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Biomedical subjects

H Itoh

Publications and source records attributed to H Itoh.

At least 865 records · Page 48Linked to original sources

[Improved perseveration with amantadine].

We report here 3 patients who showed marked improvement of clonic and intentional perseverations following the administration of amantadine. Patient 1 had a subacute encephalitis of unknown etiology. Magnetic resonance imaging documented lesions predominantly in the bilateral putaminal and frontal subcortical areas, and positron emission tomography revealed frontal glucose hypometabolism. Daily amantadine hydrochloride of 200 mg with or without 10 mg of trihexyphenidyl, reduced his clonic and intentional perseverations. The diagnosis of patients 2 and 3 was vascular dementia with multiple subcortical ischemic lesions, and single photon emission CTs showed reduced cerebral blood flow in the frontal lobes. Their clonic perseveration subsided and intentional perseveration disappeared after the administration of 150 mg of daily amantadine hydrochloride. Associated Parkinsonism and confusional state also improved in patient 1, but not in patients 2 or 3. Amantadine increases the pre-synaptic synthesis and release of dopamine, and works as a dopamine system activator. Our findings suggest that the disturbance of dopamine system, especially meso-limbofrontal projection, has some contributions to the perseveration of these patients.

Aged↗

Effects of high-molecular-weight sodium hyaluronate on experimental osteoarthrosis induced by the resection of rabbit anterior cruciate ligament.

Sodium hyaluronate (HA) with a molecular weight of 202 x 10(4) (HA-202) was administered into the right knees of mature rabbits for the treatment of experimental osteoarthrosis induced by resection of the anterior cruciate ligament. At six and 12 weeks after the initiation of administration, the test group was compared with a group administered physiological saline solution to determine the effects on articular cartilage and synovial tissue. In both the six- and the 12-week period, cartilage degeneration proceeded with the lapse of time in both groups; however at 12 weeks, the efficacy of HA-202 in inhibiting degeneration was clearly observed at the lateral condyle of the femur and tibia where relatively marked degeneration was observed in the saline group. A comparison was also made among three groups administered HA-95 (sodium hyaluronate with a molecular weight of 95 x 10(4)), HA-202, and saline, respectively, for 12 weeks. The saline group showed the greatest cartilage degeneration accompanied by complete disorganization of the cartilage layer and the disappearance of chondrocytes. The degeneration was less in the HA groups, and it was more significantly inhibited in the HA-202 group than in the HA-95 group.

Animals↗

Effect of high-molecular-weight sodium hyaluronate on immobilized rabbit knee.

Experimental osteoarthrosis of the knee joint was induced in rabbits using a polyethylene binding brace. A 1% solution of sodium hyaluronate (HA) of molecular weight 1.73 x 10(6) (HA-173) was administered intraarticularly at a dosage of 0.1 ml/kg body weight twice a week. Changes in articular cartilage and synovial membrane, and joint contracture were compared with a saline control group at intervals throughout a six-week period of immobilization. In all groups, articular cartilage degeneration and joint contracture progressed with time but were inhibited by the administration of HA-173. Additionally, the results of a 1% solution of HA of molecular weight 9.8 x 10(5) (HA-98), a 1% solution of HA of molecular weight 2.02 x 10(6) (HA-202), and saline, each administered twice a week for five weeks at a dose of 0.1 ml/kg body weight, were compared. It was clear that the articular cartilage degeneration was significantly inhibited by HA as compared with saline, and that the effect was more potent with the higher molecular weight, HA-202, than with HA-98. Furthermore, joint contracture was inhibited by HA, and the effect was more potent with the higher molecular weight, HA-202, than with HA-98.

Animals↗

[Aggressive management of prolapsed fetal membranes earlier than 26 weeks' gestation by emergent McDonald cerclage combined with amniocentesis and bladder overfilling].

During the period January, 1987-December, 1992, 32 pregnant women (33 fetuses) earlier than 26 weeks' gestation were admitted to our perinatal unit with incompetent cervix and prolapsed fetal membranes through the cervix (hourglassing). Eighteen pregnant women (19 fetuses) were managed aggressively with emergent double McDonald cerclage, which included preoperative amniocentesis and bladder overfilling to decompress and replace prolapsed fetal membranes. Fourteen pregnant women were managed conservatively with bed rest, tocolysis, and antibiotic therapy. The perinatal results of aggressive management were clearly more favorable than those of conservative management when compared: Prolongation of pregnancy 35.2 +/- 39.7 vs. 3.5 +/- 2.6 days (p < 0.01), gestational age at delivery 27.3 +/- 5.3 vs. 24.2 +/- 1.2 weeks' (p < 0.05), birth weight 1,260 +/- 909 vs. 690 +/- 124 grams (p < 0.05), and fetal salvage rates 74(14/19) vs. 7(1/14)%, respectively.

