Biomedical subjects

M Terada

Publications and source records attributed to M Terada.

At least 109 records · Page 6Linked to original sources

PubMed1999

Regression and prevention of autochthonous tumors induced by 3-methylcholanthrene after injection of a T-cell receptor alpha /beta positive and CD4/CD8 double negative T-cells.

Both the therapeutic and preventative effects of a murine T-cell line, tMK-2, with T-cell receptor (TCR) alpha/beta positive and CD4-/8- double negative (DN) phenotype against autochthonously tumors induced by subcutaneous (s.c.) injection of 3-methylcholanthrene (MC) were examined. Complete regression of the tumor was observed when administration of tMK-2 cells was begun on tumors 5 mm in diameter. The tumor mass in five out of five mice was reduced in size after the administration of tMK-2 cells regardless of the routes of administration: s.c. injection of tMK-2 cells (5 x 10(7) cells) once a week around tumors, intraperitoneal (i.p.) injection (5 x 10(7) cells), or intravenous (i.v.) injection (1 x 10(7) cells). The tumors regressed to the status of a scar within 1 month of initial injection, and this status was maintained throughout the remainder of the 3 months period of tMK-2 cell injection. One month after discontinuation of tMK-2 cell administration, the diameter of the tumors had not increased regardless of the route of injection. The control groups consisted of either untreated mice, mice with i.v. injection of 1 microg of recombinant murine interleukin (IL)-12 once a week, or mice with s.c. injection of autologous splenocytes (5 x 10(7)) from BALB/c mice once a week. Continuous growth of tumors was observed in each group and all control mice died due to bleeding ulcerations of the tumors. Tumor development was effectively prevented when tMK-2 cells were administrated 1 week after the s.c. injection of MC. In the groups receiving s.c., i.p., and i.v. injection of tMK-2 cells, no MC-induced tumors developed, whereas four out of five of the control mice developed autochthonous tumors. The tMK-2 cells also exerted in vitro NK-like cytotoxic activity, and their killing activity was strongly increased in the presence of both IL-2 and IL-12. These results suggest that the injected T-cells with TCR alpha/beta positive and CD4- /8- DN phenotype and NK-like activity are important in the therapy as well as the prevention of tumor development.

Animals↗

PubMed1999

Molecular cloning of Frizzled-10, a novel member of the Frizzled gene family.

The Frizzled genes encode WNT receptors. Frizzled-10 (FZD10), a novel member of the Frizzled gene family, has been cloned and characterized. Nucleotide sequence analysis showed that human FZD10 gene encodes a seven-transmembrane-receptor of 581 amino acids, with the N-terminal cysteine-rich domain and the C-terminal Ser/Thr-Xxx-Val motif. Larger amounts of FZD10 mRNA, 4.0 kb in size, were detected in the placenta and fetal kidney, followed by fetal lung and brain. In adult brain, FZD10 mRNA was abundant in the cerebellum. Among cancer cell lines, FZD10 was highly expressed in a cervical cancer cell line, HeLa S3, and moderately in a colon cancer cell line, SW480. The FZD10 gene was mapped to human chromosome 12q24.33. FZD10 shares 65.7% amino-acid identity with Frizzled-9 (FZD9). FZD10 and FZD9 constitute a subfamily among the Frizzled genes.

Adult↗

PubMed1999

Mutagenicity of 4-nitroquinoline 1-oxide in the MutaMouse.

As part of a collaborative study, the Mammalian Mutagenesis Study Group (MMS), a sub-organization of the Environmental Mutagen Society of Japan (JEMS) conducted mutagenicity tests in MutaMouse. Using a positive selection method, we studied the organ-specificity and time dependence of mutation induction by 4-nitroquinoline 1-oxide (4NQO). A single dose of 4NQO was administered intraperitoneally (7.5 or 15 mg/kg) or orally (200 mg/kg) to groups of male mice. On days 7, 14 and 28 after treatment, we isolated the liver, kidney, lung, spleen, bone marrow, testis and stomach in the intraperitoneal administration experiment and the liver, lung, bone marrow, testis and stomach in the oral administration experiment. In addition, we performed the peripheral blood micronucleus test to evaluate clastogenicity. In the mice treated intraperitoneally at 7.5 mg/kg, we found increased mutant frequency (MF) only in the lung, where the MF did not vary with expression time. In the mice treated at 15 mg/kg, we found increased MF in the liver, bone marrow and lung. In orally treated mice, the MF was high in the lung and liver and very high in the bone marrow and stomach while the increase in the testis was negligible. As the expression time was prolonged, the MF tended to increase in the liver, decrease in the bone marrow, and remain stable in the lung, testis and stomach. The incidence of micronucleus induction in peripheral blood cells was significantly increased (p<0.01) in the 4NQO groups when compared with the vehicle control group by intraperitoneal treatment. Thus, these assay systems appeared to be of use in detecting not only genetic mutation but also chromosomal aberration.

