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Biomedical subjects

Y Morimoto

Publications and source records attributed to Y Morimoto.

At least 235 records · Page 13Linked to original sources

Expression of matrix metalloproteinases, tissue inhibitors of metalloproteinases, and extracellular matrix mRNA following exposure to mineral fibers and cigarette smoke in vivo.

To determine the effect of mineral fibers and cigarette smoke on remodeling of lung tissues, we examined matrix metalloproteinase-1 (MMP-1), MMP-2, tissue inhibitors of metalloproteinase-1 (TIMP-1), TIMP-2, and types I and IV collagen mRNA levels from rat lungs exposed to mineral fibers and/or cigarette smoke in vivo. Male Wistar rats (10 weeks of age) were given a single intratracheal instillation of 2 mg of chrysotile or alumina silicate ceramic fibers (RCF). Animals were then exposed to cigarette smoke (side stream) 5 days per week for 4 weeks. Transcriptional levels of mRNA extracted from the lungs were assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Exposure to cigarette smoke induced increases in MMP-1 and TIMP-1 mRNA levels and decreased TIMP-2 and type I collagen mRNA levels in lung. Chrysotile or RCF stimulated the expression of MMP-1 mRNA in the lung. The mineral fibers and cigarette smoke had more than additive effects on the expression of MMP-2 and TIMP-1 in the lung. These data suggest that the imbalance of the expression of MMPs, TIMPs, and extracellular matrix may be associated with the remodeling of lung tissues induced by mineral fibers and/or cigarette smoke.

Administration, Inhalation↗

A 15N GC/MS study of in vivo glutamine synthesis in liver failure rats.

To clarify the nature of nitrogen metabolism between branched chain amino acid (BCAA) and glutamine (Gln) in liver failure, we measured arterial plasma concentrations of Gln and 15N uptake to amino-N and amide-N of Gln in normal and D-galactosamine-induced fulminant hepatic failure (FHF) rats after 15N-leucine (Leu) injection. Fifteen, 30 and 60 min after Leu injection, the arterial plasma concentrations of Gln were significantly higher in FHF rats than in controls. The concentrations of amino-15N Gln were also significantly higher in FHF rats than in controls at 5, 15, 30 and 60 min after injection. The concentrations of amide-15N Gln did not significantly differ between FHF and controls at 5, 15 and 30 min. However, at 60 min, the concentration was significantly higher in the FHF rats. The higher uptake of 15N to amino-N of Gln in FHF rats suggests the presence of an enhanced ability to synthesize Gln from Leu in FHF rats. The higher uptake of 15N to amide-N of Gln in FHF rats at 60 min after injection suggests that excessive administration of BCAA to patients with severely impaired urea-cycle capacity suffering with hepatic failure may lead to greater levels of hyperammonemia.

Animals↗

Circulating vascular cell adhesion molecule-1 (VCAM-1) in atherosclerotic NIDDM patients.

Vascular cell adhesion molecule-1 (VCAM-1) has been shown to be highly expressed in atherosclerotic lesions. Although the soluble form of VCAM-1 (sVCAM-1) is detected in human sera, the relation between the degree of atherosclerosis and serum sVCAM-1 level has not been defined. In the present study, sVCAM-1 concentrations were measured in sera from 101 Japanese NIDDM patients. The mean +/- SD serum sVCAM-1 concentration in 26 patients with symptomatic atherosclerotic vascular diseases (789 +/- 187 ng/ml) was higher than that in 75 patients without the disease (664 +/- 175 ng/ml). Among the 101 NIDDM patients, 56 had atherosclerotic change of the carotid arteries, based on the evaluation by high-resolution B-mode ultrasonography. Their sVCAM-1 level was 759 +/- 201 ng/ml, higher than that in 45 patients without any detectable atherosclerosis of the carotid arteries (619 +/- 130 ng/ml). In addition, there was a positive correlation between sVCAM-1 concentration and thickness of the intimal plus medial complex (IMT) of the carotid arteries in the NIDDM patients (r = 0.41, P < 0.0001). Multivariate regression analysis revealed significant predictors of mean IMT value to be sVCAM-1 concentration (F = 62.88, P = 0.0001) and age (F = 9.59, P = 0.0026). By contrast, sVCAM-1 concentration was not increased in nondiabetic patients with atherosclerotic change of the carotid arteries (668 +/- 191 ng/ml; n = 36) compared with those without the atherosclerotic change (632 +/- 177 ng/ml; n = 28), and there was no correlation between sVCAM-1 level and IMT of the carotid arteries in the nondiabetic subjects. These results indicate that circulating sVCAM-1 may be a marker of atherosclerotic lesions in NIDDM patients with symptomatic and asymptomatic atherosclerosis.

