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Biomedical subjects

T Iwasaka

Publications and source records attributed to T Iwasaka.

At least 55 records · Page 3Linked to original sources
PubMed2001

[Gene-therapy for peripheral vascular diseases].

The prognosis for patients with chronic critical leg ischemic is often poor. The treatment of peripheral vascular disease, although greatly improved over recent decades by drug medication, surgical and minimally-invasive techniques, remains limited by vascular proliferative lesions and by our inability to modulate the progression of native disease. The therapeutic angiogenesis is now the most expected therapy for peripheral vascular diseases. This review explores some of concepts and methods of therapeutic angiogenesis including gene therapy using angiogenic growth factor such as VEGF and basic FGF and an implantation of bone marrow derived endothelial progenitor cells.

Animals↗
PubMed2001

Accuracy of technetium-99m tetrofosmin myocardial perfusion imaging in the detection of spontaneous recanalization in patients with acute anterior myocardial infarction.

To avoid the haemorrhagic risk of unnecessary thrombolysis in acute myocardial infarction (MI), early and precise diagnosis of spontaneous recanalization (SR) of the infarct-related artery is required. To clarify the accuracy of technetium-99m tetrofosmin myocardial single-photon emission tomography (SPET) in the detection of SR in patients with acute anterior MI, electrocardiography (ECG), echocardiography and 99mTc-tetrofosmin SPET imaging were performed in 49 patients with acute anterior MI before emergency coronary angiography. Defect score was calculated as the sum of the perfusion defects of each segment: from 3 (complete defect) to 0 (normal perfusion). Echocardiographic asynergic score (the sum of asynergic grades) and the greatest ST elevation of the 12-lead ECG on admission were also measured. SR was defined as Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow on emergency coronary angiography. Defect score in 11 patients with SR (9.2 +/- 3.7) was significantly lower than that in 38 patients without SR (18.5 +/- 5.0) (P < 0.001), whereas there were no significant differences in asynergic score and ST elevation between the two groups. From the receiver operating characteristic curves, the optimal cut-off points of defect score, asynergic score and ST elevation for the detection of SR were calculated to be 12, 13 and 3.5, respectively. The sensitivity and specificity of the scintigraphic defect score (91% and 89%) were significantly higher than those of the asynergic score (64% and 68%) and ST elevation (73% and 71%). Thus, 99mTc-tetrofosmin SPET imaging on admission is a very accurate method for the detection of SR in patients with acute anterior MI.

Acute Disease↗
PubMed2000

Effect of angiotensin-converting enzyme inhibitor on cardiopulmonary baroreflex sensitivity in patients with acute myocardial infarction.

We evaluated the effect of angiotensin-converting enzyme inhibition (quinapril) on cardiopulmonary baroreflex sensitivity in 30 patients with uncomplicated myocardial infarction (quinapril group, 15 patients; placebo group, 15 patients) at 5 and 10 days after the onset of myocardial infarction. This study indicates that quinapril improved cardiopulmonary baroreflex and thus reduced sympathetic outflow in patients with acute myocardial infarction.

Administration, Oral↗
PubMed2000

Angiotensin II initiates tyrosine kinase Pyk2-dependent signalings leading to activation of Rac1-mediated c-Jun NH2-terminal kinase.

Ca(2+)-sensitive tyrosine kinase Pyk2 was shown to be involved in angiotensin (Ang) II-mediated activation of extracellular signal-regulated kinase (ERK) via transactivation of epidermal growth factor receptor (EGF-R). In this study, we tested the involvement of Pyk2 and EGF-R in Ang II-induced activation of JNK and c-Jun in cardiac fibroblasts. Ang II markedly stimulated JNK activities, which were abolished by genistein and intracellular Ca(2+) chelators but partially by protein kinase C depletion. Inhibition of EGF-R did not affect Pyk2 and JNK activation by Ang II. Stable transfection with a dominant negative (DN) mutant for Pyk2 (PKM) completely blocked JNK activation by Ang II. DN mutants of Rac1 (DN-Rac1) and MEK kinase (DN-MEKK1) also abolished it, whereas those of Cdc42, RhoA, and Ha-Ras had no effect. Induction of c-Jun gene transcription by Ang II was abolished in PKM, DN-Rac1, and DN-MEKK1, in which Ang II-induced binding of ATF2/c-Jun heterodimer to the activator protein-1 sequence at -190 played a key role. These results suggest that 1) in cardiac fibroblasts activation of JNK and c-Jun by Ang II is initiated by Pyk2-dependent signalings but not by downstream signals of EGF-R or Ras, 2) Rac1 but not Cdc42 is required for JNK activation by Ang II upstream of MEKK1, and 3) ATF-2/c-Jun binding to the activator protein-1 sequence at -190 plays a key role for induction of c-Jun gene by Ang II.