Amniocentesis↗

[Evaluation of clinical usefulness of 11C-methionine positron emission tomography (11C-MET-PET) as a tool for liver functional imaging].

We studied 11C-MET-PET in 17 clinical cases, 10 patients with obstructive jaundice and 7 normal volunteers, and analyzed its efficacy for the evaluation of hepatic functional reserve in major hepatectomy candidates. Differential absorption ratio (DAR) of 11C was compared to the hepatic protein synthesis rate (HPS), which is measured as the incorporation rate of 3H-labeled leucine in protein fraction, using needle biopsied liver specimen obtained from each hepatic segment. In the cases of normal liver function, DAR was well correlated with HPS. Also in jaundice cases with two exceptions, low HPS segment was demonstrated as low DAR segment. Consequently, MET-PET images could clearly provide functional liver imaging. After injection to 11C-MET, the increase in rate of radioactivity of 11C in plasma protein fraction was higher in jaundice cases than in normal volunteers, which is in accord with the results of our former study that cholestatic liver has accelerated protein synthesis rate. In summary, since 11C-MET-PET could demonstrate liver functional imaging, it might be a possible tool for liver function assessment in major hepatectomy candidates.

Carbon Radioisotopes↗

Clonal expansion of p53 mutant cells in leukemia progression in vitro.

Using the polymerase chain reaction followed by single-strand conformation polymorphism (PCR-SSCP) analysis and direct nucleotide sequence determination, the p53 gene was analyzed in six fresh leukemia samples from which cell lines with p53 mutations were established. Mutations of the p53 gene which were identical to those in the cell lines were observed in three of the fresh samples. In the other three samples, p53 gene mutations were not detected by the conventional PCR-SSCP method. However, when analyzed using allele-specific gene amplification, less than 10% of the leukemic cell population of the three samples, which were below the detection threshold of PCR-SSCP, were shown to have p53 gene mutations. Two samples taken at the initial presentation of two patients, whose relapse samples were shown to contain p53 mutant clones, were also available for analysis. A small population of clonal cells, comprising less than 1% of the population, was shown to have p53 gene mutations in both of these initial samples. These observations provide a potential biologic basis for the frequent findings of p53 mutations in leukemia cell lines and also suggest a potential role for p53 mutations in the clonal overgrowth of cells responsible for relapse of the disease.

Acute Disease↗

Comparison of the effects of various vasodilators on the rat portal vein and mesenteric artery.

The effects of various vasodilators on isolated helical strips of rat portal vein and mesenteric artery were examined. Dilazep, ibudilast, nifedipine, verapamil and papaverine relaxed the KCl- and norepinephrine-induced contractions of the portal vein to a greater extent than they relaxed those of mesenteric artery. Dibutyryl cyclic AMP and NKH477 did not show any significant difference in terms of the concentrations that produced 50% inhibition (IC50) of the KCl-induced contraction of the portal vein and mesenteric artery. The relaxant effects of nitroprusside and isosorbide dinitrate on the KCl- and norepinephrine-induced contractions of the portal vein were less potent than their effects on contractions of the mesenteric artery. The agents that inhibited the contractions of the portal vein more potently than those of the mesenteric artery were associated with parallel shifts to the right of the concentration-response curves for CaCl2 in both preparations. These results suggest that drugs with a Ca2+ channel blocking action may be preferable to those that cause a decrease in portal pressure for treatment of portal hypertension.

Animals↗

Central action of C-type natriuretic peptide on vasopressin secretion in conscious rats.

The effect of intracerebroventricular injection of C-type natriuretic peptide (CNP) on arginine vasopressin (AVP) secretion was studied in conscious rats, and was compared to that of atrial natriuretic peptide (ANP). The AVP secretion induced by central injection of 0.1 nmol angiotensin II was significantly suppressed by the pretreatment with 1 nmol CNP. ANP at a dose of 0.1 nmol elicited almost equivalent suppressive action to 1 nmol CNP. Considering that CNP is a specific ligand for ANP-B receptor, while ANP is that for ANP-A receptor, the result demonstrates that CNP possesses the similar central action to ANP, and suggests that the distribution of ANP-A and ANP-B receptors and/or their affinity towards each natriuretic peptide are different in the central nervous system.

Angiotensin II↗

Ca2+(-)dependent and Ca2+(-)independent vasorelaxation induced by cardiotonic phosphodiesterase inhibitors.

