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Biomedical subjects

T Iwasaka

Publications and source records attributed to T Iwasaka.

At least 127 records · Page 7Linked to original sources

Telomerase activity in gynecologic tumors.

The standard telomeric repeat assay protocol (TRAP) was used to examine telomerase activity in 16 ovarian tumors, 16 cervical carcinomas, 4 uterine tumors, and 3 vaginal tumors. Telomerase activity was detected in 95% of these tumors, 88% of ovarian malignancies, and 100% of cervical, endometrial, and vaginal malignancies. In contrast, telomerase activity was not evident in normal tissues or in benign proliferative lesions, such as leiomyomas, condyloma acuminata, and simple endometrial hyperplasia. These results suggest that telomerase activation is associated with immortalization or malignant transformation of gynecologic tumors.

Adolescent↗

Correlation between human papillomavirus positivity and p53 gene overexpression in adenocarcinoma of the uterine cervix.

In the pathogenesis of cervical squamous cell carcinoma, an inverse correlation between human papillomavirus (HPV) infection and mutation of the p53 anti-oncogene has been suggested. Much less is known of a possible correlation in the case of adenocarcinoma of cervix. Twenty-five cervical adenocarcinomas and 7 adenosquamous carcinomas were analyzed for presence of HPV DNA sequences and overexpression of the p53 gene. Polymerase chain reaction revealed that 11 were positive for HPV DNA (34%). Seven were positive for HPV 16 and 5 for HPV 18. A mixed infection with HPV 16 and 18 was observed in 1 case. Patients with HPV-positive carcinoma were significantly younger than those with HPV-negative carcinoma (43 +/- 13.3 years versus 57 +/- 17.4 years, P = 0.01). Immunohistochemical staining showed that p53 was overexpressed in 11 of 32 cases (34%). Overexpression of the p53 gene was found in only 1 of 11 HPV-positive cases (9%) yet was evident in 10 of 21 HPV-negative cases (48%). This inverse association was statistically significant (P < 0.05). Prognostic analysis revealed that HPV-negative adenocarcinomas had a poorer prognosis than HPV-positive cases (P < 0.01) and that tumors with p53 overexpression also had a poorer prognosis than those without such overexpression (P < 0.01). Our observations suggest that HPV-negative or p53-positive adenocarcinomas may be a biologically distinct subset with a poorer prognosis.

Adenocarcinoma↗

The prognostic value of semiquantitative nuclear grading in endometrial carcinomas.

The objective of this study was to evaluate the prognostic value of a convenient nuclear grading system based on only the proportion of nuclei measuring more than 10 microm in length at the shortest axis in endometrial carcinomas. Of the 235 cases reviewed, 9 serous and 5 clear cell adenocarcinomas and 2 small cell carcinomas were eliminated, resulting in a study population of 219 cases of endometrial adenocarcinoma. The architectural grade was determined by the FIGO system. The criteria for nuclear grade were as follows: grade 1, no nucleus measuring more than 10 microm in length at the shortest axis; grade 2, nuclei measuring more than 10 microm in length at the shortest axis seen in percentages ranging between 0 and 10% of tumor cells in active areas; and grade 3, more than 10% of tumor cells in active areas with nuclei measuring more than 10 microm in length at the shortest axis. The criteria for combined grades were as follows: the tumors were graded according to the architectural grade, but high-grade nuclear abnormalities increased the grade by one for architectural grade 1 and 2 tumors. The cumulative 10-year survival rates for architectural grades 1, 2, and 3 were 92.4, 82.6, and 65.2%, respectively (chi2 = 17.9, P = 0.001). The survival rates for nuclear grades 1, 2, and 3 were 96.2, 76.1, and 70.1%, respectively (chi2 = 21.6, P < 0.001), while for combined grades 1, 2, and 3 the survival rates were 98.3, 83.2, and 65.2%, respectively (chi2 = 26.9, P < 0.001). Even when the cases were limited to the 147 stage I endometrial carcinomas examined, the prognostic value of the combined grading system was still found to be superior to that of the architectural grading system. Our observations therefore supported the FIGO recommendation for nuclear grade not only in stage I endometrial carcinomas, but also in all stages of endometrial carcinomas.

Adenocarcinoma, Clear Cell↗

Telomerase activation in in vitro and in vivo cervical carcinogenesis.

