Biomedical subjects

T Nikaido

Publications and source records attributed to T Nikaido.

At least 109 records · Page 6Linked to original sources

PubMed1997

Steroidal glycosides from the underground parts of Hosta plantaginea var. japonica and their cytostatic activity on leukaemia HL-60 cells.

A new C22-steroid glycoside was isolated from the underground parts of Hosta plantaginea var. japonica, together with a known furostanol saponin and three known spirostanol saponins. The structure of the new steroid glycoside was characterized by spectroscopic analysis and acid-catalysed hydrolysis as 2 alpha, 3 beta, 16 beta-trihydroxy-5 alpha-pregn-20(21)-ene-carboxylic acid gamma-lactone 3-O-¿O-beta-D-glucopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1--> 4)-beta-D-galactopyranoside¿. The isolated compounds were assayed for their cytostatic activity on leukaemia HL-60 cells. The spirostanol saponins showed cytostatic activity in a dose-dependent manner with the IC50 values ranging between 1 and 3 micrograms ml-1.

Antineoplastic Agents, Phytogenic↗

PubMed1997

Triterpenoid saponins from Mimusops elengi.

A novel minor triterpenoid saponin mimusin (3-O-[beta-D-glucopyranosyl- (1-->6)-beta-D-glucopyranosyl]-2 beta,3 beta,6 beta,23-tetrahydroxyolean- 12-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha- L- rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside was isolated from the seeds of Mimusops elengi, in addition to two known triterpenoid saponins, Mi-saponin A and 16 alpha-hydroxy Mi-saponin A. The structure of the minor saponin was established by comparing its 13C NMR and LS-MS linked-scan, ESI-MS data with FAB-MS of the mimusopsin isolated earlier from the same source.

Carbohydrate Conformation↗

PubMed1997

Vitamin D analogues up-regulate p21 and p27 during growth inhibition of pancreatic cancer cell lines.

To obtain information regarding the growth-inhibitory effect of 1,25-dihydroxyvitamin D3 and its non-calcaemic analogue 22-oxa-1,25-dihydroxyvitamin D3 on pancreatic cancer cell lines, differences in the effects of G1-phase cell cycle-regulating factors were studied in vitamin D-responsive and non-responsive cell lines. Levels of expression of cyclins (D1, E and A), cyclin-dependent kinases (2 and 4) and cyclin-dependent kinase inhibitors (p21 and p27) were analysed by Western blotting after treatment with these compounds. In the responsive cells (BxPC-3, Hs 700T and SUP-1), our observations were: (1) marked up-regulation of p21 and p27 after 24 h treatment with 10(-7) mol l(-1) 1,25-dihydroxyvitamin D3 and 22-oxa-1,25-dihydroxyvitamin D3; and (2) marked down-regulation of cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors after 7 days' treatment. In non-responsive cells (Hs 766T and Capan-1), no such changes were observed. In conclusion, vitamin D analogues up-regulate p21 and p27 as an early event, which in turn could block the G1/S transition and induce growth inhibition in responsive cells.

Antineoplastic Agents↗

PubMed1997

Solitary fibrous tumour of the renal peripelvis.

Solitary fibrous tumours (SFTs) are rare spindle cell neoplasms generally associated with the serosal surface, especially the pleura. This report describes two SFTs arising in the renal peripelvis, occurring in 33- and 36-year-old females. The lesions lacked the characteristic features of other recognized neoplasms that occur in the kidney. Immunohistochemically, the tumour cells were diffusely and strongly positive for vimentin and CD34, and some tumour cells expressed alpha-smooth muscle actin. Both tumours were diploid by flow cytometry. Both patients have had benign clinical courses with 7.5- and 1-year follow-up. The findings suggest that the SFTs may originate from peripelvic mesenchymal cells, a new location for SFT. SFT should be included in the differential diagnosis of spindle cell tumours arising in the renal pelvis and peripelvis.

Adult↗

PubMed1997

Distribution and heterogeneity of mast cells in the human uterus.

Mast cells (MCs) are widely distributed in most human tissues. Those cells that contain only tryptase are designated as T-MCs, while those that also contain chymase are referred to as TC-MCs. This study uses immunohistochemical staining for tryptase and chymase to assess the distribution and heterogeneity of these two types of MCs in the human uterus. The greatest number of MCs was found in the inner (i.e. luminal) half of the myometrium, with this area containing approximately equal proportions of T-MCs and TC-MCs. There were fewer MCs in the outer half of the myometrium and the cervix, but the proportion of TC-MCs in both of these areas was substantially higher. In contrast, the endometrium contained significantly fewer MCs, but proportionally more T-MCs. There was no change in the number of MCs between the proliferative and secretory phases of the menstrual cycle; however, there was a significantly lower number in all areas after menopause. Most of the MCs were observed in close association with uterine smooth muscle cells, as well as in the vicinity of fibroblasts and collagen, and it appears they may play an important role in the reconstruction of uterine tissues during the menstrual cycle.

