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Biomedical subjects

Y Doi

Publications and source records attributed to Y Doi.

At least 235 records · Page 13Linked to original sources

Increase in number of Weibel-Palade bodies and endothelin-1 release from endothelial cells in the cadmium-treated rat thoracic aorta.

Male rats received daily intraperitoneal injections of cadmium sulphate (2.0 mg/kg) for 3 (Cd-3 group), 6 (Cd-6 group) and 8 days (Cd-8 group). The blood samples were prepared for endothelin (ET)-1 assay, and the thoracic aorta was investigated by both electron microscopy and immunoelectron microscopy using anti ET-1 sera. The plasma ET-1 concentrations of both Cd-6 and Cd-8 groups increased significantly in a cumulative dose-dependent manner. The cadmium-treated rat aorta showed an increase in the number of Weibel-Palade (WP) bodies in endothelial cells, and degranulation and exocytosis of WP bodies occurred exclusively in the Cd-8 group. Immunoreaction for ET-1 was localized preferentially in WP bodies of both cadmium-treated and control groups, and in the rough endoplasmic reticulum of the cadmium-treated groups only. Reactivity was also found on the WP bodies undergoing exocytosis in the Cd-8 group. Cadmium intoxication induces an increase in number of ET-1-storing WP bodies in the rat aorta endothelium. The enhancement of extracellular release of their contents by exocytosis results in elevation of the plasma ET-1 concentration.

Animals↗

Association between a polymorphism in the angiotensin-converting enzyme gene and microvascular complications in Japanese patients with NIDDM.

The relationship between diabetic nephropathy and an insertion (I)/deletion (D) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene is still under debate. The association of ACE gene polymorphism with nephropathy and retinopathy was therefore examined in 362 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) and 105 healthy control subjects. Distribution of the ACE genotype did not differ between healthy control subjects and diabetic patients without complications. However, the frequency of the D allele was significantly higher in the diabetic subjects with nephropathy than in those without (0.32 in normoalbuminuric patients vs 0.44 in albuminuria patients with albuminuria) (chi 2 = 7.7; p = 0.006). There was no significant association between ACE genotype and retinopathy. These observations thus demonstrate a significant association of the ACE gene polymorphism with nephropathy, but not with retinopathy, in Japanese patients with NIDDM.

Alleles↗

Effect of glycated collagen on proliferation of human smooth muscle cells in vitro.

While non-enzymatic glycation of long-lived tissue proteins such as collagen has been implicated in chronic complications of diabetes mellitus, its role in the aetiology of diabetic macroangiopathy has not been elucidated. To test the hypothesis that glycation of collagen abolishes the inhibitory effect of native collagen on the proliferation of human smooth muscle cells, we obtained smooth muscle cells from human gastric arteries and cultured them on dishes coated with glycated or non-glycated collagen. The proliferation of human smooth muscle cells in the presence of 10% fetal calf serum or platelet derived growth factor-BB (10 ng/ml) was inhibited by type 1 collagen coated on the dishes. Glycation of collagen with glucose 6-phosphate for 7 days abolished the growth-inhibitory effect of native collagen. Succinylation of collagen, which like glycation blocked the lysyl residues in collagen, also abolished the growth-inhibitory effect. Adhesion of human smooth muscle cells to collagen-coated dishes was not affected by glycation of collagen. Addition of glycated albumin to the medium did not affect the growth of human smooth muscle cells on plastic dishes. The inhibition of human smooth muscle cell proliferation by collagen was not reversed by the glycation of collagen in the presence of aminoguanidine. Results suggest that early glycation abolishes the inhibitory effect of collagen on human smooth muscle cell proliferation and may thus participate in the progression of macro-angiopathy in diabetes.

Cell Division↗

Adsorption kinetics of bacterial PHB depolymerase on the surface of polyhydroxyalkanoate films.

