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T Nikaido

Publications and source records attributed to T Nikaido.

At least 127 records · Page 7Linked to original sources

In-vitro model of uterine leiomyomas: formation of ball-like aggregates.

To clarify the biological characteristics of uterine leiomyomas, cells explanted and cultured from uterine leiomyomas and from normal myometrial tissue were observed by time-lapse cinemicrography and phase-contrast microscopy. The histological characteristics were evaluated by electron microscopy and immunofluorescence microscopy, and these observations revealed significant differences. By time-lapse cinemicrography, the cells cultured from leiomyomas and myometrium differed in their behaviour. Cells from the myometrium started to grow in parallel with the cell's major axis and formed topographically uniform hills and valleys by day 21 of culture. In contrast, the cells from leiomyomas started to grow irregularly, as if having no contact inhibition, and formed ball-like aggregates of cells by day 21 of culture. The aggregates resembled the nodules of leiomyoma in vivo. Ultrastructurally, cells from both leiomyomas and myometrium had typical features of smooth muscle. Immunofluorescently, a different distribution of alpha-smooth muscle actin-positive filaments and different staining of cellular fibronectin and N-cadherin between the cells from leiomyomas and myometrium were observed, which may contribute in part of the different behaviour of the cells. Given that the explant cell culture system resembles the features of uterine leiomyomas in vivo, this suggests that it can be used as an in-vitro model.

Antibodies↗

Actions of picrodendrin antagonists on dieldrin-sensitive and -resistant Drosophila GABA receptors.

1. A series of terpenoid compounds, recently isolated from Picrodendron baccatum, share a picrotoxane skeleton with picrotoxinin, an antagonist of ionotropic GABA receptors. Referred to as picrodendrins, they inhibit the binding of [35S]-tert-butylbicyclophosphorothionate (TBPS) to rat GABAA receptors. Hitherto, their effects on GABA receptors have not been investigated electrophysiologically. Under two-electrode voltage-clamp, the actions of picrodendrins and related terpenoids have been assayed on homooligomeric GABA receptors formed by the expression of a Drosophila GABA receptor subunit (RDLac) in Xenopus oocytes. 2. All the terpenoids tested, dose-dependently antagonized currents induced by 30 microM (EC50) GABA. 3. Tutin and its analogues (dihydrotutin and isohyenanchin) differ in the structure of their axial C4 substituents. Of these compounds, tutin, which bears an isopropenyl group at this carbon atom, was the most potent antagonist of RDLac homo-oligomers, whereas isohyenanchin, which bears a hydroxyisopropyl group, was the least potent antagonist tested. 4. Picrodendrins differ mainly in the structure of their C9 substituents. The IC50s of picrodendrins ranged from 17 +/- 1.3 nM (picrodendrin-Q) to 1006 +/- 1.3 nM (picrodendrin-O). As such, the most potent picrodendrins (Q, A and B) were approximately equipotent with picrotoxinin as antagonists of RDLac homo-oligomers. 5. Certain picrodendrin compounds effected a use-dependent blockade of RDLac homo-oligomers. Such a biphasic block was not observed with tutin analogues. 6. Picrotoxin-resistant RDLacA3025 homo-oligomers, which have a single amino acid substitution (A302S) in the 2nd transmembrane region, were markedly less sensitive to picrodendrin-O than the wild-type, dieldrin-sensitive, homo-oligomers. 7. The relative potency of tutin analogues demonstrates that the structure-activity relationship of the C4 substituent of picrotoxane-based compounds is conserved in vertebrates and insects. However, the relative order of potency of picrodendrins on RDLac homo-oligomers is distinctly different from that observed in previous radioligand binding studies performed on vertebrate GABAA receptors. As picrodendrin compounds differ in the structure of their C9 substituents, these data suggest that the optimal convulsant pharmacophores of vertebrate GABAA receptors and RDLac homo-oligomers differ with respect to this substituent.

Animals↗

A new cytotoxic cholestane bisdesmoside from Ornithogalum saundersiae bulbs.

