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Biomedical subjects

Y Fujimoto

Publications and source records attributed to Y Fujimoto.

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

Preoperative diagnosis of intraductal papillary-mucinous tumors of the pancreas with attention to telomerase activity.

BACKGROUND: It has been reported that, in patients with intraductal papillary-mucinous tumor (IPMT) of the pancreas, it is difficult to distinguish adenoma from carcinoma preoperatively. Recently, it has also been reported that telomerase activity was detected in many patients with carcinoma. In this report, the authors used the method of telomerase repeat amplification protocol (TRAP) assay on pancreatic juice retrieved by endoscopic retrograde pancreatic juice aspiration (ERP aspiration). METHODS: Pancreatic juice was collected from 28 patients (13 with intraductal carcinoma and 15 with adenoma) using ERP aspiration at either Hiroshima University Hospital or its affiliated hospitals. Two samples of pancreatic juice were collected from each patient. Each sample was examined by cytology for Papanicolaou staining and TRAP assay. RESULTS: Four of 13 IPMT patients (31%) with intraductal carcinoma were diagnosed accurately by cytology. Seven of nine patients who were classified with benign tumors by cytologic assessment had tumors that expressed telomerase activity. Overall, 11 of 13 IPMT patients (85%) with intraductal carcinoma were diagnosed correctly by cytology associated with telomerase activity. All of the IPMT patients with adenoma were classified with benign tumors by cytologic assessment, and telomerase activity was not expressed. CONCLUSIONS: In this study, the authors found that telomerase activity was expressed with a comparatively high probability in intraductal carcinoma. These results suggest that telomerase activity in pancreatic juices may be used as an adjunct to cytologic diagnosis and may aid further in distinguishing between benign IPMT and malignant IPMT of the pancreas preoperatively.

Adenocarcinoma, Mucinous↗
PubMed2001

Tetrahydrobiopterin attenuates modulation of platelet 12-lipoxygenase and cyclooxygenase activities by nitric oxide.

Endothelial cells secrete large amounts of 5,6,7,8-tetrahydrobiopterin (BH(4)) in septic conditions. BH(4) is a cofactor for nitric oxide (NO) synthase and an essential regulator of its activity. We recently showed that NO can be a modulator of both platelet 12-lipoxygenase and cyclooxygenase activities. In the present study, we investigated the effect of BH(4) on the activities of 12-lipoxygenase and cyclooxygenase in rabbit platelets. The influence of BH(4) on NO-induced modulation of these enzyme activities was investigated. Exogenous BH(4) did not affect platelet 12-lipoxygenase and cyclooxygenase activities. The modulatory effects of NO on the two enzymatic pathways were reversed by addition of BH(4) but not by reduced glutathione. These results suggest that exogenous BH(4) is not essential for NO synthase activity of platelets, but that it is an important regulator of the action of NO released from other sources on platelet 12-lipoxygenase and cyclooxygenase activities.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed2001

Surgical repair of double-orifice of the mitral valve in cases with an atrioventricular canal defects.

OBJECTIVE: A Double-orifice in the mitral valve is an uncommon congenital cardiac lesion which occurs as an isolated anomaly or in association with other cardiac malformation. This report deals with our surgical experience of a double-orifice of the mitral valve in cases with an atrioventricular canal defect. PATIENTS AND METHODS: From 1991 through 1999, ten patients were diagnosed to have a double-orifice of the mitral valve at Shizuoka Children's Hospital. Each patient had associated major cardiac malformations, among which atrioventricular canal defect underwent surgical management, with five of these undergoing complete correction with or without previous pulmonary artery banding. Of these 10, the five cases were enrolled in this study. Two of these had a complete type, and the other three had a partial type. The cleft in the left-sided atrioventricular valve was closed partially in four and left untouched in one. Bridging tissue, when present, was left intact. There was no regurgitation from any accessory orifice and no repair for an accessory orifice was needed. RESULT: There was no late death and no replacement of the valve with prosthesis. During follow-up ranging from 1 to 4 years, none of the patients developed severe stenosis or progressive regurgitation in the left-sided atrioventricular valve. CONCLUSION: Meticulous surgical management of a double-orifice in the mitral valve in association with atrioventricular canal defect an achieve an acceptable midterm result without developing severe dysfunction in the left-sided atrioventricular valve.