Angiotensin II↗
PubMed2000

Mild mitral regurgitation was associated with increased prevalence of thromboembolic events in patients with nonrheumatic atrial fibrillation.

Although several studies demonstrated that the presence of significant mitral regurgitation was associated with reduced occurrence of thromboembolism, little data is available concerning the effect of mild mitral regurgitation on the occurrence of thromboembolic events. To evaluate the association between mild mitral regurgitation and thromboembolic events, we reviewed 232 patients' records between January 1996 and September 1997 who had nonrheumatic atrial fibrillation. There were 59 patients (25%) with mitral regurgitation > or = grade 2, 69 patients (30%) with grade 1 mitral regurgitation, and 104 patients (45%) with no mitral regurgitation. Patients with grade 1 mitral regurgitation had significantly higher prevalence of thromboembolic events (28%) than those with mitral regurgitation > or = grade 2 (8%, P=0.006) or those with no mitral regurgitation (11%, P=0.007). A history of previous thromboembolic events were compared between 173 patients with grade 1 mitral regurgitation and those with no mitral regurgitation using the logistic regression analysis adjusted for age, sex, administration of warfarin, and presence of hypertension, diabetes mellitus, structural heart disease, enlarged left atrium (> or = 40 mm), chronic atrial fibrillation, and grade 1 mitral regurgitation. Grade 1 mitral regurgitation (odds ratio=2.689, 95% confidence interval=1.039-7.189, P=0.0434) and no warfarin administration (odds ratio=0.045, 95% confidence interval=0.002-0.242, P=0.0036) were significantly associated with the history of thromboembolic events. The presence of mild mitral regurgitation in nonrheumatic atrial fibrillation was associated with higher prevalence of thromboembolic events.

Aged↗
PubMed2000

Telomerase activity in Papanicolaou smear-negative exfoliated cervical cells and its association with lesions and oncogenic human papillomaviruses.

OBJECTIVE: The goal of this study was to evaluate telomerase activity in exfoliated cervical cells and its association with cytology, pathology, and human papillomavirus (HPV). METHODS: Telomerase activity and HPV DNA sequences were examined in the exfoliated cervical cells from a general population of 245 women aged more than 30 years undergoing routine cervical screening by Papanicolaou smear. The women who were found to have telomerase activity or abnormal cytology in their exfoliated cervical cells were examined for cervical lesions by colposcopy and biopsy. RESULTS: Cytology for our population (mean, 56 years) revealed only one abnormal smear (1/245, 0.4%), in which a cervical intraepithelial neoplasia grade I (CIN I) lesion was found. The exfoliated cervical cells used to prepare the smear were negative for telomerase and contained low-risk HPV DNA. Telomerase activity was found in 16 exfoliated cell samples (16/245, 6.5%); high-risk HPV DNA was found in 9 of these samples (9/16, 56%) and 9 of the biopsy specimens that could be evaluated from patients testing positive for telomerase revealed CIN I lesions (9/11, 82%). CONCLUSIONS: Telomerase activity is often associated with high-risk HPV infection and it is suggested that telomerase assay can help to detect occult cervical lesions.

Adult↗
PubMed2000

Transactivation of EGF receptor induced by angiotensin II regulates fibronectin and TGF-beta gene expression via transcriptional and post-transcriptional mechanisms.

