Cardiac interleukin-6 in ischemic myocardium.
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Animals↗
Biomedical subjects
T Kanda
Publications and source records attributed to T Kanda.
Adeno-associated virus type 2 nonstructural protein Rep78 suppresses translation in vitro.
Adeno-associated virus type 2 nonstructural protein Rep78 [621 amino acids (aa) long] affects the expression of various cellular and viral genes. In this study we examined the effects of Rep78 on expression of the luciferase gene from the human cytomegalovirus immediate-early promoter in HeLa cells and on translation of RNA encoding luciferase in rabbit reticulocyte lysate. When Rep78 and luciferase were coexpressed, the luciferase activity decreased despite increased levels of luciferase mRNA in the cells. Purified Rep78 or Rep68 fused with Escherichia coli maltose binding protein suppressed translation of luciferase RNA in vitro, but Rep52/40 fusion proteins did not. A mutated Rep78, which is 520 aa long and truncated at its C-terminus, did suppress the in vitro translation, whereas a similarly truncated Rep78 of 420 aa did not. The results indicate that Rep78/68 function to suppress gene expression through translation inhibition, which requires the N-terminal region contained within aa 1-520.
Animals↗
DNA vaccination of mice with plasmid expressing human papillomavirus 6 major capsid protein L1 elicits type-specific antibodies neutralizing pseudovirions constructed in vitro.
Human papillomavirus 6 (HPV 6) causes benign condylomata. As a model for HPV vaccine development, we tested a HPV 6 DNA vaccine candidate, constructed by subcloning the major capsid protein (L1) gene into an expression plasmid having the cytomegalovirus promoter, for its immunogenicity in BALB/c mice. Three intracutaneous inoculations of the plasmid with a gene gun at 2-week intervals elicited anti-L1 serum antibodies. The antibodies were found to recognize highly type-specific, conformation-dependent epitopes, including those to neutralize pseudovirions capable of inducing beta-galactosidase in infected monkey COS-1 cells. The data support the idea that immunization with DNA capable of expressing HPV L1 can be used as an HPV vaccine strategy for humans.
Animals↗
The dynamics of acentric chromosomes in cancer cells revealed by GFP-based chromosome labeling strategies.
Autonomous replicons, such as viral episomes and oncogene containing double minute chromosomes (DMs), lack centromeres and consequently should be lost rapidly when the nuclear membrane breaks down at mitosis. Surprisingly, they are not. This raises the important question of the mechanisms that enable their efficient transmission to daughter cells. We review recent developments in GFP-based chromosome labeling strategies that enable real time analyses using high resolution light microscopy to provide insights into this issue. The results reveal that episomes and DMs both adhere to host chromosomes, a process referred to as "chromosome tethering". Such association enables acentric molecules to use the chromosomal centromere in trans, thereby achieving efficient transmission to daughter cells. This unique mechanism of mitotic segregation also raises the possibility of developing a new class of anti-cancer drugs that work by selectively eliminating growth enhancing genes from cancer cells. J. Cell. Biochem. Suppl. 35:107-114, 2000.
Animals↗
Combined use of the adenosine A(2A) antagonist KW-6002 with L-DOPA or with selective D1 or D2 dopamine agonists increases antiparkinsonian activity but not dyskinesia in MPTP-treated monkeys.
The novel selective adenosine A(2A) receptor antagonist KW-6002 improves motor disability in MPTP-treated parkinsonian marmosets without provoking dyskinesia. In this study we have investigated whether KW-6002 in combination with l-DOPA or selective D1 or D2 dopamine receptor agonists enhances antiparkinsonian activity in MPTP-treated common marmosets. Combination of KW-6002 with the selective dopamine D2 receptor agonist quinpirole or the D1 receptor agonist SKF80723 produced an additive improvement in motor disability. Coadministration of KW-6002 with a low dose of L-DOPA also produced an additive improvement in motor disability, and increased locomotor activity. The ability of KW-6002 to enhance antiparkinsonian activity was more marked with L-DOPA and quinpirole than with the D1 agonist. However, despite producing an enhanced antiparkinsonian response KW-6002 did not exacerbate L-DOPA-induced dyskinesia in MPTP-treated common marmosets previously primed to exhibit dyskinesia by prior exposure to L-DOPA. Selective adenosine A(2A) receptor antagonists, such as KW-6002, may be one means of reducing the dosage of L-DOPA used in treating Parkinson's disease and are potentially a novel approach to treating the illness both as monotherapy and in combination with dopaminergic drugs.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Induction of VEGF gene transcription by IL-1 beta is mediated through stress-activated MAP kinases and Sp1 sites in cardiac myocytes.