Endocardial Cushion Defects↗
PubMed2001

Prognostic factors and therapeutic strategy for anaplastic carcinoma of the thyroid.

Although anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancies, a few patients survive for a fairly long time after modern intensive treatment. We tried to identify prognostic factors of ATC to assist in deciding on the proper therapeutic strategy in individual patients. Of 47 patients with ATC (1976-1999), 3 patients with "incidental" ATC (largely differentiated thyroid carcinoma with a small region of ATC) were excluded because they had a favorable outcome. The 1-year survival rate of the remaining 44 patients with clinically distinct ATC was 16%. The presence of acute symptoms, large tumor (> 5 cm), distant metastasis, and leukocytosis (white blood cell count > or = 10,000/mm3) proved to be significant risk factors. Multivariate analysis by the Cox proportional hazard model showed that these four factors were independent factors for predicting death from ATC. We devised a novel prognostic index (PI) based on the number of these four unfavorable characteristics the patient possessed. Patients with a PI of < or =1 had a 62% survival rate at 6 months, whereas no patients with a PI of > or =3 survived longer than 6 months. All patients with a PI of 4 died from their disease within 3 months. Nine patients received multimodal treatment with a combination of surgery, external irradiation, and chemotherapy and had a long survival (mean 333 +/- 68 days; one patient is still alive and tumor-free), with a mean PI of 0.6. Our PI is useful as a means of selecting patients for aggressive therapy. When the PI is low, multimodal treatment should be attempted to obtain the best survival results; if it is high most patients are too seriously ill to tolerate intensive treatment and palliative therapy is recommended.

Adult↗
PubMed2001

Triterpenoids from Dysoxylum malabaricum.

Two triterpenes 21R,23R-epoxy-21alpha-ethoxy-24S,25-dihydroxyapotirucall-7-en-3-one and 24R-acetoxy-3beta,25-dihydroxycycloartane were isolated from the leaves of Dysoxylum malabaricum together with eight known compounds lupeone, lupeol. sitosterol, dipterocarpol, cycloart-25-ene-3beta,24-diol, 24R,25-dihydroxycycloartan-3-one, 3beta,24R,25-trihydroxycycloartane and ergosta-5,24(24(1))-diene-3beta,4beta,20S-triol. The complete 1H and 13C NMR spectral assignment of the new apotirucallene triterpenoid has been achieved by 1H-1H COSY, HMQC and HMBC experiments.

India↗
PubMed2001

Flavonoid glucuronides from Helicteres isora.

Five flavonoid glucuronides were obtained from the fruit of Helicteres isora, three of which were previously unknown compounds: isoscutellarein 4'-methyl ether 8-O-beta-D-glucuronide 6"-n-butyl ester. isoscutellarein 4'-methyl ether 8-O-beta-D-glucuronide 2", 4"-disulfate and isoscutellarein 8-O-beta-D-glucuronide 2",4"-disulfate. The structures were determined on the basis of spectroscopy and hydrolysis experiments.

Flavonoids↗
PubMed2001

Specific inhibitor of puromycin-sensitive aminopeptidase with a homophthalimide skeleton: identification of the target molecule and a structure-activity relationship study.

2-(2,6-Diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (2: PIQ-22) was found to be a potent and specific inhibitor of puromycin-sensitive aminopeptidase (PSA). Lineweaver-Burk plot analysis showed that PSA is inhibited by PIQ-22 in a non-competitive manner. Structure -activity relationship studies indicated that tautomerism of the imidobenzoylketone group in the cyclic imide moiety of the PIQ-22 skeleton is important for the inhibitory activity.

Aminopeptidases↗
PubMed2001

Molecular cloning of bovine (Bos taurus) cDNA encoding a 94-kDa glucose-regulated protein and developmental changes in its mRNA and protein content in the mammary gland.

