Accelerated accumulation of somatic mutations in the senescence-accelerated mouse.
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Aging↗
Biomedical subjects
K Takemoto
Publications and source records attributed to K Takemoto.
Inhibition of sea urchin fertilization by jaspisin, a specific inhibitor of matrix metalloendoproteinase.
Jaspisin, originally isolated from a marine sponge as an inhibitor of the hatching of the sea urchin (Hemicentrotus pulcherrimus) embryo, causes inhibition of sea urchin fertilization. Electron microscopic examination revealed that the acrosome reaction was induced in jaspisin-treated sperm when they were incubated with an intact egg. The acrosome-reacted sperm bound to the vitelline layer by the acrosomal material surrounding the acrosomal process. However, fusion of the acrosomal process and the egg plasma membrane failed to take place. Membrane potential changes were monitored using eggs preloaded with a membrane potential-sensitive fluorochrome, di-8-ANEPPS. Depolarization of the membrane potential, normally observed in the fertilized egg was not observed in the egg inseminated in the presence of jaspisin, indicating the absence of electrical continuity between the jaspisin-treated egg and sperm. Jaspisin inhibited the activities of matrix metallo-endoproteinase members but not of other types of proteinases. These results provide strong, albeit indirect, evidence that a matrix metallo-endoproteinase(s) is involved in the process of gamete fusion during sea urchin fertilization.
Acrosome↗
Studies on cardiac ingredients of plants. XIII: Chemical modification of gitoxin to cardiotonic compounds without vascular effect.
Nitrated gitoxins (4) and bufotoxin homologues with various lengths of alkyl chain at C-3 of the steroid nucleus (10) were prepared from gitoxin (1). The pharmacological activities of the resulting compounds (4 and 10) were evaluated by measurement of inhibitory effect on NA+, K(+)-adenosine triphosphatase (ATPase) prepared from dog kidney, positive inotropic effect (PIE) on isolated guinea-pig papillary muscle preparations, and the effect on smooth muscle using the mesenteric artery from spontaneously hypertensive rats. Most of the compounds showed a smaller contractile effect on the arterial muscle. Among these compounds, gitoxin 3"-nitrate (4g) exhibited the most desirable biological activities, such as PIE comparable to that of 1, 1.25 times wider concentration-dependent range than 1, and lack of contractile activity on vascular muscle.
Animals↗
[Postoperative epidural fentanyl administration in patients for hysterectomy with para-aortic lymph node resection].
In our experience, continuous epidural administration of fentanyl in doses of 12.5 micrograms.h-1, has not been sufficient to relieve postoperative pain in patients after hysterectomy with para-aortic lymph node resection. Thus, a prospective, randomized, single-blind study was performed to compare the analgesic efficacy of fentanyl 25 micrograms.h-1 with 12.5 micrograms.h-1 in these patients for 48 hours after surgery. Twenty-one women undergoing hysterectomy with para-aortic lymph node resection were allocated into three groups; Group C (control, n = 7): fentanyl 12.5 micrograms.h-1, infusion rate 2 ml.h-1, Group S2 (double speed, n = 7): fentanyl 25 micrograms.h-1, infusion rate 4 ml.h-1, and Group C2 (double concentration, n = 7): fentanyl 25 micrograms.h-1, infusion rate 2 ml.h-1. At postoperative 0, 2, 6, 12, 24, and 48 hours, the degree of analgesia was evaluated by visual analogue scale (VAS) and verbal pain scores at both rest and movement. Groups S2 and C2 showed significantly lower VAS scores than group C at the postoperative 6- and 24-hour points. At movement, the analgesic efficacy was not sufficient in any groups, but, at rest, groups S2 and C2 experienced significantly less pain than the group C. The degree of pain relief was not different between groups S2 and C2. In conclusion, epidural fentanyl 25 micrograms.h-1 provided significantly superior analgesia compared with epidural fentanyl 12.5 micrograms.h-1.