Interleukin-1 beta (IL-1 beta) is a multipotent cytokine participating in a variety of cardiovascular diseases. In this study, we examined the effects of IL-1 beta on the expression of vascular endothelial cell growth factor (VEGF) and pursued the molecular mechanisms underlying this effect. Treatment of cultured neonatal rat cardiac myocytes with IL-1 beta increased the levels of VEGF mRNA in a time- and a concentration-dependent manner. These effects were completely abolished by SB203580 and SB202190 (p38 MAPK inhibitors) but not by PD98059 (MEK1 inhibitor), calphostin C (protein kinase C inhibitor), or genistein (tyrosine kinase inhibitor). While IL-1 beta phosphorylated c-Jun N-terminus protein kinase (JNK) rapidly and transiently, the effect of IL-1 beta on p38 mitogen-activated protein kinase (MAPK) was gradual and persistent. Transient transfection assays showed that IL-1 beta increases the transcription from the VEGF promoter. A series of 5;-deletion and site-specific mutation analyses indicated that IL-1 beta as well as overexpression of p38 MAPK and JNK activate VEGF promoter activity through two G+C-rich sequences located at -73 and -62. Electrophoretic mobility shift and supershift assays showed Sp1 and Sp3 proteins specifically bind to the G+C-rich sequences. The half-life of VEGF mRNA was significantly increased in cells treated with IL-1 beta. Together, these results indicate that IL-1 beta induces VEGF gene expression at both transcriptional and post-transcriptional levels, and IL-1 beta evokes p38 MAPK and JNK signalings, which in turn stimulate the transcription of the VEGF gene through Sp1-binding sites. These findings suggest the role of IL-1 beta as a cytokine inducing VEGF in cardiac myocytes, and imply that activation of stress-activated MAP kinases regulate Sp1 sites-dependent transcription.
Animals↗
Effect of interleukin-18 on viral myocarditis: enhancement of interferon- gamma and natural killer cell activity.
Encephalomyocarditis virus causes viral myocarditis with myocyte necrosis and inflammatory cell infiltration in mice. Because previous studies have shown that some cytokines prevent the sequelae of myocarditis, we assessed the effect of a newly identified cytokine, interleukin-18 (IL-18), in preventing the sequelae of myocarditis. Murine IL-18 (10 microg/day/mouse) was given peritoneally for 10 days in C3H mice infected with EMC virus. Mice were divided into group IL-18 (infected-treated), saline group (infected-untreated), group IL-18-2 (treatment started on day 2), group IL-18-5 (treatment started on day 5). Although the 14-day survival rate in saline group was 20%, that in the group IL-18 increased to 80% (P<0.05). Either mice in group IL-18-2 or in group IL-18-5 did not survive longer than saline group. The viral titer of the heart on day 3 was lower in group IL-18 compared to the saline group (1.00+/-0.20 log(10)tissue culture infected dose (TCID)(50)/mg wet weight v 1.42+/-0.12 log(10)TCID(50)/mg, n=3 of each). Mice in group IL-18 had less myocardial necrosis and cellular infiltration than the saline group. The myocardial expression of interferon- gamma (IFN- gamma) mRNA in group IL-18 was significantly (P<0.05) greater than the saline group on days 1 and 3 after viral inoculation. Circulating IFN- gamma was significantly elevated on days 1, 5, and 7, but significantly reduced on day 3. The natural killer cell activities in the spleen on days 1, 3, and 5 were significantly (P<0.05) greater in group IL-18 than in the saline group (41+/-9%v 10+/-6% on day 3, 4 of each). We conclude that IL-18 reduces the severity of EMC viral myocarditis by inducing cardiac expression of IFN- gamma mRNA and increasing splenic natural killer cell activity.
Animals↗
Circulating interleukin-6 significantly correlates to thyroid hormone in acute myocardial infarction but not in chronic heart failure.
