Search PubMed⌕ Search

Biomedical subjects

T Nagase

Publications and source records attributed to T Nagase.

At least 91 records · Page 5Linked to original sources

Achieving natural shading of the nostril in the reconstruction of a half nose.

The secondary deformities in a patient who had a half nose that had been reconstructed in childhood using a median forehead flap and the corrective procedures subsequently employed are described. The secondary deformities included elevation of the right alar rim and a completely visible nasal floor. These deformities were corrected with a scalping forehead flap and by changing the orientation of the reconstructed right nostril and nasal cavity. Nasal airway reconstruction may not always be needed, particularly in a congenital half nose such as described here. Instead, the aesthetic importance of the orientation of the reconstructed nasal cavity in order to obtain a normal shaded appearance in the nostril is emphasised.

Adult↗

The effect of muscle repair on postoperative facial skeletal growth in children with bilateral cleft lip and palate.

The effect of orbicularis muscle repair on postoperative facial skeletal growth in bilateral cleft lip and palate patients was studied by analysis of cephalometric radiographs and dental casts. Sixty-two patients operated on between 1961-1989 were selected for the study. They were divided into three groups, group 1a (muscle repair; n = 12), group 1b (failed attempt at muscle repair; n = 5), and group 2 (no attempt at muscle repair; n = 45). Comparison of the morphological measurements among these three groups showed that there was a trend towards crossbite in the muscle repair group, but this difference was not significant. Mechanisms by which muscle repair might influence maxillofacial skeletal growth include the possibility that the area around the nasal septum might be the growth centre. The choice of operative technique in bilateral cleft lip and palate should be important.

Cephalometry↗

Microsurgical medial plantar flap banking: a method of choice for digital tip injury?

A tip injury of the left thumb was repaired via microsurgical medial plantar flap banking. The medial plantar flap was transferred temporarily to the lower abdominal wall and was anastomosed microsurgically to the deep inferior epigastric artery and vein as a banked flap. It was later grafted to the thumb in a manner similar to a pedicled flap. The flap was transferred successfully, and the tissue texture and bulk was sufficient, with considerable sensory recovery and minimal donor site deformity. This method may be worthwhile to consider as one of the options of digital tip reconstruction, and the concept of microsurgical flap banking may be promising in the field of reconstructive microsurgery.

Foot↗

Mutations in fibroblast growth factor receptor 2 gene and craniosynostotic syndromes in Japanese children.

We examined the gene mutations of fibroblast growth factor receptor 2 (FGFR2) in Japanese syndromic craniosynostotic patients. Subjects included 1 patient with Apert's syndrome, 1 patient with Crouzon's syndrome, and 3 patients with Pfeiffer's syndrome, as well as two control patients. The genomic deoxyribonucleic acid of each patient was extracted, and the mutation sites of the FGFR2 gene were amplified and sequenced. One patient with Apert's syndrome showed a FGFR2 mutation of S252W (TCG-->TGG), 1 patient with Crouzon's syndrome had a mutation of C342W (TGC-->TGG), and the 3 patients with Pfeiffer's syndrome had mutations of T341P (ACG-->CCG), C342S (TGC-->TCC), and D321A (GAC-->GCC). The role of FGF families and the effect of FGFR2 mutations on craniofacial morphogenesis are discussed.

Acrocephalosyndactylia↗

Vertical symphyseal osteotomy.

For the treatment of mild crossbite with increased bigonial distance, the authors performed a vertical symphyseal osteotomy on six patients in the last 3 years. Three of these patients had cleft lip deformities and the others had operations for orthodontic or aesthetic reasons. After exposing the mandible through the buccal mucosal incision, both premolars were extracted with or without conventional segmental osteotomy. The two vertical symphyseal osteotomies were performed with approximately 1 cm between them, and the central part of the mandibular bone was discarded. The bilateral segments of the mandibular body were fixed in the midline using titanium miniplates. Satisfactory results were obtained with a reduction in the size of the mandibular arch, which produced better three-dimensional proportions in the bimaxillary area. No patients had temporomandibular joint problems, however postoperative orthodontics were essential for this type of operation.

