Biomedical subjects

T Iwasaka

Publications and source records attributed to T Iwasaka.

At least 37 records · Page 2Linked to original sources

PubMed2001

Retinoic acid and interferon-alpha effects on cell growth and differentiation in cervical carcinoma cell lines.

OBJECTIVE: To investigate and compare the efficacy of all-trans retinoic acid (RA) and/or interferon-alpha (IFN-alpha) on premalignant and malignant models of cervical cancer. METHODS: Cell growth rate was examined after treatment for 4, 7, and 10 days with RA and/or IFN-alpha of human papillomavirus type 18 (HPV 18)-immortalized endo- and ectocervical cells, nontransformed serum-adapted cells, transformed cells, three adenocarcinoma, and three squamous cell carcinoma cell lines. The effect on epithelial differentiation by RA and IFN-alpha was examined in organotypic culture. Induction of apoptosis was examined by modified terminal transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) and DNA fragmentation. RESULTS: Cell growth rate was inhibited by RA, 84-96% in HPV 18-immortalized endocervical cells, SiHa, and ME180, 0% in OMC-4, and 18-62% in other cell lines; and by IFN-alpha about 75% in SiHa and ME180 and 14-40% in the other cell lines. Combining RA and IFN-alpha increased the antiproliferative effect in premalignant cell lines and some cancer cell lines except OMC-4, SiHa, and HT-3. In rafts, RA treatment reversed human endocervical cell metaplasia and HPV 18-immortalized endo- and ectocervical cell dysplastic epithelial differentiation. Interferon-alpha, not RA, treatment of HPV 18-immortalized endo- and ectocervical cells induced apoptosis. CONCLUSION: Cell growth inhibition by treatment with RA, IFN-alpha, and their combination differentially depends on treatment type and time, cell origin, cell line, and oncogenic state. In a premalignant model of cervical carcinoma, RA reduces dysplastic differentiation and IFN-alpha induces apoptosis. These data confirm that these treatments may be effective for preventing or treating premalignant cervical lesions.

Adenocarcinoma↗

PubMed2001

Prevalence and mortality of the Brugada-type electrocardiogram in one city in Japan.

OBJECTIVES: We sought to study the prevalence and mortality of subjects exhibiting the Brugada-type electrocardiogram (ECG) in a community-based population in Japan. BACKGROUND: The Brugada syndrome has been associated with sudden death in subjects without structural heart disease. Hospital-based studies showed 11% to 38% annual fatal arrhythmic events in patients with the Brugada syndrome. METHODS: Prevalence and mortality of the Brugada-type ECG were studied in subjects who had ECGs during a health examination in Moriguchi, Osaka, Japan. Information about death and relocation from Moriguchi city was obtained prospectively. RESULTS: The Brugada-type ECG was found in 98 of 13,929 study subjects (0.70%, 95% confidence interval [CI]: 0.57% to 0.86%). The typical coved-type with an rsR' pattern in V(1) lead ("typical" Brugada-type) was found in 0.12% of subjects (95% CI: 0.07% to 0.20%). The prevalence for male subjects with the Brugada-type ECG (81%) was significantly higher than it was for those without (26%, p < 0.0001). In male subjects, the Brugada-type ECG was found in 2.14% (95% CI: 1.70% to 2.66%), and the "typical" Brugada-type was found in 0.38% (95% CI: 0.21% to 0.64%). After 2.6 +/- 0.3 years of follow-up, there was 1 death (1.0%, 95% CI: 0.03% to 5.6%) of a subject with the Brugada-type ECG, whereas there were 139 deaths (1.0%, 95% CI: 0.85% to 1.2%) of those without the Brugada-type ECG (p = 0.9943, log-rank test). CONCLUSIONS: A substantial number of the Brugada-type ECG were observed in subjects in a community-based population in Japan, especially in men. The total mortality of subjects with the Brugada-type ECG did not differ from the mortality of those without the Brugada-type ECG in a community-based population.