Analgesia, Epidural↗
Interactions of the F1-ATPase subunits from Escherichia coli detected by the yeast two-hybrid system.
Subunit interactions among the F1-ATPase subunits were studied by the yeast two-hybrid system. Various pairwise combinations of genes encoding alpha, beta, gamma, delta and epsilon subunits of Escherichia coli H+-ATPase fused to the DNA-binding or activation domain of the yeast GAL4 gene were introduced into yeast and expression of a reporter gene encoding beta-galactosidase was detected. Combinations of the alpha and beta subunit genes, and of the epsilon and gamma subunit genes showed high levels of reporter gene expression, while those of alpha and delta, beta and delta, gamma and delta, and delta and epsilon demonstrated weak but significant reporter gene expression. However, combinations of alpha and gamma, beta and gamma, alpha and epsilon, and beta and epsilon did not induce reporter expression. None of the fused genes alone induced reporter gene expression. These results suggested that specific and strong interactions between the alpha and beta, gamma and epsilon, and weak interactions between the alpha and delta, beta and delta, and gamma and delta subunits occurred in yeast cells in the two-hybrid system. Effects of previously identified mutant beta subunits with Leu-40 to Pro. Glu-41 to Lys or Pro-332 to Gln substitutions which caused defects in molecular assembly of F1-ATPase were analyzed with regard to alpha-beta interactions. No interaction of the alpha and beta subunits was observed in this system using the beta subunit with mutation of Pro-332 to Gln. However, for the other two mutations, alpha-beta interactions were observed. This system may be useful for isolating mutants which have defects in interaction of F1-ATPase subunits.
Escherichia coli↗
Hypercoagulability and high lipoprotein(a) levels in patients with aplastic anemia receiving cyclosporine.
There is some clinical evidence that cyclosporine A (CyA) is associated with thrombotic complications of bone marrow and renal transplantation. We investigated plasma concentrations of lipoprotein(a) [Lp(a)], a potentially atherothrombotic lipoprotein, and hemostatic and vascular status in ten patients with aplastic anemia receiving CyA, eleven patients not taking it, and 38 age-matched healthy controls. Patients receiving CyA had significantly higher concentrations of plasma fibrinogen (P < 0.05), prothrombin fragment 1 + 2 (F1 + 2; P < 0.05), plasminogen activator inhibitor-1 (PAI-1; P < 0.05), and von Willebrand factor antigen (P < 0.05) than did patients not taking CyA. Plasma concentrations of Lp(a) were higher in CyA-treated patients than those not receiving it (P < 0.05) or healthy controls (P < 0.05). The difference in the Lp(a) concentration between controls and patients who did not receive CyA-treatment was not significant. Our results suggest that hypercoagulability is likely to occur during CyA therapy. Further, the presence of high concentrations of Lp(a) may accelerate the process of atherosclerosis and increase thrombotic events in patients receiving long-term CyA.
Adult↗
Synthesis and biological activities of optically active 6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quinolinone (OPC-18790).
The enantiomers of 6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quinolinon e (OPC-18790), a novel cardiotonic agent, were synthesized and evaluated for positive inotropic activity. The key intermediates, 2,3-epoxypropoxy derivatives, were obtained by the alkylation of 6-hydroxy-2(1H)-quinolinone with optically active epichlorohydrin and subsequent ring closure. In an in vitro study, the (R)-(+)-isomer was about 10-fold more potent than the (S)-(-)-isomer.
Animals↗
Mechanism on disorders of coagulation and fibrinolysis in diabetes.
Determination of various important parameters of coagulation and fibrinolysis, clinical characteristics, and levels of serum lipid were compared in 193 patients with NIDDM and 50 control subjects. Levels of fibrinogen, tissue factor pathway inhibitor (TFPI), thrombin-anti-thrombin complex, and plasminogen activator inhibitor 1 in plasma increased significantly in the diabetic patients. Levels of TFPI correlated significantly with levels of total cholesterol. In the patients with coronary heart disease or cerebral infarction, levels of lipoprotein(a) increased significantly. From these results, we have concluded that there is a thrombotic tendency or at least an imbalance between the hemostatic and thrombosis-protecting system in diabetic patients, especially in patients with angiopathy.
