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Biomedical subjects

S Saito

Publications and source records attributed to S Saito.

At least 109 records · Page 6Linked to original sources
PubMed2001

Orexin-A suppresses the pulsatile secretion of luteinizing hormone via beta-endorphin.

Orexins, the novel hypothalamic neuropeptides that stimulate feeding behavior, have been shown to suppress the pulsatile secretion of LH in ovariectomized rats. However, the mechanism of this action is still not clear. We examined the effect of naloxone, a specific opioid antagonist, on the suppression of the pulsatile secretion of LH by orexins to determine whether beta-endorphin is involved in this suppressive effect. We administered orexins intracerebroventricularly and injected naloxone intravenously in ovariectomized rats, and we measured the serum LH concentration to analyze the pulsatile secretion. Administration of orexin-A significantly reduced the mean LH concentration and the pulse frequency, but coadministration of naloxone significantly restored the mean LH concentration and the pulse frequency. Administration of orexin-B also significantly reduced the mean LH concentration and the pulse frequency, and coadministration of naloxone did not restore them. These results indicate that orexin-A, but not orexin-B, suppresses GnRH secretion via beta-endorphin.

Animals↗
PubMed2001

Highly regioselective cyclotrimerization of 1-perfluoroalkylenynes catalyzed by nickel.

We report the highly regioselective cyclotrimerization of the 1-perfluoroalkylenynes in the presence of Ni(PPh3)4. The substituent effects on the reactivity of the enynes were investigated. We also succeeded in the nickel-catalyzed cocyclization of the 1-perfluoroalkylenynes with (trimethylsilyl)-acetylene. The possible structures of the intermediates of the cyclotrimerization and the reasons for the observed high regioselectivity were discussed.

Journal Article↗
PubMed2001

Antiallodynic effect of intrathecally administered 5-HT(2) agonists in rats with nerve ligation.

We examined the antiallodynic effect of intrathecally administered serotonin receptor agonists including 5-HT(1A), 5-HT(1B), 5-HT(2) and 5-HT(3) receptor subtypes in a rat model using spinal nerve ligation at L5 and L6. Administration of the 5-HT(2) receptor agonist, alpha-methyl-5-hydroxytryptamine maleate (alpha-m-5-HT; 3-100 microg) or (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI; 10-100 microg), showed dose-dependent antiallodynic actions with no associated motor weakness. The antiallodynic action of alpha-m-5-HT was more potent than that of DOI. The effects of 5-HT(2) agonists on tactile allodynia were reversed by intrathecal pretreatment with the selective 5-HT(2) antagonist ketanserin and with the mixed 5-HT(1) and 5-HT(2) antagonist methysergide. Neither the mixed 5-HT(1A) and 5-HT(1B) antagonist cyanopindolol nor the selective 5-HT(3) antagonist MDL72222 attenuated antiallodynic effects induced by 5-HT(2) agonists. In contrast, the selective 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)-tetralin hydrobromide (8-OH-DPAT; 1-50 microg), the 5-HT(1B) agonist 5-methoxy-3-(1,2,5,6-tetrahydro-4-pyridinil)-1H-indol (RU-24969; 10-100 microg) and the 5-HT(3) agonist 2-methyl-5-hydroxytryptamine maleate (2-m-5-HT; 30-300 microg) all lacked significant antiallodynic action with intrathecal administration. These results indicate that the 5-HT(2) receptor plays an essential role in spinal suppression of neuropathic pain by 5-HT.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

Involvement of the Oct-1 regulatory element of the gadd45 promoter in the p53-independent response to ultraviolet irradiation.

The gadd45 gene, a growth arrest and DNA damage (gadd)-induced gene, is transcriptionally activated by UV irradiation through two distinct pathways. One requires the sequence-specific binding of the p53 tumor suppressor protein to a responsive element within the third intron of the gadd45 gene, and the other is p53-independent activation of the gadd45 promoter region, although the UV-response element that mediates this has yet to be defined. To investigate the sequences involved in induction of gadd45 by UV irradiation in a p53-independent pathway, we performed mutation analyses of the human gadd45 promoter fused to the luciferase reporter gene in cell lines in which p53 was inactivated. We found that the UV-responsive element was involved in the Oct-1 binding site at -99 bp relative to the transcription start site. Electrophoretic mobility shift assays showed that Oct-1, a transcription factor, bound this element on the gadd45 gene, although the intensity and mobility pattern of the retarded bands were not altered by UV irradiation. These results suggest that the Oct-1 regulatory element might be one of the essential elements involved in the activation of the gadd45 promoter by UV irradiation in a p53-independent pathway.

