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S Kyo

Publications and source records attributed to S Kyo.

At least 73 records · Page 4Linked to original sources
PubMed1998

Detection of human telomerase reverse transcriptase messenger RNA in voided urine samples as a useful diagnostic tool for bladder cancer.

Activation of telomerase and stabilization of telomeres are thought to be required for cellular immortality and oncogenesis. Telomerase activity is detected in >90% of various cancers, including urothelial cancers. Of the three subunits comprising telomerase complex, human telomerase reverse transcriptase (hTERT) is a rate-limiting determinant of the enzymatic activity of telomerase. In the present study, spontaneously voided urine specimens from 33 patients with bladder cancer and 26 without bladder lesions were examined for the expression of hTERT mRNA, and the usefulness of detecting hTERT mRNA in urine samples for screening of bladder cancer was evaluated. RT-PCR analysis revealed that approximately 80% of urinary sediments from patients with bladder cancer expressed hTERT mRNA, regardless of clinical stage or pathological grade, whereas only 4% of sediments from patients without urothelial lesions did. Interestingly, hTERT mRNA expression was observed, even in some urine samples from bladder cancer patients with negative urinary cytology. These findings suggest that the expression of hTERT in urine sample may be a useful diagnostic marker for bladder cancer.

Aged↗
PubMed1997

Expression of telomerase activity in human chorion.

Telomerase activation is required for cellular immortalization and is found in most malignant tumors. Normal somatic cells are generally telomerase-negative, except for stem cells in renewing tissues. During pregnancy, human trophoblast continues to proliferate and acts as proliferating stem cells for the development of chorion and the formation of placenta. In the present study, a total of 105 chorions from placentas at various weeks of gestation were examined for telomerase activity using the telomeric repeat amplification protocol (TRAP) assay. Twenty-five of 33 (76%) normal early chorions at 5 to 9 weeks gestation were telomerase-positive. Chorions from early spontaneous abortions also exhibited telomerase activity but at a low level. In contrast, only 2 (4%) late chorions at 34 to 41 weeks gestation expressed telomerase activity. Significant telomerase activity was observed in trophoblast cell fractions of chorion, demonstrating trophoblast to be the source of the activity. Expression of human telomerase catalytic subunit (hTRT) was observed in early chorions, but not in late placenta, and there was a close correlation between telomerase activity and hTRT expression. In contrast, expression of human telomerase RNA component (hTR) was observed in both early and late chorions and was not liked to telomerase activity. These findings suggest that telomerase activity in chorion is critically regulated over the course of gestation, associated with hTRT expression. The findings of the present study also appear to support the emerging concept that normal somatic cells with stem cell-like characteristics can express telomerase activity.

Choriocarcinoma↗
PubMed1997

The 5' region of the human papillomavirus type 31 upstream regulatory region acts as an enhancer which augments viral early expression through the action of YY1.

Cis-elements which control human papillomavirus early gene expression have previously been localized to sequences in the upstream regulatory region (URR) which are proximal to the E6 open reading frame. These elements include an enhancer element which functions preferentially in keratinocytes as well as promoter elements. The function of the remaining approximate 500-bp region of the URR in regulating viral expression in the high risk papillomaviruses has been largely uncharacterized. In HPV 6, a negative regulator of early expression, or silencer, has been identified in this 5' region of the URR. In this study, we have investigated the role of the 5' portion of the HPV 31 URR in regulating viral expression. Sequences in this region were found to exert a minimal negative effect on homologous or heterologous promoters. In contrast, a 128-bp sequence within this region was found to exhibit enhancer activity on heterologous and homologous promoters. This enhancer also augmented the activity of the previously identified minimum keratinocyte enhancer. The cellular factors, YY1 and TEF-1, were determined by DNase I footprint analysis and electrophoretic mobility shift assays (EMSAs) to bind the 128-bp enhancer. The binding of YY1 to two of these sites was found to be important for enhancer activity.

Base Sequence↗
PubMed1997

Application of telomerase assay for the screening of cervical lesions.

Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends. The expression of telomerase is thought to be required for cellular immortality and oncogenesis. Telomerase activity has been detected not only in most cancers but also in some types of premalignant lesions, such as squamous intraepithelial lesions (SILs). In the present study, we used the telomerase assay to detect uterine cervical lesions in cervical scraping samples. A total of 82 cervical scraping samples were obtained from women with or without cervical lesions and examined by nonradioisotope telomeric repeat amplification protocol assay. Fifteen of 17 (88%) cervical cancer specimens exhibited telomerase activity, whereas 5 of 8 (63%) and 14 of 24 (58%) specimens from low-grade and high-grade SILs, respectively, also exhibited telomerase activity. In contrast, 3 of 33 (9%) specimens from normal cervices exhibited telomerase activity. Dilution telomeric repeat amplification protocol assay was performed to estimate telomerase activity; it revealed that high levels of activity were often expressed in cervical cancer. Cytological examination was also performed by Pap smear test, and 4 of 8 (50%) low-grade SILs, 21 of 24 (88%) high-grade SILs, and 16 of 17 (94%) cervical cancers were found to have cytological abnormalities. There were discordances in some cases between findings of smear abnormality and telomerase positivity. In particular, we found five cases of SILs without smear abnormality but with telomerase activity, suggesting that some lesions with false negative cytology can be detected by telomerase assay. These findings suggest that telomerase assay using cervical scrapings might be a useful screening method for cervical lesions especially when combined with a Pap smear test.

Biomarkers, Tumor↗
PubMed1997

Usefulness of transesophageal echocardiography in detecting changes in flow dynamics responsible for malperfusion phenomena observed during surgery of aortic dissection.

Intraoperative transesophageal echocardiography (TEE) was performed in order to study the flow dynamics in the descending aorta during surgery of aortic dissection Stanford A. TEE was seen to be a sensitive and accurate method to promptly detect severe decrease in retrograde pump flow and to clarify some of the mechanisms that can result in malperfusion during cardiopulmonary bypass.

Adult↗
PubMed1997

Telomerase activity in human endometrium.

Human uterine endometrium undergoes a complex pattern of changes in proliferation and secretory activity during the menstrual cycle. In the present study, telomerase activity in normal endometrium was examined using a non-radioisotope PCR-based telomeric repeat amplification protocol assay. Various levels of telomerase activity were detected in the 60 normal endometrial samples examined, depending on the phase of the menstrual cycle. Of 21 proliferative-phase endometrial samples, 20 (95%) expressed telomerase activity, whereas 8 of 19 (42%) secretory-phase or menstrual endometrial samples did (P = 0.002). Five of nine (56%) samples from atrophic endometrium from postmenopausal women also expressed telomerase activity. Eleven of 21 (52%) endometrial samples in the proliferative phase expressed high telomerase activity detectable after 100-fold dilution of extracts, whereas none of the 19 endometrial samples from the secretory phase or during menstruation and none of the 9 postmenopausal endometrial samples did (P < 0.001). The highest activity was observed in the late proliferative phase, but activity dramatically decreased with the progression of the secretory phase. Surprisingly, the levels of telomerase activity detected in the late proliferative phase were comparable to those detected in the endometrial cancers examined. Immunohistochemical analysis of the expression of proliferating cell nuclear antigen revealed that telomerase activity is closely correlated with endometrial cell proliferative activity. These findings indicate that normal endometrium expresses telomerase, the activity of which changes dramatically over the course of the menstrual cycle, suggesting in turn that telomerase is a regulated enzyme linked to cellular proliferation and that hormone functions may be involved in its regulation.

Biomarkers↗
PubMed1997

Intravascular ultrasound assessment of regional aortic wall stiffness, distensibility, and compliance in patients with coarctation of the aorta.