Telomerase activity is found in the majority of human cancers, but not in most normal tissues. It is generally accepted that there is a multistep process in human carcinogenesis. Studying the role of telomerase activation in this process may provide new information to further our understanding of the pathological process of clinical lesions. In the present study, telomerase activity was found in HPV-immortalized and cigarette smoke condensate (CSC)-transformed malignant cell lines established in a cervical carcinogenesis model and in cell lines derived from cervical intraepithelial neoplasias (CINs) and carcinomas. With exfoliated cell samples, telomerase activity was detected in 3 of 41 (7%) normal cervices, 10 of 25 (40%) CINs, and all 20 (100%) carcinomas. Telomerase activation was significantly higher in CINs than in normal cervices (chi2 = 7.42, P < 0.01) and was much higher in invasive carcinomas than in CINs (chi2 = 18.00, P < 0.005). Our observations suggest that telomerase activation is a relatively early-stage event in cervical carcinogenesis, and this activation is associated with the initiation and progression of cervical lesions. Detection of telomerase activity may serve as a tool for diagnosis and prognosis of cervical neoplasias.

Carcinoma↗

The effects of infusion of trieicosapentaenoyl-glycerol emulsion on extravascular lung water during myocardial ischemia and reperfusion in dogs.

To test the effects of eicosapentaenoic acid (EPA) infusion on pulmonary edema induced by coronary ligation and reperfusion, extravascular lung water (EVLW) was measured in situ by the thermal-dye double indicator dilution method in dogs. In the control group of five dogs, 30 mL of a 10% soybean oil emulsion was infused through a leg vein. One hour after infusion, the left anterior descending coronary artery below the first diagonal branch was ligated for 15 min and then reperfused for 30 min. In the EPA group, six dogs were similarly treated with an emulsion of a 10% trieicosapentaenoyl-glycerol (90% pure). EVLW, pulmonary capillary wedge pressure, mean pulmonary artery pressure, mean blood pressure, and cardiac index were measured before and 15 min after coronary ligation, and 15 min and 30 min after coronary reperfusion. There were no significant differences in the hemodynamic indices between the two groups. EVLW significantly increased up to two times of baseline during coronary ligation in the control group (P < 0.05) and more during reperfusion (P < 0.01), whereas EVLW did not increase in the EPA group. In conclusion, EPA inhibited EVLW accumulation and may be useful for ameliorating one of the ischemia-reperfusion-induced complications, pulmonary edema.

Animals↗

Association of preceding angina with in-hospital life-threatening ventricular tachyarrhythmias and late potentials in patients with a first acute myocardial infarction.

We studied 140 patients with a first acute myocardial infarction to examine the effect of preceding angina as a marker of ischemic preconditioning on clinical ventricular arrhythmias and late potentials. Preceding angina was defined as the presence of ischemic chest pain within 24 hours before onset of myocardial infarction lasting no longer than 30 minutes and seen three or more times per day or at rest. Clinical features, angiographic findings, and late potentials were compared between patients with and without preceding angina. Thirty-four (24%) patients had preceding angina. Although the incidence of life-threatening ventricular tachyarrhythmias significantly differed (p = 0.0219), other clinical findings, including presence of late potentials, were not different between the two groups. Of 14 patients with life-threatening ventricular tachyarrhythmias, five events were considered as reperfusion arrhythmias. In patients who had successful reperfusion therapy, the incidence of life-threatening ventricular tachyarrhythmias had a tendency to be lower in patients with preceding angina than in those without preceding angina (p = 0.0586). Severe angina within 24 hours of onset of acute myocardial infarction is suggested to reduce occurrence of life-threatening ventricular tachyarrhythmias mainly associated with reperfusion during hospitalization.

Action Potentials↗

Importance of left ventricular diastolic function on maintenance of exercise capacity in patients with systolic dysfunction after anterior myocardial infarction.

