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Biomedical subjects

Y Mimura

Publications and source records attributed to Y Mimura.

At least 73 records · Page 4Linked to original sources

[A battery model of the eyeball to calculate standing potential of the eye].

Variation of the resting potential caused by eye movements was analyzed by applying a battery model to the eyeball. A formula that gives the potential between the inner canthus and the outer canthus of the eye was derived on the basis of the electric theory in electromagnetics, on the assumption that the eyeball was floating in a homogeneous conductor. The variations of the resting potentials were represented using the distance from the center of the eyeball to the potential detecting position and the deflection angle of the position with respect to the optical axis of the eyeball. To verify the validity of the formula, the variation of the resting potential caused by the various amplitudes of bilaterally symmetrical eye movements were measured. The calculated results were found to be in good agreement with the experimental ones.

Electrooculography

Role of cytoskeleton and acidification of endocytic compartment in asialoglycoprotein metabolism in isolated rat hepatocyte couplets.

The process of receptor-mediated endocytosis is common to a variety of species and cell types. One of the best characterized receptor-ligand systems is the hepatocyte receptor for asialoglycoproteins. We investigated the morphological features of the uptake and intracellular transport of gold-conjugated asialofetuin in isolated rat hepatocyte couplets. We assessed the effects of colchicine, lumicolchicine, cytochalasin B, and chloroquine on the uptake and intracellular transport of asialoglycoproteins. Isolated rat hepatocyte couplets were incubated with gold-conjugated asialofetuin, and transmission electron micrographs of these cells were analyzed to determine the density and distribution of gold particles in the peripheral and pericanalicular areas. Results were analyzed morphometrically. Colchicine significantly inhibited the uptake and intracellular transport of asialoglycoproteins, but did not affect membrane fusion of endocytic compartments in the peripheral area. Lumicolchicine and cytochalasin B had minimal effects on these processes. Chloroquine inhibited the uptake of asialoglycoproteins, but did not affect the intracellular transport of asialoglycoproteins. Results suggest that the microtubule is essential for intracellular movement of endocytosed asialoglycoproteins and receptor recycling, and that endocytic structures in the peripheral regions can fuse in the absence of intact microtubules. We also found that uptake and intracellular transport of asialoglycoproteins were independent of the microfilaments, and the pH gradient in endocytic compartments was important in receptor-mediated endocytosis of asialoglycoproteins.

Acids

Mechanisms of adaptation to hypoxia in energy metabolism in rats.

BACKGROUND: Oxygen supply to the tissues is needed in the early postoperative period to meet the energy requirements for maintaining cellular activity. This study was done to investigate energy metabolism in rats during hypoxia in order to determine the mechanism underlying the acclimatization of energy production to oxygen depletion. STUDY DESIGN: Wistar rats were divided into two experimental groups: hypoxic and normoxic, which were supplied with 10 and 21 percent oxygen for 20 hours, respectively. At the end of the experiment, blood and hepatic tissue samples were taken to determine endocrine and metabolic responses to hypoxia. Energy expenditure during hypoxia was also evaluated. RESULTS: Hypoxia resulted in marked increases in blood concentrations of triglycerides, free fatty acids, catecholamines, and corticosterone. Hypoxia marked by depressed resting energy expenditure and respiratory quotient, and produced a stable hepatic adenosine triphosphate (ATP) level. The cytosolic redox state, represented by the ratio of lactate to pyruvate concentrations in the liver, and the arterial ketone body ratio declined during hypoxia. With hypoxia, an increase in alanine and decreases in glutamine and glutamate levels in the liver were observed. CONCLUSIONS: These results suggest that hypoxia depresses energy expenditure, which leads to a normoxic level of hepatic ATP. Fat is a main metabolic fuel during hypoxia. Hypoxia leads to the development of a pathway that shunts pyruvate and glutamate to alanine and alpha-ketoglutarate, allowing efficient energy production.

Adaptation, Physiological

Effects of extracellular matrices on tube formation of cultured rat hepatic sinusoidal endothelial cells.