Aged↗

[A case of reflex sympathetic dystrophy following a retinous surgery].

We present a case of a 54-year-old female with post-operative severe continuous ocular pain which occurred 3 months after retinal operation. Her general and mental conditions were good. We diagnosed it reflex sympathetic dystrophy and treated with stellate ganglion blocks (SGB) and continuous cervical epidural blocks. SGB and continuous cervical epidural blocks were effective. With increasing numbers of retinal surgery in recent years, more patients will suffer from postoperative ocular pain. We conclude that SGB or epidural block is useful for the therapy of ocular pain which can not be controlled by drugs and other therapy.

Analgesia, Epidural↗

[Total intravenous anesthesia with propofol and fentanyl for laparoscopic cholecystectomy].

The postoperative antiemetic effect of total intravenous anesthesia with propofol and fentanyl was evaluated in 40 patients for laparoscopic cholecystectomy. Patients were divided into 2 groups. In group P, anesthesia was induced with intravenous fentanyl 0.1 mg and propofol 2 mg.kg-1 and maintained with continuous infusion of propofol. In group I, anesthesia was induced with intravenous thiopental 5 mg.kg-1 and maintained with nitrous oxide 60% in oxygen and isoflurane. Post-operative nausea and vomiting were recorded for 8 h after surgery. Nausea scores (range 1-4) were significantly lower in group P as compared with group I at 0 h after surgery, but no difference between the groups at 2 h, 4 h, 8 h after surgery. No significant differences were found in the incidence of vomiting between the groups. These results suggest that total intravenous anesthesia with propofol and fentanyl is superior to inhalational anesthesia with nitrous oxide and isoflurane in postoperative nausea. This antiemetic effect is, however, limited in the early period after anesthesia.

Aged↗

Feeding experiments of pyridoxine derivatives as vitamin B6.

In order to compare the nutritional effect of vitamin B6 derivatives, long-term feeding experiments with rats were carried out using pyridoxine-alpha-D-glucoside (PN-alpha-Glc), pyridoxine-beta-D-glucoside (PN-beta-Glc) or epsilon- (N-phosphopyridoxyl)lysine (PNP-Lys) with test diets consisting of basically the AIN-76 composition, except for the addition of 0.1 mg pyridoxine equivalent (PN eq.)/100 g diet. During 21 days of pair-feeding against the vitamin B6-deficient diet group, body weight gain, urinary excretion of xanthurenic acid and pyridoxic acid were measured. After the feeding experiment, rats were killed and examined in terms of liver kynureninase activity (EC 3.7.1.3) with and without adding exogenous pyridoxal 5'-phosphate (PLP), erythrocyte aspartate aminotransferase activity (EC 2.6.1.1), as well as PLP concentration in blood. Rats fed with PN-alpha-Glc grew well, relative to the PN group. On the contrary, PN-beta-Glc poorly served as vitamin B6 source, because average bioavailability was only about 22% in comparison to that of PN (100%). From this long-term feeding experiments, we have shown that PN-alpha-Glc (average bioavailability about 84%) is a good source of vitamin B6 similar to PN.

Animals↗

[Successful use of propofol for anesthesia for plasty of eyelids in epidermolysis bullosa].

A 21-year-old male with recessive dystrophic epidermolysis, required anesthesia for plastic surgery of eyelids. We took special care for the attachment of monitoring equipment and placing an intravenous cannula. Anesthesia was induced by intravenous propofol 1 mg.kg-1 and maintained with local injection of 1.0% lidocaine and continuous infusion of propofol 3-4 mg.kg-1.hr-1. Tracheal intubation was not performed and oxygen was given through a nasal cannula and spontaneous breathing was maintained throughout the anesthetic management. Respiratory condition was monitored by measuring Spo2 and end-tidal CO2 by capnography obtained from the nasal cannula. Operation was performed successfully and he was discharged without any major complications.

