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Y Yokoyama

Publications and source records attributed to Y Yokoyama.

At least 19 recordsLinked to original sources
PubMed1998

PMA-induced reduction in invasiveness is associated with hyperphosphorylation of MARCKS and talin in invasive bladder cancer cells.

Protein kinase C (PKC) plays a critical role in signal transduction for a variety of cell activation processes. Enhanced PKC activity is often found in cancer cells that show marked invasive and/or metastatic potential. Thus, a specific PKC inhibitor may serve as a tool to reduce invasive or metastatic potential of cancer cells. We show here that phorbol 12-myristate 13-acetate (PMA), a PKC activator, also reduces invasiveness of EJ invasive transitional carcinoma cells. PMA-induced reduction in invasiveness was parallel with inhibition of cell motility. PMA neither induced E-cadherin expression nor augmented cell-matrix adhesion of EJ cells. PMA caused retraction of microspikes from the rim of the cells and consequently rounding of the cellular rim, and the disappearance of microfilaments from the cytoplasm. PMA at 10(-7) M, at which concentration the motility of EJ cells was completely inhibited, down-regulated PKC activity over 5 hr after transient translocation of PKC activity to the membrane fraction. At the same time, PMA induced hyperphosphorylation of MARCKS and talin. During the process of cell movement, actin-binding proteins are in a cycle of phosphorylation and dephosphorylation. Once this cycle is interrupted, cells can no longer maintain the dynamics of cytoskeletal structure. We suggest that retention of the hyperphosphorylated state of MARCKS and talin is responsible for the mechanism(s) by which PMA produces inhibitory activity against invasiveness of EJ cells.

Actins↗
PubMed1998

Dihydroheptaprenyl and dihydrodecaprenyl monophosphates induce apoptosis mediated by activation of caspase-3-like protease.

Dolichyl phosphate, an essential carrier lipid in the biosynthesis of N-linked glycoprotein, has been found to induce apoptosis in rat glioma C6 cells and human monoblastic leukemia U937 cells. In the present study, dolichyl phosphate and structurally related compounds were examined regarding their apoptosis-inducing activities in U937 cells. Dihydroheptaprenyl and dihydrodecaprenyl phosphates, of which isoprene units are shorter than that of dolichyl phosphate, induced apoptosis in U937 cells. This phenomenon occurred in a dose- and time-dependent manner, as seen with dolichyl phosphate-induced apoptosis. Derivatives of the same isoprene units of dolichyl phosphate, such as dolichol, dolichal or dolichoic acid, did not induce DNA fragmentation. Farnesyl phosphate and geranylgeranyl phosphate also failed to induce apoptosis. During apoptosis, the caspase family of cysteine proteases play important roles. We observed that apoptosis induced by dihydroprenyl phosphate was mediated by caspase-3-like (CPP32-like) activation but not by caspase-1-like (ICE-like) activation. This caspase-3-like activation was inhibited by a specific inhibitor of caspase-3, DEVD-CHO, but not by an caspase-1 inhibitor YVAD-CHO. We interpret these results to mean that dihydroprenyl phosphates with more than seven isoprene units have apoptosis-inducing activity and that their signal is mediated by caspase-3-like activation.

Apoptosis↗
PubMed1998

DNA cleavage and 8-hydroxydeoxyguanosine formation caused by tamoxifen derivatives in vitro.

