Biomedical subjects

M Tani

Publications and source records attributed to M Tani.

At least 109 records · Page 6Linked to original sources

PubMed1998

Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA.

The hOGG1 gene encodes a DNA glycosylase that excises 8-hydroxyguanine (oh8Gua) from damaged DNA. Structural analyses of the hOGG1 gene and its transcripts were performed in normal and lung cancer cells. Due to a genetic polymorphism at codon 326, hOGG1-Ser326 and hOGG1-Cys326 proteins were produced in human cells. Activity in the repair of oh8Gua was greater in hOGG1-Ser326 protein than in hOGG1-Cys326 protein in the complementation assay of an E. coli mutant defective in the repair of oh8Gua. Two isoforms of hOGG1 transcripts produced by alternative splicing encoded distinct hOGG1 proteins: one with and the other without a putative nuclear localization signal. Loss of heterozygosity at the hOGG1 locus was frequently (15/ 23, 62.2%) detected in lung cancer cells, and a cell line NCI-H526 had a mutation leading to the formation of the transcripts encoding a truncated hOGG1 protein. However, the oh8Gua levels in nuclear DNA were similar among lung cancer cells and leukocytes irrespective of the type of hOGG1 proteins expressed. These results suggest that the oh8Gua levels are maintained at a steady level, even though multiple hOGG1 proteins are produced due to genetic polymorphisms, mutations and alternative splicing of the hOGG1 gene.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1998

Purification and characterization of a novel ceramidase from Pseudomonas aeruginosa.

We report here a novel type of ceramidase of Pseudomonas aeruginosa AN17 isolated from the skin of a patient with atopic dermatitis. The enzyme was purified 83,400-fold with an overall yield of 21.1% from a culture supernatant of strain AN17. After being stained with a silver staining solution, the purified enzyme showed a single protein band, and its molecular mass was estimated to be 70 kDa on SDS-polyacrylamide gel electrophoresis. The enzyme showed quite wide specificity for various ceramides, i.e. it hydrolyzed ceramides containing C12:0-C18:0 fatty acids and 7-nitrobenz-2-oxa-1, 3-diazole-labeled dodecanoic acid, and not only ceramide containing sphingosine (d18:1) or sphinganine (d18:0) but also phytosphingosine (t18:0) as the long-chain base. However, the enzyme did not hydrolyze galactosylceramide, sulfatide, GM1, or sphingomyelin, and thus was clearly distinguished from a Pseudomonas sphingolipid ceramide N-deacylase (Ito, M., Kurita, T., and Kita, K. (1995) J. Biol. Chem. 270, 24370-24374). This bacterial ceramidase had a pH optimum of 8.0-9.0, an apparent Km of 139 microM, and a Vmax of 5.3 micromol/min/mg using N-palmitoylsphingosine as the substrate. The enzyme appears to require Ca2+ for expression of the activity. Interestingly, the 70-kDa protein catalyzed a reversible reaction in which the N-acyl linkage of ceramide was either cleaved or synthesized. Our study demonstrated that ceramidase is widely distributed from bacteria to mammals.

Adult↗

PubMed1998

Orthotopic growth and metastasis of human non-small cell lung carcinoma cell injected into the pleural cavity of nude mice.

We have constructed a metastatic model of human non-small cell lung cancer (NSCLC) by injection of NSCLC cell lines directly into the left pleural cavity of BALB/c nude mice. All of seven NSCLC cell lines, which are tumorigenic after subcutaneous injection, were successfully transplanted in the pleural cavity, while only three of the seven cell lines produced lung metastatic colonies after intravenous injection. Tumors grew extensively in the pleural cavity and infiltrated into the lung parenchyma directly. Furthermore, tumors metastasized to the mediastinum and contralateral pleural cavity through lymphatic routes. Since this model is easy to perform and the result is reproducible, it would be useful for studies on the biological behavior and treatment of human NSCLC in vivo.

Animals↗

PubMed1998

Expression of the Elm1 gene, a novel gene of the CCN (connective tissue growth factor, Cyr61/Cef10, and neuroblastoma overexpressed gene) family, suppresses In vivo tumor growth and metastasis of K-1735 murine melanoma cells.