BACKGROUND: Impaired aortic pulsatility has been demonstrated by angiography in children and in studies of experimental animals with coarctation of the aorta. OBJECTIVES: The purpose of this study was to assess regional aortic stiffness, distensibility, and compliance before and after balloon dilation in patients with coarctation of the aorta. METHODS AND RESULTS: Intravascular ultrasound examination was performed in 13 pediatric patients with the diagnosis of coarctation of the aorta to yield aortic diameter. Area transverse sections at both systolic and diastolic period were measured at three aortic levels: the proximal, distal, and coarctation segments. Balloon dilation was also performed in eight of 13 patients. By using pressures measured in the same areas, an aortic stiffness index (beta) was calculated as In(Ps/Pd)/(Ds-Dd), where In is natural logarithm, Ps is systolic pressure, Pd is diastolic pressure, Ds is systolic diameter, and Dd is diastolic diameter. Aortic distensibility and an estimation of aortic compliance were also calculated. The beta stiffness index of the coarctation and the proximal segments of the aorta were significantly greater than that of the distal segment of the aorta (p < 0.01). The aortic wall stiffness beta index did not acutely change after successful balloon dilation, but the distensibility and compliance of distal aorta were nonetheless significantly decreased after balloon dilation (p < 0.01, p < 0.05) as a function of changes of pulsatility of flow. CONCLUSIONS: Abnormal proximal aortic stiffness may be a strong contributing factor that promotes the genesis of hypertension in patients with coarctation even after successful repair or balloon angioplasty.

Adolescent↗
PubMed1997

Telomerase activity in human urothelial tumors.

Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends by using an RNA component as a template. Telomerase extends the telomeric repeats, which prevents telomere shortening during cell division, contributes to chromosomal stability, and, possibly, leads to immortalization of the cells. The telomerase activity in 22 urothelial tumors, including 13 bladder cancers, 8 ureter cancers, and 1 renal pelvic cancer, as well as in 12 adjacent normal tissues, was examined with the use of a nonradioisotope polymerase chain reaction (PCR)-based telomeric repeat amplification protocol assay. Different levels of telomerase activity were detected in the urothelial tumors. No significant activity was observed in normal adjacent tissues; however, two cases exhibited weak activity. Nine tumors retained positive telomerase signals after 100-fold dilution of extracts, which suggests that these tumors express high levels of telomerase activity. These findings indicate that telomerase activation may be a critical step in the pathogenesis of urothelial tumors. Unexpectedly, no significant correlation was observed between high levels of telomerase expression and the clinicopathologic features of the tumors, including clinical stage, pathologic grade, tumor multiplicity, and status of recurrence.

Adenocarcinoma↗
PubMed1997

Expression of AP1 during cellular differentiation determines human papillomavirus E6/E7 expression in stratified epithelial cells.

E6 and E7 oncoproteins of human papillomavirus (HPV) play significant roles in the pathogenesis of cervical cancer. However, the pattern of E6/E7 expression during the productive virus life cycle in differentiating epithelia of the uterine cervix remains unclear. In addition, little is known about the cellular factors regulating E6/E7 expression in differentiating epithelia. In the present study, using transient expression assays and DNA binding assays, we demonstrated that E6/E7 transcription is critically regulated by the cellular factor AP1, a Jun/Fos heterodimer complex. Immunohistochemical analyses of various uterine cervical lesions showed AP1 expression in lower cell layers of normal cervix and low-grade cervical intraepithelial neoplasia (CIN), while it was detected throughout all layers in high-grade CIN and invasive cancer. In situ RNA-RNA hybridization analyses of organotypic raft culture specimens of an HPV-31-containing cell line revealed that E6/E7 transcripts were expressed in most cell layers, with reduced expression in differentiated cells. This pattern of HPV expression correlated with the pattern of AP1 expression detected by immunohistochemical analyses. These findings suggest that E6/E7 expression in differentiating epithelia is dependent on AP1, which appears to be associated with proliferative activity of the cells. Since E6/E7 expression induces cell proliferation, co-expression of AP1 and E6/E7 in undifferentiated cell layers might create a positive regulatory loop, probably contributing to maintenance of initial HPV infection and subsequent activation in basal and suprabasal cell layers.

Binding Sites↗
PubMed1997

[Serratia marcescens prosthetic mitral valve endocarditis associated with hemolytic anemia].

A 57-year-old female who had been performed mitral valve replacement (MVR) using 31 mm prosthetic valve 32 months before entered the hospital for the evaluation of long standing severe hemolytic anemia without infectious sign. Transesophageal echocardiogram revealed a moderate sized vegetation on the atrial site of the prosthetic valve. The size and number of the vegetation were increased after deterioration of infectious illness. Blood culture grew serratia marcessans and alpha-hemolytic Streptococcus. Re-MVR was carried out with the diagnosis of prosthetic valve endocarditis (PVE). As the symptom of PVE, hemolytic anemia without infectious sign is a rare condition. TEE is an useful method to make diagnosis of PVE by detecting the vegetations and evaluating their change of size and methods and to evaluate the effectiveness of the treatment.