Adult↗

Japanese sisters with Pfeiffer syndrome and achondroplasia: a mutation analysis.

The authors report the rare existence of a family that includes an older sister with Pfeiffer syndrome and a younger sister with achondroplasia. Gene analysis of these patients showed a T341P mutation in the FGFR2 gene in the patient with Pfeiffer syndrome, and a G380R mutation in the FGFR3 gene in the patient with achondroplasia. Both mutations have been reported previously. Their parents had no mutation in either locus. This result suggests the possibility that there may be predisposing factors for different FGFR mutations.

Achondroplasia↗

Airway hyperresponsiveness to methacholine in mutant mice deficient in endothelin-1.

Endothelin-1 (ET-1) has recently been reported to have a potential pathophysiologic role in bronchial asthma. In the current study, we hypothesized whether ET-1 and a gene encoding ET-1 might be involved in airway hyperresponsiveness (AHR), which is a major feature of bronchial asthma. To test this hypothesis, we investigated airway responsiveness in ET-1(+/-) heterozygous knockout mice, which genetically produce lower levels of ET-1, and in ET-1(+/+) wild-type mice. Airway responsiveness was assessed through the concentration of an agonist required to double lung resistance (EC200 RL). Unexpectedly, airway responsiveness to methacholine was markedly enhanced in ET-1(+/-) heterozygous mice as compared with ET-1(+/+) wild-type mice (EC200 RL: 1.8 +/- 0.1 versus 21.6 +/- 5.6 mg/ml, p < 0.002). Pretreatment with the nitric oxide (NO) synthase inhibitor Ng-monomethyl-L-arginine (L-NMMA) significantly enhanced methacholine responsiveness in ET-1(+/+) wild-type mice, but not in ET-1(+/-) heterozygous mice. Meanwhile, there was no difference between ET-1(+/-) heterozygous mice and the wild-type mice in airway responsiveness to 5-hydroxytryptamine (5-HT). In sensitized mice, no significant differences in responsiveness to antigen were observed between the two groups. These findings suggest that the gene encoding ET-1 may be potentially involved in the etiology of airway hyperreactivity, and that the decrease in ET-1 concentration is associated with AHR to methacholine. In mice, ET-1 as well as NO may have a significant role in the homeostasis of airway physiology.

Airway Resistance↗

Isolation and chemical composition of the sheath of Sphaerotilus natans.

A sheathed bacterium, Sphaerotilus natans, was cultured with vigorous shaking in a medium containing peptone. Then the biomass was harvested and treated with lysozyme, sodium dodecyl sulfate, and protease. With treatment, 1.6 mg of sheaths was obtained from 15 mg of biomass. For the preparation of sheaths of high purity, cultivation must be in the absence of glucose with sufficient aeration to prevent poly(3-hydroxybutyrate) accumulation. Carbohydrate (54.1%), protein (12.2%), and lipid (1-3%) were detected in the sheaths by colorimetric reactions and solvent extraction. Gas-liquid chromatography showed glucose and galactosamine to be present in the molar ratio of 1:4. The most abundant amino acids in the sheath protein were glycine (49.2 mol%) and cysteine (24.6 mol%). The sheaths were resistant to agents that reduce disulfide bonds (dithiothreitol and 2-mercaptoethanol) and to protease. However, sheathes were degraded completely by hydrazine, and a heteropolysaccharide composed of glucose and galactosamine (1:4) was released. The weight-average molecular weight of the polysaccharide was estimated to be 1.2 x 10(5) by gel filtration chromatography with a low-angle laser-light scattering photometer and a rotation index detector. A ladder of 1.5-kDa peptides separable by sodium dodecyl sulfate gel electrophoresis was obtained by partial hydrolysis of sheaths, suggesting the sheath protein has repeating units of 1.5 kDa.

Amino Acids↗

[Influence of kyphosis on the age-related decline in pulmonary function].