Blood Coagulation Disorders↗
[SA channels are mechanosensors of cells?].
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Animals↗
[Epidural catheterization dose not meet our expectation].
According to the roentgenographically confirmed intervertebral space at which an epidural catheter was placed, 241 patients who underwent abdominal or orthopedic hip surgery were allocated into 3 groups. Groups A, B, and C received epidural catheterization at Th7-10, Th10-L1, and L1-4, respectively. In each group, we examined the intervertebral space, which the anesthesiologist who had placed epidural catheter had determined, and the one which had been confirmed roentgenographically. We also investigated the catheter movement during the postoperative period. Catheters were barely placed at the same intervertebral space which had been confirmed roentgenographically. Considering the iliac crest as a landmark of L3-4 intervertebral space, the puncture point agreed with the roentgenographically confirmed intervertebral space with a percentage of 33 in group A. The extent of agreement increased up to 47 and 55 percent, in groups B and C, respectively. In contrast, when we counted down from the cervical prominent vertebra, a landmark of C7, the agreement was better in group A (55%) than in group C (33%). In the postoperative period, catheters came out more frequently in groups A and B than in group C, resulting from the early ambulation in abdominal surgery groups. There results suggest that, to place the epidural catheter more properly, (1) we should start to count from the landmark which is close to the puncture point and (2) we should keep it in mind that catheters come out accidently in patients who are encouraged to ambulate in the early postoperative period.
Aged↗
[Intraoperative ST-T depression during extreme hemodilution].
A 45 year old woman undergoing a removal of cerebral arterio-venous malformation, suffered an unexpected massive bleeding. With transfusion of plasma constituents, her hemoglobin concentration decreased to about 5 g.dl-1, but her hemodynamic parameters remained unchanged. Electrocardiogram showed a depressed ST segment, indicating myocardial ischemia, when hemoglobin concentration decreased to 2.2 g.dl-1. Accompanied with the ECG change, her blood pressure fell down from 110/70 mmHg to 70/40 mmHg and an elevation of CVP was observed. With rapid transfusion of concentrated red cell and whole blood, hemodynamic parameters as well as ECG change were restored to normal. With hemodilutional myocardial ischemia which is caused by acute massive bleeding, hemoglobin concentration of about 2 g.dl-1 would be critical.
Anesthesia, General↗
Predominant induction of kinetochore-containing micronuclei by extracts of diesel exhaust particulates in cultured human lymphocytes.
The aneuploidy-inducing activity of extracts of diesel exhaust particulates from light duty (LD) and heavy duty (HD) engines was investigated in cultured peripheral blood lymphocytes of 8 healthy donors using the cytokinesis-block micronucleus test with the kinetochore labelling modification. A majority of the subjects tested showed a significant kinetochore-positive micronucleus induction after treatment with the highest dose (150 micrograms/ml) of LD extract, although some subjects also showed induction of kinetochore-negative micronuclei. Only one subject had significantly increased numbers of kinetochore-positive micronuclei at a dose of 400 micrograms/ml of HD extract. These results suggest that diesel extract, at least LD extract, possesses the ability to induce whole chromosome loss (aneuploidy) preferentially, although there are also chromosome breaks.
Adult↗
Micronucleus induction in cytokinesis-blocked mouse bone marrow cells in vitro following in vivo exposure to X-irradiation and cyclophosphamide.