Bioassay-guided fractionation of the MeOH extract of Ornithogalum saundersiae bulbs led to the isolation of a new cholestane bisdesmoside with potent cytotoxic activities toward leukemia HL-60 and MOLT-4 cells. The structure was deduced mainly from spectroscopic information.

Antineoplastic Agents, Phytogenic↗

Immunohistochemical detection of CDK4 and p16INK4 proteins in cutaneous malignant melanoma.

p16INK4 gene, which encodes a specific inhibitor of cyclin-dependent kinase 4 (CDK4), has been recently reported as an important tumour suppressor gene. It is mapped to chromosome 9p21, which is frequently deleted or mutated in many tumour cell lines including malignant melanoma. Since the CDK4/cyclin D complex propels a cell to go through the G1 check point of the cell cycle, a critical phase of cell division, alteration of the p16INK4 gene could lead a cell to uncontrolled proliferation and malignant transformation. To clarify any role for p16INK4 and CDK4 proteins in the development of human malignant melanoma, we have examined, immunohistochemically, the expression of these two proteins in melanocytic neoplasms including 19 primary lesions of non-familial melanoma. Intense nuclear and/or cytoplasmic expression of the CDK4 protein was observed in 11 of 19 cases (58%) of melanoma. In contrast, virtually no nuclear or cytoplasmic staining for CDK4 protein was detected in 28 benign melanocytic naevi, including six Spitz naevi. Expression of p16INK4 protein was observed in three of 19 melanomas (16%) and in 17 of 28 benign naevi (61%). Inverse expression of CDK4 and p16INK4, at individual cell level, was detected in one case of melanoma. The present study suggests that CDK4 overexpression is characteristic for malignant melanoma, and probably reflects its autonomous accelerated cell proliferation. The expression rate of p16INK4 protein in malignant melanoma was lower than that in benign naevi, although the significance of p16INK4 deletion in melanoma development has not been definitely confirmed.

Carrier Proteins↗

Steroidal saponins from the bulbs of Triteleia lactea and their inhibitory activity on cyclic AMP phosphodiesterase.

The chemical compounds in the bulbs of Triteleia lactea have been analysed as a part of our systematic study of plants of the subfamily Allioideae in Liliaceae. Thirteen steroidal saponins, seven of which appeared to be new compounds, were isolated. The structures of the new saponins were elucidated on the basis of the spectroscopic analysis, including two-dimensional NMR techniques, and hydrolysis. Inhibitory activity of the isolated saponins on cyclic AMP phosphodiesterase was evaluated to identify new compounds with medicinal potential.

3',5'-Cyclic-AMP Phosphodiesterases↗

Steroidal saponins from the tubers of Dichelostemma multiflorum and their inhibitory activity on cyclic-AMP phosphodiesterase.

Phytochemical examination of the tubers of Dichelostemma multiflorum led to the isolation of three new steroidal saponins together with two known saponins. The structures of the new compounds were determined by spectral data and a few chemical transformations to be (25R)-5 alpha-spirostane- 1 beta,3 beta-diol (brisbagenin) 1-O-[O-alpha-L-rhamnopyranosyl-(1-->3)-4-O- acetyl-alpha-L-arabinopyranoside], brisgabenin 1-O-[O-alpha-L-rhamnopyranosyl-(1-->2)-O- [alpha-L-rhamnopyranosyl-(1-->3)]-4-O-acetyl-alpha-L-arabinopyranosid e] and (22S,25S)-5 alpha-spirostan-3 beta-o1 3-O-[O-beta-D-galactopyranosyl- (1-->2)-O-[beta-D-xylopyranosyl-(1-->3)]-O-beta-D-glucopyranosyl-(1-->4) -beta-D-galactopyranoside]. The known compounds were identified as desglucolanatigonin II and gitonin, with certain amounts of the corresponding C-25S isomers. Inhibitory activity of the isolated saponins and their derivatives on cAMP phosphodiesterase was evaluated to identify new compounds with medicinal potential.

3',5'-Cyclic-AMP Phosphodiesterases↗

Steroidal saponins from Allium chinense and their inhibitory activities on cyclic AMP phosphodiesterase and Na+/K+ ATPase.