Cell Division↗
PubMed2001

Evaluation of the electroosmotic medium pump system for preparative disk gel electrophoresis.

This paper describes an improved electroosmotic elution system for preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) based on the epochal idea of H. V. Tan et al. (Nucleic Acids Res. 1988, 16, 1921-1930). In this elution system, a semipermeable membrane, mounted under the gel terminal end, works as the elution pump as well as the partition of the elution chamber. We refer to this system as the "electroosmotic medium pump system." Operation of the constructed apparatus (3.6 cm i.d. disk gel column) and resolution of the protein bands were examined by separation of the model protein mixture (bovine serum albumin (BSA), ovalbumin, bovine carbonic anhydrase, soybean trypsin inhibitor) and purification of the membrane protein, dipeptidyl peptidase IV (DPP IV). The Spectra/Por 7 dialysis membrane provided a better flow profile for the elution buffer. The four model proteins of the protein mixture were able to be completely separated from each other and recovered without dilution. The maximum protein concentration of eluate achieved was 93 mg/ml, when applying a single component, BSA fraction V, as a sample. Furthermore, the multifunctional ectoenzyme, DPP IV, was purified in a single step.

Animals↗
PubMed2001

Are DNA mismatch repair deficiencies responsible for accumulation of genetic alterations in epithelial ovarian cancers?

To investigate the association of DNA mismatch repair deficiencies in the development and/or progression of epithelial ovarian cancers, the relationship between replication errors (RERs) and genetic alterations in three genes (p53, c-erbB2, K-ras) and loss of heterozygosity (LOH) on 6q27 was investigated in 70 patients with epithelial ovarian cancers. The presence of RERs was examined by PCR using five microsatellite markers. Mutations of p53 were analyzed by PCR-SSCP and sequencing. Amplification of c-erbB2 was analyzed by Southern blot hybridization. Point mutations of K-ras codon 12 were identified by PCR-PHFA, while 6q27LOH was examined by Southern blot hybridization. As a result, 18 of 70 patients with epithelial ovarian cancers (26%) were RER-positive and 52 patients (74%) were RER-negative. Tumors with two or three genetic alterations accounted for 28% and 33% of RER-positive tumors, respectively, and these were significantly more frequent than in the RER-negative tumors (17% and 6%, respectively)(P =.002). These results are consistent with mismatch repair deficiencies being involved in the development and/or progression of a proportion of epithelial ovarian cancers through accumulation of genetic alterations.

Adenocarcinoma↗
PubMed2001

Aromatization of enamines promoted by a stoichiometric amount of palladium(II) salts: a novel method for the synthesis of aromatic amines.

Enamines (1a-r) prepared from cyclohexanones, cyclohexane-1,3-diones, or tetralones led to arylamines (2a-r) in one pot when treated with a stoichiometric amount of palladium salts [PdCl2-(MeCN)2] in acetonitrile in the presence of triethylamine at room temperature or at elevated temperature, in some cases for 5 min to 2 h. The initial electrophilic attack of palladium chloride on the beta-carbon of the enamines led to a sigma-palladium species (8) which triggered a series of reactions (-->9-->10-->11-->12) destined for aromatization to give 2a-r in good yields. The intervention of such a sigma-palladium species has been attested by a trapping experiment. On the basis of this reaction mechanism, we have developed another new process capable of transforming acyclic compounds having 6-en-2-one frameworks (16, 23, 25) to arylamines (2s-u) when their enamines were treated under the similar conditions as above, featuring again the formation of sigma-palladium species such as 8 as the initial key intermediate.

Journal Article↗
PubMed2001

Palladium-catalyzed addition of alcohol pronucleophiles to alkylidenecyclopropanes.

Palladium-catalyzed addition of alcohol pronucleophiles 1 to alkylidenecyclopropane derivatives 2 afforded the corresponding allylic ethers 3 in excellent to moderate yields. Catalyst optimization indicated the Pd(PPh3)4-P(o-tolyl)3 combination as the best system among all catalysts tested. Intramolecular reaction also proceeded smoothly. A plausible mechanism for this catalytic reaction was proposed.

Journal Article↗
PubMed2001

Differential involvement of p38 MAP kinase pathway and Bax translocation in the mitochondria-mediated cell death in TCR- and dexamethasone-stimulated thymocytes.