A cytokinesis-block micronucleus (MN) method for the simultaneous but separate measurement of chromosome damage in erythroid and myeloid bone marrow cells is described. MN induction in cytokinesis-blocked mouse bone marrow cells in vitro following in vivo exposure to x-ray or cyclophosphamide (CP) was investigated. Immediately after whole body irradiation with acute doses of either 0, 1, 2 or 4 Gy x-rays, or 2 hr after treatment with either 0, 12.5, 25, or 50 mg CP/kg body weight, bone marrow cells were collected and then cultured in medium supplemented with 3.0 micrograms/ml cytochalasin B for 24 hr. The binucleated cells were scored in erythroid, myeloid, lymphoid and other cells. The myeloid/erythroid (M/E) ratio was decreased by x-irradiation or CP treatment in a dose-dependent manner. The dividing index (DI; binucleated cells/binucleated + mononucleated cells; %) was decreased in both erythroid and myeloid cells in the same manner. Dose-dependent increases in MN frequency were observed following x-irradiation in both erythroid and myeloid cells. A similar dose-dependent MN induction was observed with CP. The MN frequency in myeloid cells was much greater than in erythroid cells (about 4-fold following 4 Gy exposure, and more than 10-fold after 50 mg/kg CP). Lymphoid and other cells were not suitable for scoring DI and MN frequency because of insufficient numbers of binucleated cells. These results suggest that micronuclei can be identified in both myeloid and erythroid cells and that myeloid cells are more susceptible to x-ray or CP-induced chromosomal damage than erythroid cells as expressed by MN induction.
Animals↗
Sperm and its soluble extract cause transient increases in intracellular calcium concentration and in membrane potential of sea urchin zygotes.
Fertilization is known to initiate a transient increase of intracellular calcium concentration and an accompanying change of membrane potential in sea urchin eggs. If the fertilization membrane and hyaline layer are removed, sperm can again enter fertilized eggs (refertilization). We have found that Ca2+ and voltage transients were repeatedly induced in fertilized eggs during refertilization. Similar changes were also obtained by external application of a soluble extract of sperm to fertilized eggs. This sperm extract caused no changes in unfertilized eggs. The active factor in the sperm extract survives heating (100 degrees C, 10 min) and incubation with pronase. Its molecular weight is less than 1300.
Animals↗
Increased susceptibility to oxidative DNA damage in regenerating liver.
Spontaneous and hepatocarcinogen (2-nitropropane, 2-NP)-induced levels of 8-hydroxy-2'-deoxyguanosine (oh8dG) in the nuclear DNA of regenerating liver [24, 48, 72 h and 7 days after partial hepatectomy (PH)] of male Sprague-Dawley rats were analysed for the verification of a hypothesis that the high susceptibility of proliferating hepatocytes to DNA damage is related to the well-known high susceptibility to carcinogens after PH. Interestingly, the spontaneous level of nuclear oh8dG in regenerating liver was significantly decreased (P < 0.01) at 48 h after PH (1.05 +/- 0.31 oh8dG/10(5)dG) compared with the level in normal rats (1.90 +/- 0.41). 2-NP induced an oh8dG level of 4.49 +/- 0.86 in nuclear DNA of rat liver without PH. However, in rats administered 2-NP (injections were performed 6 h before each sacrifice) after PH, the oh8dG level was significantly higher at 24 h (5.45 +/- 1.41, P < 0.05), 48 h (5.85 +/- 0.88, P < 0.01) and 72 h (5.67 +/- 1.07, P < 0.05) after PH than those with 2-NP exposure alone. Therefore, it is suggested that nuclear DNA in proliferating hepatocytes is in a stage susceptible to exogenous attack by 2-NP, and consequently this phenomenon might be related to the induction of hepatocarcinogenesis after PH.
8-Hydroxy-2'-Deoxyguanosine↗
Inductions of oxidative DNA damage and mesothelioma by crocidolite, with special reference to the presence of iron inside and outside of asbestos fiber.