The saponin fraction prepared from the methanolic extract of Allium chinense bulbs exhibited inhibitory activities on cyclic AMP phosphodiesterase (cAMP PDE) (43.5%) and Na+/K+ ATPase (59.3%) at a sample concentration of 100 micrograms ml-1, respectively. Attempted purification of the active fraction through column chromatography on silica gel and ODS silica gel resulted in the isolation of six steroidal saponins, one of which appeared to be a new compound and one to be the first isolation from a natural source. (25R,S)-5 alpha-Spirostan-3 beta-ol tetrasaccharide showed inhibitory activities on both cAMP PDE and Na+/K+ ATPase, while (25R)-3 beta-hydroxy-5 alpha-spirostan-6-one di- and tri-saccharides inhibited only cAMP PDE.

3',5'-Cyclic-AMP Phosphodiesterases↗

Shear and tensile bond testing for resin cement evaluation.

OBJECTIVES: The aim of this study was to compare the tensile and shear bond strengths of one experimental and four commercially available resin cements following the ISO document TR 110405 for bond measurement. METHODS: Tensile and shear bond tests were performed using bovine enamel and dentin as the tooth substrate with each of the resin cements. Resin composite rods were cemented to the prepared tooth surfaces. The bond strengths were obtained 24 h after cementation, and mode of failure was classified after fracture of the bonds, both visually and by SEM observation. RESULTS: Significant differences existed between the two bond test methods for all materials with enamel and three of the five cements when bonded to dentin. The shear test results were always the higher of the two test methods. Mode of fracture varied little for the visual classification, but the morphology from SEM observations showed considerable differences. SIGNIFICANCE: Although there are deficiencies in the current test methods these may be outweighed by substrate variables. A test model should be designed to determine which stresses, tensile or shear, are the greatest for different types of restorations. With this information, the type of test selected could provide appropriate information before clinical trials are commenced.

Aminosalicylic Acids↗

Effect of air-powder polishing on adhesion of bonding systems to tooth substrates.

OBJECTIVES: The air-powder polisher was introduced to provide a method to quickly remove stains and plaque. The purpose of this study was to evaluate what effect preparing teeth with an air-powder polisher (Air-flow 2, Shofu) has on bonding to enamel and dentin substrates. METHODS: The bonding systems used in this study were one-step etching/priming systems (KBT-5, Kanebo; and Clearfil Liner Bond II, Kuraray) and a two-step etching/priming system (Superbond D-Liner Plus, Sun Medical). Bovine enamel and dentin surfaces were prepared and finished with 600-grit silicon carbide paper. Then the surfaces were either not treated (control) or air-powder polished for 15 s. A 4-mm bonding area was demarcated, and the tooth substrates were bonded with the three bonding systems according to the manufacturers' instructions. Tensile bond strengths were measured 24 h after storage in water at 37 degrees C. Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) analyses were performed on air-powder polished specimens to determine changes in the surface morphology and detect residual material from the air-powder polisher. SEM and transmission electron microscopic (TEM) observations of the interface between the bonding resins and dentin were performed to detect variations in the hybrid layers of the control and treated specimens. RESULTS: The results indicated that air-powder polishing did not influence the tensile bond strength to enamel, but adversely affected the tensile bond strength to dentin for the one-step systems, but not for the two-step system. Changes to the enamel surface after air-powder polishing were minimal, but an increase in surface roughness and complete removal of the smear layer were observed on dentin. SEM and TEM observations of the resin/dentin interface suggested that the air-powder polisher might cause superficial maceration of the collagen fibers on the dentin surface. This change may have decreased the ability of the etching/priming agents and bonding resin to penetrate into the dentin, which would have resulted in a poor quality hybrid layer. SIGNIFICANCE: For those systems that contain only an acidic primer for dentin conditioning, the use of air-powder polishing for surface preparation prior to restoration of dentin margin cavities is contraindicated because of the loss of reliable bonding.

Air Pressure↗

Influence of temperature and relative humidity on early bond strengths to dentine.