Mitochondria play a central role in many apoptotic reactions. Although mitochondrial apoptotic changes and caspase activation have been demonstrated in the apoptotic thymocytes, cell death signal through mitochondria in TCR-stimulated thymocytes has not been fully understood. In this study, we show that TCR stimulation induced disruption of mitochondrial transmembrane potential (Delta Psi(m)), the cytochrome c release from mitochondira, capase-3 activation, and the cell death of thymocytes. Bongkrekic acid, an inhibitor of Delta Psi(m) disruption, blocked the cytochrome c release from mitochondria and the following caspase-3-mediated cell death. Furthermore, a pro-apoptotic Bcl-2 family protein, Bax, but not Bad or Bid, was translocated from cytosol to mitochondria in TCR-stimulated thymocytes. This translocation and the following apoptotic changes were inhibited by SB203580, a p38 kinase inhibitor, in a specific manner. These results suggest that activated p38 kinase pathway by TCR stimulation induces translocation of Bax to mitochondria, causing Delta Psi(m) disruption, and the release of cytochrome c, which finally induces caspase-3-mediated apoptosis in thymocytes.

Animals↗
PubMed2001

Activated human T cells directly induce osteoclastogenesis from human monocytes: possible role of T cells in bone destruction in rheumatoid arthritis patients.

OBJECTIVE: To elucidate the direct role of human T cells in the induction of osteoclastogenesis in rheumatoid arthritis (RA), by studying human monocytes and the pathogenetic roles of receptor activator of nuclear factor kappaB ligand (RANKL), RANK, and osteoprotegerin (OPG). METHODS: Synovial tissue obtained at total knee replacement was stained immunohistologically using anti-RANKL, CD3, and CD4 antibodies. Synovial fluid was obtained from patients with RA, osteoarthritis (OA), gout, or trauma. Concentrations of the soluble form of RANKL (sRANKL) and OPG in the synovial fluid were measured by enzyme-linked immunosorbent assay. Activated T cells from peripheral blood mononuclear cells (PBMC) of healthy volunteers were cultured with human monocytes from PBMC. RESULTS: Immunostaining of the synovial tissue of RA patients demonstrated that RANKL-positive cells were detected in a subset of fibroblast-like synoviocytes and infiltrating mononuclear cells. Double immunostaining revealed that RANKL-positive cells were detected in a subset of CD3+ cells and CD4+ cells. An increased concentration of sRANKL and a decreased concentration of OPG were detected in synovial fluid from RA patients. The ratio of the concentration of sRANKL to that of OPG was significantly higher in synovial fluid of RA patients than in synovial fluid of patients with OA or gout. The activated T cells expressing RANKL induced osteoclastogenesis from autologous peripheral monocytes. The role of RANKL in this osteoclastogenetic process was confirmed by dose-dependent inhibition by OPG. CONCLUSION: The present study is the first to demonstrate osteoclastogenesis using human-derived T cells and monocytes. In addition, the present findings suggest that excess production of RANKL by activated T cells increases the level of sRANKL in synovial fluid and may contribute to osteoclastic bone resorption in RA patients.

Antibodies↗
PubMed2001

Symmetric echo acquisition for absolute-value display in solid-state NMR imaging.

A method of solid-state NMR imaging that permits echo Fourier transformation (FT) has been devised using a magic echo train. The echo FT imaging can be implemented simply by modifying the gradient pulse sequence in the previous magic echo imaging (TREV-16TS) so that the one-dimensional k-space trajectory follows the sampling points which are symmetric about the k origin. The implemented ability of echo FT improves the performance of the magic echo imaging: the sensitivity gained by radical2, the phase correction is made unnecessary, and the digital resolution is doubled. One- and two-dimensional imaging experiments have been conducted on some solid samples, confirming the improved performance and revealing a TREV-16TS adjustment parameter that is critical for the successful echo FT imaging.

Echo-Planar Imaging↗
PubMed2001

Electroconvulsive therapy impairs systolic performance of the left ventricle.

PURPOSE: In this observational study, we examined left ventricular systolic performance during electroconvulsive therapy (ECT), using an echocardiographic automated border detection system. METHODS: Nine ASA I or II patients scheduled for ECT were studied. Bilateral ECT was performed after the administration of propofol 1 mg x kg(-1), succinylcholine 1 mg x kg(-1), and assisted mask ventilation with 100% oxygen. Cardiac function was monitored by transthoracic echocardiography, prior to anesthesia induction and throughout the ECT procedure until ten minutes after the seizure. RESULTS: Increased end-systolic area and decreased fractional area change were observed at one minute after the seizure compared to the awake condition. No regional wall motion abnormalities were observed in all patients both at baseline condition and during the ECT CONCLUSION: Systolic performance of the left ventricle estimated by echocardiography decreased transiently in the immediate period after the electric shock.