The signaling cascade elicited by angiotensin II (Ang II) resembles that characteristic of growth factor, and recent evidence indicates transactivation of epidermal growth factor receptor (EGF-R) by G protein-coupled receptors. Here, we report the involvement of EGF-R in Ang II-induced synthesis of fibronectin and TGF-beta in cardiac fibroblasts. Ang II stimulated fibronectin mRNA levels dose-dependently with a maximal increase (approximately 5-fold) observed after 12 h of incubation. Ang II-, or calcium ionophore-induced fibronectin synthesis was completely abolished by tyrosine kinase inhibitors and intracellular Ca2+ chelating agents. Ang II-induced fibronectin mRNA was not affected by PKC inhibitors or PKC depletion, whereas specific inhibition of EGF-R function by a dominant negative EGF-R mutant and tyrphostin AG1478 abolished induction of fibronectin mRNA. We isolated the rat fibronectin gene including the 5'-flanking region and found that the AP-1 binding site present in the promoter region was responsible for the Ang II responsiveness of this gene. Gel retardation assay revealed the binding of nuclear protein to the AP-1 site, which was supershifted with anti-c-fos and anti-c-jun but not anti-ATF-2 antibodies. Conditioned medium from Ang II-treated cells contained TGF-beta bioactivity and addition of neutralizing TGF-beta antibody modestly (46%) inhibited induction of fibronectin. Ang II-induced synthesis of TGF-beta was also abolished by inhibition of EGF-R function. The effect of TGF-beta was exerted by stabilizing fibronectin mRNA without affecting the promoter activity and required de novo protein synthesis. We concluded that Ang II-induced expression of fibronectin and TGF-beta is mediated by downstream signaling of EGF-R transactivated by Ca2+-dependent tyrosine kinase, and that Ang II-induced fibronectin mRNA expression is regulated by two different mechanisms; transcriptional control by binding of c-fos/c-jun complex to the AP-1 site, and post-transcriptional control by mRNA stabilization due to autocrine and/or paracrine effects of TGF-beta. Thus, this study suggested that the action of Ang II on extracellular matrix formation should be interpreted in association with the EGF-R signaling cascade.

Angiotensin II↗
PubMed2000

Alterations of myoepithelial cells in the rat mammary gland during pregnancy, lactation and involution, and after estradiol treatment.

Hormone-induced alterations of myoepithelial cells in the mammary gland have not been fully investigated. The aim of the present study was to examine whether myoepithelial cells are altered in response to hormonal conditions. The immunohistochemical findings of smooth muscle actin for myoepithelial cells were studied during pregnancy, lactation and involution, and after estradiol dipropionate (ED) treatment (50, 500, 1000 microg/kg per week for 1-4 weeks) using a total of 71 Wistar female rats. Myoepithelial cells showed a stratified appearance around ducts during pregnancy, extended cytoplasmic processes with wider distance during lactation, and vacuolated cytoplasm after weaning. ED treatment (50-1000 microg/kg per week) for 1 week increased myoepithelial cells to a variable degree, achieving a level similar to that in pregnancy, but ED treatment for 4 weeks reduced them as the dose elevated. The present study showed that the myoepithelial cells became hyperplastic or hypertrophic by low-dose ED treatment within the physiological range, while weaning pups, and excess high-dose ED treatment beyond the physiological range or prolonged ED treatment induced reduction of the myoepithelial cells. Results indicate that myoepithelial cells themselves are also altered by hormonal conditions coordinating the mammary gland development.

Actins↗
PubMed2000

Cardiovascular response to combined static-dynamic exercise of patients with myocardial infarction.

BACKGROUND: Graded dynamic exercise-stress testing of patients with acute myocardial infarction prior to discharge from hospital has an important diagnostic and prognostic implication. Although many daily tasks involve combinations of static and dynamic exercise, little is known about cardiovascular responses during combined static-dynamic exercise. OBJECTIVE: To determine the difference between cardiovascular responses during two types of combined static-dynamic exercise (a 10 kg weight in one hand, and a 10 kg weight bearing on the shoulder). METHODS: We studied 27 male patients who had recently suffered myocardial infarction using ear densitography. The patients were divided into two groups: group 1 was comprised of 14 patients with resting left ventricular end-diastolic volumes > or = 140 ml, and group 2 was comprised of 13 patients with left ventricular end-diastolic volumes < 140 ml. RESULTS: For eight patients in group 1 we detected positive electrocardiographic changes during one-hand weight-carrying exercise, but for none of these patients was there an electrocardiographic change during weight-bearing exercise. All the patients in group 2 completed both types of exercise without significant ST-segment change. Although there were no significant differences between values of any of the indices measured for the two groups during weight-bearing exercise, patients in group 1 had significantly shorter diastolic times/min (21.8 +/- 2.1 versus 25.1 +/- 2.4 s/min, P < 0.01) during one-hand weight carrying. CONCLUSIONS: In addition to decrease in subendocardial coronary blood flow associated with increase in left ventricular end-diastolic volume, shortening of diastolic perfusion time during one-hand weight-carrying exercise for patients in group 1 can potentially contribute to subendocardial ischemia, which was favorably altered by bearing a weight on the shoulder.