Cell Count↗

PubMed1997

Effects of a GnRH analogue on human smooth muscle cells cultured from normal myometrial and from uterine leiomyomal tissues.

Leiomyomas are tumours of uterine smooth muscle tissue that are oestrogen and progesterone dependent. When explants of these tumours were grown in culture, the proliferating tissue formed characteristic ball-like aggregates (BLA), rather than the usual hill and valley (HV) pattern of growth of normal myometrial tissue in culture. Immunocytochemical staining with fluorescein isothiocyanate (FITC)-labelled gonadotrophin-releasing hormone (GnRH) revealed that both myometrial and leiomyomal cells have membrane receptors for this hypothalamic releasing hormone. Furthermore, polymerase chain reactions (PCR) with primer sets that were specific for GnRH receptor mRNA, as well as GnRH mRNA, showed that transcripts for both of these nucleic acids are present in myometrial and leiomyomal tissues. The treatment of cultured explants of leiomyomal tissue with a GnRH analogue (buserelin, HOE766) diminished the formation of BLA, but this synthetic hormone had only a moderate effect on the HV topography of normal myometrial tissue. A colorimetric assay indicated that GnRHa inhibited cell proliferation in leiomyomal tissue in a dose-dependent manner. Western blotting, to detect the expression of G1 phase cell cycle-related gene products, showed that cyclin E and p33cdk2 formation in leiomyomas were inhibited by high concentrations of GnRHa. In conclusion, GnRHa might suppress leiomyomal growth by interfering with the expression of cell cycle factors.

Base Sequence↗

PubMed1997

Analysis of stem cell factor for mast cell proliferation in the human myometrium.

The proliferation and differentiation of human mast cells (MCs) occur under the influence of the mitogenic agent known as stem cell factor (SCF). This study analyses the distribution of SCF and SCF receptor in human myometrial tissue to further the understanding of the role(s) of MCs in the uterus. Immunohistochemical staining revealed that the majority of uterine MCs are located in close proximity to myometrial smooth muscle cells, and also among fibroblast-like spindle shaped cells. RNA extracts from myometrial tissues were subjected to reverse transcription. The resulting cDNA population was amplified by polymerase chain reaction (PCR) using a pair of 20-mer primers that were specific for SCF cDNA. Electrophoresis of the PCR products showed that the myometrial tissues contained transcripts for SCF. In-situ reverse transcription-PCR also revealed the expression of the transcripts for SCF in myometrial smooth muscle cells. Furthermore, enzyme-linked immunosorbent assays confirmed that the cultured myometrial cells produced SCF. Since immunohistochemical staining indicated there are SCF receptors on the surface of myometrial MCs, the results suggest that MC proliferation and differentiation in the myometrium is regulated by SCF secretion from the uterine smooth muscle cells. The mature MCs might, in turn, secrete mediators that influence tissue remodelling during the human menstrual cycle.

Base Sequence↗

PubMed1997

Minimal deviation adenocarcinoma of the uterine cervix has abnormal expression of sex steroid receptors, CA125, and gastric mucin.

To provide clues to the histological differentiation between minimal deviation adenocarcinoma (MDA) of the uterine cervix and normal cervical glands, we analyze the histochemical expression of ovarian steroid receptors [estrogen receptor (ER) and progesterone receptor (PR)], mucosubstances such as gastric mucin, CA125, and carcinoembryonic antigen (CEA) in normal cervical glands (10 cases) and MDA (seven cases). Mucin histochemistry showed that gastric mucin was focally demonstrated in all the cases of MDA but in none of the normal cervical glands. ER and PR were not expressed in MDA, whereas both receptors were invariably expressed in normal cervices. Expression of CA125 was significantly decreased in MDA, but was diffusely positive in normal endocervical glands. CEA was focally positive in all cases of MDA, but it was consistently negative in normal cervical glands. These results suggest that MDA lacks expression of the characteristic müllerian-type substances such as ER, PR, and CA125, and that a proportion of its cells contain gastric epithelial substances, comprising gastric mucin and CEA. In conclusion, loss of the expression of ER and PR, decreased expression of CA125, and staining for gastric mucin and CEA could be used for histologic discrimination of MDA from benign cervical glands.

