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Biomedical subjects

A Miyazaki

Publications and source records attributed to A Miyazaki.

At least 181 records · Page 10Linked to original sources
PubMed1992

Exposure of rat peritoneal macrophages to acetylated low density lipoprotein results in release of plasma membrane cholesterol. An efficient substrate for esterification by acyl-CoA:cholesterol acyltransferase.

In J774 macrophages and murine macrophages stimulated with acetylated low density lipoprotein (acetyl-LDL), the plasma membrane free cholesterol (FC) became accessible to acyl-CoA:cholesterol acyltransferase (ACAT) as substrate, the result being an accumulation of cholesteryl esters (CE) (Tabas, I., Rosoff, W. J., and Boykow, G. C (1988) J. Biol. Chem. 263, 1266-1272). As the route of delivery of FC to ACAT was not well characterized, we examined this route in the present study. In foam cells derived from rat peritoneal macrophages by preincubation with acetyl-LDL, esterification of the exogenously labeled [3H]FC was low (1.3% of total labeled cholesterol). In contrast, when cells were first labeled with exogenous [3H]FC and then chased with acetyl-LDL, the esterification was more extensive (9.2% of the total labeled cholesterol). During this experiment a significant portion of cellular [3H]FC was released into the medium (up to 33.4% of the total labeled cholesterol). In experiments using a two-compartment chamber in which cells in the lower and upper chambers were separated by filter paper yet the cells in both compartments could communicate without direct contact, [3H]FC released into the medium was biologically active and could serve as an efficient substrate for ACAT. Thus, when acetyl-LDL is not included in culture medium, FC delivery from the macrophage plasma membrane to ACAT is not enhanced, whereas in the presence of acetyl-LDL, plasma membrane FC released and bound to acetyl-LDL may re-enter the cells, possibly through the scavenger receptor. This would provide a significant route for CE synthesis in macrophages.

Animals↗
PubMed1992

Transformation of vitamin D3 to 1 alpha,25-dihydroxyvitamin D3 via 25-hydroxyvitamin D3 using Amycolata sp. strains.

To enzymatically synthesize active metabolites of vitamin D3, we screened about 500 bacterial strains and 450 fungal strains, of which 12 strains were able to convert vitamin D3 to 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] via 25-hydroxyvitamin D3 [25(OH)D3]. The conversion activity was only detected in strains belonging to the genus Amycolata among all the organisms tested. A preparative-scale conversion of vitamin D3 to 25(OH)D3 and 1 alpha,25(OH)2D3 in a 200-1 tank fermentor using A. autotrophica FERM BP-1573 was accomplished, yielding 8.3 mg 25(OH)D3/l culture and 0.17 mg 1 alpha,25(OH)2D3/l culture. A related compound, vitamin D2, could be also converted to 25-hydroxyvitamin D2 and 1 alpha,25-dihydroxyvitamin D2 using the same strain. The cytochrome P-450 of FERM BP-1573 was detected by reduced CO difference spectra in whole-cell suspensions. Vitamin D3 in the culture induced cytochrome P-450 and the conversion activity simultaneously, suggesting that the hydroxylation at C-25 of vitamin D3 and at C-1 of 25(OH)D3 originates from cytochrome P-450.

Actinomycetales↗
PubMed1992

Evaluation of morphological changes of the atherosclerotic aorta by enhanced computed tomography.

Enhanced and non-enhanced computed tomography (CT) were performed in 405 subjects (222 men; 183 women; mean age 57 years). Intimal atherosclerotic changes of the aorta were quantified by enhanced CT, revealing the atheromatous intima to be projecting and thick-walled, while non-enhanced CT demonstrated aortic calcification. We measured the degree of aortic intimal changes at various segments of the aorta. In 224 cases, CT was performed from the aortic root to the bifurcation of the abdominal aorta. Intimal changes were found predominantly at the aortic arch, the middle descending thoracic and the infrarenal abdominal aorta. As for the intimal changes, aortic calcification and aortic pulse wave velocity were significant atherosclerotic characteristics. The aortic diameter did not show a significant association with intimal change. Among the various atherosclerotic risk factors, intimal change was significantly associated with age, systolic blood pressure, serum total cholesterol and diabetes mellitus, whereas gender, diastolic blood pressure, relative weight and cigarette use were not significantly related. For coronary artery disease and arteriosclerosis obliterans, aortic intimal changes constituted a significant atherosclerotic feature. In cerebrovascular disease, however, aortic intimal change did not play a significant role.

Adolescent↗
PubMed1992

Adhesion molecule expression in Graves' thyroid glands; potential relevance of granule membrane protein (GMP-140) and intercellular adhesion molecule-1 (ICAM-1) in the homing and antigen presentation processes.

