Search PubMed⌕ Search

Biomedical subjects

Kazuyuki Shimada

Publications and source records attributed to Kazuyuki Shimada.

At least 73 records · Page 4Linked to original sources
PubMed2004

Gene transfer of nitric oxide synthase via the use of adeno-associated virus vectors.

Adeno-associated virus (AAV) is a replication-defective dependovirus and is not known to cause disease in humans. AAV vectors have a broad host range and can transduce both dividing and nondividing cells. Five primate AAV serotypes have been characterized in the literature and are designated as AAV types 1-5 (AAV1-5). There is divergence in homology and tropism for various AAV serotypes. AAV vectors can be produced by triple plasmids transfection system (adenovirus-free system) and purified by ultracentrifugation using CsCl gradient. The titer of AAV vectors is determined by dot-blot analysis. We have produced the AAV type 2 vectors encoding endothelial NOS (eNOS) gene and transduced rat aortic segments.

Animals↗
PubMed2004

Variations in the tensor veli palatini muscle with special reference to its origin and insertion.

OBJECTIVE: Previous research on the tensor veli palatini muscle (TVP) has produced conflicting descriptions of its functions and topographical relationships with other orofacial structures. The goal of this study was to describe the morphology of the TVP in a systematic and comprehensive manner. METHODS: One hundred nineteen sides of 77 human heads from donated cadavers were partially dissected under a binocular microscope. Histological examination of the hard tissue-muscle interfaces was also undertaken. RESULTS: There were two adjacent origins of the TVP: the cranial base origin (CB origin) and the auditory tube cartilage origin (AT origin). The CB origin always lay anterior to the AT origin and there was no septum or loose tissue between the two muscular laminae leading from these origins. The muscle fibers converged on a central tendinous plate in the muscle belly, which gradually became a common tendon that rounded the pterygoid hamulus before inserting into the palatine aponeurosis. Notably, secondary insertions were found on the maxillary tuber (33.6%) and/or in the submucosal tissue near the palatoglossal arch (37.8%). Maxillary insertions were almost exclusively associated with an AT origin that was wide as or wider than the CB origin. Histological observations confirmed that the hamulus acted purely as a pulley and suggested that a connecting band to the tensor tympani had no or few functions of an intermediate tendon. CONCLUSIONS: The TVP appears to act as the dilator tubae and that this function can be maintained by preserving or reconstructing the maxillary insertion during push-back surgery, even if hamulotomy is necessary.

Adult↗
PubMed2004

Conditioning regimen of melphalan, fludarabine and total body irradiation in unmanipulated HLA haploidentical stem cell transplantation based on feto-maternal tolerance.

Unmanipulated hematopoietic stem cell transplantation from haploidentical family donors is frequently associated with graft failure and severe graft-versus-host disease (GVHD). We employed a myeloablative conditioning regimen consisting of 125 mg/m2 of fludarabine, 140 mg/m2 of melphalan and TBI of 10 to 12 Gy for three patients. The donor in each case was a haploidentical two-loci HLA mismatch mother or son. Engraftment failure was observed in one patient. In the other two patients, engraftment was confirmed within 15 days after transplantation. Acute and chronic GVHD was observed, but was controllable in both cases. HLA mismatched transplantation based on feto-maternal tolerance may provide an alternative option for patients who do not have HLA-matched donors.

Adult↗
PubMed2004

Anatomical study of meandering and functions of human intralaryngeal artery.

In recent years, partial laryngectomy and partial reconstruction are increasingly intended for conservation of functions of phonation and swallowing. In partial reconstruction, it is important to comprehend morphological characteristics of the blood vessels distributed in the larynx, but there have been only few reports discussing detailed information about them. Previous reports on laryngeal blood vessels have shown that branches of some arteries show remarkable "meandering". In the present study, we devised a method for objectively determining the morphological nature, "meandering" and assessed functions of the arteries. Intralaryngeal arteries were excised from the larynx of cadavers prepared for practice in anatomy, and images of the "meandering" artery were analyzed with NIH Image. The extent of "meandering" was expressed mainly as the ratio of the total length of the blood vessel to the distance between the starting point and the end point of meandering. The results showed that there was a significant difference in the extent of meandering between superior posterior and medial posterior branches of superior laryngeal artery. These arteries, which were distributed in the arytenoid region, were found to be of primary importance in partial laryngectomy and partial reconstruction of the larynx.

Aged↗
PubMed2004

[Relationship between redox state of whole arterial blood glutathione and left ventricular function after acute myocardial infarction].