To investigate the role of left ventricular (LV) diastolic function in the maintenance of exercise capacity in patients with systolic dysfunction, symptom-limited cardiopulmonary exercise testing combined with radionuclide ventriculography was performed in 24 patients with an LV ejection fraction < 35% after anterior myocardial infarction. The ratio of pulmonary artery wedge pressure (PAWP) to LV end-diastolic volume (EDV), an index of global diastolic function, correlated significantly with peak oxygen consumption at peak exercise (r = -0.55; p = 0.006), whereas ejection fraction at peak exercise did not. The change in PAWP/EDV ratio from rest to peak exercise was related to the increases in stroke volume (r = -0.54; p = 0.006) and cardiac output (r = -0.51; p = 0.01) during exercise, but the change in ejection fraction was not. Resting hemodynamics did not differ between patients with preserved exercise capacity (group 1, n = 8) and those with exercise impairment (group 2, n = 16). At peak exercise, stroke volume, cardiac output, and EDV were significantly higher, and PAWP and PAWP/EDV ratio were significantly lower in group 1 than in group 2, but ejection fraction and end-systolic volume were similar in both groups. Although the incidences of hypertension, LV hypertrophy, and infarct-related coronary artery lesions did not differ between the two groups, group 2 had a significantly higher incidence of non-infarct-related coronary artery lesions than group 1 (p < 0.05). Thus in patients with LV systolic dysfunction after anterior myocardial infarction, the major cause of exercise impairment and failure to increase LV performance during exercise was diastolic dysfunction associated with the presence of non-infarct-related coronary artery lesions with the potential for exercise-induced ischemia of the noninfarcted areas.

Adult↗

Successful treatment of a patient with Graves' disease on hemodialysis complicated by antithyroid drug-induced granulocytopenia and angina pectoris.

We report here a patient with recurrent Graves' disease on hemodialysis. She also suffered from angina pectoris, which was probably a manifestation of Graves' disease due to the increased oxygen demands in the presence of fixed coronary lesions. Although antithyroid drugs induced mild granulocytopenia, propylthiouracil (PTU) or methimazole (MMI) was not discontinued during the administration of granulocyte colony-stimulating factor (G-CSF). The patient received sodium iodine-131 therapy, and became euthyroid with no chest pain. To our knowledge, this is the first case that illustrated the usefulness of G-CSF for antithyroid drug-induced granulocytopenia prior to thyroid ablation for Graves' disease complicated with chronic renal failure and angina pectoris.

Agranulocytosis↗

Conservative treatment using a methotrexate-lipiodol emulsion containing non-ionic contrast medium for a cervical ectopic pregnancy.

We present a case in which a viable cervical pregnancy was successfully treated with preservation of the uterus. A 26 year old female presented with a 6 week cervical pregnancy with acute moderate bleeding. On the day of admission the patient underwent embolization of the descending uterine artery to decrease the bleeding. The following day, 4 mEq potassium chloride and methotrexate (MTX)(1 mg/kg) dissolved in saline was injected into the amniotic cavity using transvaginal sonographic guidance. The fetal heart beat ceased; however, the urinary beta-human chorionic gonadotrophin (HCG) concentration increased and the gestational sac size also increased. After a second injection of an emulsion of MTX (1 mg/kg) dissolved in a non-ionic contrast medium, iopamidol and lipiodol, the betaHCG concentration in the urine began to decrease. After a third injection with the same emulsion, the cervical mass became necrotic. The betaHCG concentrations in the urine and serum were undetectable and the external cervix returned to normal 44 days after admission. No vaginal bleeding or significant side effects of MTX were observed throughout the treatment. An in-vitro dissolution test revealed that the dissolution rate of MTX was slower from MTX-lipiodol-iopamidol with sonication than without sonication. The present study indicates that use of an MTX emulsion enables slow release of MTX and may be applicable for conservative treatment of ectopic pregnancies, including cervical pregnancy.

Adult↗

Local immune response in endometrial carcinomas.