Anemia, Hemolytic↗
PubMed1996

[Indication and clinical results of heart transplantation in the terminal stage of ischemic cardiomyopathy].

The results of medical therapy has been very poor for ischemic cardiomyopathy with inoperable coronary artery disease and left ventricular ejection fraction less than 20%, therefore, heart transplantation is considered to be definite indication for those patients. However, the limited supply of suitable donor organs imposes constraints upon the decision of whether patients are selected for transplantation or for alternative therapy including coronary artery bypass grafting (CABG), semipermanent use of implantable left ventricular assist device, or cardiomyoplasty even in the western countries. The heart transplantation therapy has not been accepted in Japan at the present time, therefore, such alternative therapy should be tried still more aggressively in our country. CABG is most established surgical technology among the alternative therapies for transplantation and realistic in availability. Many institutes in the western countries adopt the therapeutic strategy of aggressive trial of CABG for ischemic cardiomyopathy in the first stage and to use ventricular assist device as a bridge for heart transplantation in failure cases. Although the effects of CABG may not be permanent and ultimate heart transplantation may be required for those patients, still CABG therapy is considered reasonable, because of the shortage of supply of donor heart, rejection and the progression of coronary artery disease of transplanted heart in the chronic stage. The necessity and indication of heart transplantation for ischemic cardiomyopathy have not been discussed adequately in Japan, however, more than 5000 patients under 60-year-old are killed annually due to ischemic heart disease in our country. More hot discussion on heart transplantation is deems to be necessary for ischemic cardiomyopathy.

Cause of Death↗
PubMed1996

[Papillary muscle rupture complicating acute myocardial infarction--treatment with mitral valve replacement and coronary bypass surgery in acute phase].

Complete rupture of a papillary muscle following acute myocardial infarction is a severe complication that is typically associated with acute left ventricular failure, pulmonary edema, and relentless clinical deterioration. The reported mortality rates without surgical intervention is almost 90%, therefore, prompt operation without prolonged attempts at medical stabilization is the key to decrease operative mortality. Although the complete coronary revascularization in conjunction with mitral valve replacement is advocated in the western medical academic society, there is only a few case of conjunct surgery has been reported in Japan. Three successful cases of conjunct surgery of mitral valve replacement and coronary complete revascularization in acute phase within one week from the onset of acute myocardial infarction (AMI) are described. There were one male and two female patients with an average age of 60-year-old (range 48-67), who developed cardiogenic shock and admitted to our hospital. The average interval between onset of AMI and the appearance of mitral regurgitation (MR) was 38 hours, and that of the appearance of MR and admission was 40 hours. Surgeries were performed within 26 hours (average 13 hours) after admission. The mitral valve was replaced with a mechanical valve (St. Jude Medical Valve) and a complete coronary revasculatization was done using saphenous vein graft. The average period of operation time and aortic cross clamping time were 6 hours 22 minutes and 109 minutes respectively. The average number of coronary grafting was 2.3 (range 1-3). Postoperative recovery from cardiogenic shock was uneventful in all three patients. The average periods of ICU stay and hospital stay were 5 days and 43 days respectively. All patients have regained their social activities with mean follow up period of 52 months. Since ischemic heart disease remains the leading cause of death in such patients, it is suggested that complete coronary revascularization should be performed immediately in conjunction with valve replacement even in the acute phase after onset of AMI.

Aged↗
PubMed1996

[Aortic inner surface morphology in aortic disease by three-dimensional transesophageal echocardiography].