The effect of temperature and relative humidity (RH) on the early tensile bond strengths to bovine dentine of two bonding systems (Liner Bond System, and Scotchbond Multi-purpose), and an experimental system (KB-110) were tested. Two environmental conditions, room temperature (23 degrees C/50% RH) and oral temperature (30 degrees C/80% RH), were used in a controlled temperature and humidity chamber. Bond strengths were recorded immediately after, 10 min and 24 h following light curing. The tensile bond strengths did not vary between the two test conditions, but the mode of fracture was observed to change. The 30 degrees C/80% RH condition exhibited a slightly greater degree of adhesive type failures compared with the 23 degrees C/50% RH group. This was particularly so for the experimental system, indicating that different bonding systems may be more or less sensitive to changes in RH and temperature. Failures occurred partially or totally within the resin composite at the early test times, and it was concluded that the bond strengths of the systems tested tended to exceed the early cohesive strengths of the resin composite.

Adhesiveness↗

Spindle cell hemangioendothelioma: an immunohistochemical and flow cytometric study of six cases.

Six cases of spindle cell hemangioendothelioma (SCH) are presented with immunohistochemical and flow cytometric analyses. One case was associated with Maffucci's syndrome. All lesions were solitary or multifocal in the extremities, and prepresentation duration ranged from years to decades. One case recurred but none had metastases. Histologically, in four of the six cases the main lesions appeared to arise within vessels, predominantly muscular vessels. All lesions consisted of cavernous hemangioma-like areas and solid cellular areas resembling Kaposi's sarcoma. Cellular atypia was minimal. At the periphery of the lesions, a cluster of large thick or thin walled, and probably malformed, vessels were observed. Immunohistochemically, factor-VIII related antigen, CD34, vimentin, and lectin binding Ulex europaeus agglutinin 1 stained endothelial cells lining vascular channels, and vacuolated, or epithelioid cells. Spindle cells in the solid areas were negative for these endothelial markers except for vimentin, but showed divergent positive immunoreactions of HHF35, alpha-smooth muscle actin, desmin, and collagen type IV. Five cases were diploid and one was aneuploid. There was no significant correlation among DNA ploidy, S-phase fraction, and local recurrence in SCH although the number of cases examined was small. These results suggest SCH may be a benign lesion, probably a reactive process, rather than a low-grade angiosarcoma.

Adult↗

Prediction of histopathologic features and proliferative activity of uterine leiomyoma by magnetic resonance imaging prior to GnRH analogue therapy: correlation between T2-weighted images and effect of GnRH analogue.

To predict the histological features and proliferative activity of leiomyomas and to evaluate the effect of GnRH analogues (GnRHa) by MR images, the correlation between MR images and histopathologic findings was studied on 137 leiomyomatous nodules from 79 patients. The correlation among cellularity, proliferative activity and MR images was studied on sections of 42 leiomyomatous, nodules stained with hematoxylin-eosin and immunohistochemistry for proliferating cell nuclear antigen. The utility of MR imaging in assessing response to therapy with a GnRHa (buserelin 900 micrograms/day, intranasal for 16 weeks) was studied on 62 leiomyomatous nodules from 29 patients. On T2-weighted MR images, we encountered five major images. According to the increase of signal intensity relative to that of the myometrium and/or the endometrium, the images were classified as Type 1, Type 2, Type 3, Type 4, and Type 5. Histopathologically, the majority of Type 1, Type 2 and Type 3 images had features of typical leiomyoma. Almost all cellular leiomyomas and bizarre leiomyomas had Type 4 images. Variable degenerative features were observed in the nodules with Type 5 images. According to the increase of signal intensity, leiomyomas had a tendency to show a high degree of both cellularity and proliferative activity. Moreover, the reduction rate of leiomyomatous nodules after GnRHa therapy correlated with the tumor signal intensity on T2-weighted images before therapy. The reduction rate was the lowest in Type 1 images (20.9%) and the highest in Type 4 images (50.7%). These results suggest that increased the signal intensity on T2-weighted MR images correlates with the cellularity and proliferative activity of leiomyomas, and with tumor response to GnRHa treatment. MR imaging enables quantitative monitoring of GnRHa therapy in patients with leiomyomatous nodules, and allows us to predict the histopathology, cellularity, proliferative activity, and shrinkage rate of nodules before GnRHa treatment.