To assess the potential role of adhesion molecules in the pathogenesis of Graves' disease, we examined the expression of several of these adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM-1) and granule membrane protein-140 (GMP-140), in sections of Graves' thyroid glands and control thyroids, using immunohistochemical techniques. Up-regulated expression of GMP-140 was frequently observed on endothelial cells (EC) of post-capilliary venules in all Graves' thyroids examined, compared with an occasional weak staining on EC control glands. Some capillary EC around thyroid follicles (perifollicular EC) were strongly positive for GMP-140 in the Graves' thyroids in contrast to a negative staining on the same structures in the control glands. In addition, there was a correlation between the reactivity and frequency of GMP-140 expression on EC and the severity of mononuclear cell (MNC) infiltration in the Graves' thyroids. The expression of ICAM-1 was up-regulated on perifollicular EC and EC of small venules in some thyroids of both Graves' and control groups. Conversely, no significant expression was observed on any type of EC for both endothelial-leucocyte adhesion molecule-1 (ELAM-1) and VCAM-1. However, dendritic-like cells, present within lymphocytic infiltrates, were positive for VCAM-1 in most of the Graves' thyroids examined, especially in those with a severe lymphocytic infiltration. Thyrocytes were constantly negative for the expression of all four adhesion molecules investigated. These data suggest that GMP-140, as well as ICAM-1, could play an important role in the initiation of MNC infiltration in Graves' disease. ELAM-1 and VCAM-1 appear not to be relevant for the migration of MNC from the blood vessels into the target gland, although VCAM-1 expression on dendritic-like cells might play an additively tissue-selective role in autoantigen presentation and subsequent elicitation of autoimmune phenomena.

Cell Adhesion Molecules↗
PubMed1992

Analysis of left ventricular regional wall motion in normal neonates.

OBJECTIVE: To investigate neonatal circulatory change by quantitative analysis of left ventricular regional wall motion. DESIGN: Random prospective study. SETTING: Department of paediatrics in a teaching hospital. PARTICIPANTS: 66 neonates born after a normal pregnancy, labour, and delivery. INTERVENTIONS: Quantitative analysis of left ventricular regional wall motion was performed on cross sectional echocardiograms. M mode, cross sectional, and Doppler echocardiograms were obtained simultaneously. MAIN OUTCOME MEASURES: Manually traced endocardial contours at end diastole and at end systole were realigned by superimposing the centre of the ventricular mass and the axis. The contours were divided into 24 segments with 24 radii of equal arc from the centre. Then the ratio of the change in area between the outline of the contour and the two hemiaxes was calculated automatically. RESULTS: There was hyperkinesis of the interventricular septum in the first 24 hours after birth which continued until the end of the first week. Simultaneous echocardiographic examination showed evidence of pulmonary hypertension, as indicated by an increase in the ratio of the right pre-ejection period to the right ventricular ejection time (RPEP/RVET) and of the diameter ratio of the pulmonary artery to the aorta and a shortening of the acceleration time of pulmonary arterial blood flow. These features disappeared within a week. CONCLUSIONS: Hyperkinesis of the interventricular septum may reflect circulatory changes that are characteristic of the early neonatal period.

Diastole↗
PubMed1992

[Magnetic resonance imaging: evaluation of the Blalock-Taussig shunts and anatomy of the pulmonary artery].

The morphology and circulation of the pulmonary arteries and shunt vessels were evaluated by magnetic resonance imaging (MRI) in 8 patients with cyanotic heart disease after a Blalock-Taussig shunt operation. Their ages ranged from one month to 17 years. MRI permitted assessment of the size and patency of the Blalock-Taussig shunts, as well as the size and morphology of the pulmonary arteries in all patients. Measurements of the vessel diameters on MRI correlated well with the angiographic measurements (main pulmonary artery, r = 0.98; right pulmonary artery, r = 0.98; left pulmonary artery, r = 0.98; and Blalock-Taussig shunt, r = 0.97). MRI successfully imaged 3 of 4 shunt obstructions and 3 of 4 pulmonary stenoses with high resolution. In assessing peripheral pulmonary stenosis or obstruction, MRI was superior to echocardiography, the latter being unable to image peripheral pulmonary arteries satisfactorily. We concluded that MRI is an excellent noninvasive method for serially evaluating the anatomy and function of Blalock-Taussig shunts and pulmonary arteries, which is particularly useful for children with cyanotic congenital heart disease.

Adolescent↗
PubMed1991

Chemical cross-linking alters high-density lipoprotein to be recognized by a scavenger receptor in rat peritoneal macrophages.