Adult↗

Quality control of human IVF/ICSI program using endotoxin measurement and sperm survival test.

Quality control is essential for maintenance and improvement of a successful human in vitro fertilization and embryo transfer (IVF/ET)/intracytoplasmic sperm injection(ICSI) program. Quality control of medium, serum and equipments were performed using endotoxin measurement and human sperm survival test. It was proved by high pregnancy rate that the method of quality control at present study was essential for the development of the program.

Embryo Transfer↗

Precise chromosomal locations of the genes for dentatorubral-pallidoluysian atrophy (DRPLA), von Willebrand factor (F8vWF) and parathyroid hormone-like hormone (PTHLH) in human chromosome 12p by deletion mapping.

The precise chromosomal localization of the gene for dentatorubral-pallidoluysian atrophy (DRPLA) was detected by deletion mapping. Segregation patterns of genotypes of polymerase chain reaction products of DRPLA, von Willebrand factor (F8vWF), antigen CD4(p55) (CD4) and parathyroid hormone-like hormone (PTHLH) loci were studied in patients with del(12)(p13.3p13.3), del(12)(p12.3-p11.2), del(12)(p12.1-p11.2), del(12) (p11.2p11.2) and their parents. The gene for DRPLA was assigned to p13.1-p12.3 of chromosome 12. In addition, genes for F8vWF and PTHLH were mapped to p13.2 and p11.2 of chromosome 12, respectively.

Alleles↗

Improvement of rat liver graft function by insulin administration to donor.

BACKGROUND & AIMS: The nutritional status of a donor is considered to be an important factor affecting organ viability. The purpose of the present study was to examine hepatic energy status in connection with posttransplantation liver function. METHODS: The following five groups of donor rat livers were prepared and stored in University of Wisconsin solution at 4 degrees C: fasted group, rats fasted for 24 hours; fed group, rats provided standard laboratory chow; fed plus insulin group, fed rats treated with insulin before harvest; fasted plus insulin group, fasted rats treated with insulin before harvest; and fed plus glucagon group, fed rats pretreated with glucagon. RESULTS: Hepatic levels of adenosine triphosphate and total adenine nucleotides were maintained in the decreasing order of the fed plus insulin, fed, fasted plus insulin, fasted, and fed plus glucagon groups during preservation. Lactate production rate and fructose 2,6-bisphosphate level increased in the order of the fed plus insulin, fed, fed plus glucagon, fasted, and fasted plus insulin groups. Liver function after transplantation evaluated by the bile flow rate and enzyme leakage was well restored in the fed plus insulin group. CONCLUSIONS: Insulin administration to nutritionally well-supported livers before harvest improved energy metabolism during preservation and liver function after transplantation.

Adenosine Triphosphate↗

Insulin pretreatment protects the liver from ischemic damage during Pringle's maneuver.

BACKGROUND: Although maintenance of adenosine triphosphate (ATP) levels is important to restore liver functions during anoxia, ATP production by oxidative phosphorylation is inhibited during Pringle's maneuver, and only a little ATP can be supplied by glycolysis. The glycolytic activity of the liver is controlled by the nutritional condition and hormones. Enhancement of glycolytic activity by insulin may increase ATP production and thus may protect the liver from ischemia. METHODS: Rats were divided into three groups: fasted group, food was withheld for 24 hours; fed group, food was provided ad libitum; and insulin group, fed rats were administered insulin (12 units/kg during a 30-minute period) before portal triad clamping (PTC) was performed. After laparotomy was performed, PTC was performed for 30 minutes. The fructose 2,6-bisphosphate (F-2,6-BP) level, the hepatic levels of lactate and ATP, the bile flow rate, the plasma levels of aspartate transaminase and lactate dehydrogenase, and the indocyanine green clearance were measured at appropriate times. RESULTS: The hepatic F-2,6-BP levels before PTC in the fasted, fed, and insulin groups were 6.2 +/- 3.8, 55.6 +/- 10.6, and 122.2 +/- 31.3 nmol/gm dry weight liver, respectively. The glycolytic activity of the insulin group before PTC was significantly enhanced compared with that of the other groups. Lactate was more rapidly accumulated in livers of the insulin group during PTC than in those of the other groups. The ATP level and energy charge during PTC of the insulin group were higher than those of the other groups. The bile flow rate and indocyanine green clearance after PTC were restored in the order of the insulin, fed, and fasted groups. CONCLUSIONS: Insulin administration before PTC increased the hepatic F-2,6-BP content and enhanced glycolytic activity. Insulin pretreatment combined with feeding improved the hepatic energy metabolism during PTC and restored the liver functions after PTC. Insulin has protective effects on the liver during PTC.