Blood Pressure↗
PubMed2000

Expression of prolactin mRNA in rat mammary gland during pregnancy and lactation.

We studied the expression of prolactin (PRL) mRNA in the mammary gland of resting, pregnant, lactating, and weanling rats using in situ and solution reverse transcriptase-polymerase chain reaction (RT-PCR). In mid- to late pregnancy and throughout lactation, PRL mRNA was detected in both in situ and solution RT-PCR. These PRL mRNA signals were clearly identified in the cytoplasm of alveolar and ductal mammary epithelial cells by the in situ RT-PCR method. In mid- to late pregnancy, such as at the initiating point of PRL mRNA expression, we confirmed in some cases a lack of PRL mRNA by solution RT-PCR. In addition, in the early weaning phase, no signals were detected by solution RT-PCR. However, slight focal signals were detected in some poorly vacuolated cytoplasm of regressing acinar cells by in situ RT-PCR. These findings suggest that PRL mRNA in rat mammary gland begins in mid- to late pregnancy in parallel with the development of the mammary gland, continues throughout lactation, and declines in the early phase of weaning, with regression of mammary epithelial cells.

Animals↗
PubMed2000

Effect of sarpogrelate hydrochloride on platelet-derived microparticles and various soluble adhesion molecules in diabetes mellitus.

We measured platelet-derived microparticles, activated platelets, and various adhesion molecules in 48 patients with diabetes mellitus. We also performed a comparative study of these parameters before and after administration of sarpogrelate hydrochloride. The numbers of platelet-derived microparticles and activated platelets were increased significantly in diabetic patients, and CD63-positive platelets were increased in patients with diabetic complications and poorly controlled blood glucose. Soluble adhesion molecules and thrombomodulin were also increased significantly. After administration of sarpogrelate hydrochloride, not only CD62p- and CD63-positive platelets, but also platelet-derived microparticles were decreased significantly. Soluble adhesion molecules and thrombomodulin were also significantly decreased after the treatment. These data suggest that (a) in patients with diabetes, antiplatelet therapy with sarpogrelate hydrochloride is a useful antithrombin therapy because it suppresses the production of intrinsic coagulants by activated platelets; and (b) sarpogrelate hydrochloride decreases endothelial cell damage via adhesion molecules.

Antigens, CD↗
PubMed2000

A novel synthetic triazolotriazepine derivative JTT-606 inhibits bone resorption by down-regulation of action and production of bone resorptive factors.

In the search for a new class of bone-sparing agents, we have conducted random screening of the domestic chemical library using 45Ca release assay from prelabeled cultured neonatal mouse calvariae and identified a novel synthetic triazolotriazepine JTT-606 as a candidate for a potent inhibitor of bone resorption. JTT-606 inhibited 45Ca release dose dependently not only in the control calvarial culture but also in the stimulated cultures by interleukin-1alpha (IL-1alpha), fibroblast growth factor 2 (FGF-2), and parathyroid hormone (PTH). JTT-606 also inhibited both basal and stimulated osteoclast-like (OCL) cell formation in the coculture of mouse osteoblastic cells and bone marrow cells dose dependently, indicating its inhibitory effect on osteoclast differentiation. Ex vivo OCL cell formation by cultured bone marrow cells collected from ovariectomized (OVX) mice also was decreased dose dependently by in vivo application of JTT-606 to a level similar to that from sham-operated mice. Furthermore, JTT-606 inhibited resorbed pit formation by isolated mature osteoclasts as well as by unfractionated bone cells derived from rabbit long bones in the control and FGF-2-stimulated cultures dose dependently, indicating both the direct and the indirect actions of JTT-606 on mature osteoclast function. In addition, JTT-606 reduced production of IL-1alpha, tumor necrosis factor alpha (TNF-alpha), IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the human peripheral blood mononuclear cell culture. In vivo analyses of mature OVX rats revealed that the application of JTT-606 for 12 weeks increased the BMD of the lumbar spine and decreased the levels of serum osteocalcin and urine deoxypyridinoline to levels similar to those of 17beta-estradiol-treated OVX rats. We propose that JTT-606 may inhibit both osteoclast differentiation and function by down-regulating both the action and the production of bone resorptive factors. It is speculated that JTT-606 could be a potent agent for the treatment of osteopenic disorders with elevated osteoclastic bone resorption.

