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Biomedical subjects

T Iwasaka

Publications and source records attributed to T Iwasaka.

At least 91 records · Page 5Linked to original sources
PubMed1999

Multiple spontaneous small bowel perforations due to systemic cholesterol atheromatous embolism.

A-65-year-old man was admitted for coronary and peripheral angiography to evaluate angina pectoris and peripheral vascular disease. Following angiography, he suffered from blue toes, livedo reticularis and progressive renal failure. The patient's condition continued to deteriorate, including the development of malnutrition. Four months later he suddenly developed panperitonitis, went into shock and died. The autopsy verified multiple perforations of the small bowel with disseminated cholesterol atheromatous embolism. The other organs including kidney were also invaded by atheroembolism. This was a rare case of multiple spontaneous perforations of small bowel due to systemic cholesterol atheromatous embolism.

Acute Kidney Injury↗
PubMed1999

Differential kinetics of circulating angiotensin IV and II after treatment with angiotensin II type 1 receptor antagonist and their plasma levels in patients with chronic renal failure.

BACKGROUND: Angiotensin II (Ang II) C-terminal hexapeptide (referred to as Ang IV) possesses the characteristics of a real hormone with specific receptors and biological effects. Clinical application of Ang II type 1 receptor (AT1-R) antagonists cause an increase in plasma Ang II level, which may result in enhanced production of Ang IV. PATIENTS AND METHODS: In this study, we measured plasma Ang IV and Ang II levels in patients with chronic renal failure (CRF), and also examined the changes in Ang IV and Ang II levels after administration of an ATI-R antagonist. RESULTS: Ang II and Ang IV levels in CRF patients untreated with hemodialysis (n = 16) were 15.8+/-3.6 and 6.0+/-1.1 pg/ml, respectively, which did not differ significantly from Ang II (20.6+/-2.4) and Ang IV levels (8.6+/-1.1) in normal controls (n = 23). The ratio of Ang IV to Ang II was 38%, similar to that in the controls (41%). Ang II or Ang IV levels in CRF patients treated with hemodialysis (n = 12) were also similar to the control values. Ang IV levels had a significant correlation with Ang II levels (r = 0.59). When hypertensive patients were treated with an AT1-R antagonist candesartan for 7 days, Ang II and Ang IV levels were increased 5.5- and 4.1-fold relative to the control levels, respectively. Ang II levels 28 and 56 days after treatment were significantly lower than those 7 days after treatment, whereas Ang IV levels did not differ significantly from those 7 days after treatment. Similar differential kinetics in Ang II and Ang IV levels after long-term (90 days) treatment with an AT1-R antagonist was also confirmed in experiments using rats. Significant decrease in blood pressure continued during long-term treatment with an AT1-R antagonist. CONCLUSION: These findings demonstrated that plasma Ang IV levels in patients with CRF did not differ significantly from those in normal subjects, and that treatment with an AT1-R antagonist caused marked increases in both Ang II and Ang IV levels. In contrast, during long-term treatment plasma Ang II levels were more rapidly decreased than Ang IV levels, suggesting longer-lasting enhancement of the action of Ang IV rather than that of Ang II after treatment with an AT1-R antagonist.

Aged↗
PubMed1999

Optimum threshold values of 201Tl SPET in the determination of the left ventricular border and extent of myocardial infarction.

The aim of this study was to determine the optimum threshold value of the left ventricular border and the extent of myocardial infarction using quantitative 201Tl single photon emission tomography (SPET). We used the unfolded map method to determine the size of the left ventricle and the extent of myocardial infarction in 10 patients, because it has been shown to be superior to the conventional polar map method. The relative differences in the size of the left ventricle and extent of infarction between 201Tl SPET and post-mortem examination were calculated. The optimum threshold value was determined when the relative difference = 0%. There was an excellent correlation between scintigraphic and post-mortem left ventricular size at a threshold value of 53% (r = 0.91, P < 0.001); an excellent correlation was also observed between scintigraphic and post-mortem infarct size at a threshold value of 55% (r = 0.93, P < 0.03). The optimum threshold value in determining left ventricular size using 201Tl SPET is 53% and that in determining infarct size is 55%.