4-Nitroquinoline-1-oxide↗

PubMed1999

Impaired regeneration and no amelioration with aldose reductase inhibitor in crushed unmyelinated nerve fibers of diabetic rats.

The regenerative ability of unmyelinated nerve fibers (UNFs) in diabetes and the effect of aldose reductase inhibitor (ARI) on it were ultrastructurally evaluated after sciatic nerve crush in control and untreated and tolrestat-treated streptozocin-induced diabetic rats. The density and number of UNFs were significantly increased in all groups at 5 weeks after the injury. The increase returned to the baseline level in control rats, but not in diabetic rats at 24 weeks. Although the axon size showed a marked decrease at 5 weeks and an incomplete recovery at 24 weeks in all groups, the recovery was significantly worse in diabetic than in control groups. Tolrestat did not have any effect on regeneration of UNFs in diabetes. These results suggest impaired regeneration of UNFs after nerve crush injury in diabetes and less therapeutic effect of ARI on it.

Aldehyde Reductase↗

PubMed1999

Identification of a novel promoter and exons of the c-ERBB-2 gene.

The c-ERBB-2 gene is frequently amplified in various cancers. During the course of studies on the structural characterization of the amplification units, we isolated four cDNA clones, A39, GRB7, C51 and CAB1 with corresponding genes localized on the c-ERBB-2 locus. A tentative gene, C51, was located at about 12 kb upstream of the c-ERBB-2 gene. By molecular cloning of a full-length cDNA clone of C51 and the reverse transcription PCR (RT-PCR) method, we identified a novel transcript of c-ERBB-2 containing new 5' sequences including the C51 sequence, demonstrating that the c-ERBB-2 gene has a novel promoter and new exons. The structural organization of the novel promoter and exons of c-ERBB-2 was revealed by complete sequence analysis of a total size of about 20 kb of genomic DNA clones containing the 5'-flanking region of the previously described c-ERBB-2 gene. Transient expression of the newly identified promoter-reporter gene constructs in breast cancer cell line MCF-7 showed that the elements responsible for promoter activity were contained in a 697 bp region upstream of the transcriptional start site. The new transcript may encode a protein different in the portion of the extracellular domain. Although the presence of the predicted protein product was not examined, this report is important in that it provides a new aspect of the c-ERBB-2 protooncogene products.

Adult↗

PubMed1999

Evaluation of cationic liposome suitable for gene transfer into pregnant animals.

Cationic liposome-mediated in vivo gene transfer represents a promising approach for somatic gene therapy. To assess the most suitable liposome for gene delivery into a wide range of organs and fetuses in mice, we have explored several types of cationic liposomes conjugated with plasmid DNA carrying the beta-galactosidase gene through intravenous injection into pregnant animals. Transduction efficiency was assessed by Southern blot analysis and expression of the transferred gene was evaluated by enzymatic demonstration of beta-galactosidase activity. Through the analysis of several types of recently synthesized cationic liposome/lipid formulations, DMRIE-C reagent, a liposome formulation of the cationic lipid DMRIE (1, 2-dimyristyloxypropyl-3-dimethyl-hydroxy ethyl ammonium bromide) and cholesterol in membrane-filtered water met our requirements. When the plasmid DNA/DMRIE-C complexes were administered intravenously into pregnant mice at day 11.5 post coitus (p.c.), transferred genes were observed in several organs in dams and were expressed. Furthermore, although the copy numbers transferred into embryos were low, we observed reporter gene expression in the progeny.