DNA damage caused by tamoxifen and its derivatives was examined by estimating the conversion of supercoiled pUC18 plasmid DNA to linear form by means of agarose gel electrophoresis. N-Desmethyltamoxifen induced DNA cleavage and its effect was enhanced by the addition of reducing agents such as dithiothreitol, NADPH and 2-mercaptoethanol. 4-Hydroxytamoxifen itself had little effect, but the cleavage was slightly enhanced by the addition of reducing agents. DNA damage was higher with alpha-hydroxytoremifene than with alpha-hydroxytamoxifen, which had a prominent effect only at high concentration. The cleavage by alpha-hydroxy derivatives were not enhanced by reducing agents. No damage was induced by tamoxifen, toremifene, 3-hydroxytamoxifen or N-desmethyltoremifene. The DNA cleavage by N-desmethyltamoxifen was inhibited by the addition of EDTA, mannitol, sodium azide, methionine, catalase and superoxide dismutase. The formation of 8-hydroxy-2'-deoxyguanosine was also examined with calf thymus DNA in vitro. A slight increase of its level was found with 4-hydroxytamoxifen in the presence of dithiothreitol and also with N-desmethyltamoxifen in the presence of NADPH, but alpha-hydroxytoremifene and alpha-hydroxytamoxifen were ineffective. These experimental data suggest that among metabolites of tamoxifen, N-desmethyltamoxifen and probably also 4-hydroxytamoxifen cause oxidative DNA damage in which redox cycling is involved. The DNA damage by alpha-hydroxytoremifene appears to involve a different mechanism from that by N-desmethyltamoxifen. Tamoxifen and toremifene are possibly metabolized to the forms contributing to DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

Telomerase activity in the female reproductive tract and neoplasms.

OBJECTIVE: To study a possible utility of telomerase determination for cancer diagnosis. METHODS: In a total of 227 tissue samples comprising 114 normal tissues of the reproductive age, 10 fallopian tubes of the postmenopausal age, and 103 neoplastic tissues from female reproductive tracts, telomerase activity was determined. Using densitometrical analysis, telomerase activity was compared between carcinoma tissues and normal counterparts. RESULTS: A total of 97.3% (71/73) of cancer samples comprising ovarian carcinoma, endometrial carcinoma, and epidermoid carcinoma of the cervix and 89.5% (77/86) of the epithelia of the reproductive-aged uterus and fallopian tube showed telomerase activity. The epithelia of the fallopian tube of reproductive age showed significantly higher frequency of positivity (16/18) than the postmenopausal epithelia of the tube (3/10). No difference in telomerase activity was found between endometrial carcinomas and normal proliferative endometria. A significantly higher activity was found in ovarian epithelial carcinoma and epidermoid carcinoma of the cervix than in normal counterparts, although 92% (11/12) of the normal exocervix and 30% (3/10) of the normal ovary showed telomerase activity. CONCLUSIONS: Most epithelia of the female reproductive tract maintain telomerase activity during the reproductive age. Therefore, the detection of malignancies by telomerase determination may be feasible in ovarian carcinoma and epidermoid carcinoma of the cervix, but requires accurate quantification of telomerase activity.

Adult↗
PubMed1998

Value of glutathione S-transferase pi and the oncogene products c-Jun, c-Fos, c-H-Ras, and c-Myc as a prognostic indicator in endometrial carcinomas.

OBJECTIVE: To examine the relationship between the expressions of glutathione S-transferase pi (GST-pi) and four oncogene products, c-Jun, c-Fos, c-H-Ras, and c-Myc, and clinicopathological prognostic factors and patients' prognosis in endometrial carcinomas, and to assess their prognostic value in endometrial carcinomas. METHODS: Specimens of endometrial carcinoma obtained from 63 patients were investigated immunohistochemically using respective specific antibodies. RESULTS: The overall positive rates in 63 carcinoma specimens were 34.9% for GST-pi, 44.4% for c-Jun, 34.9% for c-Fos, 47.6% for c-H-Ras, and 54.0% for c-Myc. Multivariate analysis revealed that GST-pi expression correlated independently with paraaortic lymph node (PAN) metastasis, and c-Jun expression was independently related to pelvic lymph node (PLN) and PAN metastasis. The prognosis of patients with a GST-pi-positive tumor was significantly poorer than that of those with a GST-pi-negative tumor (P < 0.05). The patients with c-Jun-positive tumor also had a significantly worse prognosis than those with c-Jun-negative tumor (P < 0.05). No significant relationship between the expressions of the remaining three oncogene products, c-Fos, c-H-Ras, and c-Myc, and the examined prognostic factors and clinical outcome was apparent. CONCLUSION: These results suggest that the expressions of GST-pi and c-Jun may reflect the metastatic potential of endometrial carcinomas and that their expressions of endometrial carcinoma may be useful as a prognostic indicator for predictive testing.