We isolated and sequenced cDNA clones encoding a 94-kDa glucose-regulated protein (GRP94) from a cDNA library constructed using bovine (Bos taurus) mammary gland poly(A)(+) RNA. The coding nucleotide sequence and the deduced amino acid sequence of bovine GRP94 shared 94.2-88.4% and 98.1-96.5% identity with those of other mammalian species, respectively. The primary structure contained a carboxyl-terminal signal sequence for retention in the endoplasmic reticulum, six potential sites for N-linked glycosylation and two potential adenosine 5'-triphosphate binding sites, similar to other mammalian and avian GRP94 homologues. In Northern blot hybridization using a cDNA probe from the bovine GRP94 cDNA sequence, a transcript 3.0 kb in size was detected. We measured the amounts of GRP94 and its mRNA in mammary glands from cows at various developmental stages of hormonally induced lactation. The highest level of GRP94 mRNA, determined by dot blot analysis, was detected in the developing stage. In contrast to the mRNA level, the amount of protein, determined by immunoblot analysis using rabbit antiserum raised against GRP94 purified from bovine brain, was higher in lactating stages than in others. The increased level of GRP94 mRNA during the developing stage and the maintenance of GRP94 protein during lactation suggest that the synthesis of GRP94 is regulated during mammary development and differentiation, and also that the protein is involved in a function related to lactation.

Amino Acid Sequence↗
PubMed2001

Catheter ablation of an epicardial accessory pathway via the middle cardiac vein guided by monophasic action potential recordings.

This report describes a case of permanent junctional reciprocating tachycardia (PJRT) that was ablated via the middle cardiac vein, guided by monophasic action potential recording. The patient was a 63-year-old woman who had been suffering from palpitation for 10 years. ECG during palpitation showed a narrow QRS tachycardia with a long RP interval. Electrophysiological study revealed that this tachycardia was an orthodromic reciprocating tachycardia, via an accessory pathway with a decremental property and a long ventriculoatrial interval (130 ms): PJRT. The earliest atrial activation during tachycardia was detected at the junction of the middle cardiac vein with the coronary sinus. Monophasic action potentials were recorded to confirm that the ablation catheter was in contact with the epicardium.

Cardiac Pacing, Artificial↗
PubMed2001

The effects of fatty acyl CoA esters on the formation of prostaglandin and arachidonoyl-CoA formed from arachidonic acid in rabbit kidney medulla microsomes.

Under physiological conditions, small amounts of free arachidonic acid (AA) are released from membrane phospholipids, and cyclooxygenase (COX) and acyl CoA synthetase (ACS) competitively act on this fatty acid to form prostaglandins (PGs) and arachidonoyl-CoA (AA-CoA). We have previously shown that palmitoyl-CoA (PA-CoA) shifts AA away from the COX pathway into the ACS pathway in rabbit kidney medulla at a low concentration of AA (5 microM, close to the physiological concentration of substrate). In the present study, we investigated the effects of stearoyl (SA)-, oleoyl (OA)- and linoleoyl (LA)- CoAs on the formation of PG and AA-CoA from 5microM AA in rabbit kidney medulla microsomes. The kidney medulla microsomes were incubated with 5microM [(14)C]-AA in 0.1 M-Tris/HCl buffer (pH 8.0) containing cofactors of COX (reduced glutathione and hydroquinone) and cofactors of ACS (ATP, MgCl(2)and CoA). After incubation, PG (as total PGs), AA-CoA and residual AA were separated by selective extraction using petroleum ether and ethyl acetate. SA- and OA-CoAs increased AA-CoA formation with a reduction of PG formation, as well as PA-CoA. On the other hand, LA-CoA decreased formation of both PG and AA-CoA. These results suggest that fatty acyl CoA esters can be regulators of PG and AA-CoA formation in kidney medulla under physiological conditions.

Acyl Coenzyme A↗
PubMed2001

Phenylbutazone radicals inactivate creatine kinase.