Adenocarcinoma↗

PubMed1997

Immunohistochemical detection of cyclin A with reference to p53 expression in endometrial endometrioid carcinomas.

Cyclins are essential proteins in cell cycle control, and their deranged expression has been reported to be associated with malignant transformation. Involvement of cyclins in the development of endometrioid carcinomas of the endometrium was studied immunohistochemically using antibodies against both cyclin A and tumor suppressor gene product p53, and their expression was compared with that of Ki-67 antigen. Sixty-two cases of endometrial endometrioid carcinoma and 20 cases of normal endometrium (10 proliferative and 10 secretory phase) were examined. Of the 62 endometrioid carcinomas, atrophic endometrium and hyperplasia were found adjacent to the cancers in 30 and 19 cases respectively. Cyclin A was expressed in < 1% of the glandular cells of normal endometrium in the proliferative phase and in hyperplasia, but was negligible in normal secretory phase and atrophic endometrium. p53 was almost always negative in normal endometrium and hyperplasia. Of the 62 endometrioid carcinomas, 12 tumors (19.4%) overexpressed cyclin A and 21 tumors (33.8%) overexpressed p53 (positive cells > 1%). Cyclin A and p53 were more frequently expressed in poorly differentiated tumors than in well differentiated tumors (cyclin A, p = 0.002; p53, p = 0.016). In addition, cyclin A-positive cells were topographically related to those cells positive for p53 as well as Ki-67. In conclusion, the abnormal expression of cyclin A and p53 is associated with high-grade endometrial endometrioid carcinomas.

Adult↗

PubMed1997

New polyhydroxylated steroidal saponins from the tubers of Brodiaea californica.

New polyhydroxylated steroidal saponins (1, 2) were isolated from the tubers of Brodiaea californica. The structures were determined by spectroscopic analysis and acid-catalyzed hydrolysis. The bisdesmosidic saponin (2) is unique in structure, and is the first representative of a steroidal saponin bearing 6-deoxy-D-gulopyranose among both the steroidal and triterpene saponins reported up to the present.

Chromatography, High Pressure Liquid↗

PubMed1997

Shear bond strengths of a single-step bonding system to enamel and dentin.

An experimental primer was developed as a single-step bonding system for resin-modified glass ionomer cements (GIC). Efficacy of this primer on adhesion of resin-modified GICs and resin composite to enamel and dentin was evaluated by shear bond test and SEM observation. Good bond strengths to enamel were obtained (> 11 MPa), whereas significantly low bond strengths to dentin were obtained using a single coat of the primer. However, double-coating improved the bond strengths to dentin (> 8 MPa). SEM observations indicated that the primer functioned as a mild conditioner to remove the smear layer on enamel or dentin surfaces. A hybrid layer was observed at the cross-sectional view of the GIC/dentin interface. These findings suggested that good adhesion to enamel and dentin could be achieved using a single-step bonding system.

Bisphenol A-Glycidyl Methacrylate↗

PubMed1997

Extrapleural solitary fibrous tumor: a report of seven cases.

Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms generally associated with the serosal surface, especially the pleura. Histopathologic, immunohistochemical, ultrastructural, and flow cytometric analyses were performed on seven SFTs of extrapleural sites (two retroperitoneal, two soft tissue, one each peritoneal, nasal cavity, and orbit). Five patients were women, and two were men, aged from 21 to 68 years (average, 39 yr). All of the lesions presented as well-circumscribed masses. The lesions ranged in size from 2 to 20 cm in greatest diameter. Histologically, these lesions were entirely comparable to the pleural SFTs and lacked the characteristic features of other recognized neoplasms that occur in these regions. One tumor contained pleomorphic and round-cell sarcomatous foci. Immunohistochemically, all of the tumors were strongly positive for vimentin and CD34. Six of the seven tumors showed varying numbers of spindle cells positive for alpha smooth muscle actin, HHF35, neuron-specific enolase, Leu 7, or glial fibrillary acidic protein. Ultrastructural examinations of three tumors showed that they were composed of primitive mesenchymal or fibroblast-like cells. Six tumors examined were diploid by flow cytometric examination. Clinical follow-up in six patients ranged from 1 to 7.5 years (average, 2.6 yr) and showed that five patients remained well with no evidence of disease after excision and that the patient with the sarcomatous elements died of recurrence 2.5 years after surgical treatment. These findings suggest that SFTs represent ubiquitous neoplasms of fibroblasts or primitive mesenchymal cells with aggressive potential.

Adult↗

PubMed1996

ATF site of human RB gene promoter is a responsive element of myogenic differentiation.