Aged↗

PubMed2001

TIMI frame count immediately after primary coronary angioplasty as a predictor of functional recovery in patients with TIMI 3 reperfused acute myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate whether higher coronary blood flow, estimated by the corrected Thrombolysis In Myocardial Infarction (TIMI) frame count (CTFC), is related to better functional and clinical outcome after successful percutaneous transluminal coronary angioplasty (PTCA) in patients with acute myocardial infarction (AMI). BACKGROUND: Experimental studies have found that functional recovery of the infarcted myocardium was associated with increased blood flow (reactive hyperemia) to the infarcted bed shortly after reperfusion. METHODS: We measured CTFC immediately after successful (TIMI 3) primary PTCA in 104 consecutive patients with their first AMI. Wall motion score index (WMSI) and the presence of pericardial effusion were assessed by two-dimensional echocardiography before and one month after PTCA. RESULTS: The patients were divided into two groups according to mean CTFC for corresponding coronary artery of the control group: TIMI 3 slow group (45 patients, 40 > CTFC > or = 23) and TIMI 3 fast group (59 patients, CTFC < 23). There were no significant differences in the baseline characteristics and WMSI before reperfusion between the two groups. Improvement of WMSI in the TIMI 3 fast group was significantly greater than that of the TIMI 3 slow group (1.33 +/- 0.52 vs. 0.60 +/- 0.34, p < 0.001). Pericardial effusion and intractable heart failure were observed more frequently in the TIMI 3 slow group than in the TIMI 3 fast group (27 vs. 10%; p < 0.05, 36 vs. 17%; p < 0.05). Corrected TIMI frame count, assessed as a continuous variable, had a significant correlation with the change in WMSI (r = 0.60, p < 0.001) after adjusting for age, gender, history of hypertension, history of diabetes, elapsed time to PTCA, collateral grade, presence of antegrade flow before PTCA and number of diseased vessels. CONCLUSIONS: Lower CTFC of the infarct-related artery immediately after PTCA was associated with greater functional recovery; and hence, CTFC can predict clinical and functional outcome in patients with successful PTCA.

Aged↗

PubMed2001

A new method to analyze basic rest-activity cycle.

A new method was proposed to analyze a basic rest-activity cycle (BRAC), termed BRAC-A. This method calculates a significant cycle length by chi-squared method and the starting points of a resting phase and an active one by analysis of the array consisting of the segmented time series in the same length. Using 20 3-day computer-simulated time series of standard deviation in fetal heart rate fluctuation with known periodicity of the BRAC, we demonstrated that the BRAC-A was a useful tool to reveal the characteristics of the BRAC.

Activity Cycles↗

PubMed2001

Changes in fractal structure of heart rate variability during a nap in one case.

The objective of the present study was to analyze fractal structures of adult heart rate (HR) variability during a nap. Fractal analysis was carried out in one case over consecutive 10-min time series of HR, which were simultaneously recorded with electroencephalogram. Scaling relationships showed cross-over patterns characterized by alphas and alphal (i.e. slopes above and below a cross-over point). The alphas and alphal were black and white noise at Stage 4 of NREM sleep, and black and 1/f noise in REM sleep. Cross-over points changed from the first to second sleep cycle. We demonstrate the multifractal structures of HR variability during a nap in the present case.

Adult↗

PubMed2001

A longitudinal study of diurnal variation in baseline fetal heart rate in one dichorionic-diamniotic twin pregnancy.

A longitudinal study to analyse the diurnal variations in baseline fetal heart rate (FHR) and sustained fetal tachycardia (SFT) in twin pregnancy was performed on one dichorionic twin. Twenty-four hour FHR recordings on twins were made at 32, 34 and 36 weeks of gestation simultaneously. Significant diurnal variations were found in both twins in all gestational weeks. The diurnal variations in baseline FHR of twins were highly correlated with no phase-lag. No coincidence was recognized in the appearance of SFT between twins. These results suggest the maternal influence equally affects FHR in each fetus of dichorionic twin since 32 weeks of gestation, while the appearance of SFT might be independent from maternal influence.

Adult↗

PubMed2001

Expression of chromogranin/secretogranin mRNA in spontaneous mammary tumors in aging Fischer-344 rats.