OBJECTIVE: To determine whether Langerhans cells act as antigen-presenting cells in endometrial carcinomas and their related lesions. SAMPLES: Frozen endometrial samples were obtained from 13 women with normal menstrual cycles, 3 postmenopausal women, 11 women with hyperplasia (simple 4, complex 4 and atypical 3) and 32 women with endometrial carcinomas. MAIN OUTCOME MEASURES: Langerhans cells (CD1), T lymphocytes (CD4 and CD8), B lymphocytes (CD22), natural killer (NK) cells (CD57) and HLA-DR were all quantitatively assessed in endometrial samples using immunohistochemical method. RESULTS: The numbers of Langerhans, CD4+, CD8+ and B cells were higher in the secretory phase than in the proliferative endometrium. The CD8+ cells appeared to be more plentiful than the CD4+ cells. When compared with the proliferative endometrium, the numbers of Langerhans cells were higher in hyperplasias and carcinomas. Most of Langerhans cells were HLA-DR+, showing a strong correlation with CD4+ cells in carcinomas. This suggests that MHC class II antigen restricted lymphocytes in carcinomas are activated by HLA-DR+ Langerhans cells. However, epithelial expression of HLA-DR in carcinomas did not show on association with high numbers of Langerhans and CD4+ cells. No correlation was observed between Langerhans cells and clinicopathologic features of carcinomas. In contrast, the number of NK cells significantly decreased in noninvasive carcinomas but increased in Grade 3 tumours. CONCLUSION: Based on the above findings, Langerhans cells are considered to act as antigen-presenting cells in carcinomas, but it was not shown that they were activated by epithelial expression of HLA-DR in carcinomas.

B-Lymphocytes↗

Local immune response in infertile patients with minimal endometriosis.

OBJECTIVE: To evaluate the role of local immunity in women with minimal endometriosis. METHODS: Uterine endometrium and endometrial implants were obtained simultaneously from 30 infertile women with minimal endometriosis and examined immunohistochemically using antibodies of T cell, B cell, macrophage, Langerhans cell, immunoglobulin (Ig)G, and complement (C) 3d. Serum IgG, IgA, IgM, C3, C4, antinuclear antibody and anti-DNA antibody were also examined in 24 of the women. Data from uterine endometrium and serum were compared with 10 fertile women without endometriosis as a control. RESULTS: Microscopic examination revealed that the endometrial implants were divided into two groups: group 1 (n = 13) showed lymphocytic infiltration in the endometrial implants and group 2 (n = 17) showed no or slight lymphocytic infiltration. The endometrial implants of group 1 showed significantly more dense T-cell infiltration than those of group 2. Other types of infiltrating cells and deposits of IgG and C3d revealed no significant differences between groups 1 and 2. The immunohistochemical examination of the uterine endometrium and the serum data revealed no significant differences among all three groups. Cumulative pregnancy rates showed no significant difference between groups 1 and 2. CONCLUSION: The difference of local immune response in endometrial implants did not affect systemic immunity.

Adult↗

Effects of platelet-activating factor on left ventricular performance in dogs.

To elucidate the mechanism by which platelet-activating factor (PAF) decreases cardiac output (CO), its effects on left ventricular (LV) performance were studied using a LV pressure-volume model in 9 anesthetized dogs. LV volume was measured with a conductance catheter and LV pressure with a manometer-tipped catheter. The slopes of the end-systolic pressure-volume (Ees), stroke work-end-diastolic volume (Mw), and arterial end-systolic pressure-stroke volume relations (Ea), and of end-diastolic pressure-volume relations (EDPVRs), were obtained to evaluate changes in LV performance. The time constant of isovolumetric relaxation (T) was computed by a logarithmic and a derivative method. After intravenous administration of PAF (1 microgram/kg), LV end-diastolic volume and pressure, end-systolic pressure, maximum dP/dt and CO decreased. Ees and Mw decreased significantly, minimum dP/dt decreased, and T increased. The arterial end-systolic pressure-stroke volume relation shifted leftward with an increase in the slope (Ea), whereas EDPVRs were shifted to the left and superimposed on their potential passive diastolic properties. These findings indicate the PAF decreases CO by reducing preload and contractility and by increasing arterial load. However, despite a prolongation of relaxation, PAF may not affect passive diastolic chamber stiffness.

Animals↗

Effects of left ventricular peak filling rate on exercise capacity 3 to 6 weeks after acute myocardial infarction.