Adult↗
PubMed1999

[Angiotensin II receptor-mediated function unmasked by gene-engineered animals].

The receptors for angiotensin (Ang) II are classified into two subtypes (AT1-R and AT2-R) by the discovery of non-peptidic ligands and AT1-R mediates most of the cardiovascular actions of Ang II. AT2-R is expressed at very high levels in the developing fetus, whereas in the adult its expression in the cardiovascular system is very low. Cardiac myocyte- or vascular smooth muscle-specific overexpression mice of AT2-R display an inhibitory effect on Ang II-induced chronotropic or pressor actions, suggesting the role of AT2-R on the activity of cardiac pacemaker cells or maintenance of vascular resistance. AT2-R also activates the kinin/nitric oxide/cGMP system in the cardiovascular and renal system, resulting in the AT2-R-mediated cardioprotection, vasodilation and pressure natriuresis. These effects transmitted by AT2-R are mainly exerted by stimulation of protein tyrosine or serine/threonine phosphatases in Gi-protein dependent manner. The expression level of AT2-R is much higher in human hearts than in those of rodents, and the AT2-R-mediated actions are likely enhanced, especially by clinical application of AT1-R antagonists.

Adult↗
PubMed1999

Measurement of serum leptin in patients with chronic renal failure on hemodialysis.

BACKGROUND: Leptin, the product of the obese gene, is produced exclusively in fat cells. SUBJECTS, MATERIALS AND METHODS: To evaluate the clinical significance of measuring serum leptin in 56 patients with chronic renal failure on hemodialysis (HD), we measured leptin levels using radioimmunoassay in 34 normal volunteers and in 56 patients on HD. RESULTS: Normal serum leptin averaged 5.7 +/- 0.7 (mean +/- SEM) ng/ml, which correlated significantly (p < 0.001) with the body fat percentage as measured by bioelectrical impedance analysis. Serum leptin in HD patients ranged from 1.3 to 142 ng/ml. The mean serum leptin analyzed after the logarithmic conversion was 5.6 ng/ml, which was not significantly different from the normal control value, although the body fat percentage was significantly lower than normal volunteers. There was a significant (p < 0.01) positive correlation between body fat percentage and serum leptin in both normal controls and HD patients. The slope of the regression curve was steeper in HD patients than in normal controls. CONCLUSION: (1) serum leptin levels to body fat mass are significantly higher in HD patients than controls; (2) the variability is much wider in HD patients; and (3) a significant relation exists between percent body fat and log serum leptin, the relation being steeper in HD patients than in controls.

Adipose Tissue↗
PubMed1999

Heart rate variability and left ventricular dilatation early after myocardial infarction.

To assess clinically whether alterations of autonomic tone precede left ventricular dilatation, heart rate variability and early left ventricular dilatation after a first myocardial infarction were assessed. Low-frequency power (LF), high-frequency power (HF), and total power (TP) were obtained by ambulatory electrocardiogram on day 1 in 53 patients with a first acute myocardial infarction. Left ventricular end-diastolic volume determined by echocardiography was obtained on day 1 and day 14. Stepwise linear regression analysis was used to assess the associations of early left ventricular dilatation with heart rate variability adjusted for clinical variables. Higher LF and TP were significantly associated with early left ventricular dilatation after adjustment for age, sex, site of myocardial infarction, acute revasucularization, peak creatine kinase level, history of hypertension, and use of angiotensin-converting enzyme inhibitors and beta-blockers. Higher LF and TP preceded early left ventricular dilatation after myocardial infarction.

Echocardiography↗
PubMed1999

[Animal models for autoimmune thyroid disease].