There is a type of human breast cancer showing a neuroendocrine differentiation. Little is known, however, about the cell origin of this cancer or the process by which it expresses neuroendocrine features. Rat mammary tumors, either spontaneous or induced, have not been subjects for the investigation of aspects regarding the neuroendocrine differentiation of mammary epithelial cells. The aim of the present study was to show the potential of rat mammary tumors for expressing chromogranin (Cg)/secretogranin (Sg) mRNA. We examined CgA, SgI and SgII mRNA expression by reverse transcription-polymerase chain reaction in rat mammary adenocarcinoma and fibroadenoma which had arisen spontaneously in aging Fischer-344 rats. CgA and SgII mRNA were expressed in both mammary tumors, but SgI mRNA was not detected in either. The results of the present study show that rat mammary tumors can express chromogranin genes.

Adenocarcinoma↗

PubMed2001

Angiotensin II signaling and HB-EGF shedding via metalloproteinase in glomerular mesangial cells.

BACKGROUND: Angiotensin II (Ang II) has been implicated in the development of glomerulosclerosis by stimulating fibronectin (FN) synthesis. The processing and release of heparin binding-endothelin growth factor (HB-EGF) are activated by protein kinase C (PKC) and Ca2+ signaling. We studied the roles of HB-EGF and endothelial growth factor (EGF) receptor (EGFR) in Ang II-induced FN expression using mesangial cells. METHODS: Mesangial cells were prepared from mouse kidneys by the explant method and cells were used at passages 4 and 5. RESULTS: Ang II stimulated FN mRNA levels dose-dependently with a maximal increase (3.4-fold) after 12 hours of incubation. This action was completely inhibited by PKC inhibitors and slightly blocked by Ca2+ chelating agents. FN mRNA accumulation by Ang II was abolished by tyrosine kinase inhibitors, a specific inhibitor for EGFR (AG1478) and extracellular signal-regulated kinase (ERK) inactivation. Addition of neutralizing anti-HB-EGF antibody, as well as pretreatment with heparin or the metalloproteinase inhibitor batimastat abolished induction of FN expression by Ang II. In mesangial cells stably transfected with a chimeric construct containing HB-EGF and alkaline phosphatase (ALP) genes, ALP activity in incubation medium was rapidly increased by Ang II (1.7-fold at 0.5 min) and reached a 4.1-fold increase at two minutes. Ang II phosphorylated EGFR (maximal at 2 min) and ERK (maximal at 8 min) in a PKC- and metalloproteinase-dependent manner. Ang II stimulated the expression and release of transforming growth factor-beta (TGF-beta) via EGFR-mediated signaling, and the released TGF-beta also contributed to Ang II-mediated FN expression via EGFR transactivation. CONCLUSIONS: Ang II-mediated FN expression was regulated by autocrine effects of HB-EGF and TGF-beta, suggesting a novel paradigm for cross-talk between Ang II and growth factor receptor signaling pathways.

Angiotensin II↗

PubMed2001

Clinical significance of ST-segment elevation in lead V1 in patients with acute inferior wall Q-wave myocardial infarction.

BACKGROUND: This study was designed to determine the clinical significance of ST-segment elevation in the precordial leads (leads V1 and V2) in acute Q-wave inferior wall myocardial infarction. METHODS AND RESULTS: One hundred fifty-eight consecutive patients with acute Q-wave inferior wall myocardial infarction were classified into 3 groups on the basis of the initial ST-change in V1 (group 1 = 29 patients with ST elevation, group 2 = 97 patients with ST depression, and group 3 = 32 patients with no ST-segment change). The right coronary artery was the infarct-related artery in all the patients in group 1. Although there was no significant difference between groups 1 and 2, the number of left ventricular asynergic segments was larger and the incidence of major in-hospital arrhythmias was higher in groups 1 and 2 compared with group 3. Patients in group 1 had a significantly higher incidence of proximal lesion (86%) and right ventricular infarction (69%) than the other 2 groups did. When ST elevation in leads V1 and V2 was considered, 14 of 15 patients (93%) with ST elevation only in V1 had right ventricular infarction, whereas 6 of 14 patients (43%) with ST elevation in both V1 and V2 had right ventricular infarction (P =.011). CONCLUSIONS: ST-segment elevation in V1 on admission in patients with acute Q-wave inferior wall myocardial infarction indicates a right coronary artery lesion associated with a larger infarct size and a higher incidence of major in-hospital arrhythmias.