The kinetics of adsorption and hydrolysis by an extracellular PHB depolymerase from Alcaligenes faecalis were studied at 37 degrees C on the surface of five types of polyhydroxyalkanoate (PHA) films. The films of poly[(R)-3-hydroxybutyrate] (P(3HP)), poly(3-hydroxypropionate) (P(3HP)), and poly(4-hydroxybutyrate)(P(4HB)) were hydrolyzed by the enzyme, while the films of poly[(S)-2-hydroxypropionate)(P(2HP)) and poly(6-hydroxyhexanoate)(P(6HH)) were not eroded. The PHB depolymerase with binding and catalytic domains adsorbed on the surface of all PHA films used, and the adsorption kinetics were found to obey the Langmuir isotherm. The cross-area per one molecule of enzyme binding to the surface of PHA film was estimated to be 17 +/- 8 (nm2/molecule). It has been concluded that the binding domain of enzyme is non-specific for the binding to the surface of PHA film, while the active site in a catalytic domain is specific for the hydrolysis of PHA molecules.

Adsorption↗

The use of antipoliovirus monoclonal antibodies as an improved safety test for oral live poliomyelitis vaccine.

Almost all the individual preparations of poliovirus type 3 specific monoclonal antibodies showed high neutralizing antibody titres against low-titre Sabin type 3 virus with a titer of 10(2) CCID 50/25 microliters. However, the preparations failed to neutralize high-titre virus at a titre of about 10(7) CCID50/25 microliters (undiluted virus fluid). The use of pooled monoclonal antibodies, comprising two or more individual antibodies, however, showed a high neutralizing activity for the high-titre virus suspension. The results indicate that the neutralization of high-titre Sabin type 3 virus can be achieved by the use of pooled monoclonal antibodies when appropriate antibodies are present. It seems likely that neutralization by these antibodies is achieved through the recognition of different neutralizing epitopes by specific antibodies. One of the safety tests used during the production of oral poliomyelitis vaccine (OPV) is that which employs type-specific antipoliovirus rabbit sera to detect adventitious viruses in monovalent poliovirus fluid. It has, however, proved difficult to prepare sera of this nature which can completely neutralize high-titre poliovirus having no cross-reactivity against other types of poliovirus. In our studies, pooled monoclonal antibodies showed a neutralizing activity against high-titre Sabin type 3 virus about 100-fold greater than that shown by rabbit antisera. Moreover, these antibodies appear to have two further important advantage for use in testing the safety of OPV: they showed no cross-neutralizing activity against heterotypic polioviruses; and they showed no evidence inhibiting the propagation of a number of viruses of monkey and human origin.

Animals↗

Influence of preload, afterload, and contractility on myocardial ultrasonic tissue characterization with integrated backscatter.

Influence of hemodynamic changes in preload, afterload and contractility on myocardial integrated backscatter (IB) was studied in 26 adult mongrel dogs by measuring myocardial IB calibrated with the backscatter from the blood during volume infusion (preload alteration), during aortic constriction (afterload alteration), and during dobutamine or propranolol infusion (contractility alteration). Changes in preload, afterload or contractility did not significantly affect the calibrated myocardial IB either in the septum or in the posterior wall. Changes in preload and afterload did not affect the magnitude of cyclic variation in IB. However, dobutamine produced a significant increase in the magnitude of cyclic variation in IB and propranolol significantly decreased the magnitude of cyclic variation in IB. These data indicated that the calibrated myocardial IB is independent of preload, afterload and contractility, and that the magnitude of cyclic variation in IB is influenced by contractility. We may estimate static (related to histological changes such as fibrosis, edema, necrosis, and so on) and dynamic (related to myocardial contraction such as sarcomere length, muscle fiber orientation, and so on) properties of the myocardium more precisely using myocardial IB calibrated with the backscatter from the blood in addition to the magnitude of cyclic variation in IB.

Adrenergic beta-Agonists↗

Ultrasonic myocardial tissue characterization in patients with dilated cardiomyopathy: value in noninvasive assessment of myocardial fibrosis.