Rat peritoneal macrophages possess a surface receptor for high-density lipoprotein (HDL). To obtain the functional aspect of the HDL receptor, the present study was undertaken to modify HDL with three different cross-linkers; dimethylsuberimidate, disuccinimidylsuberate and dithiobissuccinimidylpropionate (DSP) and determine their effect on the ligand activity for the HDL receptor. Upon modification at a low reagent concentration, DSP was found to be most effective in cross-linking of HDL apolipoproteins. The ligand activity of DSP-HDL for the HDL receptor was reduced by greater than 60%. Experiments with these macrophages at 37 degrees C showed; (i) the amounts of the cell-associated [125I]DSP-HDL as 3.5-fold higher than [125I]HDL; (ii) the cell-association of [125I]DSP-HDL was effectively (greater than 70%) inhibited by unlabeled DSP-HDL, whereas HDL showed a partial inhibition (30%); (iii) [125I]DSP-HDL underwent chloroquine-sensitive intracellular degradation; and (iv) DSP-HDL induced a 3-fold increase in the incorporation of [14C]oleic acid into cholesteryl oleate when compared with unmodified HDL. Experiments at 0 degrees C showed that the cellular binding of [125I]DSP-HDL was competed by acetylated low-density lipoprotein and dextran sulfate. These findings indicate that DSP-HDL is recognized as a ligand by a scavenger receptor of rat peritoneal macrophages, a notion consistent with HDL modified with tetranitromethane (Kleinherenbrink-Stins, M.F. et al. (1989) J. Lipid Res. 39, 511-520).

Animals↗
PubMed1991

Biochemical demonstration of endocytosis and subsequent resecretion of high-density lipoprotein by rat peritoneal macrophages.

To investigate the post-binding events of high-density lipoprotein (HDL), rat peritoneal macrophages were enriched by collagen gel-coated plates and incubated in a cell-suspension system with fluorescein isothiocyanate-labeled HDL (FITC-HDL), followed by fluorescence spectroscopic analyses. Upon incubation with FITC-HDL at 37 degrees C for 30 min, the microenvironmental pH of the cell-associated FITC-HDL was 6.50, whereas a 0 degree C-incubation gave a corresponding pH of 7.15. Carbonyl cyanide m-chlorophenylhydrazone, a protonophore known to dissipate the proton gradient, restored the former acidic pH (pH 6.40) to pH 7.20, but had no effect on the latter. This indicates that cell surface-bound HDL is internalized and exposed to an acidic compartment. When cells were incubated with FITC-HDL at 37 degrees C for 30 min and the cell-associated FITC-HDL was chased at 37 degrees C, the fluorescence intensity at 490 nm showed a time-dependent increase. This increase was explained by a release of endocytosed FITC-HDL into the extracellular medium but not by a simple outward dissociation of the cell-associated FITC-HDL. The microenvironmental acidic pH of the cell-associated FITC-HDL changed to a less acidic pH during the chase whereas that of FITC-HDL became constant after released into the medium, indicating that endocytosed HDL was resected back into the extracellular medium. This resection process was temperature-dependent and accelerated by HDL itself. These results provide the biochemical evidence for the presence of an endocytic-exocytic pathway for HDL in rat peritoneal macrophages.

Animals↗
PubMed1991

Involvement of the dorsal hippocampus in mediation of the antianxiety action of tandospirone, a 5-hydroxytryptamine1A agonistic anxiolytic.

The effect of tandospirone, a 5-hydroxytryptamine (5-HT)1A agonist/anxiolytic, injected directly into dorsal hippocampus, on Vogel-type conflict behavior in rats was investigated and the findings were compared with the effects of diazepam and zopiclone. Tandospirone (30 micrograms/2 microliters and 60 micrograms/2 microliters) and diazepam (40 micrograms/2 microliters) but not zopiclone (20 micrograms/2 microliters), produced a potent anticonflict action in rats. The anticonflict action of tandospirone (30 micrograms/2 microliters), injected into the dorsal hippocampus, was significantly blocked by (-)-propranolol (5 mg/kg i.p.). The present findings provide evidence that suggests that tandospirone has an antianxiety action, presumably by stimulating 5-HT1A receptors in the dorsal hippocampus.

Animals↗
PubMed1991

Disturbed metabolism of glucose and related hormones in familial amyloidotic polyneuropathy: hypersensitivities of the autonomic nervous system and therapeutic prevention.

