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J Kato

Publications and source records attributed to J Kato.

At least 55 records · Page 3Linked to original sources
PubMed2001

Inhibitory effects of triterpenoids and sterols on human immunodeficiency virus-1 reverse transcriptase.

Fifty-five triterpenoids consisting of 19 tetracyclic, 32 pentacyclic, and 4 incompletely cyclized triterpenoids, and 2 sterols, mostly isolated from various plant and fungal materials, were examined for their inhibitory effects on a purified human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. Twenty triterpenoids and one sterol showed inhibitory effects with 50% inhibition concentration (IC50) values less than 5.0 microM. Among these cycloartenol ferulate (IC50 = 2.2 microM), 24-methylenecycloartanol ferulate (1.9 microM), lupenone (2.1 microM), betulin diacetate (1.4 microM), and karounidiol 29-benzoate (2.2 microM) inhibited most effectively. Some of the triterpenoids and sterols may be potential new lead compounds to find still more potent HIV-1 reverse transcriptase inhibitors.

Cell Line↗
PubMed2001

Adrenomedullin (11-26): a novel endogenous hypertensive peptide isolated from bovine adrenal medulla.

Adrenomedullin (AM) is a potent hypotensive peptide originally isolated from pheochromocytoma tissue. Both the ring structure and the C-terminal amide structure of AM are essential for its hypotensive activity. We have developed an RIA which recognizes the ring structure of human AM. Using this RIA, we have characterized the molecular form of AM in bovine adrenal medulla. Gel filtration chromatography revealed that three major peaks of immunoreactive AM existed in the adrenal medulla. The peptide corresponding to Mr 1500 Da was further purified to homogeneity. The peptide was determined to be AM (11-26) which has one intramolecular disulfide bond. Amino acid sequences of bovine AM and its precursor were deduced from the analyses of cDNA encoding bovine AM precursor. The synthetic AM (11-26) produced dose-dependent strong pressor responses in unanesthetized rats in vivo. The hypertensive activity lasted about one minute, and a dose dependent increase in heart rate was also observed. The present data indicate that AM (11-26) is a major component of immunoreactive AM in bovine adrenal medulla and shows pressor activity.

Adrenal Medulla↗
PubMed2001

The multiple untranslated first exons system of the human estrogen receptor beta (ER beta) gene.

In order to investigate the regulatory mechanism of the expression of the human estrogen receptor beta (ER beta) gene, we have analyzed the structure of the 5'-untranslated region of the ER beta mRNA in the normal uterine endometrium and liver using the 5'-rapid amplification of the cDNA ends method. The sequence analysis revealed the presence of the two isoforms of the ER beta mRNA containing the distinct 5'-untranslated regions. The genomic analysis revealed that the two isoforms of the message originated from the two distinct untranslated first exons, termed the exon 0K and exon 0N, which were spliced to the exon 1. We termed the two isoforms of the message the ER beta mRNA (0K-1) and ER beta mRNA (0N-1). We further analyzed the distribution of the ER beta mRNA (0K-1) and ER beta mRNA (0N-1) in the ejaculated spermatozoa, liver, uterine endometrium and myometrium, and peripheral leukocytes using the reverse transcription-polymerase chain reaction. The distributions of the two mRNA isoforms were different from each other. From these results, it is indicated for the first time that the expression of the human estrogen receptor beta (ER beta) gene is regulated, at least in part, by the multiple untranslated first exons and promoters system.

5' Untranslated Regions↗
PubMed2001

Administration of subtumor regression dosage of TNF-alpha to mice with pre-existing parental tumors augments the vaccination effect of TNF gene-modified tumor through the induction of MHC class I molecule.

One obstacle in treating pre-existing parental tumors by vaccination with cytokine gene-modified tumor cells is the impaired expression of immune-related molecules such as MHC class I. In this study, to enhance MHC class I expression on pre-inoculated parental tumors, low dose TNF (300 U, 500 U, 1000 U), that is, TNF at levels shown to cause neither tumor regression nor any severe adverse reaction, was systemically injected into parental tumors bearing mice before vaccination with TNF gene-modified Meth-A cells or B-16 cells. Since the class I expression was confirmed to continue for at least 24 h following administration of TNF, TNF was administered 6 h before vaccination. Complete regression of relatively large parental tumors (M0) (8.0-10.0 mm in diameter) was observed in five of eight mice treated with 1000 U TNF, partial regression was observed in mice treated with 500 U, and a lesser yet significant regression was observed in mice treated with only 300 U. Contrarily, in the mice which had received vaccination without the TNF pretreatment, no complete regression was observed. This effect was inhibited with the anti-class I antibody or anti-CD8 antibody. Growth of a re-established, B16 tumor was significantly suppressed with a combination of TNF preadministration and vaccination of TNF gene-modified B16. These results indicate that pre-administration of low-dose TNF may be promising for enhancing vaccination effects of TNF gene-modified tumor cells.