Dilated cardiomyopathy (DCM) is usually diagnosed from the left ventricular functional viewpoint by the detection of dilated ventricular cavity and depressed myocardial contractility. Although histologic analysis of the myocardium no doubt provides clinically important information, it is possible only with microscopic examination of biopsy specimen of the myocardium. The objective of this particular study is to clarify the comparative values of the measures of ultrasonic tissue characterization, that is, calibrated myocardial integrated backscatter (IB) and the magnitude of cyclic variation in IB, with conventional echocardiographic parameters in assessing histologic condition of the myocardium. The magnitude of cyclic variation in IB and myocardial IB at end-diastole calibrate with the power of Doppler signals from the blood were measured in addition to conventional echocardiographic parameters in 14 patients with DCM. Calibrated myocardial IB was higher in patients with more fibrosis in the biopsy specimen of the heart tissue, whereas the magnitude of variation in IB or conventional echocardiographic parameters did not significantly correlate with a histologic estimate of myocardial fibrosis. Calibrated myocardial IB provides information about the myocardial fibrosis that cannot be assessable with conventional echocardiographic parameters. Calibrated myocardial IB and the magnitude of cyclic variation of IB are likely to reflect somewhat different acoustic properties of the myocardium.

Adult↗

Myocardial integrated ultrasonic backscatter in patients with old myocardial infarction: comparison with radionuclide evaluation.

The purpose of our study was to clarify whether the abnormalities in integrated backscatter may be used to assess myocardial viability in patients with old myocardial infarction by comparing these integrated backscatter parameters with conventional radionuclide and echocardiographic estimates of myocardial viability. Two myocardial integrated backscatter parameters, the magnitude of cyclic variation in integrated backscatter and the myocardial integrated backscatter calibrated with the power of Doppler signals from the blood along the same ultrasound beam (calibrated myocardial integrated backscatter), were measured in 21 normal persons and 33 patients with old anteroseptal myocardial infarction. Calibrated myocardial integrated backscatter was higher and the magnitude of cyclic variation in integrated backscatter was lower in the infarct septum compared with the septum of normal subjects. Percent thallium uptake, as assessed in scintigraphic images taken at rest or after reinjection, correlated well with the calibrated myocardial integrated backscatter (r = -0.72, p < 0.01) and more weakly but significantly with the magnitude of cyclic variation in integrated backscatter (r = 0.55, p < 0.05) in 16 of 33 patients. The measurement of calibrated myocardial integrated backscatter, in addition to the magnitude of cyclic variation of integrated backscatter, may likely be valuable in the noninvasive assessment of myocardial viability.

Adult↗

A method for evaluating the cariogenicity of oral bacteria using radio-labelled synthetic hydroxyapatite.

Radioactive hydroxyapatite was synthesized using 45Ca to evaluate the cariogenicity of oral streptococci. Discs prepared from it were suspended in media containing sucrose, then inoculated with Streptococcus mutans or Streptococcus sanguis. The radioactivity in the supernatant fluid was measured at specified time intervals. Released 45Ca in the supernatant fluids markedly increased in both species during the experimental period, while Strep. mutans showed much higher decalcification than Strep. sanguis. The present method would be useful for semi-quantitative evaluation of bacterial decalcification ability.

Calcium Radioisotopes↗

Effects of exercise on neurobehavioral function in community-dwelling older people more than 75 years of age.

OBJECTIVE: We evaluated the effects of exercise on neurobehavioral function in healthy older people more than 75 years of age. DESIGN: A randomized controlled trial with 6-month follow-up was conducted. SETTING: The study was performed in the rural town of Kahoku, Japan, the population of which is considered representative of the older population of Japan. PARTICIPANTS: We studied 42 healthy volunteers (18 men and 24 women; mean age, 79 years (range 75 to 87 years)) who were randomly assigned to one of two groups, exercise or control. INTERVENTION: Subjects assigned to the exercise group were instructed to exercise for 60 minutes twice a week for 6 months. Subjects in the control group were not instructed to engage in an specific exercise regimen. MEASUREMENTS: The following measurements were recorded for both groups at baseline and at 6-month follow-up: (1) Neurobehavioral function as determined by the following tests: Mini-Mental State Exam (MMSE), Hasegawa Dementia Scale Revised (HDSR), Visuospatial Cognitive Performance Test (VCP-test), Button score, Up & Go test, and Functional Reach; and (2) Body mass index and blood pressure. RESULTS: The effects of exercise were shown in the Up & Go test, and Functional Reach (ANOVA with repeated measures). CONCLUSION: This study demonstrates the acceptability and effectiveness of exercise on neurobehavioral function, even in older people more than 75 years of age.

Aged↗

Inhibition of aldosterone production by adrenomedullin, a hypotensive peptide, in the rat.