Animals↗

PubMed1999

Identification of receptor genes in renal cell carcinoma associated with angiogenesis by differential hybridization technique.

To screen the receptor genes in renal cell carcinoma (RCC) associated with angiogenesis, we performed differential hybridization of the cDNA library of membrane-type protein tyrosine kinases (mPTKs). Three thousand plaques of a mPTKs-enriched cDNA library were screened with mPTKs mixture probes produced from hypervascular RCC tissues and RCC cell lines. Six different cDNA fragments of the PTK genes were isolated, and the sequence analysis showed that these represented cDNAs for TIE1, KDR, FMS, FGFR-4, JAK1 and HCK. Of these genes, the expression of TIE1, KDR, and FGFR-4 was studied in RCC tissue and cell lines by Northern blot analysis. We also investigated the expression of vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and their receptor FLT-1. In all the hypervascular RCC tissues, the amounts of mRNAs for KDR and FLT-1 were increased compared to adjacent normal tissues. The TIE1 and FGFR-4 genes were also overexpressed in most of the hypervascular RCC tissues, while no mRNA of KDR, FLT-1, or TIE1 could be detected in any of the four human RCC cell lines. The amounts of the VEGF and PlGF mRNAs were increased in hypervascular RCC tissues, while VEGF mRNA was detected in the four cell lines but PlGF mRNA was not. FGFR-4 mRNA was expressed in three of the four cell lines. These results suggest that KDR, FLT-1, PlGF and TIE1 mRNAs are present in the mesenchymal cells of RCC, while VEGF and FGFR-4 genes are expressed in RCC cells themselves in vivo.

Blotting, Northern↗

PubMed1999

Low susceptibility of specific inbred colonies of rats to nickel tumorigenesis in soft tissue.

Nickel sarcomatogenesis induced by a single intramuscular injection of 10 mg of nickel subsulfide (NiSS) into the soft tissue of two different colonies of Wistar rats was studied. In spontaneously hypertensive rats (SHR), a specific inbred colony of rats derived from a certain Wistar strain, the sarcoma induction rate was lower than that in common closed colony rats of the same strain (CWR). Sarcomas were induced in only 7 of the 30 rats (23.3%) in the SHR group (15 female and 15 male) but in 21 of the 31 rats (67.7%) in the CWR group (15 female and 16 male) (P < 0.005). The incidence of sarcoma induction was lower in female rats than in male rats in both the SHR (female 13.3% < male 33.3%) and CWR (female 53.3% < male 81.4%) groups. Primary tumors in the SHR group exhibited a lower grade of metastasis to lymph nodes (P < 0.001) and lungs (P < 0.05) than in the CWR group. Our study demonstrated that rats in a certain specific inbred colony are less susceptible to nickel tumorigenesis in soft tissue than rats in a common closed colony.

Animals↗

PubMed1999

Mepanipyrim, a new fungicide, inhibits intracellular transport of very low density lipoprotein in rat hepatocytes.

We have previously reported that ingestion of mepanipyrim induces fatty liver in rats due to the inhibitory effect on the synthesis or secretion of hepatocytic very low density lipoproteins (VLDL). To clarify the mechanism by which mepanipyrim induces fatty liver, morphological and biochemical effects of mepanipyrim on the movement of VLDL in rat liver and in the primary culture of rat hepatocytes were investigated. In in vivo experiments, rats were fed for 4 days a diet containing mepanipyrim at 4,000 ppm. VLDL accumulation in the Golgi apparatus of the liver, especially in the secretory vacuoles, was observed in the treated rats and in the hepatocytes treated for 2 hr with 25 micrograms/ml mepanipyrim. Using 6-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino]caproyl-sphingosine (C6-NBD-ceramide), a selective staining agent for the Golgi apparatus, it was found that mepanipyrim inhibited C6-NBD-ceramide transport from the Golgi to the cell surface of cultured hepatocytes. The density of the VLDL-loaded secretory vacuoles isolated from the Golgi fractions was greater in mepanipyrim-treated rat livers compared with that in the control. Immunofluorescence micrograph of rat hepatocytes stained with anti-alpha-tubulin monoclonal antibody demonstrated that mepanipyrim neither affected microtubule network nor changed the intracellular ATP level. These results together suggested that fatty liver induced by mepanipyrim results mainly from the inhibition of the transport of hepatic VLDL from the Golgi to the cell surface. The inhibition of the transport of hepatic VLDL appears to result from qualitative changes in VLDL such as alteration of the apoprotein composition and/or insufficient lipidation of VLDL.