Cardiotonic agents that belong to a group of phosphodiesterase inhibitors--vesnarinone, amrinone, enoximone, pimobendan, MS-857 and E-1020--inhibited the 35 mM KCl- and 10(-7) M norepinephrine-induced contractions of helical strips from rat thoracic aorta in a concentration-dependent manner. In the absence of extracellular Ca2+, 10(-7) M phorbol 12,13-dibutyrate caused a sustained contraction of the muscle strip without an increase in intracellular Ca2+ level ([Ca2+]i). The phorbol 12,13-dibutyrate-induced contractions in Ca2+(-)free buffer were also inhibited by the cardiotonic phosphodiesterase inhibitors. A cyclic GMP-inhibited cyclic nucleotide phosphodiesterase was partially purified from rat aorta and the activity of the phosphodiesterase was inhibited by the cardiotonic agents. The inhibitory effect of these agents on the KCl-, norepinephrine-and phorbol 12,13-dibutyrate-induced contractions showed good correlations to the concentrations of the agents producing 50% inhibition (IC50) of cyclic GMP-inhibited cyclic nucleotide phosphodiesterase. Vesnarinone inhibited the norepinephrine-induced contraction with a decrease in [Ca2+]i, but inhibited the phorbol 12,13-dibutyrate-induced contraction in Ca(2+)-free buffer without significant changes in [Ca2+]i. Dibutyryl cyclic AMP and NKH477 also inhibited the phorbol 12,13-dibutyrate-induced contraction in Ca(2+)-free buffer without significant changes in [Ca2+]i. The six cardiotonic phosphodiesterase inhibitors increased the cyclic AMP contents of the muscle strips. These results suggest that the inhibitory actions of these cardiotonic phosphodiesterase inhibitors on cyclic GMP-inhibited cyclic nucleotide phosphodiesterase may cause vasorelaxation through a decrease in [Ca2+]i and an inhibitory effect on a Ca(2+)-independent contractile process (or a decrease in Ca(2+)-sensitivity of contractile elements).

Animals↗

Enhancement of cytotoxicity of doxorubicin by verapamil in the hepatic artery infusion for liver tumors in rats.

BACKGROUND: The calcium channel blocker has been demonstrated to be effective in the accumulation and retention of chemotherapeutic agents in tumor cells. METHODS: The effect of verapamil on cytotoxicity of doxorubicin was investigated in a hepatic artery infusion (HAI) for liver tumors of Walker 256 carcinosarcoma in rats. Doxorubicin was infused by way of a hepatic artery by a bolus injection intra-arterially (IA) (1 mg/kg) and a continuous infusion intra-arterially (CIA) (6 mg/kg/day for 6 days). RESULTS: Doxorubicin increased 90% and 66% in tumor tissue following HAI of verapamil by a bolus and continuous infusion (P < 0.05), respectively. However, no enhancement of the accumulation of doxorubicin in the tumor tissue was found in an intravenous administration of verapamil. The CIA infusion of verapamil with doxorubicin inhibited the tumor growth by 73% in comparison with doxorubicin only (P < 0.05). Verapamil administered intravenously (IV) could not induce this inhibitory effect. The CIA administration of verapamil reduced the serum concentration by 45% (P < 0.001) in comparison with the CIV route. Furthermore, the administration of verapamil did not increase the accumulation of doxorubicin in the normal liver and heart tissues. No enhancement of bone marrow suppression and hepatic biochemical influence by doxorubicin was revealed by the concomitant use of verapamil. CONCLUSIONS: The continuous HAI of verapamil remarkably enhanced the cytotoxicity of HAI with doxorubicin for the treatment of hepatic tumor without aggravating the side effects induced by doxorubicin.

Animals↗

Identification and partial characterization of phospholipase D in the human amniotic membrane.

The enzymatic activity of phospholipase D and its characteristics have been examined in human amnion tissue. The phospholipase D activity was not Ca(2+)- or Mg(2+)-dependent and was activated by unsaturated fatty acids. The optimal pH of phospholipase D was 5.5. The phospholipase D activity in amnion tissue was highest in the microsomal fraction, and preferentially utilized phosphatidylcholine as a substrate. The phospholipase D activity of the microsomal fraction of amnion tissue obtained at term before labor onset (34.0 +/- 16.3 nmol/hour/mg protein, mean +/- SD, n = 11) was significantly (p < 0.05) higher than the activity in this tissue obtained from women in the mid-trimester (15.0 +/- 7.5 nmol/hour/mg protein, n = 9).

Amnion↗

Immunohistochemical study of glutamine synthetase expression in early glial development.

Early glial development in the brains of rat embryos was immunohistochemically studied using antibodies to two kinds of glial-specific proteins, glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP). The results showed that GS was first expressed in the ependymal lining of the ventral side of the neural tube in the cervical segment on Embryonic Day 14 and then in the radial glia radiating from the neural tube on Embryonic Day 16. Subsequently, GS-positive glia cells increased in number with time. On the other hand, GFAP was first expressed in the fimbria hippocampi and the pial surface on Embryonic Day 18, but no marked evidence of GFAP expression was noted in the GS-positive radial glia. These results suggested that a specific protein is expressed at each stage of early glial development. Since the radial glia was positive for GS, it was thought that GS-mediated neuronal-glial interactions may play an important role in the development of the central nervous system.

Animals↗