Biomedical subjects
Publications and source records attributed to S Fujisawa.
We describe the case of an 11-year-old girl in whom glucosuria detected by urine screening at school was the first clue to the diagnosis of juvenile nephronophthisis (JN). On admission, she showed renal failure with combined proximal and distal tubular defects and progressive deterioration of renal function. JN should be considered in children with glucosuria.
The effect of LC-80 on infarct size induced by 6 hr coronary occlusion was studied in anesthetized dogs. LC-80 at a dose of 100 mg/kg, i.v. was injected 5 min after coronary occlusion and then infused at a rate of 50 mg/kg, i.v./hr until the heart was excised. The two risk areas were determined both by injecting a fluorescent dye (Thioflavin S) into the left atrium (in vivo) and by perfusing the non-occluded coronary bed with Monastral Blue (in vitro). The infarct size was determined by topographically tracing the area of myocardium unstained by triphenyltetrazolium chloride. Four zones such as Zone 1 (normal tissue), Zone 2 (tissue characterized by collateral blood flow), Zone 3a (tissue developing necrosis), Zone 3b (necrotic tissue) were delimited . As a result, (1) LC-80 significantly diminished the incidence of ventricular arrhythmias. (2) LC-80 significantly inhibited the decrease in myocardial free carnitine level in Zone 2 and Zone 3b. (3) LC-80 significantly reduced the infarct size expressed as a percentage of the risk area and increased the size of Zone 2. (4) In the electron microscopic findings, LC-80 showed lesser morphological changes such as swollen mitochondria and intracellular and extracellular edema, especially in Zone 2. (5) LC-80 may be useful for inhibiting the evolution of myocardial ischemic cell death both by the protection of ischemic myocardium and presumably by the increase in the collateral blood flow.
The interaction of methyl methacrylate (MMA), ethylene dimethacrylate (EDMA) and triethyleneglycol dimethacrylate (TEGDMA), which are widely used in dentistry, with the dipalmitoyl phosphatidylcholine (DPPC) and the DPPC/cholesterol (CS) liposome system was studied by 1H and 13C nuclear magnetic resonance spectroscopy (NMR). EDMA and TEGDMA have a larger interaction with the DPPC liposome system compared to MMA, resulting in changes in chemical shifts. The 13C chemical shift differences of C = C-C-O were larger than those of other carbon portions in methacrylate, indicating that double bonds interact predominantly with DPPC liposomes due to the hydrophobicity of methacrylates. At 37 degrees C, 1H signals from TEGDMA appeared in the DPPC/CS/TEGDMA liposome system, while signals due to H2C = C-C-OCH2CH2 did not appear in the DPPC/TEGDMA liposome system.
To clarify the mechanism of interaction of dental adhesive monomers with biological membranes at the molecular level, we studied the interaction of methacryloyloxydecyl dihydrogen phosphate (MDP) and methacrylic acid (MAA) with the dipalmitoylphosphatidylcholine (DPPC) liposome system using NMR and DSC. MDP-DPPC interaction became apparent through broadening of the DPPC phase transition as pH decreased, finally the enthalpy of MDP-DPPC (1:1 mol ratio) reduced to zero at pH 2.5. Proton chemical shifts of MDP enhanced shielding and proton signals due to the phosphatidylcholine polar group (O-CH2-CH2-N bond) of DPPC were observed. MAA-DPPC interaction was smaller than that of MDP-DPPC, even at low pH. It was concluded that the strong hemolytic activity of MDP may be due to its interaction with the phospholipid bilayers of erythrocyte membranes.
Amphiphilic compounds such as long-chain acyl carnitine accumulate in ischemic myocardium and potentially contribute to the myocardial damage, and the role of carnitine in protecting the heart against ischemic damage is interesting. It has been reported that palmitoylcarnitine causes alterations in the membrane molecular dynamics, so this study was designed to investigate whether L-carnitine had a stabilizing effect of membrane fluidity using the spin-label technique. Human erythrocytes were spin-labeled with 5-doxylstearic acids, and membrane fluidity was quantified by measuring the change in the order parameter S. The administration of palmitoylcarnitine (100 microM) altered the membrane fluidity of erythrocytes and caused significant morphological changes. L-carnitine (2mM) decreased the alteration of the fluidity of erythrocytes incubated with palmitoylcarnitine (100 microM), and improved the morphological changes in erythrocytes. These results show that L-carnitine has a stabilizing effect of membrane fluidity as a result of interaction with the palmitoylcarnitine which has a detergent effect.