Regulation of glucose metabolism was evaluated by oral glucose tolerance test (OGTT) in patients with familial amyloidotic polyneuropathy (FAP). Upon oral administration of a loading dose of glucose, plasma levels of glucose, insulin and glucagon changed abnormally in all FAP patients tested. Although plasma levels of glucose and insulin in the fasted patients were within normal ranges, 33% of FAP patients showed hypoglycemia after transient hyperinsulinemia during the examination. Furthermore, another three patients showed transient hypoglycemia during their daily life. Thus, perturbed glucose metabolism should be taken into account for treating patients with FAP. The salivary glands as well as the lacrimal glands showed transient hypersecretion after chewing a gum. Histochemical analysis at autopsy revealed significant amyloid deposition in the stroma, nerves and vessels of the pancreas, but not in Langerhans islets. Similar appearance was recognized in the salivary glands. These results suggest that denervation supersensitivity might occur not only in the exocrine glands but also in the endocrine gland.

Administration, Oral↗
PubMed1991

Retrograde coronary venous administration of recombinant tissue-type plasminogen activator: a unique and effective approach to coronary artery thrombolysis.

Recent studies of interventional therapy by way of the coronary venous system have demonstrated that it can protect acutely ischemic myocardium. To evaluate the efficacy of coronary venous retroinfusion compared with systemic intravenous administration of recombinant tissue-type plasminogen activator (rt-PA), 14 dogs were studied with a copper coil-induced thrombus in the left anterior descending coronary artery. The rt-PA (24,000 fluorescence units/kg) was administered continuously, either intravenously (n = 8) or retrogradely (n = 6), for 30 min beginning 60 min after coronary occlusion. Thrombolysis was determined by repetitive coronary angiography. All dogs were killed 3 h after termination of rt-PA infusion and infarct size was measured by the triphenyltetrazolium chloride staining technique. Complete thrombolysis occurred in five of the six dogs in the retroinfusion group and four of the eight dogs in the systemic intravenous infusion group. Partial lysis was achieved in two dogs treated by intravenous infusion. Lysis did not occur in one dog treated with retroinfusion and in two dogs treated with intravenous infusion. Time to thrombolysis was 13.4 +/- 2.3 min in the retroinfusion group versus 27.8 +/- 4.8 min in the intravenous group (p less than 0.001). Myocardial functional recovery in the ischemic zone measured by two-dimensional echocardiography 60 min after reperfusion was significant only in the retroinfusion group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Two types of autoantibodies to adrenal medullary cells in type 1 (insulin-dependent) diabetic patients: prevalence, properties and implications.

Complement-fixing adrenal medullary antibodies were examined in sera from 170 (114 Type 1 and 56 Type 2) diabetic patients and normal subjects by indirect immunofluorescence methods. Two types of antibodies were detected; one showed a homogeneous immunofluorescence pattern (homogeneous-type) and the other a spotty pattern (spotty-type) in the cytoplasm of adrenal medullary cells. Both antibodies were IgG class and adrenal medulla-specific. The prevalence of the homogeneous-type was significantly higher in Type 1 diabetic patients with disease duration under 1 year (36%) than in those with duration of 1 year or more (1.1%), in Type 2 diabetic patients (1.8%) or in normal subjects (0%; P less than 0.01). Conversely, the prevalence of the spotty-type was not significantly different among all subjects examined (3.6-4.5%). The epitope for the homogeneous-type is likely to be a glycoconjugate since binding of this antibody was abolished after periodate oxidation. The epitope for spotty-type antibody is considered to be a peptide since it was trypsin sensitive. Patients who were positive for the homogeneous-type were also positive for islet cell antibodies, although their antibody titers were not correlated. We conclude that (1) adrenal medullary antibodies are of homogeneous-type or spotty-type and the antigenic determinants of these antibodies are different, and (2) the prevalence of the homogeneous-type is significantly higher in newly diagnosed Type 1 diabetic patients and its presence is associated with that of islet cell antibodies.

Adolescent↗
PubMed1991

Positron emission tomography demonstrates that coronary sinus retroperfusion can restore regional myocardial perfusion and preserve metabolism.

