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Biomedical subjects

K Isono

Publications and source records attributed to K Isono.

At least 19 recordsLinked to original sources
PubMed2002

Adenocarcinoma of the esophagogastric junction: a summary of responses to a questionnaire on adenocarcinoma of the esophagus and the esophagogastric junction in Japan.

Adenocarcinoma of the esophagogastric junction is recognized as a distinct clinical entity; however, the choice of surgical approaches is controversial. To analyze the results of surgery among patients with adenocarcinoma of the esophagus (type I) and the cardia (type II) based on Siewert's classification in Japan, surgical procedures, histopathologic characteristics, and outcome were re-evaluated according to the TNM classification in 1263 patients with adenocarcinoma of the esophagus (type I) and the cardia (type II) through a questionnaire sent to the members of the Japanese Society of Esophageal Diseases. One hundred and thirty-four (10.6%) patients had type I tumors and 1129 (89.4%) patients had type II tumors. There were significant differences in sex distribution and associated intestinal metaplasia in the esophagus between patients with type I and type II tumors. Although different surgical approaches were performed, the overall 5-year survival rate was 53% without any difference between the two groups. The significant prognostic factors in general linear models were R category, pN category, and differentiation, but not pT category. There was no difference in survival between patients with stage IIB and III disease. The survival rate of the patients who underwent a transhiatal approach was similar to that of those undergoing a transthoracic approach. The results suggest that Siewert's classification (type I and type II) is useful in planning treatment strategy for adenocarcinoma of the esophagogastric junction. Lymph node metastasis was the most important prognostic factor, and staging based on the number of lymph node metastases or the extent of lymph node metastasis is necessary.

Adenocarcinoma↗
PubMed2002

Beta-adrenergic receptor-mediated growth of human airway epithelial cell lines.

Abnormal growth of airway epithelium and the resultant thickening of airway walls may produce narrowing of airway calibre, thereby contributing to deterioration of bronchoconstriction in chronic obstructive pulmonary disease (COPD). Beta2-adrenergic agonists have been widely used for the treatment of COPD, but their effects on the growth of airway epithelial cells is unknown. Growth of three human airway epithelial cell lines was studied in vitro. Exposure to salbutamol in serum-free medium increased 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide reduction and intracellular deoxyribonucleic acid (DNA) contents in 16-human bronchial epithelium (16-HBE) cells and NCI-H292 cells, but not in A549 cells. The growth-promoting effect of salbutamol in 16-HBE cells was equipotent to 10% foetal bovine serum and was inhibited by propranolol and a cyclic adenosine monophosphate (cAMP) antagonist, Rp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt (Rp-cAMPS). Likewise, forskolin and 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) caused cell growth and DNA synthesis. Western blot analysis showed that salbutamol, forskolin, and 8-Br-cAMP each induced expression of the phosphorylated form of mitogen-activated protein (MAP) kinase, and that the salbutamol-induced phosphorylation was inhibited by propranolol, Rp-cAMPS, and the MAP kinase-kinase inhibitor PD98059. These results suggest that in certain airway epithelial cell lines stimulation of beta2-adrenergic receptors and the consequent production of cyclic adenosine monophosphate may upregulate cell growth, probably through activation of the mitogen-activated protein kinase cascade.

Adrenergic beta-Agonists↗
PubMed2001

Mouse homologue of coq7/clk-1, longevity gene in Caenorhabditis elegans, is essential for coenzyme Q synthesis, maintenance of mitochondrial integrity, and neurogenesis.