Adult↗

PubMed2001

Type 2 iodothyronine deiodinase expression is upregulated by the protein kinase A-dependent pathway and is downregulated by the protein kinase C-dependent pathway in cultured human thyroid cells.

Type 1 and 2 iodothyronine deiodinases (D1 and D2) catalyze thyroxine (T4) activation. In human thyroid, unlike rodents', both D1 and D2 are expressed. We have investigated the effects of thyrotropin (TSH), dibutyryl cyclic adenosine monophosphate [(Bu)2cAMP] (an activator of protein kinase A [PKA]), 12-O-tetradecanoylphorbor 13-actate (TPA) (an activator of protein kinase C [PKC]), T4, and triiodothyronine (T3) on the D2 mRNA levels and activity in cultured human thyroid cells. D2 mRNA levels were increased by TSH and (Bu)2cAMP, and the increment was faster and greater than that of D1 mRNA levels. The increment of the maximum velocity (Vmax) value for D2 by (Bu)2cAMP stimulation was similar to that of D2 mRNA levels, suggesting that (Bu)2cAMP enhances D2 activity mainly at the pretranslational level. Cycloheximide, a protein synthesis inhibitor, partially inhibited the increase of D2 mRNA levels by (BU)2cAMP, suggesting that de novo protein synthesis-dependent pathways are involved. TPA suppressed the D2 mRNA levels in the presence of (Bu)2cAMP. However, T3 and T4 did not significantly change the D2 mRNA levels and activity. In conclusion, D2 expression in human thyroid cells is more rapidly and strongly upregulated by the PKA pathway than D1 expression, and is downregulated by the PKC pathway.

Bucladesine↗

PubMed2001

Transvaginal ultrasound-guided embryo transfer improves pregnancy and implantation rates after IVF.

BACKGROUND: Attempts are constantly being made to improve clinical pregnancy rates after IVF and embryo transfer. Since November 1998, we have gradually been adopting transvaginal ultrasound guidance during embryo transfer. We retrospectively examined the efficacy of this method on pregnancy and implantation rates. METHODS: The results of 846 cycles from our IVF-embryo transfer programme were analysed and comparisons were made between those carried out using ultrasound guidance and those by the clinical touch method. RESULTS: Higher pregnancy and implantation rates (28.9 and 15.2% respectively) were found in the group using the transvaginal ultrasound guidance during embryo transfer compared with those in the group using the clinical touch method (13.1 and 7.0% respectively). The differences were statistically significant (P < 0.01). There was no significant difference in ectopic pregnancy rates between the two groups. CONCLUSION: The use of transvaginal ultrasound-guided embryo transfer significantly improved both pregnancy and implantation rates. Although technically difficult, we suggest its use may maximize the chances of achieving a successful pregnancy outcome.

Adult↗

PubMed2001

Angiotensin II type 2 receptor inhibits epidermal growth factor receptor transactivation by increasing association of SHP-1 tyrosine phosphatase.

Angiotensin (Ang) II has 2 major receptor isoforms, Ang type 1 (AT(1)) and Ang type (AT(2)). AT(1) transphosphorylates epidermal growth factor receptor (EGFR) to activate extracellular signal-regulated kinase (ERK). Although AT(2) was shown to inactivate ERK, the action of AT(2) on EGFR activation remains undefined. Using AT(2)-overexpressing vascular smooth muscle cells from AT(2) transgenic mice, we studied these undefined actions of AT(2). Maximal ERK activity induced by Ang II was increased 1.9- and 2.2-fold by AT(2) inhibition, which was abolished by orthovanadate but not okadaic acid or pertussis toxin. AT(2) inhibited AT(1)-mediated EGFR tyrosine phosphorylation by 63%. The activity of SHP-1 tyrosine phosphatase was significantly upregulated 1 minute after AT(2) stimulation and association of SHP-1 with EGFR was increased, whereas AT(2) failed to tyrosine phosphorylate SHP-1. Stable overexpression of SHP-1-dominant negative mutant completely abolished AT(2)-mediated inhibition of EGFR and ERK activation. AT(1)-mediated c-fos mRNA accumulation was attenuated by 48% by AT(2) stimulation. Induction of fibronectin gene containing an AP-1 responsive element in its 5'-flanking region was decreased by 37% after AT(2) stimulation, corresponding to the results of gel mobility assay with the AP-1 sequence of fibronectin as a probe. These findings suggested that AT(2) inhibits ERK activity by inducing SHP-1 activity, leading to decreases in AP-1 activity and AP-1-regulated gene expression, in which EGFR dephosphorylation plays an important role via association of SHP-1.

