Biomedical subjects

S Soeda

Publications and source records attributed to S Soeda.

At least 19 recordsLinked to original sources

PubMed2001

Crocin suppresses tumor necrosis factor-alpha-induced cell death of neuronally differentiated PC-12 cells.

Crocus sativus L. is used in Chinese traditional medicine to treat some disorders of the central nervous system. Crocin is an ethanol-extractable component of Crocus sativus L.; it is reported to prevent ethanol-induced impairment of learning and memory in mice. In this study, we demonstrate that crocin suppresses the effect of tumor necrosis factor (TNF)-alpha on neuronally differentiated PC-12 cells. PC-12 cells dead from exposure to TNF-alpha show apoptotic morphological changes and DNA fragmentation. These hallmark features of cell death did not appear in cells treated in the co-presence of 10 microM crocin. Moreover, crocin suppressed the TNF-alpha-induced expression of Bcl-Xs and LICE mRNAs and simultaneously restored the cytokine-induced reduction of Bcl-X(L) mRNA expression. The modulating effects of crocin on the expression of Bcl-2 family proteins led to a marked reduction of a TNF-alpha-induced release of cytochrome c from the mitochondria. Crocin also blocked the cytochrome c-induced activation of caspase-3. To learn how crocin exhibits these anti-apoptotic actions in PC-12 cells, we tested the effect of crocin on PC-12 cell death induced by daunorubicin. We found that crocin inhibited the effect of daunorubicin as well. Our findings suggest that crocin inhibits neuronal cell death induced by both internal and external apoptotic stimuli.

Animals↗

PubMed2001

Deficient release of plasminogen activator inhibitor-1 from astrocytes triggers apoptosis in neuronal cells.

Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the processes of peripheral tissue remodeling and fibrinolysis through the regulation of plasminogen activation. We found that cultured human astrocytes efficiently released PAI-1, and that both mRNA expression and protein release of PAI-1 were suppressed by pretreatment of the cells with daunorubicin. To examine the role of PAI-1 in the nervous system, neuronally differentiated PC-12 cells (PC-12 neurons) were maintained in a PAI-1-deficient culture medium derived from daunorubicin-pretreated astrocytes. The deficiency of PAI-1 in the medium caused a significant reduction in Bcl-2 and Bcl-XL mRNAs and an increase in Bcl-XS and Bax mRNAs in PC-12 neurons at 3 h. The changes in balance between mRNA expressions of the anti- and pro-apoptotic Bcl-2 family proteins caused caspase-3 activation following the release of cytochrome c from mitochondria. Apoptotic morphological change and DNA fragmentation were also observed in the neuronal cells at 24 h. Addition of exogenous PAI-1 protein to the inhibitor-deficient medium blocked the apoptotic changes in PC-12 neurons. However, addition of PAI-1 antibodies to control medium caused similar apoptotic changes in PC-12 neurons. During the apoptotic processes, plasminogen activator (PA) activity in the PAI-1-deficient medium was as low as the control level. The present data suggest that PAI-1 has physiological functions other than its role as PA inhibitor for the survival of neurons.

Animals↗

PubMed2001

Synthesis and evaluation of a difluoromethylene analogue of sphingomyelin as an inhibitor of sphingomyelinase.

A sphingomyelin analogue 2, in which the long alkenyl chain and the phosphodiester moiety of sphingomyelin were replaced by a phenyl and an isosteric difluoromethylenephosphonic acid, was prepared to evaluate its inhibitory potency to sphingomyelinase. The analogue non-competitively inhibited the neutral sphingomyelinase in bovine brain microsomes with an IC50 of 400 microM. The compound had the ability to suppress tumor necrosis factor alpha-induced apoptosis of PC-12 neurons at a low concentration of 0.1 microM.

Animals↗

PubMed2001

Daunorubicin attenuates tumor necrosis factor-alpha-induced biosynthesis of plasminogen activator inhibitor-1 in human umbilical vein endothelial cells.

The anthracycline antibiotic daunorubicin is reported to induce apoptosis in cells by triggering ceramide generation through de novo synthesis or sphingomyelin hydrolysis. Treatment of human umbilical vein endothelial cells (HUVEC) with daunorubicin markedly decreased the mRNA expression and protein release of plasminogen activator inhibitor-1 (PAI-1). This cellular event was accompanied by a significant increase in the total ceramide content in HUVEC. On the other hand, tumor necrosis factor (TNF)-alpha treatment of HUVEC led to an increase in both PAI-1 mRNA expression and protein release, and an enhancement of total ceramide content was also observed. The stimulating effect of TNF-alpha on PAI-1 synthesis was attenuated by the pretreatment of HUVEC with daunorubicin. Interestingly, the daunorubicin-induced increase in ceramide content was blocked by addition of the potent ceramide synthase inhibitor fumonisin B(1), while the TNF-alpha-induced ceramide increase was not affected by this drug. Fumonisin B(1) treatment restored the daunorubicin-induced decrease in PAI-1 release to approximately 70% of the control, but did not affect the TNF-alpha-induced increase in PAI-1 release. Thus, these data imply the possibility that the subcellular topology of ceramide production determines its lipid mediator function in the regulation of PAI-1 synthesis in HUVEC, because both TNF-alpha and daunorubicin could increase the ceramide levels.