To determine the effects of extracellular matrices on the function and morphology of hepatic sinusoidal endothelial cells, isolated rat hepatic sinusoidal endothelial cells were cultured in three-dimensional fashion on collagen gel containing various extracellular matrix components. Cells cultured on type I collagen gel with or without type IV collagen formed a cobblestone appearance on the surface of the gel. Cells cultured on laminin-containing type I collagen gel invaded the gel and exhibited three-dimensional tube formation with a decreased number of characteristic endothelial pores. Morphometrically, there was a significant relationship between the length of the tube formed and the concentration of laminin in the type I collagen gel. Cells cultured on Matrigel, which contains high concentrations of laminin, type IV collagen, fibroblast growth factor, tissue plasminogen activator, and other growth factors, formed a great number of tubes into a network on the surface of the gel, as is observed in the situ hepatic sinusoidal endothelial cells. Ultrastructurally, tube-forming endothelial cells cultured on Matrigel had many endothelial pores on the cell surface, with tubes (approximately 10 microns in diameter) formed by two or three hepatic sinusoidal endothelial cells. These results indicated that extracellular matrix components, especially laminin, induced the formation of tubes in cultured rat hepatic sinusoidal endothelial cells. Tube-forming sinusoidal endothelial cells cultured on Matrigel could provide more advantages than the two-dimensional culture model for investigating the function and morphology of these cells in vitro.

Animals

Mechanisms of hyperpolarization induced by two cytokines, hTNF alpha and hIL-1 alpha in neurons of the mollusc, Onchidium.

The voltage and current responses induced by extracellular tumor necrosis factor (hTNF alpha) or interleukin-1 (hIL-1 alpha) on the Be-1 and Es-1 neurons of the Onchidium ganglia were examined. Pressure-ejected hTNF alpha or hIL-1 alpha produced an inhibitory, hyperpolarized effect in unclamped neurons. In the same neurons voltage-clamped at their resting potential levels, the same hTNF alpha or hIL-1 alpha elicited an outward current having a time course similar to that of the hyperpolarization, associated with a decreased membrane conductance. The hTNF alpha- or hIL-1 alpha-induced outward current did not reverse even at positive membrane potentials considerably above + 100 mV in the absence ouabain (a specific blocker of Na-pump). In the presence of ouabain, the hTNF alpha- or hIL-1 alpha-induced current was reduced over a wide range of membrane potential, so that the current reversed at about + 20 mV. Lowering the external Na+ concentration from 450 to 200 mM in the presence of ouabain, shifted the reversal potential from + 20 to 0 mV, to near the shift value of 20.8 mV predicted by the Nernst equation for a Na(+)-selective conductance. Neither an increase nor a decrease of extracellular K+, Cl- or Ca2+, however, significantly altered the current induced by hTNF alpha or hIL-1 alpha. These suggest that the hTNF alpha- or hIL-1 alpha-induced hyperpolarization or outward current response is mediated by two mechanisms, a decrease in Na+ conductance and activation of the Na-pump.

Animals

6H-pyrazolo[4,5,1-de]acridin-6-ones as a novel class of antitumor agents. Synthesis and biological activity.

The 7-substituted 6H-pyrazolo[4,5,1-de]acridin-6-ones with (aminoalkyl)amino and/or (hydroxyalkyl)amino groups in the side chains were synthesized by bromination using N-bromosuccinimide and the subsequent reaction with amines from the 7-substituted 5-bromo-2-methyl-6H-pyrazolo-[4,5,1-de]acridin-6-one. The substitution reaction of the amines with alkyl bromide (the C2 position) and aryl bromide (the C5 position) was accomplished by choosing the proper reaction conditions. These compounds show DNA intercalating ability in ethidium fluorescence assay and antiproliferative activity against Hela S3 cells. Impressive antitumor activity in vivo against murine P388 leukemia and murine sarcoma 180 solid tumor in mice was demonstrated for the 7-hydroxy analogs. In addition, some of these showed excellent antitumor activity against adriamycin-resistant murine P388 leukemia (P388/ADM) in mice.

Aminoacridines

Effect of acute hypoxia on phosphate excretion in rats.