We previously isolated a partial cDNA fragment of a novel gene, Elm1 (expressed in low-metastatic cells), that is expressed in low-metastatic but not in high-metastatic K-1735 mouse melanoma cells. Here we determined the full-length cDNA structure of Elm1 and investigated the effect of Elm1 expression on growth and metastatic potential of K-1735 cells. The Elm1 gene encodes a predicted protein of 367 amino acids showing approximately 40% amino acid identity with the CCN (connective tissue growth factor [CTGF], Cyr61/Cef10, neuroblastoma overexpressed gene [Nov]) family proteins, which consist of secreted cysteine-rich proteins with growth regulatory functions. Elm1 is also a cysteine-rich protein and contains a signal peptide and four domains conserved in the CCN family proteins. Elm1 was highly conserved, expressed ubiquitously in diverse organs, and mapped to mouse chromosome 15. High-metastatic K-1735 M-2 cells, which did not express Elm1, were transfected with an Elm1 expression vector, and several stable clones with Elm1 expression were established. The in vivo growth rates of cells expressing a high level of Elm1 were remarkably slower than those of cells expressing a low level of Elm1. Metastatic potential of transfectants was reduced in proportion to the level of Elm1 expression. Thus, Elm1 is a novel gene of CCN family that can suppress the in vivo growth and metastatic potential of K-1735 mouse melanoma cells.

Animals↗

PubMed1998

In situ detection of hepatitis B, C, and G virus nucleic acids in human hepatocellular carcinoma tissues from different geographic regions.

We performed a retrospective study to determine the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis G virus (HGV) genomes in formalin-fixed, paraffin-embedded liver tissues from hepatocellular carcinoma (HCC) patients in various geographic areas. The prevalence of each hepatitis virus in the liver tissues that have both carcinoma and noncarcinoma regions was different among the countries. HCV was the most prevalent in Japan (75 of 122 [61.5%]), Spain (9 of 15 [60%]), and the United States (27 of 65 [41.5%]); HBV was the most prevalent in Korea (45 of 55 [82%]) and among Japanese Americans in Hawaii (4 of 8 [50%]). Genotype II/1b was the most common genotype of HCV encountered in HCCs in these countries. In contrast, HGV RNA was undetectable in all tested HCCs. "Cryptogenic HCC," defined as HCC of unknown etiology, was seen 4 (3%) and 4 (6.2%) of Japanese and American patients, respectively, but this was not found in other countries. Interestingly, patients with HCC related to primary biliary cirrhosis (4.6%), who were excluded from analysis as hepatitis virus infections, were present only in the United States, but not in other countries. This study suggests that HCV, particularly genotype II/1b, and HBV may play an important role in hepatocarcinogenesis in these countries. There was no evidence of any relation between HGV infection and development of HCC.

Adult↗

PubMed1998

Low concentrations of adenosine receptor blocker decrease protection by hypoxic preconditioning in ischemic rat hearts.

UNLABELLED: A role for adenosine in ischemic preconditioning and hypoxic preconditioning (HP) has been established in several species but is controversial in rats, due in part to the inconsistency of the data from the different experimental design. Our objective was to investigate the role of adenosine in the protection of the ischemic myocardium by HP in rats. METHODS: perfused hearts isolated from Sprague-Dawley rats were exposed to 5 min of hypoxic perfusion before 25 min of global ischemia followed by 20 min of reperfusion. The effects of adenosine receptor antagonist, 8-(p-sulfophenyl)-theophylline (8SPT) on HP-based changes in left-ventricular function, energy metabolites, and release of creatine kinase and lactate dehydrogenase were determined. To minimise non-specific effects of 8SPT, low concentrations of agent (0.5 or 1.0 micro mol/l) were used. RESULTS: 8SPT alone had no deleterious effects on normoxically perfused hearts or on ischemic/reperfused hearts. HP improved the recovery of LV function and creatine phosphate, and reduced the release of enzymes during reperfusion. 8SPT (1.0 micromol/l) ameliorated the beneficial effect of HP on cardiac function, but did not reverse the reduction in release of enzymes by HP completely. CONCLUSION: results suggest that the protective effect of HP on myocardial contractile function may be mediated by receptor(s) that can be inhibited by low concentrations of antagonist but may not have a primary role in the reduction of cellular damage by HP in rats.

Adenosine↗

PubMed1998

High-Resolution Terahertz Spectroscopy by a Compact Radiation Source Based on Photomixing with Diode Lasers in a Photoconductive Antenna

We demonstrate generation of continuous-wave terahertz radiation and its application to molecular spectroscopy. The radiation source is based on the photomixing of two diode laser beams in a low-temperature-grown GaAs photoconductive antenna, which offered output power of several tens of nanowatts at frequencies up to 2 THz with its long term frequency stability being about 5 MHz. The pure rotational spectra of CH3CN and isotopomers of CO were measured with this source, and 1% of absorption was clearly detected with a simple amplitude modulation technique. This indicates that the present system has a potential capability for high-resolution and high-sensitivity molecular spectroscopy. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗

PubMed1998

Genomic structure and chromosomal localization of the mouse Ogg1 gene that is involved in the repair of 8-hydroxyguanine in DNA damage.