Angiotensin II↗

PubMed2001

Analysis of heart rate variability of an anencephalic fetus using a new method to determine a fractal dimension of non-stationary time-serial data.

Human fetal heart rate (HR) variabilities were analyzed using the QIS-A, which we devised to determine a fractal dimension of non-stationary time series. Fifteen 10-min HR data of an anencephalic fetus at 23 weeks and 3 days of gestation and those of 10 normal fetuses at the same weeks of gestation were obtained by ultrasonic cardiography. The anencephalus preserved the spinal cord, medulla and partial anterior hypothalamus. The fractal scaling exponent alpha of the anencephalus was compared with that of each normal fetus by Student's t-test. In results, the scaling relationship in each case had a crossover pattern characterized by alpha(s) and alpha(l), which were slopes above and below a crossover point, respectively. Differences in mean alpha(s) and mean alpha(l) between the anencephalus and each normal fetus were significant (P < 0.01): mean alpha(s), 1.0 +/- 0.1 (+/-SD) (1/f fluctuation) and 1.6 +/- 0.2 (+/-SEM); mean alpha(l), 1.6 +/- 0.2 (+/-SD) and 1.4 +/- 0.1 (+/-SEM). There were six significant differences in mean crossover point between the anencephalus and each normal fetus: 13.8 +/- 5.7 s (+/-SD) and 15.3 +/- 5.6 s (+/-SEM). These results reveal the relationship between fractal structure of fetal HR variability and the developing central nervous system (CNS). In particular, the 1/f fluctuation of HR variability in an anencephalic fetus from the 1.25 to 13.8 s time scale might have a strong relation to the defect of the CNS.

Algorithms↗

PubMed2001

Safety and availability of doxazosin in treating hypertensive patients with chronic renal failure.

Hypertension accelerates the progression of renal disease in patients with chronic renal failure. Doxazosin, an alpha1-antagonist, is an antihypertensive agent with a long half-life. In this study, 15 patients with chronic renal failure were treated only with doxazosin and diuretics for 6 months and their blood pressure, renal parameters and lipid profile were measured. The initial dose of doxazosin was 2 mg/day and it was titrated until blood pressure was normalized. The average dose was 5.6 mg/day. As expected, systolic and diastolic blood pressure were decreased with treatment (165/91 mmHg to 135/73 mmHg). The drop in blood pressure was associated with an increase in glomerular filtration and a decrease in plasma BUN and creatinine levels. Reduction in mean blood pressure and decrease in proteinuria had a significant positive correlation (r=0.048, p=0.007). Proteinuria was decreased from 1.8 mg/day to 1.3 mg/day with doxazosin treatment and triglycerides also decreased, while HDL-cholesterol was increased. No side effects were observed. These results indicate that doxazosin is an efficient depressor agent with renal protective actions and that higher doses of doxazosin can be safely given to patients with chronic renal failure.

Adrenergic alpha-Antagonists↗

PubMed2001

Clinical significance of coronary flow to the infarct zone before successful primary percutaneous transluminal coronary angioplasty in acute myocardial infarction.