Animal models for chronic thyroiditis include (1) experimental autoimmune thyroiditis induced by immunizing rabbits or rodents with thyroid extracts or thyroglobulin and (2) spontaneous thyroiditis in certain species of rodents and chickens. For Graves' disease, no spontaneous animal models are reported. An animal model for Graves' disease has been developed by xenotransplantation of Graves' thyroid tissue plus autologous immune cells to immunodeficient mice. Another animal model for Graves' disease is made by immunizing TSH receptor-peptide or protein to mice. Animal models are very useful for studying etiology of autoimmune thyroid diseases, although no current animal models are satisfactory for human autoimmune thyroid disease.

Animals↗
PubMed1999

[Anti-thyroglobulin antibodies].

Measurement of anti-thyroglobulin antibody(TgAb) is used for diagnosis of autoimmune thyroid disease(AITD). Approximately 82-100% of patients with Hashimoto's thyroiditis and 60-70% of patients with Graves' disease are TgAb positive using high sensitive radioimmunoassay. In patients with subacute thyroiditis(SAT), TgAb is usually negative. Therefore, measurement of TgAb is useful to diagnose painless thyroiditis or acute worsening of Hashimoto's thyroiditis from SAT. To predict the post-partum thyroid dysfunction and thyroid dysfunction after interferon treatment, TgAb measurement is important, since patients with positive TgAb are apt to progress thyroid dysfunction.

Autoantibodies↗
PubMed1998

Angiotensin II type 2 receptor is upregulated in human heart with interstitial fibrosis, and cardiac fibroblasts are the major cell type for its expression.

The expression pattern of angiotensin (Ang) II type 2 receptor (AT2-R) in the remodeling process of human left ventricles (LVs) remains poorly defined. We analyzed its expression at protein, mRNA, and cellular levels using autopsy, biopsy, or operation LV samples from patients with failing hearts caused by acute (AMI) or old (OMI) myocardial infarction and idiopathic dilated cardiomyopathy (DCM) and also examined functional biochemical responses of failing hearts to Ang II. In autopsy samples from the nonfailing heart group, the ratio of AT1-R and AT2-R was 59% and 41%, respectively. The expression of AT2-R was markedly increased in DCM hearts at protein (3.5-fold) and mRNA (3.1-fold) levels compared with AMI or OMI. AT1-R protein and mRNA levels in AMI hearts showed 1.5- and 2.1-fold increases, respectively, whereas in OMI and DCM hearts, AT1-R expression was significantly downregulated. AT1-R-mediated response in inositol phosphate production was significantly attenuated in LV homogenate from failing hearts compared with nonfailing hearts. AT2-R sites were highly localized in the interstitial region in either nonfailing or failing heart, whereas AT1-R was evenly distributed over myocardium at lower densities. Mitogen-activated protein kinase (MAPK) activation by Ang II was significantly decreased in fibroblast compartment from the failing hearts, and pretreatment with AT2-R antagonist caused an additional significant increase in Ang II-induced MAPK activity (36%). Cardiac hypertrophy suggested by atrial and brain natriuretic peptide levels was comparably increased in OMI and DCM, whereas accumulation of matrix proteins such as collagen type 1 and fibronectin was much more prominent in DCM than in OMI. These findings demonstrate that (1) AT2-R expression is upregulated in failing hearts, and fibroblasts present in the interstitial regions are the major cell type responsible for its expression, (2) AT2-R present in the fibroblasts exerts an inhibitory effect on Ang II-induced mitogen signals, and (3) AT1-R in atrial and LV tissues was downregulated during chronic heart failure, and AT1-R-mediated functional biochemical responsiveness was decreased in the failing hearts. Thus, the expression level of AT2-R is likely determined by the extent of interstitial fibrosis associated with heart failure, and the expression and function of AT1-R and AT2-R are differentially regulated in failing human hearts.

Adult↗
PubMed1998

Angiotensin II type 1 receptor-induced extracellular signal-regulated protein kinase activation is mediated by Ca2+/calmodulin-dependent transactivation of epidermal growth factor receptor.