Carboxylic Acids↗

PubMed2001

Uterine angiomyolipoma: case report and review of the literature.

Extrarenal angiomyolipomas (AML) have been reported at various anatomical sites, but infrequently in the gynecological region. In the uterus, only a few cases have been described. We describe a uterine angiomyolipoma occurring in a 40-year-old woman without evidence of tuberous sclerosis. The tumor arose on the right wall of the uterine body and was partially cystic, and it was associated with marked degeneration. It was composed of mature adipose tissue, anomalous blood vessels and non-vascular smooth muscle cells. Immunohistochemistry revealed that non- vascular smooth muscle cells were positive for alpha-smooth muscle actin (alpha-SMA), desmin, vimentin, antihuman muscle actin (HHF35) and progesterone receptor (PR), and negative for cytokeratin, antihuman melanoma (HMB45), CD34, S-100 and estrogen receptor (ER). It is of particular interest that non-vascular smooth muscle cells were negative for HMB45, in contrast to renal and other extrarenal AML in which HMB45 immunoreactivity has been demonstrated in these cells.

Actins↗

PubMed2001

Angiosarcoma of vagina successfully treated with interleukin-2 therapy and chemotherapy: a case report.

We report a case of angiosarcoma of the vagina in a 61-year-old woman who had undergone radical hysterectomy and pelvic irradiation for uterine cervical adenocarcinoma 14 years previously. Combination chemotherapy (cyclophosphamide, vincristine, doxorubicin and dacarbazine) and interleukin-2 induced complete remission of the tumor. The patient remained free from disease for 15 months.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

[Depression].

Explore the source record for details and available documents.

Adolescent↗

PubMed2000

Release of plasminogen activator inhibitor-1 from human astrocytes is regulated by intracellular ceramide.

The present study underscores a regulatory role of intracellular ceramide in astrocytes for the release of an extracellular serine protease, tissue-type plasminogen activator (t-PA), and its inhibitor, plasminogen activator inhibitor-1 (PAI-1). Treatment of cultured human astrocytes with N-acetylsphingosine, a cell-permeable short-chain ceramide analogue or daunorubicin that could increase intracellular ceramide via activation of ceramide synthase or sphingomyelin hydrolysis increased the release of t-PA and conversely decreased the PAI-1 release. Interestingly, treatment of the astrocytes with tumor necrosis factor (TNF)-alpha also increased the intracellular ceramide levels but caused the elevation of PAI-1 release without altering the t-PA release. These data suggest that the generation of ceramide in astrocytes is linked at least with the regulation of PAI-1 release. We also demonstrate that the suppression of PAI-1 release with daunorubicin accelerates the cell death of neuronally differentiated PC12 cells and suggest an antiapoptotic role of PAI-1 in the nervous system.

Animals↗

PubMed2000

ATP hydrolytic activity of an iron-stimulated P-type ATPase of mouse liver microsomes.

Mouse liver microsomes treated with octylthioglucoside were examined for iron-stimulated ATPase activity. The activity was about 6 mumol Pi/mg protein/hr under optimal conditions [300 mM KC1, 3 mM MgSO4, 10 mM glutathione(GSH), 100 microM FeCl3, 3 mM ATP and 50 mM acetate buffer at pH 5.0]. The Km for iron was 20 microM. A reducing agent, such as GSH or dithiothreitol, was required for the activity, and removal of Fe2+ from the reaction mixture by bathophenan-throlinedisulfonate resulted in a complete loss of the iron-stimulated ATPase activity. Vanadate inhibited the iron-stimulated ATPase activity. These results suggest that microsomes from mouse liver contain the Fe(2+)-stimulated P-type ATPase.

Adenosine Triphosphatases↗

PubMed2000

Relationship between serum cholesterol levels and meta-chlorophenylpiperazine-induced cortisol responses in healthy men and women.