The interaction of methyl methacrylate (MMA) and ethylene dimethacrylate (EDMA) with dipalmitoyl phosphatidylcholine (DPPC) liposomes was studied by 1H and 13C nuclear magnetic resonance spectroscopy (NMR). It was found that the changes in the 1H chemical shift of EDMA were larger than those of MMA when comparing membrane-bound state with free state and that the amount of EDMA incorporated into DPPC liposomes was approximately 74%, whilst MMA was approximately 41%. The major changes in chemical shifts of EDMA appeared to be due to its interaction with the acyl chains of DPPC liposomes.
The interaction of bis-GMA analogues with dipalmitoylphosphatidylcholine liposomes was studied by 1H and 13C nuclear magnetic resonance spectroscopy. It was found that bis-GMA analogues did not diffuse from liposomes once they were incorporated into the lipid bilayers of dipalmitoylphosphatidylcholine. The mobility of iso-bis-GMA was strongly disturbed by dipalmitoylphosphatidylcholine. The large changes in nuclear magnetic resonance spectra of iso-bis-GMA indicated that the interaction of iso-bis-GMA with dipalmitylphosphatidylcholine was larger than that of bis-GMA. This seems to be due to the chemical structure of iso-bis-GMA with the primary hydroxyl group.
The effects of LC-80, infused intravenously at a rate of 10 mg/kg/min for 30 min, on hemodynamics and myocardial metabolism were investigated in anesthetized open-chest dog preparations under a normal oxygen tension of arterial blood (PaO2) ranging from 100 to 120 mmHg or low PaO2 ranging from 40 to 50 mmHg. (1) Normal PaO2 + High free fatty acidemia (HFFA): HFFA was produced by the intravenous infusion of Intralipid at a rate of 0.1 ml/kg/min after the rapid intravenous injection of 500 U/kg of heparin. Under this experimental condition, no significant changes in hemodynamics and myocardial metabolism were observed in both the LC-80 treated group and control group. (2) Low PaO2 + HFFA: Under this condition, there was no significant difference in hemodynamics between the LC-80 treated group and the control group, and the myocardial function in both groups tended to decrease. However, the increase in the coronary flow of the LC-80 treated group tended to be slight as compared with that of the control group. On the other hand, the decrease in the arterio-coronary venous difference of lactate was significantly less in the LC-80 treated group as compared to that in the control group. Furthermore, the reduction in myocardial redox potential (delta Eh) of the LC-80 treated group tended to be slight as compared with that of the control group. (3) Low PaO2 + HFFA + stress load: The hemodynamic responses (heart rate, left ventricular pressure, max dP/dt and cardiac work) to isoproterenol-induced stress were slightly but not significantly better in the LC-80 treated group than in the control group. While myocardial lactate production and the reduction of delta Eh in both groups became more prominent under this experimental condition, their degrees were apparently less in the LC-80 treated group as compared to those in the control group. These results suggest that LC-80 may have an improving effect on the anaerobic myocardial metabolism under anaerobic conditions such as hypoxia or stress load.
The cardiovascular effects of levocarnitine chloride (LC-80) were investigated in in vitro and in vivo experiments, and the following results were obtained: (1) In isolated rabbit cardiac muscle preparations, LC-80 at the high concentration of 10(-2) M had little influence on the atrial rate of spontaneously beating right atria, while it caused a gradual increase in the contractile tension of both spontaneously beating right atria and electrically driven papillary muscle that reached a maximum level after 10 min of administration and lasted for 20-30 min. However, the LC-80-induced positive inotropic effect may be negligible in whole animal experiments or clinical trials, since it was elicited only after the administration of LC-80 in an extremely large dose. Furthermore, LC-80 in a high concentration (10(-2) M) had no influence on the isoproterenol-induced positive inotropic effect in electrically driven papillary muscles. (2) LC-80 in high concentrations of 10(-3)-10(-2) M did not affect the high K+-induced contraction in isolated canine left circumflex coronary artery and saphenous vein. (3) In anesthetized dogs, intraarterial injection of LC-80 in high doses of up to 10 mg did not change the blood flow of coronary, femoral, renal, mesenteric or vertebral arteries and on the adenosine-induced vasodilator action. (4) In anesthetized dogs, intravenous injection of LC-80 in doses of 100-300 mg/kg did not modify the blood pressure responses induced by norepinephrine, acetylcholine, carotid occlusion and vagal stimulation. These results suggest that the cardiovascular effects of LC-80 are extremely mild or negligible. Therefore, LC-80 may be a drug having a new pharmacological feature in its mechanism which enables it to exert a beneficial effect in the treatment of ischemic heart disease, being different from the commonly used antianginal drugs.