The signaling cascade elicited by angiotensin II (Ang II) resembles that characteristic of growth factor stimulation, and recent evidence suggests that G protein-coupled receptors transactivate growth factor receptors to transmit mitogenic effects. In the present study, we report the involvement of epidermal growth factor receptor (EGF-R) in Ang II-induced extracellular signal-regulated kinase (ERK) activation, c-fos gene expression, and DNA synthesis in cardiac fibroblasts. Ang II induced a rapid tyrosine phosphorylation of EGF-R in association with phosphorylation of Shc protein and ERK activation. Specific inhibition of EGF-R function by either a dominant-negative EGF-R mutant or selective tyrphostin AG1478 completely abolished Ang II-induced ERK activation. Induction of c-fos gene expression and DNA synthesis were also abolished by the inhibition of EGF-R function. Calmodulin or tyrosine kinase inhibitors, but not protein kinase C (PKC) inhibitors or downregulation of PKC, completely abolished transactivation of EGF-R by Ang II or the Ca2+ ionophore A23187. Epidermal growth factor (EGF) activity in concentrated supernatant from Ang II-treated cells was not detected, and saturation of culture media with anti-EGF antibody did not affect the Ang II-induced transactivation of EGF-R. Conditioned media in which cells were incubated with Ang II could not induce phosphorylation of EGF-R on recipient cells. Platelet-derived growth factor-beta receptor was not phosphorylated on Ang II stimulation, and Ang II-induced c-jun gene expression was not affected by tyrphostin AG1478. Our results demonstrated that in cardiac fibroblasts Ang II-induced ERK activation and its mitogenic signals are dominantly mediated by EGF-R transactivated in a Ca2+/calmodulin-dependent manner and suggested that the effects of Ang II on cardiac fibroblasts should be interpreted in association with the signaling pathways regulating cellular proliferation and/or differentiation by growth factors.

Animals↗
PubMed1998

Pericardial effusion after primary percutaneous transluminal coronary angioplasty in first Q-wave acute myocardial infarction.

To evaluate the incidence and clinical significance of infarction-associated pericardial effusion in patients with successful primary percutaneous transluminal coronary angioplasty, we studied 214 consecutive patients with a first Q-wave acute myocardial infarction. Based on 9 clinical variables, multivariate analysis was performed to determine the important variables related to the occurrence of pericardial effusion. Pericardial effusion was detected by echocardiography in 45 patients (21%); pericardial rub (p <0.001), number of advanced asynergic segments (p <0.001), ventricular aneurysmal motion (p = 0.03), and pulmonary capillary wedge pressure (p = 0.04) were found to be the important variables related to pericardial effusion. Among 45 patients with pericardial effusion, 29 patients with no pericardial rub had significantly higher pulmonary capillary wedge pressure than those with pericardial rub, whereas 16 patients with pericardial rub had a higher incidence of angiographic no reflow and ventricular aneurysmal motion than those without pericardial rub. Patients with pericardial effusion and a pericardial rub had a higher mortality rate than those without pericardial effusion (19% vs 3%; p = 0.02). Thus, pericardial effusion is still a relatively common clinical finding after primary percutaneous transluminal coronary angioplasty, and those with pericardial effusion and a pericardial rub were associated with more severe transmural myocardial damage and higher in-hospital mortality.

Aged↗
PubMed1998

Cardiac-specific overexpression of angiotensin II AT2 receptor causes attenuated response to AT1 receptor-mediated pressor and chronotropic effects.