To investigate relationships between thyroid states and the cardiac endocrine system, we analyzed thyrotropin (TSH), thyroid hormone, plasma levels of interleukin-6 (IL-6) and brain natriuretic peptide (BNP) in 50 patients with chronic heart failure (CHF), in 30 patients with heart failure from acute myocardial infarction (AMI), and in 15 controls. Plasma levels of IL-6 and BNP in both CHF and AMI were significantly elevated, while free triiodothyronine (FT3) was significantly decreased compared to controls. FT3/free thyroxine (FT4) ratio was significantly decreased in CHF but not in AMI compared to controls. In CHF, diuretic treatment diminished circulating BNP but not IL-6, while diuretic treatment increased FT3/FT4 ratio. In AMI, FT3/FT4 ratio was significantly decreased 72 h compared to 12 h after the onset of AMI, while BNP and IL-6 were significantly increased 72 h compared to 12 h after the onset of AMI. In both CHF and AMI, BNP significantly correlated with FT4. On the other hand, significant correlations between IL-6 and FT3, and between IL-6 and FT3/FT4 ratio were detected in AMI but not in CHF. This preliminary study suggests that IL-6, BNP and thyroid hormone reflect ventricular dysfunction in both acute and chronic heart failure, and that IL-6 significantly relates to circulating thyroid hormone in AMI but not in CHF.
Aged↗
Arterial pulse wave velocity and risk factors for peripheral vascular disease.
Non-invasive measurement of arterial pulse wave velocity (PWV) is used to diagnose peripheral vascular disease. We examined the relationship between PWV and risk factors related to peripheral vascular disease [body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), atherogenic index (AI) and blood glucose (GLU)] in 45 healthy male volunteers, aged 25-85 years. The correlation coefficient of PWV with age was r = 0.46, and the correlation coefficients of PWV with DBP, AI and GLU were r = 0.71, 0.56, and 0.22, respectively (P < 0.05). Multiple linear regression analysis revealed that 67% of the variance in PWV could be accounted for by these three variables. The relative contributions of DBP, AI and GLU to PWV were 66%, 26% and 8%, respectively. To test the applicability of PWV for clinical use, a multiple regression equation of PWV derived from these three variables was then applied to male patients with hypertension (n = 53), hyperlipidaemia (n = 35) or hyperglycaemia (n = 39). The results suggest that the multiple regression equation of PWV is an indicator that discriminates between these patient categories and healthy men.
Adult↗
Identification and characterisation of a silkworm ABC transporter gene homologous to Drosophila white.
In the silkworm, Bombyx mori, many eye- and egg-colour mutations affecting the synthesis and accumulation of ommochrome pigments have been described. In order to understand the pigment precursor transporters involved, ABC transporter genes homologous to the Drosophila white gene were isolated from the silkworm. Reverse transcriptase-polymerase chain reactions (RT-PCR) using embryonic mRNA amplified three cDNA fragments, named Bmwh1, Bmwh2 and Bmwh3 that showed homology to the white gene. Since Bmwh3 shows the highest degree of sequence identity and a similar expression pattern to the Drosophila homologue, we characterised this gene further. A 2667-bp Bmwh3 cDNA isolated from an embryonic library has one ORF encoding a polypeptide of 687 amino acids. The predicted protein has one ATP-binding domain, six transmembrane-spanning segments and high similarity to the Drosophila WHITE protein. Southern analysis indicates that Bmwh3 is a single-copy gene. Polyadenylated Bmwh3 transcripts about 2.7 kb long were detected in eggs, Malpighian tubules and pupal heads, but not in testes, posterior silk glands or fat body cells. The level of Bmwh3 mRNA was reduced in w3 and w3ol mutants but normal in other egg- and eye-colour mutants, suggesting that Bmwh3 correspond to the w3 locus. Genetic analysis was used to map the cloned gene to chromosome 10.
ATP-Binding Cassette Transporters↗
Composite tumor with papillary adenocarcinoma and squamous cell carcinoma of the esophagus: report of a case.
Papillary adenocarcinoma is extremely rare in the squamous epithelium-lined esophagus. The histopathologic and immunohistochemical characteristics were examined in a composite tumor showing distinct papillary adenocarcinoma and squamous cell carcinoma of the esophagus resected from a 66-year-old man. The esophageal tumor consisted both grossly and histologically of two distinct components: an ulcerative part showing a squamous cell carcinoma, and a polypoid part corresponding to a papillary adenocarcinoma. In addition, the in situ squamous cell carcinoma was contiguous with the esophageal tumor. Mucin secretion was found only in the papillary adenocarcinoma component. Immunohistochemically, tumor cells of the papillary adenocarcinoma component were positive for carcinoembryonic antigen, secretory component, and lactoferrin. These staining patterns were similar to those of the normal esophageal gland proper. These histologic, mucin-histochemical, and immunohistochemical findings suggest that the papillary adenocarcinoma originated from the submucosal esophageal gland and the squamous cell carcinoma from the squamous epithelium lining the esophagus.