Adult↗

Structures of steroidal saponins from the tubers of Brodiaea californica and their inhibitory activity on tumor promoter-induced phospholipid metabolism.

Phytochemical examination of the fresh tubers of Brodiaea californica resulted in the isolation of four new steroidal saponins. Their structures were determined, by extensive spectral analysis including two-dimensional (2D) NMR spectroscopy and acid-catalyzed hydrolysis, to be (25S)-spirost-5-ene-1 beta,3 beta-diol [(25S)-ryscogenin] 1-O-[O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)- beta-D-glucopyranoside] (1), (25S)-ruscogenin 1-O-[O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)-O -[beta-D-xylopyranosyl-(1-->3)]-beta-D-glucopyranoside] (2), the C-20 and C-22 isomer of 2 (3) and the 6'-O-acetyl derivative of 2 (4), respectively. The conformations of the tetrasaccharide moiety of 2 and 4 were inspected through molecular mechanics and molecular dynamics calculation studies, showing that the acetyl group attached to C-6 of the inner glucose was near the C-21 methyl of the aglycon in the calculated preferred conformation of 4, which must cause the downfield shift of 21-Me by 0.07 ppm in comparing the 1H-NMR of 4 with that of 2. The inhibitory activity of the isolated saponins on 12-O-tetradecanoylphorbor-13-acetate (TPA)-stimulated 32P-incorporation into phospholipids of HeLa cells was evaluated to identify new antitumor-promoter compounds.

Anticarcinogenic Agents↗

Effect of pulpal pressure on adhesion of resin composite to dentin: bovine serum versus saline.

The purpose of this study was to compare the tensile bond strengths of resin composite to dentin, mediated by two new bonding systems (Scotchbond Multi-Purpose and Clearfil Liner Bond II), under simulated pulpal pressure when diluted bovine serum or saline was used as the pulpal fluid. The bond strengths of the two bonding systems to dentin (under a pulpal pressure of 15 cm of water) obtained when bovine serum was used were statistically significantly higher than those obtained when saline was used. These data suggest that the primers of these bonding systems decreased the dentinal permeability when the bovine serum pulpal fluid was used through the precipitation of serum proteins by the primers in the dentinal tubules. This may have allowed better penetration of the bonding resin monomers into the conditioned dentinal structure, thus improving the bond strength. These findings support the idea that topical application of dentinal bonding systems may be an effective therapy for treating hypersensitive dentin.

Animals↗

Failure of down-regulation of estrogen receptors and progesterone receptors after medroxyprogesterone acetate administration for endometrial hyperplasias.

BACKGROUND: To determine the biologic difference between normal endometrium and endometrial hyperplasias, the authors assessed the expression of estrogen receptors (ER) and progesterone receptors (PR) in the subjects before and after oral administration of medroxyprogesterone acetate (MPA) (Hysron-H, Kyowa Hakko Kogyo Co., Ltd., Tokyo, Japan). METHODS: The authors studied the expression of ER and PR in pathologic conditions of the endometrium such as cystic, adenomatous, and atypical hyperplasias before and after MPA treatment, 600 mg daily, for 8-14 weeks, and compared this expression with that of normal endometrium. RESULTS: Stromal and epithelial components of the normal endometrium in the proliferative phase were positive for ER and PR. In the secretory phase and after MPA treatment, the epithelial component showed either negative or faint staining for ER and PR, but the stromal component showed positive staining for PR and negative or faint staining for ER. All hyperplasias exhibited ER and PR in the stromal and epithelial components, although the intensity of the staining was variable in atypical hyperplasias. After MPA treatment, in the epithelial component of cystic and adenomatous hyperplasias, down-regulation of PR was prominent, but many cells continued to express ER. The epithelial component usually was surrounded by PR-positive decidual cells. In atypical hyperplasia, many cells continued to express ER and PR in the epithelial component surrounded by both ER and PR positive stromal cells after MPA treatment. CONCLUSIONS: Among the pathologic conditions of the endometrium, cystic and adenomatous hyperplasias have mechanisms of down-regulation of PR but not ER in the glandular component after MPA treatment, whereas in atypical hyperplasia, down-regulation of ER and PR does not occur in the epithelial component. Compared with normal endometrium, the majority of endometrial hyperplasias have an impairment of down-regulation of ER in the epithelial component by MPA treatment, and atypical hyperplasia has an impairment of down-regulation of ER and PR. Endometrial hyperplasias seem to have an abnormality of down-regulatory mechanisms of sex steroid receptors in the epithelial component when treated with exogenous progesterone.