Animals↗
PubMed2000

Cryofiltration and oral corticosteroids provide successful treatment for an elderly patient with cryoglobulinemic glomerulonephritis associated with hepatitis C virus infection.

A 75-year-old man was admitted due to nephrotic syndrome, purpura on the legs, which was associated with hepatitis C virus (HCV), and type II mixed cryoglobulinemia. Renal biopsy revealed features of cryoglobulinemic glomerulonephritis. Since the patient was elderly and the HCV genotype was Ib, interferon-alpha for reducing HCV was not indicated. Four sessions of cryofiltration and the administration of corticosteroids improved the proteinuria and renal function strikingly without adverse effects. This case demonstrates that an elderly patient who has nephrotic syndrome caused by cryoglobulinemic glomerulonephritis associated with HCV can be treated safely by cryofiltration with low doses of oral corticosteroids.

Adrenal Cortex Hormones↗
PubMed2000

Histopathological study of female beagle dogs for four year treatment with subcutaneous implantation of chlormadinone acetate (CMA).

The histopathological changes related to chlormadinone acetate (CMA) implantation were examined using female beagle dogs given 10mg/kg for four years. All control animals showed sign of estrus during the experiment, with periods of anestrus of normal duration. In contrast, estrus was completely inhibited in the CMA-implanted animals. Histopathologically, uterine sections from the CMA-implanted animals showed cystic glandular hyperplasia, but no histologic evidence of endometritis, myometritis, and pyometra was found. In the ovaries of the CMA-implanted animals, developing ovarian follicles were observed but no mature follicles were noted in addition to an absence of corpus luteum. No remarkable changes were observed in the liver, adrenal, mammary gland, gallbladder and implanted site. Furthermore, the intensity of staining and number and size of ACTH-and LH-positive cells in the pituitary sections of CMA-implanted animals were not different from control animals. It was concluded, therefore, that subcutaneous implantation of CMA is a potential drug-delivery system for reducing changes due to antigonadotropic and glucocorticoid-like activities and characteristic histopathological changes in the uterus due to progestagenic activity.

Animals↗
PubMed1999

The grading of lymphovascular space invasion in endometrial carcinoma.

BACKGROUND: This study was conducted to elucidate the prognostic significance of a three-grade system for lymphovascular space invasion (LVSI). METHODS: The prognostic significance of the grading of LVSI as compared with other pathologic variables was evaluated in a study of 303 Japanese women with endometrial carcinoma. The criteria for determining the grade of LVSI were as follows: none (no LVSI), mild (a focus of LVSI was recognized around a tumor), and severe (diffuse or multifocal LVSI were recognized around the tumor or in the myometrium regardless of the degree of myometrial invasion). Both univariate and multivariate regression analyses were performed. The effects of different surgical methods and adjuvant therapies on survival were also examined. RESULTS: A univariate survival analysis showed that survival significantly correlated with surgical stage, histologic grade, depth of myometrial invasion, LVSI, cervical invasion, ovarian metastasis, and tubal metastasis. Of the three grades of LVSI, survival showed the most difference between the mild and severe groups. In multivariate analysis, the highest correlation with survival was observed for LVSI (P = 0.0008). Lymph node metastasis was also significantly associated with LVSI (P = 0. 0001). The correlation between histologic variables and survival was only slightly influenced by the differences in surgical methods and adjuvant therapies. CONCLUSIONS: The grading of LVSI was found to be an important histologic prognostic variable. The severe degree of LVSI also was found to be a good indicator of lymph node metastasis. It is therefore important to evaluate the grade of LVSI based on a histologic examination of at least one cut surface of the hysterectomy specimen that macroscopically shows the deepest myometrial invasion.

Endometrial Neoplasms↗