Adenine Nucleotides↗

Analysis of simultaneous transport and metabolism of ethyl nicotinate in hairless rat skin.

PURPOSE: Simultaneous skin transport and metabolism of ethyl nicotinate (EN), a model drug, were measured and theoretically analyzed. METHODS: Several permeation studies of EN or its metabolite nicotinic acid (NA) were done on full-thickness skin or stripped skin with and without an esterase inhibitor. Permeation parameters such as partition coefficient of EN from the donor solution to the stratum corneum and diffusion coefficients of EN and NA in the stratum corneum and the viable epidermis and dermis were determined by these studies. Enzymatic parameters (Michaelis constant Km and maximum metabolism rate Vmax) were obtained from the production rate of NA from different concentrations of EN in the skin homogenate. Obtained permeation data were then analyzed by numerical method based on differential equations showing Fick's second law of diffusion in the stratum corneum and the law with Michaelis-Menten metabolism in the viable epidermis and dermis. RESULTS: Fairly good steady-state fluxes of EN and NA through the skin were obtained after a short lag time for all the concentrations of EN applied. These steady-state fluxes were not proportional to the initial donor concentration of EN: EN and NA curves were concave and convex, respectively, which suggests that metabolic saturation from EN to NA takes place in the viable skin at higher EN application. The steady-state fluxes of EN and NA calculated by the differential equations with resulting permeation and enzymatic parameters were very close to the obtained data. CONCLUSIONS: The present method is a useful tool to analyze simultaneous transport and metabolism of many drugs and prodrugs, especially those showing Michaelis-Menten type-metabolic saturation in skin.

Animals↗

Crystallization and preliminary X-ray analysis of salicylate hydroxylase from Pseudomonas putida S-1.

Apo-salicylate hydroxylase from Pseudomonas putida S-1 has been crystallized by the dialysis method, using ammonium sulfate as the precipitant. The crystals belong to hexagonal space group P6(2) or P6(4) with unit cell dimensions of a = b = 142.8 A and c = 63.8 A, and diffract X-rays at higher than 3.5 A resolution. A heavy-atom derivative has been prepared by soaking a crystal in an ammonium sulfate solution containing p-chloromercuriphenylsulfonate.

Crystallization↗

Mechanism of cellular swelling induced by extracellular lactic acidosis in neuroblastoma-glioma hybrid (NG108-15) cells.

The mechanism of cellular swelling induced by extra-cellular lactic acidosis and the effect of diuretics were studied using neuroblastoma-glioma hybrid (NG108-15) cells. The cells were incubated in one of three lactate concentrations (0, 15, or 30 mM), each of which was randomized to one of three pH groups (7.4, 6.2, or 5.0). Analysis of the swelling was measured using a Coulter counter technique. Cellular swelling was most prominent at pH 6.2 at all lactate levels. Cellular swelling was noted to be pH dependent but not lactate dependent. The addition of 1 mM amiloride completely blocked cellular swelling, suggesting that the main mechanism of neuronal cellular swelling induced by extracellular lactic acidosis was the activation of Na+/H+ exchange. Second, three dissimilar diuretic drugs were used for cellular swelling: amiloride (Na+/H+ exchange inhibitor), mannitol (osmotic diuretic), and bumetanide (loop diuretic). Amiloride and mannitol were found effective in reducing the lactic acidosis-induced cellular swelling. Furthermore, the combination of these drugs had additive effects. However, bumetanide was not effective. The results indicate that the direct inhibition of Na+/H+ exchange and/or removal of water from the cell by mannitol was effective against cellular swelling induced by the activation of Na+/H+ exchange in NG108-15 cells.