coq7/clk-1 was isolated from a long-lived mutant of Caenorhabditis elegans, which showed sluggish behavior and an extended life span. Mouse coq7 is homologous to Saccharomyces cerevisiae coq7/cat5 that is required for biosynthesis of coenzyme Q (CoQ), an essential cofactor in mitochondrial respiration. Here we generated COQ7-deficient mice to investigate the biological role of COQ7 in mammals. COQ7-deficient mouse embryos failed to survive beyond embryonic day 10.5, exhibiting small-sized body and delayed embryogenesis. Morphological studies showed that COQ7-deficient neuroepithelial cells failed to show the radial arrangement in the developing cerebral wall, aborting neurogenesis at E10.5. Electron microscopic analysis further showed the enlarged mitochondria with vesicular cristae and enlarged lysosomes filled with disrupted membranes, which is consistent with mitochondriopathy. Biochemical analysis demonstrated that COQ7-deficient embryos failed to synthesize CoQ(9), but instead yielded demethoxyubiquinone 9 (DMQ(9)). Cultured embryonic cells from COQ7-deficient mice were rescued by adding bovine fetal serum in vitro, but exhibited slowed cell proliferation, which resembled to the phenotype of clk-1 with delayed cell divisions. The result implied the essential role of coq7 in CoQ synthesis, maintenance of mitochondrial integrity, and neurogenesis in mice.

Animals↗
PubMed2001

Structural features of a wheat plastome as revealed by complete sequencing of chloroplast DNA.

Structural features of the wheat plastome were clarified by comparison of the complete sequence of wheat chloroplast DNA with those of rice and maize chloroplast genomes. The wheat plastome consists of a 134,545-bp circular molecule with 20,703-bp inverted repeats and the same gene content as the rice and maize plastomes. However, some structural divergence was found even in the coding regions of genes. These alterations are due to illegitimate recombination between two short direct repeats and/or replication slippage. Overall comparison of chloroplast DNAs among the three cereals indicated the presence of some hot-spot regions for length mutations. Whereas the region with clustered tRNA genes and that downstream of rbcL showed divergence in a species-specific manner, the deletion patterns of ORFs in the inverted-repeat regions and the borders between the inverted repeats and the small single-copy region support the notion that wheat and rice are related more closely to each other than to maize.

DNA, Chloroplast↗
PubMed2001

Trehalose sensitivity in Drosophila correlates with mutations in and expression of the gustatory receptor gene Gr5a.

Drosophila taste gene Tre is located on the distal X chromosome and controls gustatory sensitivity to a subset of sugars [1, 2]. Two adjacent, seven-transmembrane domain genes near the Tre locus are candidate genes for Tre. One (CG3171) encodes a rhodopsin family G protein receptor [3, 4], and the other (Gr5a) is a member of a chemosensory gene family encoding a putative gustatory receptor [5-7]. We carried out molecular analyses of mutations in Tre to elucidate their involvement in the gustatory phenotype. Here, we show that Tre mutations induced by P element-mediated genomic deletions disrupt Gr5a gene organization and the expression of Gr5a mRNA, while disruption of the CG3171 gene or its expression was not always associated with mutations in Tre. In flies with the spontaneous mutation Tre(01), both CG3171 and Gr5a mRNAs are transcribed. Coding sequences of these two candidate genes were compared among various strains. A total of three polymorphic sites leading to amino acid changes in CG3171 were not correlated with the gustatory phenotype. Among four nonsynonymous sites in Gr5a, a single nucleotide polymorphism leading to an Ala218Thr substitution in the predicted second intracellular loop cosegregated with Tre(01). Taken together, the mutation analyses support that Gr5a is allelic to Tre.

Animals↗
PubMed2001

Cooperative functions of the mannoprotein-encoding genes in the biogenesis and maintenance of the cell wall in Saccharomyces cerevisiae.

To elucidate the roles of genes involved in the cell wall biogenesis and function in Saccharomyces cerevisiae, we isolated and characterized mutants that were lethal in a strain in which the SED1 gene encoding a cell wall mannoprotein was disrupted. Thus, double mutants of SED1 and either MNN9 or MNN10 were unable to grow and YOL155c on a multicopy plasmid could suppress their synthetic lethality. A Yol155cp-GFP fusion protein was found to localize to the cell wall, suggesting that it might also be a cell wall mannoprotein. Subsequently, we analysed the effects of the shut-off of SED1 in a sed1 and mnn9 double mutant: cells after the shut-off showed anomalous cellular morphology and died in the mitotic M phase. From these and other results, we postulate that these genes function cooperatively with each other and in a cell cycle-dependent manner in the biogenesis and maintenance of cell wall in S. cerevisiae.