Adult↗

Effect of tumor suppressors on cell cycle-regulatory genes: RB suppresses p34cdc2 expression and normal p53 suppresses cyclin A expression.

We show that expression of the p34cdc2 and cyclin A genes is induced by interleukin-2 in normal human T cells and present evidence to support the idea that these genes are deregulated in leukemic T cells. Our DNA sequencing data indicate that the promoter region of the p34cdc2 gene contains putative E2F-like binding sites which are recognized by Rb and binding sites for c-myb, Sp1, and ATF, and that the promoter region of the cyclin A gene contains binding sites for p53, Sp1, and ATF. In this study we focus on the effect of p53 and Rb on these cell cycle-regulatory genes. Cotransfection of Y79 human retinoblastoma cells with a p34cdc2 promoter-luciferase expression vector and a plasmid expressing the retinoblastoma gene (RB) indicated that RB suppresses p34cdc2 expression. Cotransfection of B104 rat neuroblastoma cells with a cyclin A promoter-luciferase expression vector and a plasmid expressing the normal or mutant p53 indicated that only the normal p53 suppresses cyclin A expression. In normal T cells, PHA stimulation reduces the amount of complexes in the p34cdc2 promoter between the E2F-like binding site and the RB gene product. These complexes were not detected in leukemic T cells. Our data support the idea that tumor suppressors modulate the expression of cell cycle-regulatory genes: RB regulates p34cdc2 expression and p53 regulates cyclin A expression.

Base Sequence↗

Immunohistochemical analysis of the peritoneum adjacent to endometriotic lesions using antibodies for Ber-EP4 antigen, estrogen receptors, and progesterone receptors: implication of peritoneal metaplasia in the pathogenesis of endometriosis.

This study was designed to investigate whether or not the pelvic peritoneum exhibits a metaplastic process into müllerian-type epithelium using a marker for epithelial differentiation (Ber-EP4 antigen) and markers that indicate müllerian differentiation (estrogen receptors and progesterone receptors). The peritoneum and/or ovarian surface epithelium adjacent to endometriotic lesions were obtained from 24 patients with endometriosis at operation, and peritoneum and ovarian surface epithelium without any lesions were also obtained from control patients without endometriosis. The specimens were immunohistochemically analyzed using antibodies for epithelial antigen Ber-EP4, estrogen receptor (ER), and progesterone receptor (PR) on frozen sections. Normal peritoneal mesothelium showed negative staining for Ber-EP4, ER, and PR. The mesothelium of the peritoneum adjacent to the endometriotic lesions showed focal positivity for Ber-EP4, ER, and PR. Several cases of ovarian surface epithelium from normal control ovaries and ovaries adjacent to endometriotic lesions also showed focal positivity for Ber-EP4, ER, and PR. Stromal cells accompanying these foci were sporadically positive for ER and/or PR but negative for Ber-EP4. Focal expression of Ber-EP4, ER, and PR in the mesothelium of the peritoneum and the ovarian surface epithelium adjacent to endometriotic lesions suggests that mesothelium possibly acquires characteristics of epithelial as well as müllerian-type nature. These results support an existence of a metaplastic process of the peritoneal mesothelium in the pathogenesis of endometriosis. The more frequent Ber-EP4 positivity in normal ovarian surface epithelium compared to normal peritoneal mesothelium also suggests a fundamental difference in these tissues that may be related to the greater prevalence of epithelial neoplasms arising in ovarian tissue.

Adult↗