This study evaluated the effect of acute hypoxia on renal handling of phosphate in rats in the presence and absence of parathyroid hormone (PTH). Hypoxia causes respiratory alkalosis in spontaneously breathing humans and animals. Respiratory alkalosis has been reported to induce a blunted phosphaturic response to PTH. In this study, to avoid the confounding effect of hypocapnia accompanying the hypoxia on phosphate excretion, the rats were ventilated mechanically, and arterial PCO2 levels were controlled. Rats were divided into two main groups depending on the arterial PO2 levels: a hypoxic group (n = 16) and a normoxic group (n = 18). Hypoxia was produced by ventilating with 10% oxygen, and hypocapnia was produced by hyperventilation. In response to PTH, the hypoxic rats without hypocapnia showed a greater increase in fractional excretion of phosphate (FEPi; 37.7 +/- 2.6%, mean +/- SE) compared with normoxic rats (27.4 +/- 2.5%, P < 0.02). During hypocapnia, there was no difference in FEPi between hypoxic and normoxic groups (21.2 +/- 1.5 and 19.5 +/- 1.2%, respectively), and both groups showed a significantly blunted phosphaturic response to PTH compared with normocapnia (P < 0.05 and P < 0.01, respectively). Urinary adenosine 3',5'-cyclic monophosphate (cAMP) increased similarly after PTH infusion between each group. To test whether the phosphaturic effect of PTH in hypoxia and the blunted phosphaturic effect of PTH in hypocapnia are due to steps beyond the generation of cAMP, the phosphaturic response to cAMP infusion was evaluated in 1) hypoxic and normocapnic rats (n = 6), 2) normoxic and normocapnic (control) rats (n = 6), and 3) normoxic and hypocapnic rats (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Acute hypocapnia blunts natriuretic and diuretic effects of atrial natriuretic factor in rats.

Recent studies suggest that the autonomic nervous system, when activated by respiratory alkalosis, may attenuate the renal effects of atrial natriuretic factor (ANF). We evaluated the renal responses to infusion of ANF during acute exposure to hypocapnia in the presence or absence of the renal nerves in anesthetized rats. In this study, renal function during hypocapnia was assessed and was compared with renal function during normocapnia produced by normal ventilation as well as by hyperventilation. Rats were divided into three experimental groups (n = 8): 1) a normally ventilated normocapnic (NV-N) (control) group; 2) a hyperventilated normocapnic (HV-N) group; and 3) a hyperventilated hypocapnic (HV-H) group. The innervated (Inn) right kidney served as a control for the contralateral denervated (DNX) kidney. In Inn and DNX kidneys of HV-H rats, an infusion of ANF (12 micrograms.kg-1.h-1) produced a smaller increase in urine flow rate (delta V: 9.8 +/- 3.9 and 1.3 +/- 4.2 microliters/min) and in fractional Na excretion (delta FENa: 1.35 +/- 0.52 and 0.73 +/- 0.58%) compared with NV-N rats (delta V: 37.6 +/- 4.9 and 59.9 +/- 9.7 microliters/min; delta FENa: 3.24 +/- 0.37 and 3.88 +/- 0.65%). No differences were observed in delta V and delta FENa in Inn kidney between HV-H and HV-N groups; however, the attenuated natriuretic and diuretic responses to ANF in DNX kidney of HV-H rats were also observed in comparison with HV-N rats (delta V: 27.4 +/- 4.3 microliters/min; delta FENa: 2.94 +/- 0.48%). ANF induced natriuresis in DNX kidney to the same degree in NV-N and HV-N rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

In vitro micro-autoradiography of atrial natriuretic peptide in biopsy specimens from patients with renal diseases.

We investigated the localization and density of atrial natriuretic peptide (ANP) receptors in human renal biopsy specimens by using in vitro micro-autoradiography (ARG) of [125I]-alpha-human (1-28) ANP. In a preliminary study, we measured the effect of storing tissue samples on ANP binding, using in vitro micro-ARG of Wistar rat kidney under optimal conditions. Duration of the preservation period did not affect ANP binding to renal tissue until samples had been stored at -30 degrees C for two years. A total of 11 human renal tissues were used to assay binding of ANP-ARG, including normal tissue obtained after nephrectomy because of renal cancer. ANP binding occurred predominantly within the glomerulus and, to a lesser extent, in the tubular region both in rat kidney sections and in human renal biopsy specimens. The density of ANP binding, calculated by counting grains in fixed areas, was compared with normal and pathological tissues. The density of grains tended to decrease in patients with renal dysfunction and hypertension except for one case of IgA nephropathy with normal renal function and blood pressure. The density of grains increased in a patient with nephrogenic diabetes insipidus. In the present study, we have established a method that uses in vitro micro-ARG for assessing ANP binding in human biopsy specimens.

Animals

[Sensitivities to other antiviral drugs and thymidine kinase activity of aciclovir-resistant herpes simplex virus type 1].