Adenocarcinoma↗
PubMed1998

Lymphoma arising in mucosa-associated lymphoid tissue of the duodenal bulb.

We report a case of low-grade B-cell lymphoma of the duodenal bulb arising from mucosa-associated lymphoid tissue. A barium swallow and an endoscopic examination showed multiple elevated, irregularly contoured lesions limited to the duodenal bulb. Endoscopic biopsy specimens were highly suggestive of non-Hodgkin's lymphoma. The resected specimen showed a gyriform mucosal elevation measuring 3 x 2cm in extent, with multiple small polypoid elevations scattered around it. Histologically, the small lymphocytes constituting the tumor infiltrated the duodenal mucosa and submucosa. The neoplastic centrocyte-like cells tended to grow around reactive lymphoid follicles and to invade epithelial structures, forming characteristic lymphoepithelial lesions. Monoclonal proliferation of the lymphoid tissue was demonstrated by the polymerase chain reaction method. The histologic appearance and the demonstration of monoclonality fulfilled the criteria for malignant lymphoma arising from mucosa-associated lymphoid tissue, which is extremely rare in the duodenum.

Duodenal Neoplasms↗
PubMed1998

Telomerase activity in the human endometrium throughout the menstrual cycle.

In a total of 41 endometrial tissue samples, the relationship between telomerase activity and proliferating cell nuclear antigen (PCNA) labelling index was studied. In samples of endometrium from the proliferative phase of the menstrual cycle, telomerase activity was found in 15 out of 17 cases (88%). Two samples from the early proliferative phase showed negative telomerase activity and a low PCNA labelling index. However, three out of 16 samples of early secretory phase endometrium showed telomerase activity and a PCNA labelling index. In mid- to late secretory phase endometrium, in menopausal endometrium and in decidualized endometrium induced by progesterone neither telomerase activity nor PCNA labelling was found. These results suggest that telomerase activity of the endometrium may be correlated with the proliferative potential of the epithelial cells and that its activity may be regulated by oestrogen.

Adult↗
PubMed1998

A case of concurrent uterine cervical adenocarcinoma and renal-cell carcinoma, and subsequent vaginal metastasis from the renal-cell carcinoma.

We report a case of concurrent uterine cervical adenocarcinoma and renal-cell carcinoma and a subsequent vaginal metastasis from the renal-cell carcinoma. The renal-cell carcinoma, which was located in the upper pole of the right kidney, was detected incidentally by preoperative CT scanning. We simultaneously performed in a timely manner radical hysterectomy, pelvic and paraaortic lymphadenectomies, and a right nephrectomy. Subsequently, however, the patient suffered from vaginal metastasis arising from the renal-cell carcinoma. As a result of this case, we emphasize the importance of making a thorough preoperative assessment prior to performance any definitive surgery for a gynecologic malignancy.

Adenocarcinoma↗
PubMed1998

[High-resolution CT findings in cytomegalovirus pneumonitis after bone marrow transplantation].

In order to explore the high-resolution CT (HRCT) findings of cytomegalovirus (CMV) pneumonitis after bone marrow transplantation, we retrospectively reviewed the HRCT findings in nine patients with CMV pneumonitis cytologically proven by bronchoalveolar lavege. In 67% of cases, HRCT showed ground-glass attenuation. Consolidation and bronchial wall thickening were demonstrated in 33%, pleural effusion in 22%, and micro centrilobular nodules, bronchiectasis, and reticulation in 11%, respectively. Lymphadenopathy and masses were not seen. The areas of ground-glass attenuation were distributed bilaterally in all cases, diffusely in 67%, centrilobularly in 50%, and panlobularly in 50%. Subpleural lung regions were spared in 83%. The areas of consolidation were bilateral in 67%, nonsegmental in 67%, and involved the lower lobe in all cases. A total of 25 follow-up HRCT were performed in six patients. Small centrilobular ground-glass opacities disappeared after treatment in one patient. Micro centrilobular nodules vanished after treatment in one patient. Small centrilobular ground-glass opacities developed into consolidation and resolved after treatment in one patient. In one patient, diffuse ground-glass opacities progressed to consolidation, and the patient died due to respiratory failure. No abnormal findings were observed in two patients. It may be considered that in the early phase of CMV pneumonitis HRCT shows small or micro centrilobular ground-glass opacities and nodules and that in the advanced phase these lesions progress to dense alveolar opacities as CMV infection advances, although a variety of HRCT appearances is observed in the course of CMV pneumonitis.