Aortic inner surface morphology in various pathologies was investigated using three-dimensional (3D) transesophageal echocardiography to clarify the feasibility and limitations for clinical application. Transesophageal echocardiography was performed in 16 patients with aortic disease (12 aortic dissection, 4 aortic sclerosis) and 5 with normal aorta. The transesophageal transverse view of the descending aorta was taken every 2 mm by manually withdrawing the probe. Each image was recorded using VTR during one heart beat, then stored in the memory of a personal computer as a data base for the subsequent 3D reconstruction. The aortic inner surface was displayed using distance and gradient shading. Three-dimensional reconstruction images were obtained in all patients. The aortic inner surface was reconstructed as a wall with ringed protrusion in patients with normal aorta and a rugged wall with various sized protrusions in patients with atherosclerotic plaques by 3D transesophageal echocardiography. However, it was impossible to differentiate calcified lesions from non-calcified areas of plaques. In aortic dissection, 3D reconstruction provided information regarding the spatial anatomy of the dissection in 10 of 12 patients, accurate shape and location of the intimal tears in 3 of 5 patients, and movement of the intimal flap in 9 of 12 patients. However, reconstruction of the false lumen failed in two patients who had false lumens filled with spontaneous contrast echo. Three-dimensional transesophageal echocardiography is potentially useful for estimating the inner surface morphology and spatial extent and actual location of the aortic abnormalities, but there are limitations in evaluating tissue characterization and reconstructing the lumen with spontaneous contrast echo.

Adult↗
PubMed1996

Telomerase activity in gynecological tumors.

Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends using an RNA component as a template. Extension of telomeric repeats by telomerase prevents telomere shortening with cell divisions and contributes to chromosomal stability, possibly leading to immortalization of the cells. In the present study, we determined the telomerase activity of gynecological tumors and cell lines using a newly developed non-radioisotope telomeric repeat amplification protocol. A total of 21 cell lines derived from cervical cancer, endometrial cancer, ovarian cancer, and choriocarcinoma was examined, and all lines were found to be positive for telomerase activity, although the activity varied among cell types. A total of 50 gynecological malignant tumors was also examined, and 10 of 12 (83%) cervical cancers, 12 of 13 (92%) endometrial cancers, 18 of 21 (86%) ovarian cancers, 2 of 2 tubal cancers, and 1 of 1 vulvar cancer were found to be positive for telomerase activity. A total of 88% of gynecological tumors tested was thus found to be telomerase positive. However, no significant correlation was observed between telomerase activity and clinical features for any tumor type, although ovarian tumors expressing high telomerase activity tended to be more invasive. In contrast to that in malignant tumors, telomerase expression was weak and less common in premalignant lesions, with 5 of 7 cervical intraepithelial lesions and 4 of 6 borderline ovarian tumors exhibiting faint activity. Nine benign uterine lesions were also examined, and all were negative for telomerase activity except 1 uterine myoma, which had a weak signal. Three benign ovarian cysts examined had weak telomerase activity. These findings suggest that telomerase activation is common in gynecological malignant tumors and may be a critical step in their pathogenesis. However, premalignant lesions and some types of benign tumors also express weak telomerase activity.

Female↗
PubMed1995

Transcriptional activity of human papillomavirus type 31b enhancer is regulated through synergistic interaction of AP1 with two novel cellular factors.

Transcription of human papillomaviruses (HPV) is regulated by enhancer sequences located in the upstream regulatory region. The factors regulating expression of one of the high risk genital HPV types, HPV 31b, were investigated using transient expression and protein binding assays. A region of 262 base pairs in length was identified as the minimal functional enhancer and a series of five protected binding sites were observed by footprint analyses. Electrophoretic mobility shift assays demonstrated that AP1, Oct-1, as well as three novel factors bound these sequences. Mutational analyses indicated that AP1 synergistically activated the HPV31b enhancer together with either of two novel factors. One of these novel factors bound a sequence similar to an NF1 site but was distinct from NF-1. The second factor bound sequences bearing similarity to KRF-1 binding sites which have previously been characterized in HPV 18. Competition binding assays demonstrated that this factor was not identical to KRF-1. Additional studies implicated Oct-1 as a negative regulator of HPV 31b expression as mutation of Oct-1 binding sequences resulted in an increase in viral expression. None of the factors observed to be important for HPV 31b enhancer activity was found exclusively in epithelial cells and instead were detected in a variety of cell types. Of these factors, AP1 binding correlated most strongly with enhancer function in a variety of cell types, implicating it as a principal regulator of HPV expression. Variations in the constituents of the AP1 complex that bind the HPV 31b enhancer were also observed in different cell types, suggesting that changes in the distribution of jun proteins may play a significant role in determining the tropism of HPV. These results indicate that AP1 may be a common regulator for various HPV types and that it contributes to enhancer specificity. In addition, a set of novel factors, which may be specific for each HPV type, act synergistically with AP1 for full activation of the enhancer.

Base Sequence↗