Inductions of oxidative DNA damage (oh8dG) in vitro and peritoneal mesothelioma in rats (F344, female) were compared between crocidolite (CR) and de-ironized crocidolite [DCR, washed by HCl and ethylenediamine tetraacetic acid (EDTA)] to verify the hypothesis that reactive oxygen species contribute to carcinogenesis, focusing on the role of iron present inside or outside of the CR. The yield of oh8dG was 14.6 oh8dG/10(5)dG in CR and 30.2 in DCR under simple incubation with DNA. In the incubation systems added several chemicals and H2O2, DCR induced higher levels of oh8dG than CR. Especially, the addition of Fe2O3 and H2O2 to DCR increased oh8dG in DNA depending on the Fe2O3 concentration, however, this tendency was not observed in the same system of CR. Surprisingly, 7 out of 10 rats died within 2 days after the injection of 10 mg of Fe2O3 following the DCR injection (5 mg/rat), showing necroses of hepatocytes from the surface of each lobe where CR and Fe2O3 particles had been deposited together. There was no death in other groups of rats. One year after the i.p. injection of CR (5 mg/rat, single injection), mesotheliomas were found in all rats administered DCR and Fe2O3 (2 mg/rat, once a week, for 35 weeks), in 4 rats of DCR alone (n = 10), in 5 rats of CR alone (n = 10) and in none of the rats administered Fe2O3 alone (n = 10). Therefore, present results indicate that the induction of oxidative DNA damage changed even when the same type of asbestos was washed by chemical treatment, and Fe2O3 promoted the development of mesothelioma which was induced by DCR.
Animals↗
Technetium-99m teboroxime regional myocardial washout in subjects with and without coronary artery disease.
The aim of this study was to test the hypothesis that regional myocardial washout of technetium-99m teboroxime is slowed in the presence of coronary stenosis. Washout was assessed in 33 catheterized patients and in 13 with a low likelihood of coronary artery disease, using a triple detector camera and dynamic single-photon emission computed tomography, with serial 1-minute acquisitions after injection of 20 to 25 mCi of teboroxime at the third minute of adenosine-induced hyperemia. Washout was measured as the percent change in counts between the first, second and third minutes after injection, as measured in 6 short-axis myocardial regions of interest. Myocardial regions were classified as ischemic (> or = 50% diameter stenosis and no prior myocardial infarct), infarcted, normal (no significant coronary stenosis) or "low likelihood" (from the 13 patients with a low likelihood of coronary artery disease). Teboroxime washout was significantly (p < 0.001) slowed in the ischemic myocardium (12.7 +/- 8.3%) compared with the normal (18.5 +/- 5.7%), low-likelihood (17.8 +/- 6.1%) and infarcted (17.8 +/- 4.4%) zones. There was regional variability in washout rates (% washout/min), with the anterior wall having the lowest (13.8 +/- 3.4%/min) and the inferior wall the highest (20.7 +/- 7.9%/min) values. In regard to individual coronary territories, 21 of 41 ischemic, noninfarcted territories (51%) had abnormal washout compared with 3 of 43 normal territories (7%) (p = 0.001). In conclusion, regional washout of teboroxime is detectably slowed in ischemic, noninfarcted myocardium. The clinical value of washout analysis in teboroxime single-photon emission computed tomography warrants further investigation.
Cohort Studies↗
Oxidative damage of nuclear DNA in liver of rats exposed to psychological stress.
Male Sprague-Dawley rats were exposed to conditioned emotional stimuli in a communication box, which is much more psychologically conditioned stress than the commonly used restraint and water immersion, to investigate the induction of oxidative DNA damage by psychological stress. Significantly higher levels of 8-hydroxy-2'-deoxyguanosine in rat liver nuclear DNA than in the controls [1.46 +/- 0.19 (SD) 8-hydroxy-2'-deoxyguanosine/10(5) deoxyguanosine] were detected immediately after the second (1.90 +/- 0.27, P < 0.01), third (3.10 +/- 0.94, P < 0.01), and fourth exposure (2.95 +/- 1.17, P < 0.01) to conditioned emotional stimuli. This is the first evidence that oxidative damage to nuclear DNA is induced by psychological stress.
Animals↗