Sensitivity tests of various antiviral drugs on aciclovir-resistant strains of herpes simplex virus type 1 (HSV-1) were done in vitro. Activity of thymidine kinase (TK) of the aciclovir-resistant strains was also investigated. A strain of HSV-1 isolated from a patient with herpes labialis was grown in Eagle's minimum essential medium containing 10(-6)M aciclovir (ACV) and passaged 20 times. Then ACV-resistant strains of HSV-1 were obtained. Sensitivity tests of 5 anti-herpetic agents (ACV, ganciclovir, carbocyclic oxetanocin G, (S)-9- (3-hydroxy-2-phosphonylmethoxypropyl)adenine ((S)-HPMPA), and adenine arabinoside (ara-A)) were done on these ACV-resistant strains. The ACV-resistant strains were resistant to ganciclovir and carbocyclic oxetanocin G, but they were sensitive to (S)-HPMPA and ara-A. These ACV-resistant strains showed no detectable TK activity.

Acyclovir

[Localization of bovine corneal protein 54K (BCP 54) in the prenatal mouse eye].

Localization of bovine corneal protein 54K (BCP54) in the prenatal mouse eye was examined by immunohistochemical methods using rat anti-BCP54 polyclonal antibody. BCP54 was found from an early prenatal stage in corneal epithelium, keratocytes, corneal endothelium, conjunctival epithelium, and surface ectoderm which would differentiate in other organs except the eye. In other reports, it has been ascertained that BCP54 has an aldehyde dehydrogenase activity. To take its enzyme activity into consideration, we suggest that BCP54 is involved in maintaining transparency and oxidation-reduction balance of the cornea.

Aldehyde Dehydrogenase

[Reducing cross-talk in electrooculograms made with several electrodes].

In order to discuss how to handle the contralateral effect (cross-talk) when taking an electrooculogram (EOG) with two or more electrodes, a forced duction test was used to detect cross-talk potentials. The cross-talk potentials originating from the left eye were measured at the right eye for 5 subjects when the left eye was adducted and abducted alternately with a suction contact lens while the right eye was kept fixed. The cross-talk potentials detected at the right eye did not depend on the electrode position, but the contralateral EOG potentials depended on the electrode position around the left eye. The cross-talk value is calculated as the gain, 20.log [(cross-talk potential)/(contralateral EOG potential)]. The denominator of this expression considerably affects the gain since the contralateral potential depends on the position of the electrode. We propose that the effect of the cross-talk on the potential between a pair of electrodes can be cancelled with the gain value (-15.0dB: the mean value for the 5 subjects) when the contralateral electrode is set 20 mm from the outer canthus.

Electrodes

Decreased messenger RNA of arachidonate 12-lipoxygenase in platelets of patients with myeloproliferative disorders.

On the basis of the previous work by Okuma and Uchino [Blood 54, 1258-1271, 1979], three patients with myeloproliferative disorders were investigated with a special reference to arachidonate 12-lipoxygenase in their platelets. The cytosol of the patients' platelets showed a markedly reduced activity of arachidonic acid oxygenation to 12-hydroperoxy acid. A peroxidase-linked immunoassay for the 12-lipoxygenase demonstrated only 7-12% of the normal level of the enzyme protein in the cytosol fraction of platelets. Furthermore, 12-lipoxygenase mRNA level was determined quantitatively by a reverse transcriptase-polymerase chain reaction with an internal standard cRNA which was synthesized by in vitro transcription of human platelet 12-lipoxygenase cDNA with a 105-bp deletion. The 12-lipoxygenase mRNA content was 4.7 +/- 2.0 (mean +/- S.D.) ng/10(11) platelets in 13 normal subjects. In contrast, the mRNA content was as low as 0.15, 0.11 and 0.10 ng/10(11) platelets in the three patients. Taken together, the 12-lipoxygenase deficiency in these patients was attributable to the decreased 12-lipoxygenase mRNA level and thus the impaired synthesis of the enzyme protein in their platelets.

Antibodies, Monoclonal

Degradation of fibrinogen and fibrin by plasmin and nonplasmin proteases in the chronic subdural hematoma: evaluation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot.