STUDY OBJECTIVES: To investigate the importance of early left ventricular (LV) diastolic filling on maintenance of exercise performance, we examined peak filling rate and its relation to exercise capacity during upright bicycle exercise in patients with recent myocardial infarction. DESIGN: Retrospective analysis of data of cardiopulmonary exercise testing characteristics in patients with recent myocardial infarction. SETTING: Coronary care unit in a university hospital. PATIENTS: Fifty-one patients 3 to 6 weeks after acute myocardial infarction. INTERVENTIONS: Upright bicycle exercise using a symptom-limited graded exercise protocol. MEASUREMENTS AND RESULTS: Peak filling rate increased significantly from 1.55 +/- 0.52 at rest to 3.43 +/- 1.1 end-diastolic volume per second at peak exercise. Despite no significant relation between peak filling rate at rest and peak oxygen consumption, peak filling rate at peak exercise correlated significantly with peak oxygen consumption (r = 0.50; p < 0.002), stroke volume (r = 0.51; p < 0.002), and cardiac output (r = 0.56; p < 0.002) at peak exercise. Although both end-systolic and end-diastolic volumes increased from rest to peak exercise, the increases in end-systolic volume correlated inversely with the changes in peak filling rate during exercise (r = -0.45; p < 0.02), but the increases in end-diastolic volume did not. CONCLUSIONS: During maximal upright bicycle exercise, exercise capacity and exercise hemodynamic responses were mainly dependent on early LV diastolic filling, and preserved LV systolic contraction, resulting in a cardiac suction effect following early diastole, seemed to have an important role in the enhancement of early LV diastolic filling in patients with recent myocardial infarction.

Cardiac Output↗

Prognostic significance of precordial ST-segment changes in acute inferior wall myocardial infarction.

STUDY OBJECTIVE: To examine the clinical significance of precordial ST-segment changes in patients with acute Q-wave inferior wall myocardial infarction. DESIGN: Prospective evaluation (clinical follow-up) of Q-wave inferior wall myocardial infarction over a 6-year period in patients who fulfilled the inclusion criteria. SETTING: Coronary care unit at a university hospital. PATIENTS: Two hundred consecutive patients with acute Q-wave inferior wall myocardial infarction admitted to the coronary care unit within 24 h from the onset of chest pain. MEASUREMENTS AND RESULTS: Precordial ST-segment depression resolved <24 h (transient) after admission in 84 patients, lasted > or = 24 h (persistent) in 48 patients, and was absent in 68 patients, while ST-segment elevation in V4R was detected in 60 patients. Seventy-one patients had major in-hospital complications and 18 patients died in the hospital. When nine variables were used in the multivariate analysis, right ventricular dilatation and persistent precordial ST-segment depression were the important factors related to major in-hospital complications, whereas age, alveolar arterial oxygen difference, and persistent precordial ST-segment depression were important for in-hospital deaths. CONCLUSION: Left ventricular posterior wall involvement, diagnosed by persistent precordial ST-depression, was an independent and stronger predictor of major in-hospital complications and deaths than right ventricular involvement in patients with acute Q-wave inferior wall myocardial infarction.

Adult↗

Left atrial function as a reliable predictor of exercise capacity in patients with recent myocardial infarction.

STUDY OBJECTIVE: To examine the relation between left atrial (LA) function and exercise performance. DESIGN AND SETTING: Retrospective study at a referral cardiopulmonary exercise laboratory in a university hospital. PATIENTS: Forty-one patients with recent myocardial infarction. INTERVENTIONS: M-mode echocardiography and cardiopulmonary exercise testing combined with radionuclide ventriculography. MEASUREMENTS AND RESULTS: Hemodynamic measurements were obtained at rest and peak exercise. LA fractional shortening at rest was used as an index of global LA function. LA fractional shortening had fair correlations with peak oxygen consumption (r=0.67, p<0.01) and exercise duration (r=0.71, p<0.01). Although there were no significant relations between LA fractional shortening and hemodynamic measurements at rest, LA fractional shortening was positively related to peak cardiac output (r=0.61, p<0.01) and peak stroke volume (r=0.57, p<0.01), and negatively related to peak pulmonary arterial wedge pressure (r=-0.44, p<0.05). In addition, LA fractional shortening correlated significantly with an increase in left ventricular (LV) end-diastolic volume from rest to peak exercise (r=0.48, p<0.02), but did not correlate with the changes in ejection fraction and end-systolic volume during exercise. An increase in LV end-diastolic volume during exercise was significantly related to peak oxygen consumption (r=0.46, p<0.02), peak cardiac output (r=0.60, p<0.01), and peak stroke volume (r=0.53, p<0.01), whereas the changes in ejection fraction and end-systolic volume during exercise were not related to these indexes. CONCLUSIONS: Exercise capacity and LV performance during exercise were mainly dependent on LV diastolic filling rather than systolic contraction during exercise. LA fractional shortening at rest reflected LV diastolic filling during exercise and, therefore, predicted cardiac output and stroke volume responses to exercise and exercise capacity in patients with recent myocardial infarction.