Creatine kinase (CK) was used as a marker molecule to examine the side effect of damage to tissues by phenylbutazone (PB), an effective drug to treat rheumatic and arthritic diseases, with horseradish peroxidase and hydrogen peroxide (HRP-H(2)O2). PB inactivated CK during its interaction with HRP-H(2) O(2), and inactivated CK in rat heart homogenate. PB carbon-centered radicals were formed during the interaction of PB with HRP-H(2)O2. The CK efficiently reduced electron spin resonance signals of the PB carbon-centered radicals. The spin trap agent 2-methyl-2-nitrosopropane strongly prevented CK inactivation. These results show that CK was inactivated through interaction with PB carbon-centered radicals. Sulfhydryl groups and tryptophan residues in CK were lost during the interaction of PB with HRP-H(2)O2, suggesting that cysteine and tryptophan residues are oxidized by PB carbon-centered radicals. Other enzymes, including alcohol dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, but not lactate dehydrogenase, were also inactivated. Sulfhydryl enzymes seem to be sensitive to attack by PB carbon-centered radicals. Inhibition of SH enzymes may explain some of the deleterious effects induced by PB.

Alcohol Dehydrogenase↗
PubMed2001

PI3-kinase p85alpha is a target molecule of proline-rich antimicrobial peptide to suppress proliferation of ras-transformed cells.

PR-39, which is an endogenous antimicrobial peptide, can bind to Src homology 3 domains of the NADPH complex protein p47(phox) and the signaling adapter protein p130(Cas). Recently, we have reported that PR-39 gene transduction altered invasive activity and actin structure of human hepatocellular carcinoma cells, suggesting that this peptide affects cellular signaling due to its proline-rich motif. In order to clarify the mechanism of the PR-39 functions, we transfected the PR-39 gene into mouse NIH3T3 cells which had already been transformed with human activated k-ras gene. The PR-39 gene transfectant showed a reorganization of actin structure and suppression of cell proliferation both in vitro and in vivo. Decreases of MAP (mitogen-activated protein) kinase activity, cyclin D1 expression and JNK activity were observed in the PR-39 gene transfectant. Co-immunoprecipitation analysis revealed that PR-39 binds to PI3-kinase p85alpha, which is a regulatory subunit of PI3-kinase and one of the effectors by which ras induces cytoskeletal changes and stimulates mitogenesis. The PI3-kinase activity of the PR-39 gene transfectant was decreased compared with that of the ras transformant. These results suggest that PR-39 alters actin structure and cell proliferation rate by binding to PI3-kinase p85alpha and suppressing the PI3-kinase activity.

3T3 Cells↗
PubMed2001

Molecular analysis of X-linked ichthyosis in Japan.

BACKGROUND: X-linked ichthyosis (XLI) is an inherited skin disorder caused by a deficiency of steroid sulfatase (STS). The gene and protein of STS were examined in 19 Japanese patients with XLI. RESULTS: In Western blotting analysis, no cross-reacting peptide was detected in the patients' placenta, although a single band (63 kD) corresponding to STS in a normal subject was observed. Southern blotting was performed using EcoRI digests of cellular DNA from 13 XLI patients and full-length human STS cDNA as a probe. Normal males had bands of 20, 15, 10, 9.0, 6.1, 4.2, 2.6, and 1.5 kb. Twelve of the 19 patients had only 20- and 1.5-kb bands. Only one patient had the same band pattern as that of normal males. The STS gene was analyzed by PCR in 6 of the 19 patients. PCR amplification products were sequenced to analyze the STS gene. Two cases with one-base change in the STS gene and variation in amino acids H444R and E560P were found. Mutant STS cDNA was transfected into COS-1 cells and the STS enzyme activity was assayed. The enzyme activities were less than the minimum detection value of the detection system. CONCLUSIONS: These results suggest that XLI is mainly caused by an extensive deletion of the STS gene and that the PCR method is useful for detection of STS point mutations.

Animals↗
PubMed2001

Activation of peroxisome proliferator-activated receptor gamma inhibits the growth of human pancreatic cancer.