Adult↗
PubMed1997

A possible immunosuppressant, cycloprodigiosin hydrochloride, obtained from Pseudoalteromonas denitrificans.

Cycloprodigiosin hydrochloride (cPrG.HCl), a member of the prodigiosin family, is a red pigment obtained from the marine bacterium Pseudoalteromonas denitrificans. cPrG.HCl markedly suppressed 3H-thymidine incorporation by concanavalin A stimulated murine splenocytes but had little effect on lipopolysaccharide dependent 3H-thymidine incorporation, indicating that cPrG.HCl acts as a selective inhibitor of T cell proliferation in the same way as other members of the prodigiosin family. cPrG.HCl inhibited the proliferation of the PMA stimulated Jurkat cells through an apoptotic process. Intriguingly, cPrG.HCl inhibited the H+ translocation by vacuolar type ATPase in chromaffin granule membranes without any effect on either its ATPase activity nor on the membrane conductance of phospholipid bilayers, suggesting that cPrG.HCl selectively uncouples H+ translocation from the ATPase reaction rather than acting as a non-specific ionophore. Since crystalline cPrG.HCl is highly stable, it raises the possibility of its therapeutic use as an immunosuppressant.

Animals↗
PubMed1997

Evidence for active acetylcholine metabolism in human amniotic epithelial cells: applicable to intracerebral allografting for neurologic disease.

Human amniotic epithelial (HAE) cells have been used for allotransplantation in patients with lysosomal storage disease due to lack of expression of HLA antigens. Previously, we have reported the expression of differentiation markers for both neural stem cells, and neuron and glial cells. In the present study, we investigated the presence of choline acetyltransferase (ChAT) and acetylcholine (ACh) in HAE cells using different experimental approaches. Cultured HAE cells showed strong immunoreactivity against ChAT antibody. ChAT activity in primary cells was 24.9 +/- 8.5 pmol/mg protein/h. Using HPLC with electrochemical detection, ACh was detected in both cell incubation media and cell pellets indicating that these cells synthesize and release ACh in a time-dependent manner. Additional confirmation of this hypothesis was gained from the data obtained from RT-PCR and Western blot analyses which revealed the expression of ChAT mRNA and ChAT protein, respectively, in HAE cells. Results of the present study suggest that HAE cells can possibly be applied for intracerebral allografting to treat neurologic diseases in which cholinergic neurons are damaged.

Acetylcholine↗
PubMed1997

CPP32 activation during dolichyl phosphate-induced apoptosis in U937 leukemia cells.

Treatment of U937 cells with dolichyl phosphate led to an increase in the activity of the ICE family protease CPP32, accompanied with cleavage of pre-CPP32 to generate p17. Peptide inhibitors YVAD-cmk and Z-Asp-CH2-DCB (specific to ICE) and DEVD-CHO (specific to CPP32) blocked the dolichyl phosphate-induced apoptosis. The dolichyl phosphate-induced increase of CPP32 activity was inhibited by adenylate cyclase inhibitors, SQ 22536 and 2',5'-dideoxyadenosine. Dolichyl phosphate caused a transient increase of intracellular cAMP concentration. The results suggest that modulation of cAMP synthesis due to the stimulation of adenylate cyclase by dolichyl phosphate plays a critical role in CPP32 activation and apoptosis.

Adenine↗
PubMed1997

Introduction of p21(Waf1/Cip1) gene into a carcinoma cell line of the uterine cervix with inactivated p53.