Angiotensin (Ang) II has two major receptor isoforms, AT1 and AT2. Currently, AT1 antagonists are undergoing clinical trials in patients with cardiovascular diseases. Treatment with AT1 antagonists causes elevation of plasma Ang II which selectively binds to AT2 and exerts as yet undefined effects. Cardiac AT2 level is low in adult hearts, whereas its distribution ratio is increased during cardiac remodeling and its action is enhanced by application of AT1 antagonists. Although in AT2 knock-out mice sensitivity to the pressor action of Ang II was increased, underlying mechanisms remain undefined. Here, we report the unexpected finding that cardiac-specific overexpression of the AT2 gene using alpha-myosin heavy chain promoter resulted in decreased sensitivity to AT1-mediated pressor and chronotropic actions. AT2 protein undetectable in the hearts of wild-type mice was overexpressed in atria and ventricles of the AT2 transgenic (TG) mice and the proportions of AT2 relative to AT1 were 41% in atria and 45% in ventricles. No obvious morphological change was observed in the myocardium and there was no significant difference in cardiac development or heart to body weight ratio between wild-type and TG mice. Infusion of Ang II to AT2 TG mice caused a significantly attenuated increase in blood pressure response and the change was completely blocked by pretreatment with AT2 antagonist. This decreased sensitivity to Ang II-induced pressor action was mainly due to the AT2-mediated strong negative chronotropic effect and exerted by circulating Ang II in a physiological range that did not stimulate catecholamine release. Isolated hearts of AT2 transgenic mice perfused using a Langendorff apparatus also showed decreased chronotropic responses to Ang II with no effects on left ventricular dp/dt max values, and Ang II-induced activity of mitogen-activated protein kinase was inhibited in left ventricles in the transgenic mice. Although transient outward K+ current recorded in cardiomyocytes from AT2 TG mice was not influenced by AT2 activation, this study suggested that overexpression of AT2 decreases the sensitivity of pacemaker cells to Ang II. Our results demonstrate that stimulation of cardia AT2 exerts a novel antipressor action by inhibiting AT1-mediated chronotropic effects, and that application of AT1 antagonists to patients with cardiovascular diseases has beneficial pharmacotherapeutic effects of stimulating cardiac AT2.

Angiotensin II↗
PubMed1998

Prognostic significance of progesterone receptor immunohistochemistry in endometrial carcinoma.

OBJECTIVE: The aim of this study was to evaluate the prognostic significance of steroid hormone receptors in endometrial carcinoma using immunohistochemical staining for progesterone receptor (PR) and estrogen receptor (ER). METHODS: We evaluated the correlation between PR/ER immunohistochemistry and age, clinical stage, tumor grade, myometrial tumor invasion, and disease-free survival in a series of 92 cases of endometrioid adenocarcinoma. RESULTS: Fifty (54.4%) endometrial carcinomas were PR-positive and 44 (47.8%) were ER-positive. PR immunohistochemistry of endometrial carcinoma was statistically correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage (I, II vs III, IV, P = 0.001), FIGO grade (G1 vs G2 vs G3, P = 0.007), the depth of myometrial tumor invasion (< or = 1/2 vs > 1/2, P = 0.006), and disease-free survival (living vs dead, P = 0.0025). In contrast, ER immunohistochemistry had significant correlations with the depth of myometrial tumor invasion (P = 0.026) and disease-free survival (P = 0.032). Multivariate analysis of PR/ER immunohistochemistry, stage, grade, and myometrial invasion showed that the PR immunohistochemistry was a significant prognostic factor for survival (P = 0.026). CONCLUSION: PR/ER immunohistochemistry was significantly related to survival and PR immunohistochemistry appeared to be the most reliable means for predicting survival in endometrioid adenocarcinoma of the endometrium, independent of other clinicopathological parameters.

Adult↗
PubMed1998

Neoadjuvant chemotherapy with mitomycin C, etoposide, and cisplatin for adenocarcinoma of the cervix.