We investigated the effect of cholesterol on serotonergic receptor function in 20 healthy male and 10 healthy female subjects using cortisol responses to meta-chlorophenylpiperazine (m-CPP) neuroendocrine challenge tests. M-CPP, a metabolite of the antidepressant trazodone, has been widely used in psychopharmacology research as a probe of serotonin function. In the human brain, m-CPP binds both to various serotonergic receptors, mainly 5-HT(2C), and to alpha(2)-adrenoceptors. After an overnight fast, the subjects received m-CPP (0.5 mg/kg) or identical placebo capsules orally in a randomized, double blind, crossover design. Blood was obtained for measurement of cholesterol and cortisol. In some analyses, especially in males, there were significant positive correlations between serum cholesterol levels and cortisol responses. These findings suggest the possibility that serum cholesterol levels may be positively associated with serotonergic receptor function. The existence of such an association may provide an explanation for reported increases in depression, suicide and violence in individuals with low or lowered cholesterol.

Adult↗

PubMed2000

Oversulfated fucoidan inhibits the basic fibroblast growth factor-induced tube formation by human umbilical vein endothelial cells: its possible mechanism of action.

We have previously demonstrated that chemically oversulfated fucoidan (OSF) but not native fucoidan (NF) effectively suppresses the tube structure formation by human umbilical vein endothelial cells (HUVEC) on the basement membrane preparation, Matrigel. In this study, using more defined systems where basic fibroblast growth factor (bFGF) induces the tube formation by HUVEC on collagen gel, we investigated the mechanism responsible for the inhibition of angiogenesis by OSF in vitro. Unlike NF and desulfated fucoidan (desF), OSF potently inhibited the bFGF-induced HUVEC migration and tube formation. ELISA for tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in the culture media indicated that OSF increased the bFGF-induced release of PAI-1 antigen, but not of t-PA antigen. Analyses of the binding of bFGF to HUVEC surfaces and the following protein tyrosine phosphorylation revealed that OSF could promote the cell binding and autophosphorylation of 140 and 160 kDa receptors. In heparitinase-treated HUVEC, contrarily, the bFGF binding and PAI-1 release were decreased by OSF. These results suggest that OSF is a highly sulfated unique polysaccharide that can promote the binding of bFGF to the heparan sulfate molecules required for binding to the high affinity receptors with tyrosine kinase activity. The resultant increase in PAI-1 release may play a key role for the prevention of cell migration accompanied by matrix proteolysis.

Binding, Competitive↗

PubMed2000

Synthesis and evaluation of multisubstrate analogue inhibitors of purine nucleoside phosphorylases.

1,1-Difluoro-2-(tetrahydro-3-furanyl)ethylphosphonic acids (+/-)-cis-4a and (+/-)-trans-4a possessing a (purine-9-yl)methyl functionality at the ring as well as their homologues (+/-)-cis-4b and (+/-)-trans-4b were synthesized and tested as 'multi-substrate analogue' inhibitors for purine nucleoside phosphorylases. Radical cyclization of allylic alpha,alpha-difluorophosphonates 8a,b was applied to construct the alpha,alpha-difluorophosphonate-functionalized oxacycles 9a,b. The IC50 values of the nucleotide analogues (+/-)-cis-4a and (+/-)-cis-4b were 88 and 38 nM, respectively, for human erythrocyte PNP-catalyzed phosphorylation of inosine in the presence of 100mM orthophosphate. The stereochemistry of the inhibitors was found to affect significantly the inhibitory potency. The transisomers (+/-)-trans-4a and (+/-)-trans-4b were ca. 4-fold less potent than the corresponding cis-isomers. At an intracellular concentration of orthophosphate (1 mM), (+/-)-cis-4b, the most potent compound of this series, was shown to have IC50 and Ki values of 8.7 and 3.5 nM, respectively.

Enzyme Inhibitors↗

PubMed2000

The value of pre-operative diagnostic procedures for cervical involvement in uterine corpus carcinoma.

OBJECTIVE: To assess the value of procedures for pre-operative diagnosis of cervical involvement of uterine corpus carcinoma. MATERIALS AND METHODS: Four diagnostic procedures, including cervical cytology, endocervical curettage (ECC), magnetic resonance imaging (MRI), and hysteroscopy, were performed for diagnosis of cervical involvement in 60 patients with uterine corpus carcinoma. The preoperative diagnosis based on results obtained using by each procedure was retrospectively compared with the diagnosis based on histological examination of surgical specimens. Data were analyzed according to the standard definition of sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: Cervical involvement was confirmed in 18 patients (30%). ECC showed high sensitivity (90.9%) and specificity (88.9%). Cervical cytology showed high specificity (88.6%). MRI showed very high specificity (99.2%) and high sensitivity (88.5%) in cases with cervical stromal invasion. CONCLUSION: Cervical cytology and MRI are useful for excluding cervical involvement. ECC is useful for positive diagnosis. MRI may be useful for cases with stromal invasion. The use of a combination of several procedures is essential for obtaining an accurate diagnosis of cervical involvement in cases of uterine corpus carcinoma.