Adenosine Triphosphate↗

PubMed1999

Spontaneous Enantiomeric Resolution in a Fluid Smectic Phase of a Racemate.

Right- and left-handed homochiral domains segregate in a fluid smectic phase of the racemic (R*,S*)-beta-Me-TFMHPOBC analogue shown. This CF(3)-containing liquid crystalline compound exhibits an electrooptic response in a homogeneous cell, although no macroscopic dipole is expected to exist. Moreover, the homeotropic cells of this material exhibit striped domains, which are associated with fine stripes having two opposite tilt senses with respect to the predominant stripes.

Journal Article↗

PubMed1999

Functional and phenotypical characteristics of hepatic NK-like T cells in NK1.1-positive and -negative mouse strains.

We previously reported and partially characterized a unique monoclonal antibody (mAb), U5A2-13, which recognizes a T cell subset similar to NK1.1+ T cells, not only in NK1.1-positive mouse strains but also in NK1.1-negative strains. In NK1.1-positive C57BL/6 mice, U5A2-13+ TCRalphabeta+ cells produced abundant IL-4 as well as extremely high levels of IFN-gamma upon CD3 cross-linking, but this did not occur with U5A2-13- TCRalphabeta+ cells. In NK1.1-negative C3H/He mice, U5A2-13+ TCRalphabeta+ cells produced high levels of IL-4 and IFN-gamma upon CD3 cross-linking, but this was not observed with U5A2-13- TCRalphabeta+ cells. To the best of our knowledge, this is the first direct evidence of the presence of NK-like T cells defined phenotypically by U5A2-13 mAb and functionally by IL-4/IFN-gamma production in NK1.1-negative mouse strains. We also demonstrated that U5A2-13- NK1.1+ T cells and U5A2-13+ NK1.1- T cells in C57BL/6 mice could produce both IL-4 and IFN-gamma. In addition, Vbeta8 or Vbeta7 usage by U5A2-13+ NK1.1- T cells was lower than that by U5A2-13+ NK1.1+ T cells, but remained higher than that by U5A2-13- NK1.1- T cells. Based on the present results, U5A2-13 mAb appears to be a valuable tool in the study of NK-like T cells.

Animals↗

PubMed1999

Genetic basis of autoimmune sialadenitis in MRL/lpr lupus-prone mice: additive and hierarchical properties of polygenic inheritance.

OBJECTIVE: To clarify the mode of inheritance of autoimmune sialadenitis in MRL/MpJ-lpr/lpr (MRL/lpr) lupus-prone mice and identify the susceptibility loci. METHODS: MRL/lpr, C3H/HeJ-lpr/lpr (C3H/lpr), (MRL/lpr x C3H/lpr)F1 intercross, and MRL/lpr x (MRL/lpr x C3H/lpr)F1 backcross mice were prepared, and sialadenitis in individual mice was analyzed by histopathologic grading. The genomic DNA of the backcross mice was examined by simple sequence-length polymorphism analysis, and the highly associated polymorphic microsatellite markers with sialadenitis were determined as sialadenitis susceptibility loci. RESULTS: Four susceptible gene loci recessively associated with sialadenitis were mapped on chromosomes 10, 18, 4, and 1, respectively. These loci manifested additive and hierarchical properties in the development of sialadenitis. CONCLUSION: The results indicate that sialadenitis in MRL/lpr mice is under the control of polygenic inheritance, possibly involving allelic polymorphism.

Animals↗

PubMed1999

Living-related liver transplantation for patients with fulminant and subfulminant hepatic failure.