Acidosis, Lactic↗

Extramyocardial acidosis impairs cardiac resuscitability in isolated, perfused, rat hearts.

OBJECTIVES: Patients suffering out-of-hospital cardiac arrest have various degrees of acidemia when cardiopulmonary resuscitation is initiated. Myocardial hypercarbia, rather than decreases in myocardial pH, may determine cardiac resuscitability. Accordingly, we questioned whether different degrees of acidemia accompanying cardiac arrest affect cardiac resuscitability. We evaluated the effect of different degrees of extramyocardial acidosis on cardiac performance and resuscitability after ventricular fibrillation using isolated, perfused, rat hearts. DESIGN: Prospective, randomized, controlled study. SETTING: Experimental animal laboratory in a university hospital. SUBJECTS: Thirty-one male, Sprague-Dawley rats. INTERVENTIONS: Rat hearts were perfused with N-[2-hydroxyethyl]piperazine-N-[2-ethanesulfonic acid] (HEPES) buffered solution (sodium chloride 145 mM, potassium chloride 4 mM, sodium dihydrogen phosphate dihydrate 1.25 mM, magnesium chloride 1.5 mM, calcium chloride 2 mM, HEPES 6 mM, glucose 10 mM), which was bubbled with 100% oxygen and adjusted to a pH of 7.4. The perfusion pressure was held constant at 60 mm Hg. After 60 mins of stabilization, the control perfusion solution was switched to one of the solutions titrated to pH 6.2, 6.5, 6.8, 7.1, or 7.4, using 1 N of sodium hydroxide. Hearts were allocated randomly to each group. After 15 mins of perfusion, the perfusion was discontinued, and artificial ventricular fibrillation was induced by electrical stimulation for 5 mins. The hearts were then perfused again in one of the same acidotic solutions for 30 mins. MEASUREMENTS AND MAIN RESULTS: Left ventricular developed pressure (left ventricular pressure minus end-diastolic left ventricular pressure), positive change in left ventricular pressure over time, heart rate (HR), and coronary flow were continuously measured. After 60 mins of stabilization, the values of left ventricular developed pressure, positive change in left ventricular pressure over time, HR, and coronary flow were not significantly different between groups. After 5 mins of ventricular fibrillation, all hearts were asystolic and left ventricular developed pressure, positive change in left ventricular pressure over time, HR, and coronary flow were all zero. After 30 mins of reperfusion, all values in the acidotic groups were significantly lower than the values in the pH 7.4 group. When we judged the recovery of left ventricular developed pressure at > 35 mm Hg as "resuscitated," resuscitability was impaired at a pH of < 7.1. No hearts recovered after perfusion below a pH of 6.5. CONCLUSIONS: Extramyocardial acidosis below pH 7.1 decreased cardiac performance and resuscitability after ventricular fibrillation. This result indicates that progressive acidemia during cardiac arrest is one of the important determinants of cardiac resuscitability.

Acidosis↗

Benign adult familial myoclonus epilepsy (BAFME): an autosomal dominant form not linked to the dentatorubral pallidoluysian atrophy (DRPLA) gene.

The genetic differences between two types of dominant inherited myoclonus epilepsy, dentatorubral pallidoluysian atrophy (DRPLA) and benign adult familial myoclonus epilepsy (BAFME), have been reported. A gene with a CAG repeat expansion responsible for DRPLA has been isolated. We have examined CAG repeat expansion in the DRPLA gene in five BAFME families, and the abnormal CAG expansion was not observed in the affected subjects. Linkage analysis using DNA polymorphisms in the DRPLA gene and the genes for gamma-aminobutyric acid (GABA) receptor subunits, GABAR beta 1, GABAR beta 3, and GABAR alpha 6, showed that these genes were not responsible for BAFME.

Atrophy↗