STUDY OBJECTIVE: To assess the effect of coronary flow to the infarct zone before primary coronary angioplasty on hospital complications in patients with acute myocardial infarction (MI). DESIGN: Consecutive case series analysis. SETTING: Coronary-care unit in a university hospital. PATIENTS: Two hundred sixty-four consecutive patients with ST-elevation acute MIs who had successful primary percutaneous transluminal coronary angioplasty. INTERVENTIONS: Coronary angiography on hospital admission and serial echocardiography. MEASUREMENTS AND RESULTS: The status of infarct-related artery flow before primary angioplasty was evaluated on hospital admission. Left ventricular wall motion and pericardial effusions were studied by echocardiography. One hundred ninety patients had total occlusions (Thrombolysis in Myocardial Infarction [TIMI] flow grade, 0 to 1) in the infarct-related artery (group 1), and 74 patients had antegrade flow (TIMI flow grade, 2 to 3) [group 2] before undergoing primary angioplasty procedures. When group 1 was subdivided into two groups (for the presence and absence of collateral flow), the patients with total occlusions and no collateral flow had a higher incidence of left ventricular aneurysmal wall motion (11% vs 1%, respectively; p = 0.03) and pericardial friction rub (15% vs 3%, respectively; p = 0.03) than did those in group 2. Moreover, those patients with total occlusions and no collateral flow had higher incidences of pericardial effusion (34% vs 17%, respectively; p = 0.02; and 34% vs 9%, respectively; p < 0.01) and in-hospital mortality (8% vs 1%, respectively; p = 0.04; and 8% vs 1%, respectively; p = 0.06) than did those patients in the other two groups. CONCLUSIONS: Despite successful primary angioplasty, the absence of antegrade flow in the infarct-related artery and collateral flow to the infarct zone before angioplasty resulted in a higher incidence of in-hospital complications.

Aged↗

PubMed2001

Expression of prolactin gene in spontaneous mammary tumors in aging Fischer 344 rats.

Expression of extra pituitary prolactin (PRL) has been recently reported in the mammary gland. However, spontaneous mammary tumors occurring in aging rats have not been investigated for PRL production. The present study was undertaken to examine the expression of PRL gene in rat mammary tumors spontaneously arisen in rats with pituitary prolactinomas among 130 female Fischer-344 (F-344) rats. The tumors examined were fibroadenoma (adenomatous type) in the 18-month old rat and adenocarcinoma (alveolar/tubular type) in the 21-month old rat. PRL mRNA was examined by solution and in situ reverse transcription-polymerase chain reaction (RT-PCR) method. The predicted amplified products for PRL mRNA were identified in both tumors, and its expression was confirmed to be in the cytoplasm of epithelial cells. The results of the present study showed that PRL gene is expressed in spontaneously arising mammary tumors.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2001

Lower mortality in patients with the DD genotype of the angiotensin-converting enzyme gene after acute myocardial infarction.

OBJECTIVE: The angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been associated with different serum ACE concentrations and cardiac ACE activity. We assessed whether the ACE gene I/D polymorphism influenced cardiac mortality in Japanese patients with acute myocardial infarction. METHODS AND RESULTS: The ACE gene I/D polymorphism was determined in 441 consecutive patients with a first myocardial infarction. There were 69 patients (16%) with the DD genotype, 194 patients (44%) with the ID genotype, and 178 patients (40%) with the II genotype. During a mean follow-up of 9.4 months, there were 49 cardiac deaths (DD, n = 4; ID, n = 26; II, n = 19). The DD genotype was significantly associated with a lower mortality than the other genotypes (p = 0.0363) by Cox regression analysis adjusted for age, sex, site of myocardial infarction, Killip functional class, reperfusion therapy during acute phase, ACE inhibitor use, and beta-blocker use. CONCLUSIONS: In a selected cohort of Japanese patients, the DD genotype was associated with a significantly lower cardiac mortality after a first myocardial infarction.

Female↗

PubMed2001

Regional myocardial function at the papillary muscle insertion site.

The importance of the mitral apparatus to the global left ventricular (LV) function has been suggested in several clinical studies. One recent study reported that chordal transsection induced an unloading of myocardium at the papillary muscle insertion site. We hypothesized that the regional response for afterloading at this site with intact mitral apparatus was different from that at the free wall. We investigated the end-systolic pressure-regional segment length relations (ESPLR) in two anterior LV sites, free wall (FREE) and the papillary muscle insertion site (PAP), during an increasing afterload by aortic occlusion in 7 anesthetized open-chest dogs. To measure the regional segment length at FREE and PAP, two sets of the pair of sonomicrometer crystals were implanted in the same midwall depth at the same circumferential hoop by using an echocardiographic guide. ESPLR both at FREE and PAP were always highly linear in a physiological range (r > or = 0.9). The slope of this relation at FREE (274 +/- 164 mmHg/mm) was significantly steeper than that at PAP (157 +/- 118 mmHg/mm) for each dog (p < 0.05). These data indicate that the regional response for afterloading at PAP loaded by chordal tension is different from that at FREE in the same heart.

Animals↗