8-Hydroxyguanine (7,8-dihydro-8-oxoguanine: oh8Gua) is a damaged form of guanine induced by oxygen-free radicals and causes GC to TA transversions. Previously we isolated the hOGG1 gene, a human homolog of the yeast OGG1 gene, which encodes a DNA glycosylase and lyase to excise oh8Gua in DNA. In this study, we isolated a mouse homolog (Ogg1) of the OGG1 gene, characterized oh8Gua-specific DNA glycosylase/AP lyase activities of its product, and determined chromosomal localization and exon-intron organization of this gene. A predicted protein possessed five domains homologous to human and yeast OGG1 proteins. Helix-hairpin-helix and C2H2 zinc finger-like DNA-binding motifs found in human and yeast OGG1 proteins were also retained in mouse Ogg1 protein. The properties of a GST fusion protein were identical to human and yeast OGG1 proteins in glycosylase/lyase activities, their substrate specificities, and suppressive activities against the spontaneous mutagenesis of an Escherichia coli mutM mutY double mutant. The mouse Ogg1 gene was mapped to Chromosome (Chr) 6, and consisted of 7 exons approximately 6 kb long. Two DNA-binding motifs were encoded in exons 4 through 5. These data will facilitate the investigation of the OGG1 gene to elucidate the relationship between oxidative DNA damage and carcinogenesis.

Amino Acid Sequence↗

PubMed1998

Intraoperative radiation therapy for a patient with bulky disease of mesenteric non-Hodgkin's lymphoma.

A long survival is rarely observed in patients demonstrating recurrent malignant lymphoma with bulky disease because of the appearance of chemoresistant tumor cells after extensive chemotherapy, and moreover the presence of bulky disease has also been consistently associated with a poorer response rate and a shortened survival, due to the fact that tumor size is the most significant factor for the treatment of non-Hodgkin's lymphoma. We herein describe a case of a 53-year-old woman presenting with the chief complaint of abdominal fullness, who underwent intraoperative radiation therapy (IORT) for recurrent bulky non-Hodgkin's lymphoma in the mesenterium. The patient has had no evidence of tumor recurrence, based on the findings of regular abdominal computed tomographic scans, 60 months after initial chemotherapy and 28 months after IORT.

Female↗

PubMed1998

Rational lymphadenectomy for early gastric cancer with submucosal invasion: a clinicopathological study.

Among all the patients who underwent gastrectomy for primary solitary gastric cancer at our department from 1979 to 1994, 228 patients had gastric cancer that invaded the submucosal layer. These cases were thus examined clinicopathologically, including the extent of submucosal invasion. No lymph node metastasis was found in any of the cancers measuring less than 2 cm in diameter. Macroscopic type I lesions or various combined types (IIa + IIc, IIc + IIa, IIc + III) were more likely to infiltrate deeply and were also associated with a high incidence (18%-25%) of lymph node metastasis. No lymph node metastasis or vascular invasion was found in any simple type IIa lesions. The incidence of lymph node metastasis was 3% in simple type IIc cancers measuring 3 cm or less. In addition, submucosal microinvasion (sm1) simple type IIc cancers showed no accompanying lymph node metastasis or vascular invasion. We thus conclude that a full-thickness partial resection of the stomach, such as a laparoscopic local resection, is applicable to cancers measuring 3 cm or less provided that they are either simple macroscopic type IIa or simple type IIc sm1 cancers.

Endosonography↗

PubMed1998

Successful immunochemotherapy for patients with malignant mesothelioma: report of two cases.

Malignant mesothelioma is a clinically aggressive tumor and has a poor prognosis; therefore, the selection of therapeutic strategies is important to improve the prognosis. Two patients with intraperitoneal malignant mesothelioma received combination therapy as follows: (1) case-oriented chemotherapy according to the results of a chemosensitivity test, and (2) adoptive immunotherapy using cytotoxic T lymphocytes (CTL). The chemosensitivity test was assessed by an MTT colorimetric assay. CTL was generated by a mixed culture with autologous tumor cells, and activated by immobilized anti-CD3 monoclonal antibody and interleukin-2. The MTT assay indicated that cisplatin and adriamycin were sensitive drugs in both patients, and they thus received the case-oriented chemotherapy according to the MTT assay. The activated CTL exhibited a high cytotoxicity against autologous malignant mesothelioma cells, and were transferred intraperitoneally. The patients were controllable for ascites, and the tumor masses gradually vanished (partial response). Chemoimmunotherapy is thus considered to be an effective treatment for intraperitoneal malignant mesothelioma, especially to improve the quality of life.