Positron emission tomography was used to image blood flow and metabolic tracers in risk zone myocardium after left anterior descending coronary artery occlusion during synchronized coronary venous retroperfusion. Six control and seven intervention open chest dogs had occlusion of the mid left anterior descending coronary artery. Synchronized retroperfusion commenced 25 min later. Flow tracers (rubidium-82 and nitrogen-13 ammonia) were injected retrogradely. Three hours after coronary occlusion, fluorine-18 (F-18) deoxyglucose uptake in the control and treatment groups was compared. At 200 min of occlusion, infarct size was assessed. Retrograde flow tracer uptake was observed in the risk zone in the seven intervention dogs. Fluorine-18 deoxyglucose uptake in the risk zone was increased in five of the six intervention dogs but was reduced in five of the six control dogs. The risk zone to normal zone F-18 deoxyglucose count ratio was higher in the intervention than the control group (1.13 +/- 0.39 vs. 0.59 +/- 0.51; p less than 0.05). The endocardial subsegment risk zone to normal zone F-18 deoxyglucose count ratio was also significantly higher in the intervention group. Percent infarction in the risk zone was 70% lower in the group treated with synchronized retroperfusion than in the control group (18.4 +/- 22.6% vs. 61.2 +/- 25.4%; p less than 0.02). Thus, positron emission tomography revealed that retroperfusion could deliver oxygenated blood and maintain metabolism in risk zone myocardium. Infarct size was limited to 30% of that of control. In acute closure of the left anterior descending coronary artery, synchronized retroperfusion might be considered for maintaining viability of the jeopardized myocardium if the artery cannot be reopened rapidly.

Animals↗
PubMed1991

Beneficial effects of coronary venous retroinfusion but not left atrial administration of superoxide dismutase on myocardial necrosis in pigs.

The efficacy of coronary venous versus left atrial administration of superoxide dismutase was studied in 24 open chest pigs which had 60 min of left anterior descending coronary artery occlusion followed by 3 h reperfusion. The pigs were randomly assigned to three treatment protocols: group A (n = 8) superoxide dismutase (5 mg kg-1) was infused into the great cardiac vein for 30 min beginning 15 min before reperfusion; group B (n = 8) superoxide dismutase (5 mg kg-1) was infused into the left atrium in a similar manner to group A; group C (n = 8) bovine serum albumin (5 mg kg-1) was infused into the great cardiac vein in the same manner as group A. Infarct size, expressed as percent of area at risk, was significantly smaller in group A (28.2 +/- 13.0%) than groups B (58.7 +/- 8.3%) and C (61.6 +/- 7.2%) (P less than 0.05). The results indicate that retroinfusion of superoxide dismutase into the great cardiac vein before reperfusion may be an effective treatment for the prevention of reperfusion injury, even in the absence of a well developed coronary collateral circulation. Antegrade (left atrial) administration of the same amount of superoxide dismutase did not decrease infarct size in pigs. The most likely explanation for this difference in efficacy is that drug delivery with left atrial administration is dependent on antegrade flow with reperfusion which is less reliable and less efficient than coronary venous retroinfusion. The latter provides a predictably high concentration of superoxide dismutase to the jeopardized myocardium during the period of ischaemia before reperfusion.

Animals↗
PubMed1991

Myosin in hepatocytes is essential for bile canalicular contraction.

Active dynamic contraction of bile canaliculi has been observed in cultured doublet hepatocytes using time-lapse cinephotomicrography. This contractile movement plays an important role in normal bile formation. The mechanism of bile canalicular contraction has been proved to involve the Ca(2+)-calmodulin system and pericanalicular actin filaments. However, the role of myosin in this system is still unknown. In this study, using the newly synthesized myosin light-chain kinase inhibitor ML-9, we found that the treatment of cultured doublet hepatocytes with ML-9 inhibited canalicular contraction. This inhibitory effect suggests that myosin is involved in this complex cellular function and that the integrity of the actin-myosin system, as well as the Ca(2+)-calmodulin system is essential for normal bile canalicular contraction.

Actins↗
PubMed1991

Effect of beta agonist clenbuterol on the body composition of rats with hypothyroidism induced by oral administration of propylthiouracil.

The object of this experiment was to examine whether the administration of clenbuterol exerts clenbuterol's repartitioning effects in rats with hypothyroidism induced by the oral administration of propylthiouracil (PTU). Male Wistar rats aged 5 weeks were divided into 4 groups: control, PTU administrated (PTU), clenbuterol administrated (CL), and PTU plus clenbuterol administrated (PTU/CL) groups. Rats were raised for 7 weeks at 26 degrees C and given 13 g of diet every day. The PTU and PTU/CL groups were fed a basal diet containing PTU at the level of 30 mg/kg diet throughout the experimental period. Clenbuterol was added to the diet of the CL and PTU/CL groups at the dose of 0.1 ppm from the 3rd week. Serum thyroxine concentrations of rats were significantly lower in rats in the PTU and PTU/CL groups than those in the control and CL groups. Thus, the administration of PTU succeeded to induce hypothyroidism. The clenbuterol administration seemed to exert its repartitioning effects in euthyroid rats, while the administration neither increased body protein nor decreased body fat in hypothyroid rats. This result therefore suggests that the effects of clenbuterol on the alteration of body composition may vary with the level of thyroid activity in rats.

Adipose Tissue↗