Adult↗
PubMed2001

Hepatosplanchnic oxygenation is better preserved during mild hypothermic than during normothermic cardiopulmonary bypass.

PURPOSE: To assess and compare the effects of normothermic and mild hypothermic cardiopulmonary bypass (CPB) on hepatosplanchnic oxygenation. METHODS: We studied 14 patients scheduled for elective coronary artery bypass graft surgery who underwent normothermic (>35 degrees C; group I, n=7) or mild hypothermic (32 degrees C; group II, n=7) CPB. After induction of anesthesia, a hepatic venous catheter was inserted into the right hepatic vein to monitor hepatic venous oxygen saturation (ShvO(2)) and hepatosplanchnic blood flow by a constant infusion technique that uses indocyanine green. RESULTS: The ShvO(2) decreased from a baseline value in both groups during CPB and was significantly lower at ten minutes and 60 min after the onset of CPB in group I (39.5 +/- 16.2% and 40.1 +/- 9.8%, respectively) than in group II (61.1 +/- 16.2% and 61.0 +/- 17.9%, respectively; P <0.05). During CPB, the hepatosplanchnic oxygen extraction ratio was significantly higher in group I than in group II (44.0 +/- 7.2% vs 28.7 +/- 13.1%; P <0.05). CONCLUSION: Hepatosplanchnic oxygenation was better preserved during mild hypothermic CPB than during normothermic CPB.

Cardiopulmonary Bypass↗
PubMed2001

Perioperative management of biventricular failure after closure of a long-standing massive arteriovenous fistula.

PURPOSE: To report the perioperative management of arteriovenous fistula (AVF) closure in a patient with high-output heart failure and pulmonary hypertension. CLINICAL FEATURES: In a 71-yr-old man, closure of a long-standing massive AVF between the right femoral artery and vein was performed. After closure of the AVF, his pulmonary artery pressure (PAP) increased from 52/21 mmHg to 68/26 mmHg, his cardiac index decreased from 5.27 L.min(-1).m(-2) to 3.18 L.min(-1).m(-2), and his pulmonary wedge pressure increased from 15 mmHg to 32 mmHg due to an acute increase in afterload. Co-administration of prostaglandin E and a phosphodiesterase III inhibitor improved the cardiac index and the PAP. CONCLUSIONS: Surgical closure of the fistula may not always lead to resolution of the high output cardiac failure. In this case, afterload management using arterial dilators (prostaglandin E1, phosphodiesterase III inhibitor), use of inotropic drugs (phosphodiesterase III inhibitor), and close attention to volume status was crucial for a successful outcome after surgical AVF closure.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Meningeal carcinomatosis from an ovarian primary with complete response to adjuvant chemotherapy after cranial irradiation.

Meningeal metastasis is rare in the clinical course of ovarian carcinoma, and its prognosis is poor. Meningeal dissemination of carcinoma is usually treated by intrathecal administration of methotrexate and total brain irradiation, although these treatments are usually ineffective. We experienced a case of meningeal relapse from ovarian carcinoma resistant to multiple antineoplastic agents in a 64-year-old woman who was treated with eight different chemotherapy regimens after her initial operation 7 years previously. Intrathecal administrations of methotrexate or cisplatin with dexamethasone were not effective. Fifty-Gy whole cranial irradiation inhibited increases in serum carbohydrate antigen (CA) 125 levels and further tumor growth. Adjuvant chemotherapy was required to alleviate frequent headaches and to decrease serum CA125 level and tumor size. Intravenous administration of 45 mg paclitaxel and 35 mg cisplatin, and oral administration of 50 mg etoposide were carried out for 5 days. This treatment was repeated every 3 weeks. After four courses of treatment, meningeal carcinomatosis was not detectable on computed tomography (CT) and magnetic resonance imaging (MRI) scans. The patient's serum levels of CA125 rapidly fell to beneath normal limits and remained normal. She is still alive and clinically free of recurrence 4 months after the last cycle of chemotherapy. As well as reporting our experience with this case, we also present a review of the literature on meningeal carcinomatosis from ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