RB mRNA increases during terminal differentiation of C2 myoblasts. We demonstrate that RB promoter activity increases about 4-fold during differentiation. The increase of RB promoter activity was reduced when a point mutation was designed in the ATF site. In a gel shift assay of the ATF site, two specific bands were observed. One of them, with the lower mobility, disappeared during differentiation. This band reacted with an antibody against ATF-1. We cotransfected an RB promoter-luciferase plasmid with the TREB36/ATF-1 plasmid. ATF-l suppressed the activity of the wild-type RB promoter but not of that with a point mutation at the ATF site. These results suggest that the ATF site of the RB promoter is a responsive element during myogenic differentiation of C2 cells. We hypothesize that RB promoter activity is stimulated partially due to the dissociation of ATF-1, which suppresses the promoter activity through the ATF site in C2 myoblasts.

Activating Transcription Factor 1↗

PubMed1996

Coabnormal expression of cyclin D1 and p53 protein in human uterine endometrial carcinomas.

BACKGROUND: In the normal cell cycle, tumor suppressor gene products (p53) and cyclin (cyclin D1) cooperate. Abnormalities in the cooperation of these factors may result in malignant transformation of the cell. Mutant p53 protein overexpression is defined in many human cancers, including endometrial carcinoma. This study investigated the role of cyclin D1 in the development of human uterine endometrial carcinoma. METHODS: Seventy-four patients whose pathology slides contained either normal or hyperplastic endometrium adjacent to endometrial carcinoma were studied. Immunohistochemical staining of the serial paraffin sections was performed using antibodies to p53 and cyclin D1. RESULTS: The expression of cyclin D1 was restricted to only a few cells of normal and hyperplastic endometrium, whereas it was preferentially expressed in 40% (30/74) of endometrial carcinomas. The cells that overexpressed cyclin D1 also overexpressed p53. Moreover, all 30 cases with varied distributions of cyclin D1-positive cells corresponded identically with the distribution of p53-positive cells. Diffuse positivity for cyclin D1 was specifically observed in clinically advanced stages of pathologic G2 and G3 tumors. CONCLUSIONS: The data suggest that coabnormal expression of cyclin D1 and p53 protein may contribute to the development of endometrial carcinoma and may also be involved in the progression to malignancy.

Adult↗

PubMed1996

Stepwise abnormality of sex steroid hormone receptors, tumor suppressor gene products (p53 and Rb), and cyclin E in uterine endometrioid carcinoma.

BACKGROUND: In the normal cell cycle, the appropriate interaction of factors such as tumor suppressor gene products (retinoblastoma susceptibility [Rb], p53) and cyclins is essential. Abnormalities in the interaction of these factors may result in malignant transformation of the cell. Malignant transformation of the endometrium, which is believed to be a sex steroid-dependent tumor, probably involves a process of uncoupling of these factors and sex steroid hormone receptors. This study is designed to test this hypothesis. METHODS: Fifty-six patients whose pathology slides contained either normal or hyperplastic endometrium adjacent to endometrial carcinoma were selected. Immunohistochemical staining of serial paraffin sections was performed using antibodies to estrogen receptors (ER) and progesterone receptors (PR), p53, and Rb, as well as cyclin E. RESULTS: The normal and hyperplastic endometria adjacent to carcinoma showed positive staining for ER and PR and negative staining for p53. Of 56 carcinomas, 39 (69.6%) showed homogeneous positive staining for ER and PR and negative staining for p53, whereas the remaining 17 carcinomas (30.4%) contained varied distributions of ER- and PR-negative cells, and p53-positive cells (6 were negative or focally positive for ER/PR and diffusely-positive for p53, 4 were regionally-positive for ER/PR and regionally-positive for p53, and 7 were diffusely positive for ER/PR and focally-positive for p53). The p53-positive cells corresponded to those that stained negatively for ER/PR: This topographic inverse relationship between ER/PR expression and p53 expression also correlated with the staining intensities. Furthermore, the cells with weak or negative staining for p53 had a tendency to stain positively for Rb and weakly positive for cyclin E, whereas the cancer cells with definite positivity for p53 tended to stain either weakly or negatively for Rb and definitely positive for cyclin E. The cells showing diffusely positive for p53 were present significantly in clinical Stage III and pathologic Grade G3. CONCLUSIONS: In the development of endometrial carcinoma, stepwise abnormalities of sex steroid receptors, tumor suppressor gene products, and cyclins apparently exist, and may correlate with the progression of the malignant process.