Adult↗

PubMed1999

[The influence of clomipramine-induced mania on rapid cycling affective disorder].

Rapid cycling affective disorder (RC) is defined as the presence of at least four affective episodes per year. We report two RC patients whose first manic episodes were considered to be induced by clomipramine. The first case, a 61-year-old female, suffered from RC after a manic episode with respect to oral administration of clomipramine. The second case, a 45-year-old female, showed cycle acceleration after a manic episode regarding intravenous drip infusion treatment with clomipramine. They had no manic or hypomanic episodes before the administration of clomipramine. We discuss the possible induction and worsening of RC through clomipramine-induced mania.

Adult↗

PubMed1999

Synthesis and biological evaluation of 1,1-difluoro-2-(tetrahydro-3-furanyl)ethylphosphonic acids possessing a N9-purinylmethyl functional group at the ring. a new class of inhibitors for purine nucleoside phosphorylases.

1,1-Difluoro-2-(tetrahydro-3-furanyl)ethylphosphonic acids cis-3 and trans-3 possessing a N9-purinylmethyl functionality at the ring were synthesized and tested as "multi-substrate analogue" inhibitors for purine nucleoside phosphorylases. Radical cyclization of allyic alpha,alpha-difluorophosphonate (E)-7 was applied to construct the alpha,alpha-difluorophosphonate-functionalized tetrahydrofuranyl moiety. The IC50 values of cis-3 and trans-3 for human erythrocyte PNP-catalyzed phosphorylation of inosine were determined to be 88 and 320 nM, respectively. The stereochemistry of the inhibitors was found to affect significantly the inhibitory potency.

Antineoplastic Agents↗

PubMed1999

Synthesis and biological evaluation of alpha,alpha-difluorobenzylphosphonic acid derivatives as small molecular inhibitors of protein-tyrosine phosphatase 1B.

A series of alpha,alpha-difluorobenzylphosphonic acids having a hydrophobic functional group were prepared via the Stille coupling reaction from halogenated alpha,alpha-difluorobenzylphosphonates. Evaluation of inhibitory activity toward protein tyrosine phosphatase (PTP 1B) revealed that the ethynyl, phenylethynyl and (E)-styryl groups on the benzene nuclei increased the inhibitory activity of alpha,alpha-difluorobenzylphosphonic acid. Inhibitory activities significantly increased upon introducing both (E)-styryl and bis-methylsulfonamide functional groups onto the benzene nuclei of alpha,alpha-difluorobenzylphosphonic acid.

Enzyme Inhibitors↗

PubMed1999

MR findings in primary retroperitoneal schwannoma.

OBJECTIVE: To evaluate the MR findings in primary retroperitoneal schwannoma. MATERIAL AND METHODS: Seven cases of primary retroperitoneal schwannoma, in whom the diagnosis was confirmed histopathologically, were analyzed retrospectively. The following items were reviewed at MR imaging: tumor diameter, margin, homogeneity, signal intensity as compared to normal renal parenchyma, presence/absence of infiltration into adjacent organs, and, in 1 and 4 cases, the enhancement on Gd-dynamic images and post-contrast T1-weighted images, respectively. RESULTS: Tumor diameter was 5.5 +/- 3.1 cm, ranging from 2.5 to 10 cm in the 6 benign schwannomas, and 12 cm in 1 malignant. The tumor margin was regular in all of the benign cases and irregular in the malignant one. The malignant case showed infiltration into the liver and duodenum. Four of the benign schwannomas showed a homogeneous, and 2 presented a heterogeneous pattern, while the malignant schwannoma was heterogeneous. On T1-weighted images, the benign schwannomas were hypointense in 4 cases, isointense in 1 and mixed in 1, while on T2-weighted images, they were hyperintense in 5 and mixed in 1. The malignant case showed mixed intensity on both T1- and T2-weighted images. On enhanced T1-weighted images, capsular, septal enhancement was noted in 2 cases, overall enhancement in 2, and, on Gd-dynamic images, late enhancement was shown. CONCLUSION: On MR imaging, primary retroperitoneal schwannomas show different signal intensity characteristics, including cystic degeneration. There are, however, no specific characteristics of these tumors.

Aged↗

PubMed1999

Synthesis of novel nucleotide analogues possessing a difluoromethylenephosphonato group. Evaluation of the inhibitory activity for purine nucleoside phosphorylase.

Novel nucleotide analogues 1-6 were prepared as "multi-substrate" analogue inhibitors for purine nucleoside phosphorylases (PNPs). The cyclopropane and the tetrahydrofuran moieties of the alkyl spacer connecting a nucleobase and difluoromethylene phosphonic acid were found to be effective for good inhibition of PNPs.

Actinomycetales↗