Animals↗
PubMed2001

Analysis of K-ras, APC, and beta-catenin in aberrant crypt foci in sporadic adenoma, cancer, and familial adenomatous polyposis.

BACKGROUND & AIMS: We have previously shown that aberrant crypt foci (ACF) are the putative precursor lesions of colorectal adenomas and subsequent cancer in humans using magnifying endoscopy. The present study was designed to investigate these genetic alterations in ACF biopsy specimens from normal subjects, familial adenomatous polyposis (FAP) or sporadic patients. METHODS: The non-FAP cases included 34 normal subjects, 35 colorectal adenoma patients, and 19 colorectal cancer patients; there were 4 FAP patients. Biopsies were performed on ACF by magnifying endoscopy. K-ras mutations were analyzed by 2-step polymerase chain reaction and restriction fragment length polymorphism, APC mutations by in vitro-synthesized protein assay, and beta-catenin mutations by direct sequencing. Full-length APC and beta-catenin were detected by immunofluorescence. RESULTS: In non-FAP cases, K-ras mutations were detected in 82% (89/106) of nondysplastic ACF and 63% (17/27) of dysplastic ACF. APC mutation and beta-catenin accumulation were not detected in non-FAP ACF, whereas in adenoma of these patients, positivity of APC mutation and beta-catenin accumulation were 78% (24/31), and that of K-ras mutation was 65% (20/31). FAP patients showed K-ras mutations in only 13% (1/8) of dysplastic ACF, which is the predominant form of ACF found in FAP. In FAP patients, somatic APC mutations were found in 100% of dysplastic ACF, as they are in adenoma. The frequency of K-ras mutations was 73% (8 of 11) in FAP adenoma. CONCLUSIONS: The data suggest that in sporadic colorectal carcinogenesis, assuming the biological implication of ACF as a precursor of adenomas, there is a route where K-ras mutation mainly occurs during the formation of ACF, which then become adenomas wherein APC mutation occurs. In FAP, however, somatic mutation of APC predominantly occurs during ACF formation, followed by K-ras mutation.

Adenomatous Polyposis Coli↗
PubMed2001

Glutathione S-transferase-pi overexpression is closely associated with K-ras mutation during human colon carcinogenesis.

BACKGROUND & AIMS: In colorectal adenoma and carcinoma, glutathione S-transferase-pi (GSTP1-1) is highly expressed. K-ras mutation is also known to occur frequently in colorectal adenoma and carcinoma, as well as in the putative precursor of adenoma, aberrant crypt foci (ACF). Further, forced expression of v-H-ras in rat liver epithelial cells has been shown to enhance rat pi-class GST expression. The aim of the present study is, therefore, to investigate the causative relationship between GSTP1-1 overexpression and K-ras mutation in these lesions. METHODS: Twenty-seven specimens of colorectal carcinoma, 24 of adenoma, and 28 of ACF were examined in this study. The expression of GSTP1-1 or p21(K-ras) was examined by immunohistochemistry. The GSTP1-1 messenger RNA levels were measured by TaqMan reverse-transcription polymerase chain reaction (PCR). K-ras mutation was detected by two-step PCR restriction fragment length polymorphism. v-K-ras transfection to RPMI-4788 colon carcinoma cells was carried out by the lipofection method. Activities of GSTP1-1 promoters containing AP-1 and Sp1 responsive elements in the v-K-ras transfectants were measured by a secreted form of human placental alkaline phosphatase (SEAP) assay. Nuclear protein from these transfectants bound to the GSTP1-1 promoter was analyzed by electrophoretic mobility shift assay (EMSA). RESULTS: In human colorectal carcinoma, adenoma, and ACF, close association of increased expression of GSTP1-1 with K-ras mutation was observed. v-K-ras transfectants showed significantly higher SEAP activity than that of mock-transfectant activity. EMSA showed specific interaction of AP-1 with promoter of GSTP1-1. CONCLUSIONS: It is highly plausible that GSTP1-1 overexpression in ACF, colorectal adenoma, and carcinoma is induced by K-ras mutation via AP-1 activation.