The prognosis for patients with fulminant (FHF) or subfulminant hepatic failure (SFHF) has improved since the introduction of liver transplantation. However, the death rate of patients awaiting liver transplantation is high, possibly because of the difficulty in obtaining grafts in a timely manner, given the relative shortage of cadaveric donors. Between June 1990 and June 1999, 106 patients underwent living-related liver transplantation (LRLT) at Shinshu University Hospital. Among them, 8 patients had FHF and 6 had SFHF; these 14 patients are the subjects of this report. The graft volumes (GV) ranged from 231 mL to 625 mL, corresponding to 35% to 105% of the recipients' standard liver volume (SLV). The postoperative courses of all donors were uneventful. Following liver transplantation, all grafts functioned favorably, with normalization of serum total bilirubin within 3 to 5 days and normalization of coagulation profiles within 4 to 7 days. Thirteen of the 14 recipients are still alive. The actuarial 6-month, 1-year, and 5-year survival rates were 100%, 90%, and 90%, respectively. In the present study, when the ratio of the GV to the recipient's SLV was more than 35%, the graft was able to support the patient's metabolic demand after liver transplantation for FHF or SFHF. Because of the urgent nature of liver transplantation in this clinical condition, concerns over informed consent may be even greater than for elective LRLT. Nevertheless, the high success rate and low donor risk may justify this option for pediatric patients, as well as for a limited population of adult patients suffering from FHF or SFHF.

Adolescent↗

PubMed1999

First case of cadaveric liver transplantation in Japan.

The first case of liver transplantation from a brain-dead donor in Japan is described. The recipient was a 43-year-old man with familial amyloid polyneuropathy who manifested various neuropathic symptoms and autonomic dysfunction at the time of transplantation. The graft had three arteries, for which a single trunk was created at the back table. A side-to-side cavacaval anastomosis was performed as an outflow reconstruction. To avoid portal congestion, a temporary shunt between the right posterior branch of the portal vein and the vena cava was constructed, instead of a venovenous bypass. The graft preservation time was 7.2 h and the operation time was 12.2 h. Although sufficient blood flow in the hepatic artery, portal vein, and hepatic vein was confirmed intra- and postoperatively, using Doppler ultrasound, transient graft dysfunction was observed immediately after surgery, but there was spontaneous improvement. The patient was discharged 100 days after transplantation.

Adult↗

PubMed1999

Apple chlorotic leaf spot virus 50 kDa protein is targeted to plasmodesmata and accumulates in sieve elements in transgenic plant leaves.

We investigated the in situ localization of the 50 kDa protein encoded by ORF2 of Apple chlorotic leaf spot virus (ACLSV) genome which is thought to be a movement protein. In immunogold electron microscopy of ACLSV-infected Chenopodium quinoa leaves, the 50 kDa protein was localized on plasmodesmata and nearby cytoplasm. Observation of transgenic Nicotiana occidentalis leaves expressing the 50 kDa protein fused to enhanced green fluorescent protein (EGFP) by fluorescence and confocal laser scanning microscopes revealed that green fluorescence was observed as spots on the cell wall or strands passing through the cell wall of several cell types, i.e., epidermal, palisade and spongy mesophyll and collenchyma cells. In transverse and longitudinal sections of leaf veins of transgenic plants showed that the 50K-EGFP fusion accumulated in sieve elements and formed an extensive interconnecting network of threadlike structure. These results indicated that ACLSV 50 kDa protein can target plasmodesmata and traffic into sieve elements.

Chenopodiaceae↗

PubMed1999

Time course of endothelin-1 and adrenomedullin after the Fontan procedure.

BACKGROUND: The endothelium-derived vasoconstrictor endothelin (ET)-1 might contribute to the physiology of blood flow regulation and play a role in cardiovascular disease. Adrenomedullin (AM) is a potent vasodilator peptide that has major effects on cardiovascular function and has multiple biologic effects involved in cardiovascular homeostasis. Although pulmonary vascular resistance is known to be one of the most important factors to determine the indications for a Fontan procedure, the time course of the plasma cytokine before and after the Fontan procedure is not known. METHODS: Sixteen patients were divided into two groups, 8 patients (1 to 14 years) who had the Fontan procedure (atriopulmonary connection) and 8 age-matched controls who had biventricular repair with normal central venous pressure. Plasma ET-1 and adrenomedullin levels were measured in both groups immediately before cardiopulmonary bypass, immediately after cardiopulmonary bypass, and 6 and 24 hours after cardiopulmonary bypass. A thermodilution catheter was inserted during the operation, and mean pulmonary arterial pressure, pulmonary wedge pressure, and cardiac output were measured, and pulmonary vascular resistance was calculated at the same time points. Correlation between the plasma ET-1 levels and pulmonary vascular resistance data were obtained in the Fontan group. RESULTS: Plasma ET-1 levels in the Fontan group were elevated after operation and were higher than the control group at 6 and 24 hours after cardiopulmonary bypass. Plasma adrenomedullin in the Fontan group was lower than in the control group at 6 and 24 hours after cardiopulmonary bypass. A significant positive correlation was obtained between the plasma ET-1 and pulmonary vascular resistance data (r = 0.475). CONCLUSIONS: Imbalance between increased ET-1 and relatively decreased adrenomedullin after cardiopulmonary bypass in the Fontan procedure could contribute to dominant effects of ET-1, which might induce vasoconstriction after the Fontan procedure. ET-1 might play an important role in maintaining vasoconstriction after the Fontan procedure.