Recently, we conducted in vitro studies and reported that adrenomedullin, a novel hypotensive peptide, inhibits aldosterone secretion by dispersed rat adrenal zona glomerulosa cells. To assess the physiological role of this inhibitory effect, we investigated the effect of adrenomedullin on aldosterone production in vivo. Male Sprague-Dawley rats were fed a normal sodium diet before the experiments. To begin the experimental procedure, we stimulated aldosterone production with a sodium-deficient diet or bilateral nephrectomy. After 3 days of sodium depletion or immediately after nephrectomy, we injected synthetic human adrenomedullin (2.5 nmol/kg SC) and repeated the injection three times at 6-hour intervals. Two hours after the last injection, the rats were decapitated and adrenal capsular tissue was collected. Adrenomedullin had no effect on plasma and adrenal aldosterone concentrations in the rats fed a normal sodium diet. Rats fed a sodium-deficient diet had significantly increased aldosterone concentrations in both plasma (4770.1 +/- 364.3 pmol/L) and adrenal gland (57.34 +/- 3.27 pmol per adrenal). Subsequently, injection of adrenomedullin significantly inhibited increases in concentrations (plasma, 2648.9 +/- 313.2 pmol/L; adrenal, 44.28 +/- 4.94 pmol per adrenal). In nephrectomized rats, increased aldosterone concentrations in plasma and adrenal gland were also significantly inhibited by adrenomedullin. In the second part of the study, plasma renin concentration, adrenal renin activity, plasma corticosterone concentration, serum potassium concentration, and plasma immunoreactive adrenomedullin concentration were examined for adrenomedullin effects. The first four were unaffected, and the last, plasma immunoreactive adrenomedullin, was elevated 15% to 30%. These in vivo results, together with our in vitro data, suggest that adrenomedullin may indeed play a physiological role in the control of blood pressure and electrolyte balance.

Adrenomedullin↗

Coronary back flow pressure is elevated in association with increased left ventricular end-diastolic pressure in humans.

To clarify the effect of left ventricular (LV) diastolic pressure on the coronary pressure-flow relation in humans, the instantaneous diastolic coronary pressure-Doppler flow velocity relation was analyzed at rest and during papaverine-induced maximal vasodilation in 15 patients with angiographically normal coronary arteries. The values for slope (alpha PF) and zero-flow pressure intercept (Pzf index) of the instantaneous diastolic coronary pressure-flow velocity relation were obtained by a linear regression analysis. Although alpha PF did not correlate with LV end-diastolic pressure (EDP), the Pzf index correlated positively with LVEDP both at rest and during maximal vasodilation (r = 0.64, P < 0.05 and r = 0.58, P < 0.05, respectively). Thus, the back pressure to coronary inflow, as indicated by the Pzf index, may be elevated in patients with increased LVEDP, resulting in the rightward shift of the maximally dilated coronary pressure-flow relation and decreased maximal coronary flow and reserve at any given perfusion pressure.

Adult↗

Sympathetic hyperactivity in patients with vasospastic angina--assessment by spectral analysis of heart rate and arterial pressure variabilities.

The autonomic nervous system may play an important role in regulating coronary arterial tone. To evaluate the role of autonomic nervous activity in patients with vasospastic angina (VSA), we studied 10 VSA patients with patent coronary artery (mean; 56 yr, range; 44-66 yr) and 8 normal subjects (mean; 58 yr, range; 35-71 yr). ECG and arterial pressure were continuously recorded for 4 min in a supine position at 7:30 am, 10:30 am, and 4:30 pm. Low-frequency (LF; 0.04-0.15 Hz) and high-frequency (HF; 0.20 Hz) components of the beat-to-beat variabilities of the R-R interval (RRI) and systolic arterial pressure (SAP) were then estimated by autoregressive power spectral analysis. The LF-Normalized Power (LF-NP; [LF Power]/[Total Power]-[Direct Current Power]) of both the RRI and SAP variabilities were greater in VSA patients than in normal subjects (RRI: 0.51 +/- 0.07, 0.51 +/- 0.07, 0.53 +/- 0.06, vs 0.25 +/- 0.04, 0.31 +/- 0.05, 0.31 +/- 0.06, at 7:30 am, 10:30 am, and 4:30 pm respectively: p = 0.010, 0.044, 0.018. SAP: 0.62 +/- 0.06, 0.53 +/- 0.06, 0.57 +/- 0.06 vs 0.37 +/- 0.04, 0.30 +/- 0.06, 0.26 +/- 0.07, respectively: p = 0.006, 0.017, 0.003.). The LF-power of SAP variability also tended to be greater in VSA patients. There was no difference in the HF-component coefficient of variance (CCV (%) = 100 x (component power) (1/2)/ mean RR intervals) of the RRI variabilities between the 2 groups. These results indicate that increased sympathetic vasomotor tone and cardiac sympathetic predominance may play an important role in patients with VSA.