Adenoma↗
PubMed2001

Pulpal response to exposure with Er:YAG laser.

OBJECTIVE: The purpose of this study was to evaluate the pulpal response to the Er:YAG laser after accidental exposure of the pulp. STUDY DESIGN: Cavities were prepared, and pulps were exposed by either Er:YAG laser or mechanically by a slow-speed conventional handpiece (control group) in 76 maxillary first molars of male Wistar rats. Rats were killed immediately, at 3 days, 1 week, and 2 weeks. Histopathologic examinations of the pulp at the exposure site were performed and evaluated with the Mann-Whitney U test (P <.05). RESULTS: The Er:YAG laser group showed no bleeding and no dentin chips at the exposure site immediately after pulp exposure. However, they displayed an area of blood extravasation near the exposure site. Subsequently, the Er:YAG laser group formed dentin bridges at the exposure site more frequently than the control group. The Er:YAG laser group demonstrated more reparative dentin formation near the exposure site than the control group, especially at 2 weeks, which was highly significant (P <.01). CONCLUSION: According to the results of this study, Er:YAG laser-exposed pulp tissue demonstrated good healing capacity with the formation of a dentin bridge and reparative dentin. However, further investigations are suggested to study the effect of the blood extravasation, which appeared near the laser exposure sites.

Aluminum Silicates↗
PubMed2001

Use of cultured cells in assessing ethanol toxicity and ethanol-related metabolism.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Terrence M. Donohue, Jr, and Dahn L. Clemens. The presentations were (1) Characterization of single and double recombinant hepatoma cells that express ethanol-metabolizing enzymes, by Terrence M. Donohue, Jr; (2) Inhibition of cell growth by ethanol metabolism, by Dahn L. Clemens; (3) Use of transfected HeLa cells to study the genesis of alcoholic fatty liver, by Andrea Galli and David Crabb; (4) CYP2E1-mediated oxidative stress induces COL1A2 mRNA in hepatic stellate cells and in a coculture system of HepG2 and stellate cells, by Natalia Nieto; (5) Transforming growth factor-alpha secreted from ethanol-exposed hepatocytes contributes to development of alcoholic hepatic fibrosis, by Junji Kato; and (6) Effect of ethanol on Fas-dependent caspase-3 activation and apoptosis in CD4+ T cells, by Shirish S. Barve.

Acetaldehyde↗
PubMed2001

Roles of protein kinase C and Ca2+-dependent signaling in angiotensin II-induced adrenomedullin production in rat cardiac myocytes.

OBJECTIVES: We showed that angiotensin II stimulates adrenomedullin production in cultured neonatal rat cardiac myocytes, and that the secreted adrenomedullin inhibits hypertrophy of the myocytes, although the intracellular mechanisms of adrenomedullin production are still unknown. Since protein kinase C (PKC) and the Ca2+ signaling system are involved in cardiac hypertrophy, we examined the roles of these intracellular signaling systems in the production of adrenomedullin by myocytes. METHODS: Cultured neonatal rat cardiac myocytes were incubated with agonists or antagonists of PKC and Ca2+ signaling systems for 24 h. Adrenomedullin secreted into the medium and adrenomedullin mRNA expression were measured by radioimmunoassay and quantitative polymerase chain reaction, respectively. RESULTS: Both phorbol-12-myristate-13-acetate (PMA), a PKC activator and A23187, a calcium ionophore, significantly increased adrenomedullin mRNA expression and secretion from the myocytes. The induction of adrenomedullin secretion by PMA was abolished by H7, a PKC inhibitor, and by downregulation of PKC induced by pre-incubation with PMA. Similarly, the stimulation of adrenomedullin secretion by 10(-6) mol/l angiotensin II was significantly reduced following the inhibition or downregulation of PKC activity in the myocytes. Blockade of the L-type Ca2+ channel and chelation of intracellular Ca2+ both resulted in a significant reduction of the stimulation of adrenomedullin secretion by angiotensin II. In addition, the secretion was significantly attenuated by inhibitors of calmodulin (W-7) and calmodulin kinase II (KN-62), and slightly attenuated by FK506, a calcineurin inhibitor. CONCLUSIONS: These results suggest that PKC and the Ca2+/calmodulin signaling systems are involved in angiotensin II-induced adrenomedullin secretion from rat cardiac myocytes.