Adult↗

PubMed1996

Steroidal saponins from Nolina recurvata stems and their inhibitory activity on cyclic AMP phosphodiesterase.

Seven steroidal saponins were isolated from the stems of Nolina recurvata, five of which appeared to be new compounds and were assigned as spirosta-5,25(27)-diene-1 beta,3 beta-diol (neoruscogenin) 1-O--O-alpha-L-rhamnopyranosyl-(1--> 2)-O-[beta-D-xylopyranosyl-(1-->3)]-alpha-L-arabinopyranoside-, (25S)-spirost-5-ene-1 beta,3 beta-diol [(25S)-ruscogenin] 1-O-{O-alpha-L-rhamnopyranosyl-(1-->2)-O-[beta-D-xylopyranosyl-(1--> 3)]-alpha-L-arabinopyranoside}, neoruscogenin 1-O-{O-alpha-L-rhamnopyranosyl-(1-->2)-O-[beta-D-xylopyranosyl-(1--> 3)]-beta-D-fucopyranoside}, 26-O-beta-D-glucopyranosyl-22-O-methylfurosta-5,25(27)-diene-1 beta,3 beta,22 xi,26-tetrol 1-O--O-alpha-L-rhamnopyranosyl-(1--> 2)-O-[beta-D-xylopyranosyl-(1-->3)]-alpha-L-arabinopyranoside- and 26-O-beta-D-glucopyranosylfurosta-5,20(22),25(27)-triene-1 beta,3 beta,26-triol 1-O-{O-alpha-L-rhamnopyranosyl-(1--> 2)-alpha-L-arabinopyranoside}. The isolated saponins were evaluated for their inhibitory activity on cyclic AMP phosphodiesterase to identify new compounds with medicinal potential.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1996

Inhibitory effect of 220-oxa-1,25-dihydroxyvitamin D3 on the proliferation of pancreatic cancer cell lines.

BACKGROUND & AIMS: Effective chemotherapy for pancreatic cancer is urgently needed. The aim of this study was to compare the anti-proliferative activity of a new vitamin D3 analogue, 22-oxa-1,25-dihydroxyvitamin D3 (22-oxa-calcitriol), on pancreatic cancer cells lines with that of 1,25-dihydroxyvitamin D3 (calcitriol) with analysis of vitamin D receptor status. METHODS: Antiproliferative effects of both agents were compared using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method and by measuring the tumor size of xenograft inoculated into athymic mice. Vitamin D receptor contents by Scatchard analysis and mutational analysis of receptor complementary DNA were performed. RESULTS: In vitro, 22-oxa-calcitriol and calcitriol markedly inhibited the proliferation (3 of 9 cell lines) and caused a G1 phase cell cycle arrest by appearance of numerous domes. In vivo, 22-oxa-calcitriol inhibited the growth of BxPC-3 xenografts more significantly than calcitriol without including hypercalcemia. Hs 766T, showing no response to either agent, had the second highest receptor contents with no abnormalities in its primary structure deduced by receptor complementary DNA. CONCLUSIONS: 22-oxa-calcitriol may provide a more useful tool for the chemotherapy of pancreatic cancer than calcitriol. Also, the susceptibility of the cell lines to both agents is not well determined by evaluating either the contents or the mutation of vitamin D receptor.

Animals↗

PubMed1996

Relationship between the expression of cyclins/cyclin-dependent kinases and sex-steroid receptors/Ki67 in normal human endometrial glands and stroma during the menstrual cycle.

Cell cycle regulatory molecules were analysed in normal human endometrial tissue using antibodies against cyclins D1, E, A, and B1 and cyclin-dependent kinases (CDKs) cdk4, cdk2, and cdc2. The expression of these regulatory molecules in gland cells and stromal cells was compared with the expression of oestrogen receptors (ER), progesterone receptors (PR), and Ki67 (a growth-related molecule). In general, a substantially higher percentage of the gland cells stained positive for cyclins and CDKs during the proliferative phase of the menstrual cycle. Cyclin E, cdk2 and/or cdk4 were especially apparent in the cytoplasm of most of the gland cells as well as in the stromal cells. In contrast, most of the regulatory molecules were undetectable in the gland cells by the end of the secretory phase of the cycle, but they did not decline in the stromal cells. The data also revealed that ER, PR, and Ki67 in both gland cells and stromal cells follow the same basic pattern of expression as the cyclins and CDKs. These results suggest that cyclins and CDKs are functionally involved in the rhythmic proliferation of normal human endometrial tissue, and the action of these agents may be related to the endometrial levels of sex steroids and Ki67.

Cyclin-Dependent Kinases↗