OBJECTIVES: To investigate the role of oxidative stress in left ventricular function after acute myocardial infarction. METHODS: We studied 41 patients with acute myocardial infarction (30 men and 11 women, mean age 61.7 +/- 11.6 years) with Thrombolysis in Myocardial Infarction grade 3 recanalization of occluded coronary arteries within 12 hr after onset. Cardiac catheterization was performed at the time of admission and before discharge. Three markers for oxidative stress were measured: plasma lipid hydroperoxide, plasma creatol and whole arterial blood glutathione at the time of admission. RESULTS: Mean time from onset to recanalization was 5.2 +/- 0.6 hr. The patients were divided into two groups according to the changes in left ventricular wall motion (LVWM); patients who showed improvement in LVWM and those without improvement. There were no significant differences in age, sex, coronary risk factors, severity of coronary artery disease, time from onset to recanalization or ejection fraction between two groups. Maximum creatine kinase and C-reactive protein levels in patients without LVWM improvement were significantly higher than in patients with improvement. Plasma levels of lipid hydroperoxide and creatol did not differ significantly between two groups. On the other hand, reduced glutathione/oxidized glutathione ratio in arterial blood in patients without LVWM improvement was significantly lower than in patients with LVWM improvement (69.8 +/- 3.4 vs 85.5 +/- 2.9, p < 0.05). CONCLUSIONS: Our results suggest that whole arterial blood glutathione is more oxidized in acute myocardial infarction patients without LVWM improvement than in patients with improvement. Redox state of arterial blood can be a predicting factor for left ventricular function after acute myocardial infarction.

Aged↗
PubMed2003

Greater impact of coexistence of hypertension and diabetes on silent cerebral infarcts.

BACKGROUND AND PURPOSE: Silent cerebral infarcts (SCIs), often found in the elderly and hypertensives, have been proposed as an indicator of poorer cerebrovascular prognosis. The aim of this study was to evaluate the prevalence and determinants of SCI in hypertensives with or without diabetes mellitus (DM). METHODS: We studied 360 asymptomatic hypertensive subjects with or without DM (mean age, 67.4 years; range, 41 to 88 years). We performed 24-hour ambulatory blood pressure (BP) monitoring and brain MRI. The subjects were classified into a diabetic hypertension group with DM (DHT, n=159) or a non-DM hypertension group (non-DHT, n=201). RESULTS: SCIs (presence of > or =1) were found in 82% of the DHT and 58% of the non-DHT (P<0.001) group; multiple SCIs (the presence of > or =3) were found in 62% of the DHT and 35% of the non-DHT group (P<0.001); and 24-hour ambulatory BP levels were comparable between groups. DM was a powerful determinant of both SCIs (odds ratio [OR], 2.95; P<0.01) and multiple SCIs (OR, 3.05; P<0.001) independently of age and 24-hour systolic BP, whereas only multiple SCIs were associated with 24-hour systolic BP. When patients were subclassified by ambulatory BP and the presence of DM (sustained hypertension [SHT]+DM, white-coat hypertension [WCHT]+DM, SHT, and WCHT groups), the prevalence of SCI and multiple SCIs was higher in the SHT+DM than in the SHT group, and only multiple SCIs were higher in the WCHT+DM than the WCHT group. CONCLUSIONS: Diabetes was the major determinant of SCIs in both SHT and WCHT.

Adult↗
PubMed2003

Comparison of candesartan with lisinopril on ambulatory blood pressure and morning surge in patients with systemic hypertension.

We performed a prospective crossover study in 73 essential hypertensives to compare the effects of candesartan and lisinopril on ambulatory blood pressure (BP) and early-morning BP. Twenty-four-hour ambulatory BP monitoring was performed at baseline and for each active treatment. Small doses of thiazide diuretic were added as needed. The effects of both drugs on 24-hour BP were almost identical and satisfactory. When we classified patients into the morning surge group (the highest quartile of morning systolic BP surge >36 mm Hg) and the non-morning surge group (the remaining 3 quartiles of morning BP surge), candesartan was superior in decreasing morning BP and morning BP surge.

Aged↗
PubMed2003

DNA microarray analysis of in vivo progression mechanism of heart failure.

Dahl salt-sensitive rats are genetically hypersensitive to sodium intake. When fed a high sodium diet, they develop systemic hypertension, followed by cardiac hypertrophy and finally heart failure within a few months. Therefore, Dahl rats represent a good model with which to study how heart failure is developed in vivo. By using DNA microarray, we here monitored the transcriptome of >8000 genes in the left ventricular muscles of Dahl rats during the course of cardiovascular damage. Expression of the atrial natriuretic peptide gene was, for instance, induced in myocytes by sodium overload and further enhanced even at the heart failure stage. Interestingly, expression of the gene for the D-binding protein, an apoptotic-related transcriptional factor, became decreased upon the transition to heart failure. To our best knowledge, this is the first report to describe the transcriptome of cardiac myocytes during the disease progression of heart failure.

Animals↗
PubMed2003

Antiapoptotic effect of endothelin-1 in rat cardiomyocytes in vitro.