Adrenomedullin↗
PubMed2001

A case of successful management of portosystemic shunt with autosomal dominant polycystic kidney disease by balloon-occluded retrograde transvenous obliteration and partial splenic embolization.

We describe a patient with autosomal dominant polycystic kidney disease who was successfully managed for severe abdominal distension, impaired liver function and a portosystemic shunt by interventional therapies. The patient's intra-hepatic portal vein was compressed and narrowed by multiple liver cysts, which resulted in a decrease of the portal blood flow and portal hypertension due to a huge gastro-renal shunt These haemodynamic changes were assumed to contribute to insufficient protein synthesis in the liver. Therefore, we first repeatedly performed minocycline hydrochloride instillations to treat the multiple liver cysts. Then, we conducted a partial splenic embolization to prevent elevation of the portal vein pressure prior to balloon-occluded retrograde transvenous obliteration which was performed to increase the portal blood flow. The portal blood flow markedly increased, and protein synthesis in the liver also recovered and the clinical symptoms improved. The patient has been monitored for more than two years up to the present and her liver function parameters have remained within the normal range. Renal insufficiency is known to be a major prognostic factor in autosomal dominant polycystic kidney disease. In some cases, however, liver involvement with multiple cysts may result in a fatal outcome. In such cases, interventional therapies, as provided to this patient, should be considered.

Cysts↗
PubMed2001

Frameshift mutations at mononucleotide repeats in RAD50 recombinational DNA repair gene in colorectal cancers with microsatellite instability.

To identify additional genes targeted for microsatellite instability (MSI), we search for human genes which contain mononucleotide repeats in their coding region, selected 7 genes (RAD50, DNA-PKcs, FLASH, Apaf-1, XPG, CtIP, and MLSN1), and analyzed frameshift mutations in them. Here we report that 60% (3 out of 5) of human colorectal cancer cell lines exhibiting a high frequency of MSI (MSI-H) and 46% (6 out of 13) of MSI-H primary colorectal tumors had mutations in the (A)9 repeat of RAD50 recombinational repair gene. In contrast, no frameshift mutations were found in any of the 5 MSI-negative colorectal cancer cell lines, 8 colorectal tumors exhibiting a low frequency of MSI (MSI-L), or 28 MSI-negative colorectal tumors. No mutations were found in the mononucleotide repeats of 6 other genes, even in MSI-H cancers. These results suggest that RAD50 frameshift mutations may play a role in the tumorigenesis of MSI-H colorectal cancers.

Colorectal Neoplasms↗
PubMed2001

The polymerase L528M mutation cooperates with nucleotide binding-site mutations, increasing hepatitis B virus replication and drug resistance.

After receiving lamivudine for 3 years to treat chronic hepatitis B, 67-75% of patients develop B-domain L528M, C-domain M552I, or M552V mutations in the HBV polymerase that render hepatitis B virus (HBV) drug-resistant. The aim of this study was to evaluate the influence of these mutations on viral replication and resistance to antiviral agents. We investigated the replication fitness and susceptibility of the wild-type and five mutant HBVs (L528M, M552I, M552V, L528M/M552I, and L528M/M552V) to 11 compounds [lamivudine, adefovir, entecavir (BMS-200475) (+)-BCH-189 (+/-)-FTC (racivir) (-)-FTC (emtricitabine) (+)-FTC, L-D4FC, L-FMAU (clevudine), D-DAPD, and (-)-carbovir] by transfecting HBV DNA into hepatoma cells and monitoring viral products by Southern blotting. The replication competency of the single C-domain mutants M552I and M552V was markedly decreased compared with that of wild-type HBV. However, addition of the B-domain mutation L528M restored replication competence. Only adefovir and entecavir were effective against all five HBV mutants, and higher doses of these compounds were necessary to inhibit the double mutants compared with the single mutants. The B-domain mutation (L528M) of HBV polymerase not only restores the replication competence of C-domain mutants, but also increases resistance to nucleoside analogues.

Antiviral Agents↗
PubMed2001

Chemotaxis of the nematode Caenorhabditis elegans toward cycloheximide and quinine hydrochloride.

We investigated the chemotaxis of the nematode Caenorhabditis elegans toward cycloheximide, denatonium benzoate, 6-n-propyl-2-thiouracil, and quinine hydrochloride. Interestingly, C. elegans was strongly attracted to cycloheximide, while avoiding quinine hydrochloride. This is the first report thus far to describe the chemotactic responses of C. elegans toward bitter tastants for humans.

Journal Article↗
PubMed2001

Isolation and characterization of the Enterobacter cloacae cheR mutant defective in phosphate taxis.