The beneficial effect of LC-80 in the therapy for organic acidemias, especially propionic acidemia and methylmalonic acidemia, was compared with those of its optical isomers, d-carnitine chloride (d-isomer) and dl-carnitine chloride (dl-isomer) in rat liver mitochondria. LC-80 at concentrations of 5 and 10 mM did not inhibit the mitochondrial function, while the d-isomer at a concentration of 5 mM significantly reduced the respiratory control ratio (RCR) of mitochondria. In addition, the dl-isomer at concentrations of 10 and 20 mM also significantly reduced RCR in a concentration-dependent manner. Thus, it seems likely that the d-isomer inhibits the mitochondrial function. On the other hand, the inhibition of mitochondrial function induced by a preincubation with propionate (4.76 mM) was significantly reversed by LC-80 (5 and 10 mM) in a concentration-dependent manner, while the d-isomer (5 mM) had no effect on the inhibitory effect of propionate. Moreover, although the dl-isomer (10 and 20 mM) significantly reversed the inhibitory effect of propionate as compared with the d-isomer, its effect was significantly weaker as compared with the effect of LC-80. The substrate specificity of rat liver mitochondrial carnitine acetyltransferase (CAT) was more potent with propionyl CoA than with acetyl CoA. Kinetic studies indicate that the d-isomer is a competitive inhibitor of CAT. These results suggest that LC-80 is useful in the clinical treatment of organic acidemias, whereas the d-isomer has a harmful effect in clinical application.
The correlation of variation in serum IgE and IgE-RAST in 364 cases of patients with atopic dermatitis (AD) aged 4 months to 78 years was analysed by comparison with the scatter diagram and fifth dimension regression curve representing the serum IgE and IgE-RAST scores of mite, egg white, milk, soybean, wheat and rice. The antigens indicating a high IgE-RAST score varied according to age. They were egg white and milk in infancy and mite from one to fifteen years of age. Rice and wheat came later. A high value of serum IgE with AD was seen to depend on the production of specific mite IgE antibody and to be influenced by each specific IgE antibody production, which varied according to age. It seemed that egg white and milk were initiators of AD and mite acted as a promotor. Rice and wheat were accelerators in patients with adult type AD. It was confirmed that, for AD patients of all ages, improvement of the environmental antigens and diet therapy was necessary.
The specific thiol protease inhibitor, NCO-700, which is related to L-trans-epoxysuccinylpeptides, inhibited oxidant production by chemoattractant-stimulated rabbit polymorphonuclear leukocytes. NCO-700 could also scavenge active oxygen generated from sodium hypochlorite-hydrogen peroxide and hypoxanthine-xanthine oxidase systems.
Haemolytic uraemic syndrome (HUS) associated with Yersinia enterocolitica gastroenteritis is reported in a 6-year-old girl. Y. enterocolitica of biotype 03 was isolated from the patient's initial stool sample and was subsequently identified as serotype 03 based on the rising agglutinin titres. This paper shows that yersiniosis should be suspected as a possible cause of HUS, and investigations should include the measurement of serum agglutinin titres against antigen preparations of the genus Yersinia.
To clarify the mechanism of the interaction of eugenol with odontoblast membranes compared with that of phenol and triethyleneglycol dimethacrylate (TEGDMA), we employed dipalmitoylphosphatidylcholine (DPPC) liposomes as a model system for odontoblast membranes. 1H and 13C nuclear magnetic resonance spectroscopy (NMR) was used as the spectroscopic approach in the study of this interaction. No signals of 1H and 13C due to eugenol in the DPPC/eugenol liposomes were observed, indicating that the mobility of eugenol was strongly disturbed by DPPC and that eugenol did not diffuse from the liposomes once it was incorporated. The change in chemical shifts due to phenol between the free state and the DPPC/phenol liposomes was not found, indicating that phenol resides in the aqueous phase or near the surfaces of liposomes, its interaction being markedly weaker than that of eugenol. The signals due to TEGDMA in the DPPC/TEGDMA liposomes were split into two peaks: a lower-field peak (free TEGDMA) and a higher-field one (membrane-bound TEGDMA). TEGDMA with ethyleneglycol groups seemed to be activated on the liposomes as a surfactant-like agent.
We attempted 24 percutaneous renal biopsies under orthogonal ultrasonic guidance in 23 children with renal diseases aged 1 to 17 years old. We used a 5 MHz linear-array transducer which was positioned on the side of the abdomen and aligned parallel to the biopsy needle so that projected ultrasound reaches the needle orthogonally. Thus, we could clearly and continuously monitor the biopsy needle and transverse plane of the kidney during the biopsy. We obtained diagnostically sufficient renal specimens in all subjects and found no significant complications, including macroscopic hematuria, in any case. We found that our method simultaneously visualized the biopsy needle and kidney much more clearly and made the biopsy far easier and safer than any other method previously proposed and we recommend the procedure be widely used in adult as well as child patients.
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