Apoptosis of cardiac myocytes is thought to be a feature of many pathological disorders, including congestive heart failure (CHF) and ischemic heart disease (IHD). Because recent investigations indicate that endothelin-1 (ET-1) plays an important role in CHF and IHD, we investigated the effect of ET-1 on cardiomyocyte apoptosis. The presence of apoptosis in rat cardiomyocytes (H9c2 and neonatal) was evaluated by morphological criteria, electrophoresis of DNA fragments, 4',6'-diamidine-2'-phenylindole staining, and TUNEL analysis. ET-1, but not angiotensin II, prevented apoptosis induced by serum deprivation via ETA receptors in a dose-dependent manner (1 to 100 nmol/L). ET-1 also prevented cytochrome c release from mitochondria to the cytosol. The use of specific pharmacological inhibitors demonstrated that the antiapoptotic effect of ET-1 was mediated through a tyrosine kinase pathway (genistein and AG490) but not through protein kinase C (PKC; calphostin C), mitogen-activated protein kinases (PD98059 and SB203580), or PKA (KT5270) pathways. Adenovirus-mediated gene transfer of kinase-inactive (KI) c-Src reversed the antiapoptotic effect of ET-1. We further investigated whether Bcl-xL, an antiapoptotic molecule, would be upregulated by using a luciferase-based reporter system. ET-1 upregulated Bcl-xL, and this upregulation was inhibited by genistein or AG490 but not by calphostin C. The experiments with KI mutants for various tyrosine kinases revealed that c-Src and Pyk2 (but not JAK1, Jak2, Syk, and Tec) are involved in ET-1-induced upregulation of Bcl-xL expression. These findings suggest that ET-1 prevents apoptosis in cardiac myocytes through the ETA receptor and the subsequent c-Src/Bcl-xL-dependent pathway.

Animals↗
PubMed2003

Morning surge in blood pressure as a predictor of silent and clinical cerebrovascular disease in elderly hypertensives: a prospective study.

BACKGROUND: Cardiovascular events occur most frequently in the morning hours. We prospectively studied the association between the morning blood pressure (BP) surge and stroke in elderly hypertensives. METHODS AND RESULTS: We studied stroke prognosis in 519 older hypertensives in whom ambulatory BP monitoring was performed and silent cerebral infarct was assessed by brain MRI and who were followed up prospectively. The morning BP surge (MS) was calculated as follows: mean systolic BP during the 2 hours after awakening minus mean systolic BP during the 1 hour that included the lowest sleep BP. During an average duration of 41 months (range 1 to 68 months), 44 stroke events occurred. When the patients were divided into 2 groups according to MS, those in the top decile (MS group; MS > or =55 mm Hg, n=53) had a higher baseline prevalence of multiple infarcts (57% versus 33%, P=0.001) and a higher stroke incidence (19% versus 7.3%, P=0.004) during the follow-up period than the others (non-MS group; MS <55 mm Hg, n=466). After they were matched for age and 24-hour BP, the relative risk of the MS group versus the non-MS group remained significant (relative risk=2.7, P=0.04). The MS was associated with stroke events independently of 24-hour BP, nocturnal BP dipping status, and baseline prevalence of silent infarct (P=0.008). CONCLUSIONS: In older hypertensives, a higher morning BP surge is associated with stroke risk independently of ambulatory BP, nocturnal BP falls, and silent infarct. Reduction of the MS could thus be a new therapeutic target for preventing target organ damage and subsequent cardiovascular events in hypertensive patients.

Aged↗
PubMed2003

Matrix metalloproteinases and coronary artery diseases.

Matrix metalloproteinases (MMPs) play an important role in cardiovascular remodeling by degrading the extracellular matrix. Enhanced MMP expression has been detected in the atherosclerotic plaque, and activation of MMPs appears to be involved in the vulnerability of the plaque. Circulating MMP levels are elevated in patients with acute myocardial infarction and unstable angina. Increased MMP expression is also observed after coronary angioplasty, which is related to late loss index after the procedure. These observations suggest that MMP expression may be not only related to instability of the plaque, but also to the formation of restenotic lesions. The development of therapeutic drugs targeted specifically against MMPs may be useful in the prevention of atherosclerotic lesion development, plaque rupture, and restenosis.

Coronary Artery Disease↗
PubMed2003

Efficient gene transfer of a simian immuno-deficiency viral vector into cardiomyocytes derived from primate embryonic stem cells.

BACKGROUND: Embryonic stem (ES) cells continually proliferate and can generate large numbers of differentiated cells. Genetic manipulation of transplantable cells derived from primate ES cells offers considerable potential for development research and regenerative cell therapy. However, protocols for efficient gene transfer into primate ES-cell-derived cells have not yet been established. METHODS: Spontaneously contracting areas were derived from cynomolgus monkey ES cells. Features of cardiomyocytes in the area were analyzed according to gene expression (RT-PCR), morphology (immunostaining and electron microscopy), and function (intracellular calcium transience). Beating cells were transduced using a simian immunodeficiency virus (SIV) vector expressing enhanced green fluorescence protein (EGFP), then transplanted into ischemic rat myocardium. RESULTS: Beating cells derived from monkey ES cells displayed gene expression, ultrastructural and functional properties of early-stage cardiomyocytes. Highly efficient (97% cardiac phenotype) and stable transduction of these ES-cell-derived cardiomyocytes was achieved using SIV vector without altering contractile function. In addition, transduced cardiomyocytes survived in the myocardium of a rat myocardial infarction model. CONCLUSIONS: A lentiviral vector system based on SIV represents a useful vehicle for genetic modification of cardiomyocytes derived from primate ES cells, and can extend the application of primate ES cells to gene therapy.

Animals↗