Adenocarcinoma, Papillary↗
Serum level of vascular endothelial growth factor is decreased by hormone replacement therapy in postmenopausal women without hypercholesterolemia.
The administration of hormone replacement therapy (HRT) to postmenopausal women (PMW) reportedly has beneficial effects on their levels of lipid and lipoproteins. Estrogen retards the development of atherosclerosis induced by a high-fat diet in animals. Although vascular endothelial growth factor (VEGF) may be involved in the development of atherosclerosis in humans, there is no information on effect of estrogen administration on VEGF level and lipid metabolism. We evaluated 64 healthy normotensive or hypertensive PMW before and during the administration of HRT (0.625 mg conjugated equine estrogen combined with 2.5 mg medroxyprogesterone acetate orally) daily for 6 months. All hypertensive PMW were well-controlled on antihypertensive drug therapy. According to their total cholesterol level at baseline, we divided the PMW with HRT (n=54) into a normocholesterolemic group (NC, total cholesterol <220 mg/dl, n=35) and a hypercholesterolemic group (HC, total cholesterol >/=220 mg/dl, n=19). We evaluated the serum levels of VEGF at baseline, and again at 3 and 6 months after starting HRT. HRT significantly (P<0.01) reduced the mean VEGF level from 31.5+/-4.3 pg/ml at baseline to 18.2+/-2.3 pg/ml after 6 months in the NC group. However, the VEGF levels in the HC group and the control group exhibited no significant change at either 3 or 6 months after starting HRT. In summary, HRT, using a combination of conjugated equine estrogen and medroxyprogesterone acetate, reduced the level of VEGF in normocholesterolemic PMW more effectively than in those with hypercholesterolemia.
Aged↗
Artificial insemination using cryopreserved sperm in the silkworm, Bombyx mori.
We report in this paper that female moths artificially inseminated with cryopreserved sperm (-196 degrees C) could oviposit eggs when the sperm was preserved for 356days, and that the fertilization rate and the number of eggs laid were almost equivalent to those obtained in normally mated moths. The optimal cooling rate for sperm freezing was 5-65 degrees C/min for maintaining a high fertility of sperm. The simple and reliable method of cryopreservation was to put the semen first in a deep freezer at -80 degrees C and thereafter put them in liquid nitrogen. When female moths of 'white 2' egg-color mutant strain were inseminated with a mixture of frozen-thawed sperm from males of normal-colored egg strain and non-frozen sperm from males of the 'white 2', female moths deposited a majority of 'white 2' eggs and a very small number of eggs of normal color. The result shows that there was a competitive fertilization of sperm between the two strains of the silkworm, and that sperm fertility was reduced to a considerable extent by freezing at -196 degrees C. These results may contribute not only to basic studies on fertilization in Lepidoptera but also to the development of long-term preservation procedure of genetic resources by using cryopreserved sperm of Bombyx mori.
Journal Article↗
Human leukocyte antigen DRB1 1302 protects against bile duct damage and portal lymphocyte infiltration in patients with chronic hepatitis C.
BACKGROUND/AIMS: To confirm the immune reaction of hosts in chronic hepatitis C, we examined the association of human leukocyte antigen (HLA) DR with the histopathological outcome including bile duct damage and steatosis, which are characteristic of hepatitis C virus (HCV) infection. METHODS: One hundred and fifty-five patients with chronic HCV infection were examined. The pathological appearance of liver biopsy specimens was evaluated by both Knodell's histological activity index and examination of bile duct damage and steatosis. HLA DRB1 was determined by the polymerase chain reaction sequence-specific oligonucleotide probe method. RESULTS: HLA DRB1 1302 was found with significantly higher frequency in patients without than with bile duct damage (34.8% vs. 4.7%, p=0.0001, p corrected by Bonferroni's inequality method=0.002). It was also found more frequently in patients without marked portal lymphocyte infiltration (28.6% vs. 7.7%, p=0.0015, p corrected by Bonferroni's method=0.03). HLA DRB1 1101 was found more frequently in patients without than with piecemeal necrosis (p=0.004). In contrast, the frequency of HLA DRB1 1502 tended to be higher in patients with than without piecemeal necrosis and marked portal lymphocyte infiltration (p=0.015 and p=0.03, respectively). HLA DRB1 1201 and 0802 were seen more frequently in bile duct damage-negative (p=0.02) and piecemeal necrosis-negative patients (p=0.03), respectively. Interestingly, serum HCV levels of HLA DRB1 1302-positive patients were significantly higher than those of 1302-negative patients (mean: 7.7 Meq/ml vs. 3.1 Meq/ml, p=0.0007). CONCLUSION: These findings suggest that some histopathological changes in chronically HCV-infected livers could be caused by the host's immune reaction regulated by HLA DR.