Amino Acid Sequence↗
PubMed2001

Serum p53 antibody as a useful marker for monitoring of treatment of superficial colorectal adenocarcinoma after endoscopic resection.

BACKGROUND: Mutation of the p53 gene is a genetic alteration found in human cancers. Overexpression of p53 has been found to induce antibody production in serum, and, recently, the simple detection of serum antibody has been made possible. The aim of this study was to evaluate the potential role of serum p53 antibody in the early diagnosis of superficial colorectal cancer and in the monitoring of its treatment after endoscopic resection. METHODS: In a prospective study, our subjects were 27 patients with superficial colorectal adenocarcinomas, whose results were compared with those in 38 patients with benign adenomas; all patients were treated by endoscopic resection. The correlation between serum p53 antibody levels before and within 3 weeks after resection was determined, using an immunoassay. Immunohistological staining for p53 was also performed, and its sensitivity was compared with that of two other tumor markers. RESULTS: Preoperatively, serum p53 antibody was detected in 63.0% (17/27) patients with adenocarcinoma and in 2.6% (1/38) patients with adenoma, showing a significant difference (P < 0.001). However, the two other markers carcinoembryonic antigen (CEA) and carbohydrate antigen CA19-9, showed no significant difference between superficial colorectal adenocarcinoma and adenoma. The serum p53 antibody status was strongly correlated with p53 immunostaining in adenocarcinoma (P = 0.0065), but there was no significant correlation in adenoma (P = 0.973). Sixteen (94.1%) of 17 seropositive adenocarcinoma patients, showed negative conversion after complete tumor resection, and all these 16 patients remained seronegative. CONCLUSION: The detection of serum p53 antibody is expected to serve as a new genetic marker, determined by serological analyses, for aiding in the early diagnosis of superficial colorectal cancer and indicating its local curability after endoscopic treatment.

Adenocarcinoma↗
PubMed2001

Prognosis of patients with advanced carcinoma of the esophagus with complete response to chemotherapy and/or radiation therapy: a questionnaire survey in Japan.

BACKGROUND: We estimated the survival of patients with advanced carcinoma of the esophagus in Japan who achieved complete response (CR) with chemotherapy and/or radiation therapy. METHODS: A questionnaire was designed for patients with cancer of the esophagus with pretreatment stage II-IV (excluding organ metastasis [M1]), who were treated with chemotherapy and/or radiation therapy and achieved either a clinical CR continuing for more than 1 year, or a pathological CR in surgical specimens. All patients were treated between January 1, 1990, and December 31, 1997, in Japan. RESULTS: Of the 169 eligible patients for whom adequate data were available, 106 patients with continuing clinical CR were defined as group A and 63 with pathological CR as group B. The overall survival rates at 5 years were 62.4% in group A and 64.8% in group B. In each of groups A and B, there was no significant difference in overall survival among subgroups of patients classified by initial pretreatment clinical stage. In group A, the survival rate of patients with concurrent chemotherapy and radiation therapy was significantly better than the rates for patients with chemotherapy alone or radiotherapy alone. In group A, the frequency of first failure at the local site of esophageal carcinoma was 7.7%. Of the 12 patients in group B (19%) who died less than 1 year postoperatively, 6 died of postoperative complications. CONCLUSION: The effect of CR to chemotherapy and/or radiation therapy for carcinoma of the esophagus on survival was marked. In patients with esophageal carcinoma who achieve CR, the prognosis may be independent of the initial pretreatment stage. Local failure in group A patients remains a problem, however.

Adult↗
PubMed2001

Molecular cloning, genetic mapping, and expression of the mouse Sf3b1 (SAP155) gene for the U2 snRNP component of spliceosome.