Adult↗

PubMed1998

Do chemokines mediate leukocyte recruitment in post-traumatic CNS inflammation?

Hematogenous leukocytes infiltrate the CNS after inflammatory stimuli, including infection, mechanical trauma and excitotoxic neuronal necrosis. However,the role of leukocytic inflammation in promoting or hindering tissue repair is poorly understood. Identification of signals that lead to leukocyte recruitment and activation is essential for the designing of interventions that modulate inflammation, thus improving neurological outcome. Chemokines are small pleiotropic chemoattractant cytokines whose target specificity suggests an important role in determining the cellular composition of inflammatory infiltrates. Chemokine expression profiles in the CNS during autoimmune and post-traumatic inflammation correlate well with the composition of leukocyte infiltrates, and expression studies in systems such as transgenic mice, suggest that chemokines have potent functional attributes in CNS physiology. We propose that selective chemokine expression by CNS cells is crucial for post-traumatic leukocyte accumulation.

Animals↗

PubMed1998

Photosensitive dermatitis caused by pyridoxine hydrochloride.

Few photosensitive reactions caused by pyridoxine hydrochloride have been reported. There have been no reports of detailed photosensitivity studies on patients who have developed photosensitivity from pharmacologic doses of pyridoxine. Two patients with pyridoxine photosensitivity are described. Photopatch tests were positive for pyridoxine hydrochloride. The minimal erythematous dose (MED) for UVA decreased after the intravenous injection of pyridoxine hydrochloride in both patients. Normal controls gave negative results in photopatch tests for pyridoxine hydrochloride and phototest for vitamin B complex containing pyridoxine hydrochloride. On the basis of these results, we believe both patients had a photoallergic reaction to pyridoxine hydrochloride.

Dermatitis, Photoallergic↗

PubMed1998

Inhibitory effects of antiarrhythmic drugs on phenacetin O-deethylation catalysed by human CYP1A2.

AIMS: The aim of the study was to clarify whether the pharmacokinetic interaction between theophylline and mexiletine is mediated by inhibition of CYP1A2 and to assess the possible interaction potential of other antiarrhythmic drugs with drugs metabolized by CYP1A2. METHODS: The inhibitory effects of mexiletine and 10 antiarrhythmic drugs on phenacetin O-deethylation, a marker reaction of CYP1A2, were studied using human liver microsomes and cDNA-expressed CYP1A2. RESULTS: Propafenone and mexiletine inhibited phenacetin O-deethylation with IC50 values of 29 and 37 microM, respectively. Disopyramide, procainamide and pilsicainide produced negligible inhibition of phenacetin O-deethylation (IC50 >1 mM). Amiodarone, bepridil, aprindine, lignocaine, flecainide and quinidine inhibited phenacetin O-deethylation in a concentration-dependent manner, although the inhibitory effects were relatively weak with IC50 values ranging from 86 to 704 microM. Propafenone and mexiletine selectively abolished the high-affinity component of phenacetin O-deethylation in human liver microsomes. In addition, propafenone and mexiletine inhibited phenacetin O-deethylation catalysed by cDNA-expressed CYP1A2. CONCLUSIONS: These data suggest that, among the antiarrhythmic drugs studied, propafenone and mexiletine are relatively potent inhibitors of CYP1A2, which may cause a drug-drug interaction with drugs metabolized by CYP1A2.

Anti-Arrhythmia Agents↗

PubMed1998

RER phenotype and its associated mutations in familial gastric cancer.

To clarify the genetic background of gastric cancer, we collected 28 familial gastric cancers (FGCs) with reference to the Amsterdam criteria in hereditary non-polyposis colorectal cancer (HNPCC) and investigated the frequency of replication error (RER) at six microsatellite loci and frameshift mutations in its related genes in these tumors. RER was detected in seven (25%) of the 28 gastric cancers. Five (18%) cases showed RER at more than two loci. The apparent increased incidence of RER in FGC was not detected compared with that reported in sporadic gastric cancers previously. Among four cases with RER at more than three loci, frameshift mutations in the (A)8 track of the hMSH3 gene were detected in all the four cases and mutations in the (A)10 track of the transforming growth factor-beta type II receptor (TGF-beta RII) gene were detected in the three of them. Histologically, three of the four cases were of the intestinal type, and the other one was the diffuse type. No mutation was detected in the (C)8 and (GT)3 tracks of the hMSH6 and TGF-beta RII genes respectively. These results indicate that the acquisition of the RER phenotype equally influences the gastric carcinogenesis of both sporadic and familial cases, and that the majority of FGC is pathogenetically distinct from HNPCC.