Adolescent↗

PubMed1999

The long-term results of commissure plication annuloplasty for congenital mitral insufficiency.

BACKGROUND: Mitral valve repair in the pediatric population remains demanding because of a diversity of apparatus anomalies and the young age of the patients. METHODS: We reviewed our clinical results for mitral valve repairs for congenital mitral insufficiency. Forty-nine consecutive patients aged 2 months to 34 years (mean, 4.4 years) had mitral valve repair between June 1984 and December 1996. Forty-one patients (83.7%) had associated cardiac anomalies. The predominant pathologies for the regurgitations were chordal anomalies in 34 patients (69%), annular dilatation in 8 (16%), and leaflet anomalies in 7 (14%). Mitral valve repair included commissure plication annuloplasty in 43 patients (88%), modified DeVega in 11, cleft closure in 5, plication of the anterior leaflet in 3, triangular resection of the anterior leaflet in 2, chordal shortening in 1, and placement of artificial chordae in 1. Several combined techniques were required in 19 patients. RESULTS: There were no early or late deaths. The follow-up period was from 6 to 166 months (mean, 88.4 months). Forty-seven patients (95.9%) were in New York Heart Association class I. The long-term echocardiographic studies showed that 2 of 30 patients without reoperation had moderate regurgitation. The actuarial freedom from reoperation was 85.6% (95% confidence limits, 72.8%, 98.4%) at 13 years. Five patients (10.2%) required valve replacement from 13 days to 75 months after the valve repair. Two patients had cerebral ischemic events as a result of cardiomegaly and atrial fibrillation. CONCLUSIONS: Valve repair for congenital mitral insufficiency gave adequate results in combination with commissure plication annuloplasty and other techniques with excellent long-term functional status.

Adolescent↗

PubMed1999

Gastric cancers of the microsatellite mutator phenotype display characteristic genetic and clinical features.

BACKGROUND & AIMS: Colon cancer of the microsatellite mutator phenotype (MMP) exhibits significant genotype differences from cancer without the MMP. Twenty-nine MMP-positive gastric cancers were analyzed to clarify if these genotype differences were also associated with distinctive clinicopathologic features. METHODS: Alterations of p53, beta2-microglobulin (beta2M ), hMLH1, and hMSH2 genes were analyzed by using polymerase chain reaction, single-strand conformational polymorphism, sequencing, microallelotyping, hypermethylation assays, and immunostaining. The results were contrasted with mutations in BAX, hMSH3, and hMSH6, genes target for the MMP. RESULTS: Tumors with the MMP had a significantly lower incidence of p53 gene mutations than the other tumors and often contained beta2M gene somatic mutations. Many tumors contained concomitant genetic and epigenetic alterations in DNA mismatch repair genes, hMLH1, hMSH2, hMSH3, and hMSH6. Gastric cancer of the MMP was associated with well/moderate differentiation, distal location, and better survival. CONCLUSIONS: Analysis of somatic alterations in microsatellite sequences and in cancer genes target for the MMP is useful for the classification of groups of gastric cancers with different prognosis. The results further support the concept that (gastric) cancer of the MMP represents a distinctive oncogenic pathway because the mutated cancer genes are usually different from those found in tumors without the MMP.

Adaptor Proteins, Signal Transducing↗