Adult↗

The roles of the marginal veins in the differentiation of the rat hind limb bud: an immunocytochemical study.

Rat hind limb buds, aged between prenatal days 14 and 18, were used for electron microscopy and immunocytochemistry of fibronectin, laminin and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining indicative of DNA fragmentation. Fibronectin and laminin were actively synthesized in the rough endoplasmic reticulum of epidermal cells in the apical ectodermal ridge between prenatal days 14 and 15, but most cells underwent apoptosis after prenatal day 15. As the regression of the apical ectodermal ridge progressed, mesenchymal cells associated with the marginal veins were successively incorporated into the endothelium devoid of the basal lamina. No mitotic figures of endothelial cells were recognized either in the marginal vein or in the surrounding growing capillaries. Extracellular matrix components connected the adjacent mesenchymal cells, with the endothelium of such vessels immunoreacting to fibronectin and laminin. In addition, fibronectin-immunoreactive networks among the interstices of the mesenchymal cell cords developed in the avascular zone between the epidermis and the growing capillaries at prenatal day 15, but became inconspicuous at prenatal day 16. These results indicate that the apoptosis of the epidermal cells is the major reason for the regression of the apical ectodermal ridge, and that the capillary ingrowth from the marginal veins to the avascular zone is accelerated by transformation of mesenchymal cells to endothelial ones. Fibronectin and laminin seem to play crucial roles in capillary growth, especially in the adhesion between endothelial cells of the pre-existing vessels and mesenchymal cells.

Animals↗

[Two cases of Candida endocarditis associated with abdominal disease].

Two cases of Candida endocarditis are reported. The first case was of a 63-year-old man who had a positive blood culture for Candida albicans during treatment for liver abscess and early gastric cancer. He was transferred to our department, and aortic and tricuspid regurgitation due to Candida endocarditis was diagnosed. The patient was successfully treated with aortic valve replacement, tricuspid valve plasty and anti-fungal agents. The second case was of a 65-year-old man who complained of fever. Despite a diagnosis of common bile duct cancer and resection of the tumor, the fever persisted. He was transferred to our department and was diagnosed having aortic regurgitation due to Candida endocarditis, complicated by heart failure. Although intense medical therapy including antifungal agents, diuretics, catecholamines and digoxin was initiated, the patient died from multiple embolisms 9 days later. In the treatment of Candida endocarditis, early diagnosis and early decision-making for either surgical or medical therapy is indispensable. Although the prevalence of Candida endocarditis is low, the differentiation of this disease should be taken into account in febrile elderly patients with long-standing therapy with antibiotics.

Aged↗

[An elderly patient with Leriche syndrome complicated by congestive heart failure and rhabdomyolysis].

A 64-year-old man, who had had bilateral intermittent claudication and leg pain for five years, was admitted because of sudden onset of severe leg pain, and acute respiratory failure. Laboratory data showed markedly elevated serum CK of 73,050 IU/L, and urinary myoglobin of 430,000 ng/ml. A diagnosis of rhabdomyolysis was made. Renal dialysis was required for the next two days because of acute renal failure. The aortogram was performed on the 32nd day and disclosed complete obstruction of the abdominal aorta immediately distal to the bilateral renal arteries. Good collateral flow was noted to the popliteal arteries. On the 49th day, the patient successfully underwent extra-anatomical bypass surgery (axillo-bifemoral bypass). The mechanism of rhabdomyolysis in this elderly patient was discussed.

Heart Failure↗