To characterize local hyperfibrinolysis in the pathogenesis of chronic subdural hematoma (CSDH), fibrin degradation products (FDPs) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to identify each FDP fragment (fragments HMW, YY, DY and DD) by immunoblotting. The electrophoretic patterns of FDP in 40 hematomas from 33 patients could be categorized into 3 patterns; (i) type 1, the sharp DY and DD bands; (ii) type 2, the broad DY and DD bands; and (iii) type 3, the sharp DY and DD with two bands with higher molecular weights than fragment DY and DD. The broadening of DY and DD bands was reproduced by incubating the sample containing sharp DD and DY bands with the hemolyzed peripheral blood cells. These results indicated that the hyperfibrinolysis in CSDH could be characterized by the constant and incomplete proteolysis of fibrinogen and fibrin by plasmin and further degradation of FDPs by non-plasmin proteases released from hemolyzed blood cells.

Electrophoresis, Polyacrylamide Gel

Affinity maturation of anti-hapten antibodies in a single mouse analyzed by two-dimensional affinity electrophoresis.

Affinity maturation of anti-hapten antibodies in an inbred mouse (BALB/c) was analyzed by two-dimensional affinity electrophoresis (2D-AEP) in which the antibodies specific to a hapten of dinitrophenyl (DNP) group were separated into a large number of IgG families according to the differences in their isoelectric points (pI) and in their affinities for the ligand of DNP immobilized in the gel matrices. Each of the IgG families consisted of several spots showing an identical affinity for the ligand but different pI, and the spots were specifically stained by immunostaining with an anti-murine IgG subclass antibody. These results lead us to the conclusion that each of the IgG families is derived from a single clone of antibody-producing cells specific to DNP. The mass and affinity of the IgG families varied in the course of immunization with DNP-conjugated chicken serum albumin (DNP-CSA). The first injection of DNP-CSA induced a small amount of IgG families showing a wide variety in their affinity for DNP. The second injection induced a large amount of IgG families, especially of families having a medium affinity for DNP. Additional injections, however, did not change the mass or affinity of the IgG families significantly. This suggests that an antigen-induced somatic mutation of the immunoglobulin gene does not occur frequently to mature the affinity of antibodies by the additional injections after the second injection. 2D-AEP enables us to analyze the affinity maturation of antibodies in vivo in a single mouse and to document the subclass switch of the antibody in the course of immunization.

Animals

Treatment of cerebrotendinous xanthomatosis with low-density lipoprotein (LDL)-apheresis.

We studied the effects of LDL-apheresis on the biochemical and clinical abnormalities of 5 patients with cerebrotendinous xanthomatosis (CTX). Levels of both cholestanol and cholesterol decreased to approximately 60% of those of pretreatment after one perfusion and gradually returned to their initial levels within 2 weeks. Improvement of clinical manifestations and regression of Achilles tendon xanthomas were detected after several perfusions, though dramatic changes could not be recognized. EEG abnormalities were improved immediately after LDL-apheresis in one patient. We conclude that LDL-apheresis may affect the serum cholestanol level and clinical manifestations in patients with CTX.

Achilles Tendon

Chemical structure-activity of cnidium rhizome-derived phthalides for the competence inhibition of proliferation in primary cultures of mouse aorta smooth muscle cells.

Inhibitory effects of cnidium rhizome-derived phthalides on competence and progression phases of fetal bovine serum (10%)-induced proliferation were compared in primary cultures of mouse aorta smooth muscle cells (SMC). Their potencies for the competence inhibition were in the order of senkyunolide L ((Z)-6-hydroxy-7-chloro-6,7-dihydroligustilide) > senkyunolide H ((Z)-6,7-dihydroxy-6,7-dihydroligustilide) > senkyunolide J ((3S)-(E)-6,7-dihydroxy-3,6,7,8-tetrahydroligustilide) > senkyunolide I ((E)-6,7-dihydroxy-6,7-dihydroligustilide) > ligustilide = senkyunolide A ((3S)-3,8-dihydroligustilide) > butylidenephthalide. The order of their potencies for the progression inhibition was parallel with that for the competence inhibition. Senkyunolide L is considered to have been formed during the extraction of cnidium. These results demonstrate that the (Z)-6,7-dihydroxy isomer of the dihydroligustilide derivatives is essential for the anti-competent effect on proliferation of the SMC in primary culture. Senkyunolide H in cnidium rhizome may be a prototype for a new anti-atherosclerotic drug.

4-Butyrolactone