Adult↗

PubMed1998

Mutation analysis of the Smad2 gene in human colon cancers using genomic DNA and intron primers.

In mammals, one of the Mad homologues, Smad2, was reported to be a mediator of TGF-beta signaling, and was found mutated in some cases of colon and lung cancers. To extend the analysis of this gene, we previously investigated the genomic organization of the human Smad2 gene and defined the structure of 12 exons and flanking introns. In this study, we designed 11 sets of intron-based primers to examine the entire coding region of the Smad2 gene. By the PCR-SSCP method using these primers, we screened genomic DNA sequences of colorectal cancers for mutations of the Smad2 gene. Though there was no mutation within all exons of the Smad2 gene, two of 60 sporadic colorectal cancers displayed deletions in the polypyrimidine tract preceding exon 4. Deletions of this region were also detected in colon cancer cell lines, and were clustered within cells exhibiting microsatellite instability. Deletions in the polypyrimidine tract had various effects on pre-mRNA splicing, but had no effect on the splicing of the Smad2 gene in these cases. However, our data support the idea that the polypyrimidine tract in the splicing acceptor site is a target of mutations in mismatch repair-deficient tumors.

Base Sequence↗

PubMed1998

Different effects of class Ic and III antiarrhythmic drugs on vagotonic atrial fibrillation in the canine heart.

Effects of class Ic drug pilsicainide and class III drug MS-551 were determined in the canine model of atrial fibrillation (AF) induced under vagal stimulation. Pilsicainide injected intravenously at a dose of 1.0 mg/kg over 3 min terminated AF in six of six dogs. After pilsicainide injection, the effective refractory period (ERP) of the right atrium (RA) increased (104 +/- 22 to 122 +/- 31 ms; p < 0.05), and intraatrial conduction time (CT) increased (24%; p < 0.05) in the RA during vagal stimulation. Wavelength index (WLI; ERP/CT), an estimate of the wavelength for reentry, was decreased slightly but significantly (-2%; p < 0.05) in the RA after pilsicainide. MS-551 injected intravenously at a dose of 0.5 mg/kg over a 3-min period terminated AF in three of eight dogs. An additional dose of 0.5 mg/kg of MS-551 terminated AF in three of the remaining five dogs. After MS-551 injection, ERP increased (100 +/- 30 to 143 +/- 28 ms; p < 0.05), but CT remained unchanged in the RA, and therefore WLI was increased significantly (48%; p < 0.01). Immediately before termination of AF with test drugs, mean AF intervals (FF intervals) increased, whereas the standard deviation of FF intervals did not change significantly. In conclusion, both pilsicainide and MS-551 effectively terminated vagotonic AF after an increase in FF intervals. However, changes in WLI were different between the two test drugs. Vagotonic AF could, therefore, be terminated either by prolongation of ERP or suppression of conduction with antiarrhythmic drugs.

Animals↗

PubMed1998

Myocardial uptake of iodine-125-labeled 15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid is decreased in chronic diabetic rats with changes in subcellular distribution.

Iodine-123-labeled 15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid (123I-BMIPP) is widely used to detect myocardial metabolic changes, but the preferred energy substrates in the myocardium would be expected to be altered in the presence of metabolic disorders such as diabetes mellitus (DM). We investigated the metabolism of branched-chain fatty acids in the myocardium of rats with DM. Streptozotocin-induced DM rats were examined 48 h (acute; AD) and 6 weeks (chronic; CD) after injection of streptozotocin. Hearts were excised 15 min or 60 min after injection of 0.185 MBq of 125I-BMIPP, followed by homogenization in an EDTA-Tris buffer. The homogenates were subjected to differential centrifugation to obtain the mitochondrial (MF) and cytoplasmic (CF) fractions. Myocardial 125I uptake tended to increase in the AD group, but the change was not significant. Myocardial 125I uptake at 15 min was significantly lower in the CD group than in the control group, even in the insulin-treated rats [control (CC), 4.4+/-0.4; not treated (CDN), 3.3+/-0.5; insulin-treated (CDI), 3.4+/-0.4 x 10(4) cpm/g, p<0.05 in each case]. The 125I count value corrected for the blood count (counts/min (cpm) per g of protein divided by blood cpm) in the MF decreased by 40% at 60 min in the CC group, but increased by 60% in the CDN group. The results of the present study suggest that the myocardial uptake of branched-chain fatty acids is decreased in rats with chronic diabetes, probably as a result of mitochondrial dysfunction.

Acute Disease↗