To examine the influence of kyphosis on pulmonary function in the elderly, 300 consecutive healthy subjects (aged 20-94 years old) were evaluated using pulmonary function tests (TLC, VC, FEV1, RV) and static maximal pressures (PImax and PEmax). Kyphosis of the thoracic bones was measured at Cobb's angle. VC, FEV1. PImax and PEmax showed a significant age-dependent decline. Cobb's angle had a positive relationship with age and was negatively correlated with TLC, VC, FEV1 and PImax. Further, RV/TLC strongly correlated with Cobb's angle and PImax. Stepwise regression analysis revealed that the kyphotic angle was an independent determinant for PImax and RV/TLC. These results indicate that kyphosis significantly affects lung volume and maximal inspiratory pressure in the elderly and those affected should have careful assessment of their pulmonary function and respiratory pressures.

Adult↗

Antigen-induced responses in lung parenchymal strips during sinusoidal oscillation.

We have recently demonstrated that tissue resistance increases during the early response to antigen challenge in sensitized Brown-Norway rats. The purpose of the present study was to investigate in vitro the dynamic tissue response to antigen challenge and the involvement of the mediators, i.e., serotonin (5HT) and leukotriene D4 (LTD4). In addition, we questioned whether strips from sensitized rats responded differently to nonspecific challenge compared with those of unsensitized controls. We sensitized Brown-Norway rats with ovalbumin and performed experiments using strips of subpleural parenchyma. Tissue strips were challenged with ovalbumin in the bath; in some experiments the tissues were exposed to methysergide (10(-6) M), a 5HT antagonist, or MK-571 (10(-6) M), a LTD4 receptor antagonist, or both, prior to challenge. At the end of the experiment all tissues were exposed to carbacholine (10(-3) M). Oscillation mechanics of tissue strips were studied and values of resistance (R), elastance (E), and hysteresivity (eta) were obtained. During ovalbumin challenge in sensitized tissues, R, E, and eta increased significantly (% change in R, 12.1 +/- 2.1%; % change in E, 3.8 +/- 1.3%; % change in eta, 9.3 +/- 2.8%). Both methysergide and MK-571 reduced the increase in R (3.0 +/- 0.6 and 3.2 +/- 0.8%, respectively, p < 0.05 vs. ovalbumin). There was no difference between sensitized and unsensitized strips in the response to carbacholine challenge. These data suggest that the oscillatory behaviour of tissue strips from sensitized rats is altered after ovalbumin challenge. The mechanism of that response is mediated by both 5HT and LTD4.

Animals↗

[Determinant factors of pulmonary function and respiratory muscle strength on exertional dyspnea in patients with chronic obstructive pulmonary disease (COPD)].

The effects of pulmonary function and respiratory muscle strength on exertional dyspnea in patients with chronic obstructive pulmonary disease (COPD) have not been fully elucidated. We examined the relationships between pulmonary function, static respiratory pressure, and dyspneic sensation during exercise in 48 patients with COPD. Dyspneic sensation during exercise was quantitated by a Borg scale slope (BSS, BS/VO2) and the threshold load of dyspnea (TLD). BSS was negatively correlated with VC, FEV1, V 25, RV/TLC (%). DLCO and PImax, whereas TLD was positively correlated with VC, FEV1, V 25, FRC and RV/TLC. Linear regression analysis revealed that FEV 1 and FRC were independent predictors for TLD, and that RV/TLC (%) was an independent predictor for BSS. These results suggest that an increase of air trapping as indicated by RV/TLC may be a major factor contributing to both decreased TLD and increased BSS, resulting in an increased sensation of dyspnea during exercise in patients with COPD.

Dyspnea↗

[The role of intercellular adhesion molecule-1 in respiratory disorders].