Between May 1990 and February 1995, 16 patients with adenocarcinoma or adenosquamous carcinoma of the uterine cervix were prescribed neoadjuvant chemotherapy consisting of cisplatin (50 mg/m2) on day 1, mitomycin C (10 mg/m2) on day 1, and etoposide (100 mg/m2) on days 1, 3, and 5 (MEP). In 2 patients stage was IB1, 5 were in stage IB2, 1 was in stage IIA, 5 were in stage IIB, 2 were in stage IIIB, and one was in stage IVB. A median of three courses of chemotherapy was given (range two to five). Of the 16 patients, 3 had a complete response and 5 had a partial response (response rate, 50%). Following termination of this chemotherapy, 12 patients with stage I or stage II carcinoma underwent radical hysterectomy. Three were given adjuvant radiotherapy because of positive pelvic nodes. One stage IIB patient, 1 stage IIIB patient and 1 stage IVB patient underwent standard radiotherapy and 1 stage IIIB patient underwent chemotherapy with another regimen because MEP therapy was without effect. Histopathological examinations revealed that changes as a result of the chemotherapy correlated well with clinical responses. Moderate or marked pathological changes occurred in 3 with a clinically complete response. The mean survival period of responders was 47.5 months while that of nonresponders was 28.3 months. Side effects of chemotherapy with MEP were within acceptable limits. The dose-limiting toxicity was myelosuppression and for only 1 patient the dose was reduced because of thrombocytopenia. Our preliminary study indicates that this chemotherapy regimen is effective for subjects with adenocarcinoma of the cervix. A prospective cooperative group trial on this regimen is ongoing.

Adenocarcinoma↗
PubMed1998

Importance of intrinsic calf vasodilator capacity in determining distribution of skeletal muscle perfusion during supine bicycle exercise in patients with left ventricular dysfunction.

BACKGROUND: Distribution of skeletal muscle perfusion during exercise is an important factor in determining exercise capacity and is markedly impaired in patients with cardiac disease. This study examined the importance of intrinsic calf vasodilator capacity in determining distribution of skeletal muscle perfusion during supine bicycle exercise in patients with left ventricular dysfunction. METHODS: We studied 19 patients with left ventricular dysfunction (left ventricular ejection fraction <45%) after myocardial infarction. All the patients underwent cardiopulmonary exercise testing with measurements of central hemodynamics, leg blood flow (LBF), and the percentage of cardiac output distributed to both legs (%LBF). Calf reactive hyperemic flow (RH) was measured by venous occlusive plethysmography at supine rest. RESULTS: LBF at peak exercise was closely related to peak cardiac output and RH. Furthermore, %LBF at peak exercise had modest correlation with peak cardiac output and good correlation with RH. Although peak cardiac output and RH were independent determinants of LBF at peak exercise by multiple regression analysis, RH had higher correlation with %LBF at peak exercise than peak cardiac output. Despite marked changes in other hemodynamic variables, nonleg blood flow during exercise was constantly maintained at a level identical to resting value. CONCLUSIONS: Calf vasodilator capacity, which was the major determinant of distribution of skeletal muscle perfusion during exercise, may have contributed to maintaining perfusion of important nonexercising regions during exercise in patients with left ventricular dysfunction.

Adult↗
PubMed1998

Telomerase activation in cervical neoplasia.

OBJECTIVE: To examine the critical point at which telomerase activation occurs in the course of cervical carcinogenesis. METHODS: Telomeric repeat assay protocol was used to measure telomerase activity in cell samples obtained from 155 Japanese women with various cervical conditions: normal cytology (n = 62), cervical intraepithelial neoplasia (CIN) (n = 63), and invasive squamous cell carcinoma (n = 30). RESULTS: Telomerase activity was detected in five (8%) women with normal cytology, in 26 (41%) patients with CIN (26% of patients with CIN I, 35% with CIN II, and 68% with CIN III), and in 29 (97%) patients with invasive carcinoma. Telomerase activation was significantly more frequent in CIN than in normal cervices (P < .001), and the positive rate in CIN III was significantly higher than that in CIN I (P < .01) and CIN II (P < .05). Furthermore, telomerase activation was significantly more frequent in invasive carcinoma than in CIN III (P < .01). CONCLUSION: Our findings suggest that telomerase activation is a relatively early event in cervical carcinogenesis and correlates well with grade of cervical lesion.

Adult↗