SAP155, a subunit of the U2 snRNP, is essential for prespliceosome assembly and splicing catalysis of the major spliceosome. Moreover, the protein has been identified in the minor (U12-dependent) spliceosome. These facts strongly suggest that SAP155 is shared by two distinct complexes owing to its importance in the removal of any type of intron. Here we have isolated a cDNA encoding the 146-kDa mouse homolog, designated Sf3b1. The amino acid sequence of Sf3b1 is very highly conserved among homologs from Schizosaccharomyces pombe (52.4% identity) to human (99.6%), and the C-terminal 825 residues of these Sf3b1 homologs show even higher identities. This C-terminal region shows significant similarity to the PR65 subunit of protein phosphatase 2A, which is composed of 15 tandem repeats of a 39 amino acid sequence. Mouse genome analyses showed Sf3bh1 to be a single-copy gene mapping to the central part of Chromosome (Chr) 1. Northern blot analysis and whole mount in situ hybridization revealed Sf3b1 to be ubiquitously expressed in a variety of adult tissues and mid-gestation embryos.

Amino Acid Sequence↗
PubMed2001

Cross-genomic analysis of the translational systems of various organisms.

We have characterized the genes encoding ribosomal proteins (r-proteins) as well as other translation-related factors of 15 eubacteria and four archaebacteria, and the genes for the mitochondrial r-proteins of Saccharomyces cerevisiae by using the complete genomic nucleotide sequence data of these organisms. In eubacteria, including two species of Mycoplasma, the operon structure of the r-protein genes is well conserved, while their relative orientation and chromosomal location are quite divergent. The operon structure of the r-protein genes in archaebacteria, on the other hand, is quite different from eubacteria and also among themselves. In addition, many archaebacterial r-proteins show similarity to rat cytoplasmic r-proteins. Nonetheless, characteristic features of several genes encoding proteins of functional importance are well conserved throughout the bacterial species including archaebacteria, as well as in S. cerevisiae. We searched for the genes encoding mitochondrial r-proteins in yeast by combining informatics and genetic experiments. Furthermore, we characterized some of the r-proteins genes by exchanging portions between Escherichia coli and S. cerevisiae and performed functional analysis of some of the genes from different evolutionary points of view. Our work may be extended towards phylogenetic analysis of organisms producing secondary metabolites of various sorts.

Bacteria↗
PubMed2001

Monitoring of p53 autoantibodies after resection of colorectal cancer: relationship to operative curability.

OBJECTIVE: To investigate the clinical use of p53 autoantibodies as a marker in the postoperative monitoring of colorectal cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: 40 patients with colorectal cancer who had p53 autoantibodies in their serum preoperatively. INTERVENTIONS: Serial assay of p53 autoantibodies by ELISA before and after resection. MAIN OUTCOME MEASURES: Interpretation by a qualitative analysis. RESULTS: A significant correlation was observed between curability by surgical resection and postoperative disappearance of p53 autoantibodies. Twenty-seven (96%) of 28 patients, who had p53 autoantibodies and whose cancer was completely removed, had no such antibodies after resection and no recurrence after 7 to 26 months. CONCLUSIONS: Postoperative assays of p53 autoantibodies are potentially useful for predicting recurrence of colorectal cancer in patients who have p53 autoantibodies preoperatively.

Colorectal Neoplasms↗
PubMed2001

Phase II evaluation of protracted infusion of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG) Trial (JCOG9407).

BACKGROUND: Surgery for advanced esophageal carcinoma has its limits as regards aggressiveness and therapeutic effect, therefore effective multimodality treatment is required to obtain better survival. The objective of this study was to evaluate whether daily continuous infusion of CDDP could achieve a higher clinical response rate with less toxicity than its drip infusion in the previous phase II study that we had conducted. METHODS: Patients with primary extensive or relapsed esophageal carcinoma after esophagectomy, which had distant organ metastasis and histologically proven SCC, were eligible for this study. A dose of 20 mg/m(2) of cisplatin and 800 mg/m(2) of 5-fluorouracil was given by continuous infusion for 24 h on days 1-5. This treatment was repeated every 4 weeks for up to four cycles. A total of 36 men and six women with a median age of 64 (range 39-75) years were registered and 36 patients were eligible. RESULTS: The overall response rate of the registered patients was 33.3% (12/36) and the median response duration was 175 days. Median survival time was 201.5 days and the 1-year survival rate was 27.8%. Change from bolus to continuous infusion of cisplatin affected neither the type nor the degree of toxicity. CONCLUSION: Daily continuous infusion of cisplatin was not associated with higher response or lower toxicity than those seen with the high-dose bolus or multibolus treatment regimens. We conclude that this regimen in this setting is not worthy of further phase III trials. JEOG is now evaluating other drug combination regimens.