A chemotaxis-defective mutant of Enterobacter cloacae IFO3320, designated EC1, was isolated after N-methyl-N'-nitro-N-nitrosoguanidine (NTG) mutagenesis. Computer-assisted capillary assays showed that EC1 failed to show chemotactic responses to peptone and inorganic phosphate (Pi). Cloning and sequence analysis showed that EC1 is a cheR mutant, suggesting that Pi taxis by E. cloacae is dependent on a methyl-accepting chemotaxis protein(s) (MCP). EC1 was further mutagenized with NTG to construct cheR pstS and cheR pstA double mutants. A recombinant plasmid pECT01.2, which contained the E. cloacae cheR gene, restored the ability of these double mutants to show chemotaxis toward peptone but not Pi. These results suggest that the phosphate-specific transport (Pst) system, together with a MCP(s), is required for detecting Pi in E. cloacae.

Chemotaxis↗
PubMed2001

Risk factors and predictors of coronary arterial lesions in Japanese hypertensive patients.

The morbidity rate of coronary artery disease has recently increased in Japan. This is attributable to changes from traditional to more westernized lifestyles. In this study, we therefore examined the risk factors and predictors of coronary arterial lesions in Japanese patients with essential hypertension. Coronary angiography was performed in 109 consecutive essential hypertension patients (57 men and 52 women; 66 +/- 8.0 years of age) with either angina pectoris or atypical chest pain, who were chosen from 485 consecutive hypertensive patients in a hypertension clinic in Sendai, Japan. Coronary arterial stenosis of greater than 50% was defined as significant and used as a dependent variable for the multiple regression analysis. Risk factors were defined as factors confirmed to have a causal relationship with coronary arterial lesions, whereas arteriosclerotic complications and hypertensive target organ damage were defined as predictors. Multiple logistic regression analysis was performed using these parameters as independent variables. Of 109 patients, 25 had a coronary arterial stenosis greater than 50%. A smoking habit (odds ratio (OR): 4.48; 95% confidence interval (CI): 1.13-17.82; p<0.05), hypercholesterolemia (OR: 5.34; 95% CI: 1.52-18.73; p<0.05), and 24-h diastolic blood pressure (OR: 2.33; 95% CI: 1.06-5.16; p<0.05) were significant risk factors, whereas carotid intima-media thickness (OR: 5.85; 95% CI: 1.48-23.2; p<0.05) was a significant predictor of coronary arterial lesion. When two of the major risk factors (a smoking habit, hypercholesterolemia, or impaired glucose tolerance including diabetes mellitus) were clustered in addition to the hypertension, the risk of coronary arterial lesions increased by 6.7 to 10.1 times. These findings indicate that the major risk factors established in Caucasians, i.e., a smoking habit, hypercholesterolemia and blood pressure level, are also risk factors for coronary arterial lesions in Japanese with essential hypertension. The presence of two or more risk factors increases the risk of coronary arterial lesions synergistically in the presence of hypertension.

Aged↗
PubMed2001

Biosynthesis and secretion of adrenomedullin and proadrenomedullin N-terminal 20 peptide in a rat model of endotoxin shock.

To study the biosyntheses and pathophysiological roles of adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) in septic shock, we compared the time course of plasma concentrations of these peptides and blood pressure in rats injected with either 0.9% saline (control group) or lipopolysaccharide (LPS group). The plasma AM concentration in the LPS group did not increase 30 and 60 min after LPS injection, at which time points the blood pressure remained low. Thereafter, AM rapidly increased, and it amounted to 35 times the basal value 4 h after injection, when the blood pressure returned to the basal level. The increment of plasma PAMP in the LPS group was lower than that of AM. We also examined the tissue concentration of AM and PAMP--as well as the tissue expression of proadrenomedullin (proAM) mRNA--in the LPS and control groups. LPS significantly increased the tissue concentrations of AM and PAMP in the lung, but decreased them in the adrenal gland and cardiac atrium. The LPS injection augmented proAM gene transcription in the lung, adrenal gland and aorta. In an immunohistochemical examination, AM staining was intense in alveolar endothelial cells of the lung in the LPS group. Thus, this septic shock model had high plasma levels of PAMP as well as AM, while the biosynthesis and secretion of the two peptides may have been differentially regulated in various tissues of rats injected with LPS. The present results suggest that these two bioactive peptides may play different roles in the pathophysiology of septic shock.

Adrenomedullin↗