OBJECTIVE: In the present study, we examined the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in human pancreatic cancer and the possible effects of its ligand engagement on cell growth. METHODS: Seven human pancreatic cancer cell lines and 7 surgically resected human pancreatic cancer tissues were used as samples. The expression of PPARgamma was analyzed with reverse transcription-polymerase chain reaction and immunoblotting. The interaction between PPARgamma and PPAR-responsive element (PPRE) was examined by gel shift assay. Growth inhibition by thiazolidinediones was confirmed with anchorage-dependent and anchorage-independent growth assays. RESULTS: PPARgamma was detected in all cell lines tested and in 5 out of 7 cancer tissues (71%), but was not found in adjacent normal pancreatic tissues. Gel shift analysis revealed that the proteins in nuclear extracts of the pancreatic cancer cell line PANC-1 specifically bind to the PPRE. Cell growth was significantly inhibited by treatment with troglitazone and rosiglitazone in a dose- and time-dependent manner (p < 0.01). In contrast, a nonfunctional metabolic analog of troglitazone did not affect cell growth. CONCLUSION: These observations suggest that PPARgamma plays an important role in human pancreatic cancer growth and that ligand-induced activation of PPARgamma would be a useful strategy for treatment of human pancreatic cancer.

Antineoplastic Agents↗
PubMed2001

RIP 140 modulates transcription of the steroidogenic acute regulatory protein gene through interactions with both SF-1 and DAX-1.

Coregulators have been suggested to act as a bridging apparatus between nuclear receptors and the transcriptional machinery. The orphan receptor SF-1 plays a role in controlling the basal and cAMP-stimulated expression of the human steroidogenic acute regulatory protein gene. DAX-1 is the gene responsible for X-linked adrenal hypoplasia congenita and blocks steroid biosynthesis by impairing the expression of steroidogenic acute regulatory protein. In the present study we examined the role of coregulators in the actions of SF-1 and DAX-1 on the human steroidogenic acute regulatory protein promoter. We found that the coregulator RIP 140 interacts with SF-1 in the yeast two-hybrid system. Glutathione-S-transferase pull-down assays and coimmunoprecipitations confirmed the interaction between RIP 140 and SF-1. RIP 140 was also shown to interact with DAX-1. When an RIP 140 expression vector was introduced into Y-1 cells, basal and cAMP-stimulated human steroidogenic acute regulatory protein promoter activities decreased. The inhibitory effect of RIP 140 on human steroidogenic acute regulatory protein promoter activity was dependent upon the presence of SF-1. The cAMP response of an SF-1 response element was inhibited by both RIP 140 and DAX-1 expression vectors at low concentrations of plasmids. We conclude that RIP 140 binds to the orphan nuclear receptor SF-1 and DAX-1 and modulates their actions on the human steroidogenic acute regulatory protein promoter.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Apoptosis and mitochondrial damage in INS-1 cells treated with alloxan.

To evaluate the participation of mitochondrial damage, oxygen radicals and cell death in diabetes mellitus, we designed a way to investigate INS-1 cells, rat pancreatic beta-cell line, to die by treatment with alloxan which generate reactive oxygen species (ROS). Incubation of INS-1 cells with alloxan for 24 h resulted in a decrease in viability of cells as well as inhibition of glucose-stimulated insulin release; this could be prevented by antioxidants, vitamin E and butylated hydroxyanisol (BHA). The formation of a DNA ladder and the distribution of phosphatidylserine at the external surface of plasma membrane were observed as indicators of apoptosis in the cells treated with alloxan at concentrations below 0.5 mM. The formation of DNA ladder was prevented by vitamin E, BHA and catalase, suggesting that the ROS is involved in the process of apoptosis in INS-1 cells treated with alloxan. Lower levels of intracellular ATP, collapse of mitochondrial membrane potential and release of cytochrome c from mitochondria were also observed in INS-1 cells treated with alloxan, suggesting that alloxan caused the damage of mitochondria in cells and was related to the process of apoptosis. In contrast, rat liver RLC-18 cells treated with alloxan were not observed in the decrease of viability. It follows from the present study that mitochondrial damages by ROS generated from alloxan is linked to apoptosis in INS-1 cells.

Adenosine Triphosphate↗