Adult↗

Serial assessment of sympathetic reinnervation in a patient with myocardial infarction.

Resting [123I]MIBG and 201TI imaging were performed at 2 wk and 4 and 12 mo after successfully reperfused myocardial infarction. Although [123I]MIBG uptake of the infarcted segments revealed significant improvement in the early image at 4 mo, delayed image displayed decreased [123I]MIBG uptake. However, decreased [123I]MIBG uptake of the delayed image became almost uniform at 12 mo. These observations suggest that reinnervation initially occurs in norepinephrine uptake and then in retention ability. On the other hand, a 201TI defect remained in the infarcted segments at 12 mo. Thus, reinnervation can occur not only in the peri-infarct area but also in the infarcted area.

3-Iodobenzylguanidine↗

[Usefulness of magnetic resonance imaging for managing patients with prosthetic carbon valve in the mitral position].

The safety, findings and clinical usefulness of magnetic resonance (MR) imaging were assessed in patients with a prosthetic carbon valve in the mitral position. In vitro deflection, heating and image distortion due to the magnetic field of a 1.5 tesla MR machine were examined in three carbon valves (CarboMedics, St. Jude Medical and Björk-Shiley valves). In vivo MR imaging of the left ventricular horizontal long-axis, vertical long-axis and short-axis views was performed by electrocardiographically synchronized spin echo and field (gradient) echo techniques in eight patients with prosthetic mitral carbon valves, consisting of six CarboMedics valves, one St. Jude Medical valve and one Björk-Shiley valve. No deflection and significant heating was seen in all three valves in vitro. Although little image distortion was shown in the CarboMedics and St. Jude Medical valves, a small distortion toward the frequency encoded direction was seen in the Björk-Shiley valve but caused no difficulty in assessing the surrounding images. Four of the eight patients had normal sinus rhythm and the other four had atrial fibrillation. The prosthetic valves were depicted as signal voids in the images taken by both spin echo and field echo techniques in vivo. Clear structural information with little image distortion of the adjacent tissues of the prosthetic valves were obtained in all patients, although the image of the Björk-Shiley valve which contained stainless steel in the frame had a slightly stronger distortion than those of the CarboMedics and St. Jude Medical valves which contained titanium. The stainless wire suture material used to close the sternal incision was depicted as a signal void, and the areas of the signal loss were larger in the images taken by the field echo technique than those by the spin echo technique. The images taken by the spin echo technique in patients with atrial fibrillation had reduced quality due to the irregularity of repetition time. Cine MR imaging by the field echo technique showed physiological mitral regurgitant jets as signal loss within the flowing blood, which appeared as high signal intensity, bidirectionally in the bileaflet mechanical valve and unidirectionally in the monoleaflet mechanical valve. An abnormal cavity was seen behind the basal left ventricular myocardium in one patient with a CarboMedics valve. The wall of the abnormal cavity was disrupted abruptly and the rest of the wall consisted of pericardium and adjacent tissue in the image taken by the spin echo technique. The image taken by the field echo technique showed an abnormal jet flow from the basal part of the left ventricular cavity into the abnormal cavity, which was compatible with left ventricular pseudoaneurysm. Two-dimensional echocardiography and Doppler color flow mapping disclosed the abnormal cavity and the abnormal flow inside, but failed to show the connection between the left ventricle and the cavity due to reverberation of the ultrasound signal by the prosthetic valve. These findings suggest that MR imaging is a safe and promising method to assess the complications and valvular function in patients with a prosthetic carbon valve in the mitral position.

Aged↗

Diastolic time during exercise-induced myocardial ischemia in patients with myocardial infarction.

The relation between diastolic time and myocardial perfusion defect redistribution of the infarct-related region was studied during upright bicycle exercise with thallium-201 scintigraphy in 37 patients with recent anterior myocardial infarction. In addition to the higher incidence of residual stenosis of the infarct-related artery, a disproportionate shortening of diastolic time in patients with myocardial perfusion defect redistribution permitted further reduction of subendocardial blood flow during exercise.

Diastole↗