Inflammatory processes are a key event in various respiratory disorders. Adhesion to microvascular endothelial cells is essential for the migration of leukocytes into inflamed tissues. Intercellular adhesion molecule-1 (ICAM-1) is a member of the immunoglobulin superfamily and a ligand for lymphocyte function-associated antigen-1 alpha (LFA-1 alpha). It has been shown to be required for leukocyte migration into inflamed tissues, and to play a significant role in inflammatory diseases, including rhinovirus infections. Clinical and experimental investigations have demonstrated a close relationship between the ICAM-1/LFA-1 alpha pathway and the pathogenesis of asthmatic responses and acute respiratory distress syndrome. Further progress in research on the antagonism of ICAM-1 and LFA-1 alpha may provide new therapeutic approaches to inflammatory lung diseases.

Animals↗

Role of cytosolic phospholipase A2 in allergic response and parturition.

Phospholipase A2 (PLA2) comprises a superfamily of enzymes that hydrolyse the ester bond of phospholipids at the sn-2 position. Among the members of this superfamily, cytosolic PLA2 has attracted attention because it preferentially hydrolyses arachidonoyl phospholipids and is activated by submicromolar concentrations of Ca2+ ions and by phosphorylation by mitogen-activated protein kinases (MAP kinases). Here we investigate the function of cytosolic PLA2 in vivo by using homologous recombination to generate mice deficient in this enzyme. These mice showed a marked decrease in their production of eicosanoids and platelet-activating factor in peritoneal macrophages. Their ovalbumin-induced anaphylactic responses were significantly reduced, as was their bronchial reactivity to methacholine. Female mutant mice failed to deliver offspring, but these could be rescued by administration of a progesterone-receptor antagonist to the mother at term. Considered together with previous findings, our results indicate that cytosolic PLA2 plays a non-redundant role in allergic responses and reproductive physiology.

Anaphylaxis↗

Trans-regulation of myogenin promoter/enhancer activity by c-ski during skeletal-muscle differentiation: the C-terminus of the c-Ski protein is essential for transcriptional regulatory activity in myotubes.

c-ski gene product is a nuclear protein with myogenesis-promoting and transforming activities. We have analysed the effects of c-ski transfection on the promoter/enhancer activity of the upstream region of the myogenin gene during in vitro myogenesis using CAT reporter assay. When co-transfected with c-ski into myogenic C2C12 cells, promoter/enhancer activity was efficiently suppressed in proliferating cells, but the myogenesis-induced increase in activity was potentiated approximately ten times more (150-fold in the ski-transfected cells) than the ordinary increase (12-fold in the mock) 48 h after induction of differentiation. In non-myogenic 10T1/2 cells, c-ski transfection caused persistent suppression of promoter/enhancer activity in both proliferating and growth-arrested (i.e. myogenesis-inducing) conditions. Thus the ski-dependent potentiation of myogenin gene transcriptional activity appears to be specific for myogenesis. The C-terminal region (amino acids 595-663) of the c-Ski protein was essential for the potentiating activity in myotubes. Other members of the ski-gene family, snoN and snoA, were ineffective in transactivation, possibly because of the defect in the corresponding C-terminal region. c-Ski protein underwent a mobility shift on SDS/PAGE after in vitro myogenesis which may explain the conversion of the activity from suppressive in myoblasts to potentiating in myotubes. Deletion analysis of the upstream region of the myogenin gene revealed that a responsive element to c-ski in myotubes is located at a distinct site upstream of the basal promoter/enhancer region.

Animals↗

Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro.

As a part of our project for accumulating sequence information of the coding regions of unidentified human genes, we herein report the sequence features of 78 new cDNA clones isolated from human brain cDNA libraries as those which may code for large proteins. The sequence data showed that the average size of the cDNA inserts and their open reading frames was 6.0 kb and 2.8 kb (925 amino acid residues), respectively, and these clones produced the corresponding sizes of protein products in an in vitro transcription/translation system. Homology search against the public databases indicated that the predicted coding sequences of 68 genes contained sequences similar to known genes, 69% of which (47 genes) were related to cell signaling/communication, nucleic acid management, and cell structure/motility. The expression profiles of these genes in 14 different tissues have been analyzed by the reverse transcription-coupled polymerase chain reaction method, and 8 genes were found to be predominantly expressed in the brain.

Brain Chemistry↗

Characterization of cDNA clones in size-fractionated cDNA libraries from human brain.