Adult↗
PubMed2001

[Effect of endothelin on DNA synthesis in human bronchial epithelium: role of MAP kinase cascade].

To elucidate the effect of endothelin (ET) on airway epithelial cell proliferation, we measured intracellular DNA levels and assessed a possible contribution of mitogen activated protein kinase (MAPK) cascade to the ET action. Incubation of transformed human bronchial epithelial (16 HBE) cells with ET in the serum-free medium caused time-dependent increases in DNA synthesis and MTT reduction, an effect that was attenuated by the MAPK kinase inhibitor PD 98059 in a concentration-dependent manner. Western blot analysis showed that ET induced the expression of phosphorylated MAPK protein, indicating an activation of MAPK, and that this effect was inhibited in the presence of PD 98059 or the ETA receptor antagonist BQ-123. These results suggest that ET may stimulate the proliferation of human airway epithelium via ETA receptors and the concomitant activation of MAPK cascade.

Bronchi↗
PubMed2000

A putative binding protein for lipophilic substances related to butterfly oviposition.

A unique protein of 23 kDa (Jf23) was found in the tarsus of the female swallowtail butterfly, Atrophaneura alcinous. Jf23 has 38% identity with a bilin-binding protein, which was found in the cabbage butterfly, Pieris brassicae, and which has two consensus sequences in common with the members of the lipocalin family, suggesting that it is a binding protein for lipophilic ligands. Western blot analysis showed that Jf23 was expressed only in the female, and not in the male. Electrophysiological response of the female tarsi was stimulated by methanolic extract of their host plant, Dutchman's pipe (Aristolochia debilis). The stimulated response was depressed by the presence of Jf23 antiserum. These results suggest that Jf23 is one of the chemosensory signaling proteins, which plays one or more roles in female butterfly oviposition.

Amino Acid Sequence↗
PubMed2000

Effect of suplatast tosilate, a Th2 cytokine inhibitor, on steroid-dependent asthma: a double-blind randomised study. Tokyo Joshi-Idai Asthma Research Group.

BACKGROUND: Th2 cytokines play an important part in the pathogenesis of asthma. Our aim was to study the effect of suplatast tosilate, a selective Th2 cytokine inhibitor, on asthma control and asthma exacerbations during reduction of inhaled corticosteroid dose in patients with steroid-dependent asthma. METHODS: 85 patients with moderate to severe asthma taking high doses (> or = 1500 microg per day) of inhaled beclometasone dipropionate, were assigned suplatast tosilate (100 mg three times daily) or placebo for 8 weeks in a double-blind, randomised, parallel-group, multicentre trial. During the first 4 weeks, other medications remained unchanged (add-on phase); during the next 4 weeks, the doses of beclometasone were halved (steroid-reduction phase). Main outcome measures were pulmonary function, asthma symptoms, and use of beta2-agonists. FINDINGS: Data were available from 77 patients. During the add-on phase, suplatast tosilate treatment, compared with placebo, was associated with higher forced expiratory volume in 1 s (mean difference between groups for changes from baseline at week 4, 0.20 L [95% CI 0.16-0.24], p=0.043), morning peak expiratory flow (18.6 L/min [14.1-23.1], p=0.037), and less diurnal variation in peak expiratory flow rate, asthma symptom scores (7.1 [6.6-7.6], p=0.029), and serum concentrations of eosinophil cationic protein and IgE. In the steroid-reduction phase, pulmonary function, asthma symptoms, and use of beta2-agonist deteriorated significantly more in the placebo group than in the suplatast group. INTERPRETATION: Treatment with a Th2 cytokine inhibitor in steroid-dependent asthma improves pulmonary function and symptom control, and allows a decrease in dose of inhaled corticosteroid without significant side-effects. Some improvements in pharmacokinetics are, however, needed.

Administration, Inhalation↗