In carcinomas of the uterine cervix of which p53 is frequently inactivated by papilloma viruses, gene transfer of p21, effector of p53, is an alternative tool to suppress cell growth. We introduced the p21 gene into HeLa cells. The transfectant with p21 showed a significant growth retardation by blockage of G1 to S transfer of the cell cycle. This cell line showed significantly reduced anchorage-independent growth as well as attenuated telomerase activity. These data suggest that gene transfer of p21 is an effective tool to lead carcinoma cells with inactivated p53 into less malignant phenotype.

Cell Division↗
PubMed1997

Erythrocyte magnesium and prostaglandin dynamics in chronic sleep deprivation.

BACKGROUND AND HYPOTHESIS: The mechanism of sudden cardiac death occurring in patients with chronic fatigue is controversial. This study was designed to define a hypothesis that coronary arterial spasm and thrombus formation can occur during chronic fatigue. METHODS: For evaluating the feasibility of coronary arterial spasm, erythrocyte magnesium (Mg) was measured. Blood coagulability was evaluated by the change of prostaglandin concentration. Subjects included 16 healthy male volunteers (mean age 21.6 +/- 2.5 years). Test conditions were as follows: (A) control state: a day following a night of good sleep; (B) temporary sleep deprivation: a day preceded by < 3 h of sleep; (C) chronic sleep deprivation: a day preceded by a month during which sleep lasted < 60% of that in condition (A) above. The erythrocyte Mg concentration was measured by the atomic absorption method. The plasma concentration of thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured in eight subjects by radioimmunoassay method. RESULTS: (1) Mean erythrocyte Mg concentration was significantly less in chronic sleep deprivation (1.1 +/- 0.4 mg/dl) than in the control state (1.8 +/- 0.4 mg/dl, p < 0.01) or in temporary sleep deprivation (1.6 +/- 0.4, p < 0.01). (2) The level of thromboxane B2 was significantly higher during chronic sleep deprivation than under control conditions (104.4 +/- 78.0 vs. 20.4 +/- 9.0 pg/ml, p < 0.05). (3) There were no significant intergroup differences in 6-keto-prostaglandin F1 alpha level. CONCLUSION: These findings could support the hypothesis that coronary arterial spasm and thrombus formation occur in chronic sleep deprivation.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Indispensability of pelvic and paraaortic lymphadenectomy in endometrial cancers.

The purposes of this study were to analyze the relationship between retroperitoneal lymph node (RLN) metastasis and clinical and pathologic risk factors in endometrial cancers, and to clarify the correlation between RLN metastasis and survival of patients with the disease. This analysis included 63 patients with endometrial cancer who underwent simultaneous pelvic lymph node (PLN) and paraaortic lymph node (PAN) dissection between April 1988 and December 1995. Patients with stage Ia grade 1 and stage IV disease were excluded from this analysis. Both PLN and PAN metastases were found in 10.0% (4/40) of patients with stage I (FIGO, 1988) disease. Of 14 cases with PLN metastases, 8 (57.1%) had PAN metastases simultaneously, whereas 4 (8.2%) of 49 cases without PLN metastases had PAN metastases. There was no significant relationship between the sites or numbers of positive PLN and PAN metastases. Multivariate analysis revealed that poor grade and deep myometrial invasion had an independent relationship with PAN metastases, whereas vascular space invasion and cervical invasion were independently associated with PLN metastases. When divided into the groups of stage I-II and stage III, the prognosis of patients with RLN metastases was significantly poorer than that of patients without RLN metastases in each stage. Furthermore, survival of patients with PAN metastases was significantly worse compared with that of patients with only PLN metastases (44.4 and 80.0%, respectively, P < 0.05). These results reveal that PLN and PAN metastases occur frequently even in early-stage endometrial cancer, and that RLN metastases, especially PAN metastases, have a serious impact on patient survival. In conclusion, systemically simultaneous pelvic and paraaortic lymphadenectomy is essential for all the patients with endometrial cancer except those with stage Ia grade 1 and stage IV to provide prognostic information and select suitable postoperative treatment as well as to perform accurate FIGO staging, provided the condition of the patient permits.

Adult↗