To evaluate the size-fractionated cDNA libraries of human brain previously constructed (O. O'hara et al. DNA Research, 4, 53-59, 1997), the occurrence of chimeric clones and the content of clones with coding potentiality were analyzed using the randomly sampled clones with insert sizes of 5 to 7 kb. When the chromosomal location of 30 clones was determined by the radiation-hybrid mapping method, the map positions assigned from the 3'- and 5'-end sequences separately were coincident for 29 clones, suggesting that the occurrence of chimeric clones is at most 1/30. Using 91 clones mapped to chromosome 1, the content of clones that have the potentiality coding for proteins larger than 100 amino acid residues was estimated to be approximately 50% (46 out of 91 clones) on the basis of nucleotide sequence analysis and coding potentiality assay in vitro. No significant open reading frames were detected in the remaining clones. Although the clones coding for short peptides may not have been included in the above estimation, the libraries constructed from the whole brain mRNA fraction appear to contain a considerable amount of clones corresponding to the 5'-truncated transcripts in an unprocessed form and/or those with long 3'-untranslated regions.

Animals↗

Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.

In this series of projects of sequencing human cDNA clones which correspond to relatively long transcripts, we newly determined the entire sequences of 100 cDNA clones which were screened on the basis of the potentiality of coding for large proteins in vitro. The cDNA libraries used were the fractions with average insert sizes from 5.3 to 7.0 kb of the size-fractionated cDNA libraries from human brain. The randomly sampled clones were single-pass sequenced from both the ends to select clones that are not registered in the public database. Then their protein-coding potentialities were examined by an in vitro transcription/translation system, and the clones that generated proteins larger than 60 kDa were entirely sequenced. Each clone gave a distinct open reading frame (ORF), and the length of the ORF was roughly coincident with the approximate molecular mass of the in vitro product estimated from its mobility on SDS-polyacrylamide gel electrophoresis. The average size of the cDNA clones sequenced was 6.1 kb, and that of the ORFs corresponded to 1200 amino acid residues. By computer-assisted analysis of the sequences with DNA and protein-motif databases (GenBank and PROSITE databases), the functions of at least 73% of the gene products could be anticipated, and 88% of them (the products of 64 clones) were assigned to the functional categories of proteins relating to cell signaling/communication, nucleic acid managing, and cell structure/motility. The expression profiles in a variety of tissues and chromosomal locations of the sequenced clones have been determined. According to the expression spectra, approximately 11 genes appeared to be predominantly expressed in brain. Most of the remaining genes were categorized into one of the following classes: either the expression occurs in a limited number of tissues (31 genes) or the expression occurs ubiquitously in all but a few tissues (47 genes).

Blotting, Northern↗

Construction and characterization of human brain cDNA libraries suitable for analysis of cDNA clones encoding relatively large proteins.

Analysis of proteins registered in the PIR protein database implied that most of relatively large proteins are related to important functions in higher multicellular organisms, but not many large proteins have been registered to date. To establish a protocol for efficient analysis of cDNA clones coding for large proteins, we constructed a series of strictly size-fractionated cDNA libraries of human brain, where the average insert sizes of cDNA clones ranged from 3.3 kb to 10 kb. As judged by hybridization analysis with probes derived from mRNAs of known sizes, the libraries with insert sizes up to 7 kb, at least, contained the clones corresponding to full-length transcripts in addition to truncated products of longer transcripts, but few chimeric clones. Using one of the fractionated libraries with an average insert size of 7 kb, the single-pass sequences from both the ends of randomly sampled clones were determined and sarched against DNA databases. Approximately 90% of the clones were found to be new with respect to their 5'-sequences while their 3'-sequences were frequently similar to the registered expression sequence tags. Examination of the protein-coding capacity in an in vitro transcription/translation system showed that about 20% of the clones direct the synthesis of proteins with apparent molecular masses larger than 50 kDa. The set of libraries constructed here should be very useful for the accumulation of sequence data on large proteins in the human brain.

Brain↗