Adolescent↗
Specific inactivation of Escherichia coli tRNA(Phe) by antisense DNA-treatment under Mg2+-deficient conditions.
The preparation of an Escherichia coli tRNA mixture lacking several specific species may be useful for applications ranging from cell-free protein preparation to protein engineering. We have already demonstrated that tRNA(Asp) can be inactivated, or 'knocked out', with practical specificity by an antisense strategy. In the present study, we synthesized five tRNA(Phe)-targeted antisense oligonucleotides and tested if this tRNA can also be inactivated specifically. The salt conditions used previously for the tRNA(Asp) inactivation were not applicable to tRNA(Phe). Instead, Mg2+-deficient conditions were found to be useful for the inactivation of tRNAPhe by the antisense oligonucleotides. These conditions were also applicable to the inactivation of tRNA(Asp). The susceptibility to the antisense DNAs can change drastically, depending on the concentration of Mg2+.
Base Sequence↗
Inhibitory effects of apple polyphenols and related compounds on cariogenic factors of mutans streptococci.
The inhibitory effects of apple polyphenols (APP) on the synthesis of water-insoluble glucans by glucosyltransferases (GTF) of streptococci of the mutans group and on the sucrose-dependent adherence of the bacterial cells were examined in vitro. APP markedly inhibited the activity of GTF purified from the cariogenic bacterial cells. However, APP showed no significant effect on the growth of the cariogenic bacteria. The strongest GTF inhibitors in APP were apple condensed tannins (ACT), a mixture of procyanidins. The 50% inhibitory doses of ACT against the GTF of S. sobrinus and that of S. mutans were 1.5 microgram/mL and 5 microgram/mL, respectively. The ACT efficacy largely depended upon the degree of polymerization. Interestingly, while the other polyphenols known to inhibit GTF such as tannic acid markedly inhibited salivary alpha-amylase activity, APP and ACT only scarcely inhibited that enzyme activity. This means that APP and ACT might selectively inhibit the bacterial GTF activity under oral conditions.
Bacterial Adhesion↗
Water-soluble organotellurium compounds: catalytic protection against peroxynitrite and release of zinc from metallothionein.
The antioxidant properties of a number of water-soluble diorganyl tellurides have been investigated. These organotellurium compounds efficiently protect against peroxynitrite-mediated oxidation of dihydrorhodamine 123, hydroxylation of benzoate, and nitration of 4-hydroxyphenyl acetate. The peroxidation of the zinc storage protein, metallothionein, by tert-butyl hydroperoxide is also catalyzed by the water-soluble organotellurium compounds. As compared to selenium-containing compounds (e.g., ebselen and selenocystamine), some of the tellurides that were tested ¿e.g., 3-[4-(N,N-dimethylamino)benzenetellurenyl]propanesulfonic acid, sodium salt¿ exhibit a significantly higher reactivity in these assays, making them some of the most effective compounds tested thus far. The catalysis of destruction of zinc-sulfur clusters by water-soluble organotellurium compounds could have implications for the bioavailability of zinc in vivo. These compounds might be lead compounds for the development of a new class of water-soluble, tellurium-based antioxidant and zinc-releasing drugs.
Benzoates↗
Germline transformation of the silkworm Bombyx mori L. using a piggyBac transposon-derived vector.
We have developed a system for stable germline transformation in the silkworm Bombyx mori L. using piggyBac, a transposon discovered in the lepidopteran Trichoplusia ni. The transformation constructs consist of the piggyBac inverted terminal repeats flanking a fusion of the B. mori cytoplasmic actin gene BmA3 promoter and the green fluorescent protein (GFP). A nonautonomous helper plasmid encodes the piggyBac transposase. The reporter gene construct was coinjected into preblastoderm eggs of two strains of B. mori. Approximately 2% of the individuals in the G1 broods expressed GFP. DNA analyses of GFP-positive G1 silkworms revealed that multiple independent insertions occurred frequently. The transgene was stably transferred to the next generation through normal Mendelian inheritance. The presence of the inverted terminal repeats of piggyBac and the characteristic TTAA sequence at the borders of all the analyzed inserts confirmed that transformation resulted from precise transposition events. This efficient method of stable gene transfer in a lepidopteran insect opens the way for promising basic research and biotechnological applications.
Actins↗