedule A, and the dose-limiting toxicity was not observed in schedule B. Tumor response was observed in 4 of 22 patients (18%) with schedule A and 8 of 19 (42%) with schedule B. Clearances of both drugs were not affected by sequence: 111.2+/-26.8 ml/min and 107.8+/-29.0 ml/min for carboplatin (P=0.69), and 26.7+/-8.3 l/h and 22.8+/-7.0 l/h for docetaxel (P=0.19) in schedules A and B, respectively. CONCLUSIONS: Carboplatin AUC 6 followed by docetaxel 70 mg/m(2) was a favorable regimen for phase II study because of likely lower toxicity and a potentially higher response rate than the reverse sequence schedule. The mechanism of the sequence effects on toxicity and tumor response could not be explained by the pharmacokinetic interactions.

Adult↗

Interchromosomal duplication of major histocompatibility complex class I regions in rainbow trout (Oncorhynchus mykiss), a species with a presumably recent tetraploid ancestry.

Salmonid fishes are among the few animal taxa with a probable recent tetraploid ancestor. The present study is the first to compare large (>100 kb) duplicated genomic sequence fragments in such species. Two contiguous stretches with major histocompatibility complex (MHC) class I genes were detected in a rainbow trout BAC library, mapped and sequenced. The MHC class I duplicated regions, mapped by fluorescence in situ hybridization (FISH), were shown to be located on different metaphase chromosomes, Chr 14 and 18. Gene organization in both duplications is similar to that in other fishes, in that the class I loci are tightly linked with the PSMB8, PSMB9, PSMB10 and ABCB3 genes. Whereas one region, Onmy-IA, has a classical MHC class I locus (UBA), Onmy-IB encodes only non-classical class Ib proteins. The nucleotide diversity between the Onmy-IA and Onmy-IB noncoding regions is about 14%. This suggests that the MHC class I duplication event has occurred about 60 mya close to the time of an hypothesized ancestral tetraploid event. The present article is the first convincing report on the co-existence of two closely related MHC class I core regions on two different chromosomes. The interchromosomal duplication and the homology levels are supportive of the tetraploid model.

Amino Acid Sequence↗

Mating communication systems of four Plusiinae species distributed in Japan: identification of the sex pheromones and field evaluation.

The sex pheromones of four Plusiinae species in the family Noctuidae, Ctenoplusia albostriata (CA), Macdunnoughia purissima (MP), Syngrapha ain (SA), and Diachrysia stenochrysis (DS) were identified by GC-EAD and GC-MS analyses. These were subsequently evaluated by a series of field trials in different ecological habitats. CA females produced (Z)-5-decenyl acetate (I), (Z)-7-dodecenyl acetate (II), and (Z)-7-dodecen-1-ol (III) in a ratio of 2:100:13. While the antennae of CA males responded to all three components, neither I nor III was essential to capture males. The MP females produced II, III, and (Z)-5-dodecenyl acetate (IV) in a ratio of 100:80:20, and this blend captured the most MP males. Compounds II and III were also identified from SA females, and mixtures ranging from 4:1 to 2:3 were equally attractive to males. DS females only produced one active compound, (Z)-7-decenyl acetate (V), and DS is the first Plusiinae species identified as using only the omega3-compound and none of omega5-compounds, such as II and III, which are common components of Plusiinae pheromones. Using previously published chemical and biosynthetic data, together with the finding from this study, we propose a classification of the Plusiinae sex pheromones.

Acetates↗

Expression of full-length Cochlin p63s is inner ear specific.

OBJECTIVE: The COCH gene mutated in DFNA9, murine an autosomal dominant hereditary hearing impairment, encodes Cochlin. Cochlin is also suggested to be the self-antigen of autoimmune sensorineural hearing loss. We previously reported that Cochlin constitutes 70% of the inner ear proteins and is classified into three types of isoform, p63s, p44s, and p40s. To study the specificity of expression of Cochlin isoforms in various organs, here we have investigated expression of the COCH gene at both the transcriptional and translational level. METHODS: COCH gene expression was studied by RT-PCR and Southern blot analysis. Cochlin isoforms were studied by Western blot analysis using an isoform specific antibody. RESULTS: At the transcriptional level, COCH mRNA was detected only in the inner ear by RT-PCR. Southern blot analysis of RT-PCR products detected a high level of COCH mRNA in the inner ear, lower level in spleen, and very low levels in the cerebrum, cerebellum/brain stem, eye, liver and kidney. At the translational level, Western blot analysis showed that a set of isoform, p63s, p44s, and p40s was detected at high levels only in the inner ear. In contrast, multiple proteins were detected at much lower levels in other organs tested. Notably, full-length Cochlin p63s was detected only in the inner ear. CONCLUSION: Our findings demonstrate that the COCH gene is expressed preferentially in the inner ear and that expression of full-length Cochlin p63s is specific to the inner ear. These results will be central to understanding the function of Cochlin and its role in the pathophysiology of DFNA9.

Animals↗

A new, easy method for putting "U" stitches inside the chest wall.

In this report, we describe a new, easy method for putting "U" stitches inside the chest wall. The method does not require extension of the skin incision nor subcutaneous dissection and it minimizes chest wall injury. This method may also be applied to other surgical fields where needles can penetrate the wall of the cavity when it is difficult to stitch from the inside of the cavity.

Aged↗

Assessment of node dissection for clinical stage I primary lung cancer by VATS.

OBJECTIVE: The feasibility of systematic node dissection (SND) for stage I primary lung cancer by video-assisted thoracic surgery (VATS) remains controversial. The aim of this study was to assess the feasibility of SND by VATS. METHODS: Four hundred and eleven patients with clinical stage I primary lung cancer were enrolled in this study. Two hundred and twenty-one patients, VATS group, underwent a major pulmonary resection with SND by VATS through a minithoracotomy (30-70mm) and two access ports; 190 patients, open thoracotomy (OT) group, did so through anterolateral thoracotomy. The two groups were compared regarding clinical data including number of dissected nodes in each nodal station for evaluating the feasibility of SND by VATS. RESULTS: In the right side, the total number (N) of nodes dissected (VATS 31 vs OT 31, P=0.899), N of mediastinal nodes dissected (20 vs 21, P=0.553), and N of dissected nodes in each nodal station were similar between the two groups. In the left side, total N of nodes dissected (28 vs 27, P=0.714), N of mediastinal nodes dissected (16 vs 17, P=0.333), and N of dissected nodes in each nodal station were similar between the two groups. There were three (1.4%) and five (2.6%) operation related deaths in the VATS group and OT group, respectively (P=0.48). Chest tube duration was shorter in the VATS group than the OT group (5.8 vs 7.6 days, P=0.001). The incidences of chylothorax, recurrent laryngeal nerve injury and pleural effusion requiring thoracentesis after surgery were similar between the two groups (3 vs 4, P=0.709; 5 vs 3, P=0.480, 3 vs 8, P=0.122). The 5-year actuarial recurrence-free survival rate and cumulative survival rate of pathological stage IA cases were similar between the two groups (88.6 vs 92.4%, P=0.698; 92.9 vs 86.5%, P=0.358). CONCLUSIONS: The SND by VATS was as technically feasible as SND through OT regarding number of dissected nodes and morbidity. It seems acceptable as an oncological treatment for clinical stage I lung cancer.

Adenocarcinoma↗