Observation of 8B solar neutrinos in the Kamiokande-II detector.
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Journal Article↗
Biomedical subjects
H Nagashima
Publications and source records attributed to H Nagashima.
Microsurgical bisection of porcine morulae and blastocysts to produce monozygotic twin pregnancy.
Porcine morulae were bisected by a glass needle after softening of zonae pellucidae by pronase followed by a treatment with 0.05% trypsin/0.02% EDTA for decreasing intercellular junction of blastomeres. Transfer of 49 half-morulae to three recipients resulted in one pregnancy. The blastocysts were bisected symmetrically so as to leave a cellular bridge between the sister half-embryos after the softening of zonae followed by or without the trypsin/EDTA treatment. Transfer of 47 monozygotic (MZ) pairs of half-blastocysts to nine recipients resulted in four pregnancies. A litter of nine fetuses was obtained from seven MZ pairs of half-blastocysts, demonstrating that at least two pairs of MZ twin fetuses were produced. It is thought that the procedure for bisecting blastocysts developed in this study is one of the potential methods of producing porcine MZ twins.
Animals↗
Presynaptic effect of muscle relaxants on the release of 3H-norepinephrine controlled by endogenous acetylcholine in guinea pig atrium.
The influence of nondepolarizing muscle relaxants (MR) on the resting and electrically evoked release of tritiated norepinephrine (3H-NE) was investigated, in the absence and presence of 10(-4) mol/l cocaine, in the in vitro right atrium preparation of guinea pigs (g.p.) preloaded with 3H-NE. In the absence of MR both resting and stimulated 3H and 3H-NE release remained relatively constant throughout the experiment and the ratios of the evoked release of 3H during consecutive stimulation periods (i.e. S2/S1, S3/S2) were close to unity. None of the MR had any effect on resting 3H release. Atropine (3 x 10(-7) mol/l), gallamine (7 x 10(-5) mol/l), and pancuronium (2 x 10(-6) mol/l), but not d-tubocurarine (5 x 10(-6) mol/l) significantly increased stimulated release of 3H-NE. The effect of MR on resting or evoked release of 3H-NE was not influenced by 10(-4) mol/l cocaine. In the presence of atropine gallamine and pancuronium did not affect the release of 3H-NE. This finding indicates that the effect of MR was mediated via presynaptic muscarinic receptors. Muscle relaxants and atropine inhibited these receptors and removed the tonic inhibitory effect of acetylcholine (ACh) released from the parasympathetic nerve endings on the release of NE from the sympathetic nerve. This was substantiated by the finding that in the present of cholinesterase inhibition, when the effect of endogenous ACh was amplified and thereby the cholinergic tone was dominant, the total release of 3H-NE evoked by stimulation was much lower and muscle relaxants and atropine were much more effective to enhance 3H-NE release. Gallamine and pancuronium also increased the force of contraction of the electrically stimulated atria. These findings indicate that the acceleration of the heart rate observed with gallamine and pancuronium in anesthetized man is due to increased release from, and not the inhibition of reuptake of NE by the sympathetic nerve endings of the right atrium.
Acetylcholine↗
Rapid elevation of liver hydroxyproline content following a single administration of various chemical carcinogens to rats.
The liver hydroxyproline content increased 14 days following a single administration of various chemical carcinogens, 2-N-fluorenylacetamide (FAA), 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB), diethylnitrosamine (DEN), dimethylnitrosamine (DMN), and thioacetamide, to rats. The rapid elevation of hydroxyproline following FAA administration, which did not induce liver cell necrosis, was accompanied by an increase in liver collagenase activity. These findings are of interest in relation to the regulatory mechanism of liver fibrogenesis.
2-Acetylaminofluorene↗
Cloning of a cDNA associated with acute and chronic hepatitis C infection generated from patients serum RNA.
In order to clone hepatitis C (blood-borne non-A, non-B hepatitis) virus, lambda gt11-cDNA library was constructed from RNA extracted from 100 liters serum collected from 1,047 donors with elevated ALT levels and negative for hepatitis B virus-DNA. The library was immunoscreened on Y1090 cells with pooled serum obtained from patients with acute hepatitis C or chronic hepatitis C. By screening 29 clones specific for Japanese hepatitis C infection were isolated. The specificity of these clones for hepatitis C infection was determined by panels constructed in 3 laboratories. Of these, 12 clones were specific for American hepatitis C infection as well. The nucleotide sequence (201 bp) of one of them was determined to be unique compared to known human viruses including hepatitis A virus, hepatitis B virus and hepatitis D virus. Southern blot analysis showed the absence of the sequence of the human genome in the clone. The predicted amino acid sequence is rich in residues of lysine, arginine, glutamic acid and asparagine, while lacking leucine, cysteine and methionine.
Acute Disease↗
Heterogeneity of presynaptic muscarinic receptors involved in modulation of transmitter release.
In order to extend the characterization of muscarinic receptors at presynaptic sites their inhibitory effect on the stimulation-evoked release of [3H]noradrenaline and [3H]acetylcholine from different axon terminals was studied and the dissociation constants and potencies of different antagonists were estimated, in guinea-pig and rat. While oxotremorine reduced the release of [3H]acetylcholine and [3H]-noradrenaline in a concentration-dependent manner from different release sites (Auerbach plexus, noradrenergic neurons in the right atrium, cerebral cortex), McN-A 343, an M1 receptor agonist, enhanced their release evoked by field stimulation. When the inhibitory effect of oxotremorine on transmitter release was studied, pancuronium, pirenzepine and atropine were competitive antagonists of presynaptic muscarinic receptors located on the noradrenergic axon terminals of the atrium. While atropine and pirenzepine inhibited the muscarinic receptors of cholinergic axon terminals in the Auerbach plexus, pancuronium and gallamine had a very low affinity. Significant differences were found in the affinity constants of antagonists for muscarinic receptors located in the cholinergic axon terminals of Auerbach plexus and cerebral cortex, and noradrenergic axon terminals of the atrium. While atropine and pirenzepine exerted similar effects on these presynaptic sites, pancuronium, gallamine and (11-(2-[diethylamino)-methyl)-1-piperidinyl)acetyl)-5, 11-dihydro-6(1-pyrido(2,3-b)(1,4)-benzodiazepin-6-on) were much more effective on muscarinic receptors controlling acetylcholine release from the cerebral cortex and noradrenaline release from the heart. There was more than 100-fold (2.0 pA2 units) difference in affinities of these antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic Fibers↗
Effect of atracurium and laudanosine on the release of 3H-noradrenaline.
We examined the effects of atracurium and its breakdown product, laudanosine, on resting and stimulation-evoked release of 3H-noradrenaline (3H-NA) from sympathetic axon terminals of isolated right atria of guinea pigs. Both atracurium 1-100 mumol litre-1 and laudanosine 1-50 mumol litre-1 enhanced the release of 3H-NA evoked by field stimulation (2 Hz, 24 stimuli), but did not affect resting release. When the production of laudanosine from atracurium was inhibited by maintaining the atracurium solution at 4 degrees C, atracurium did not enhance the release of 3H-NA as occurred when it was kept at 37 degrees C. However, atracurium antagonized the inhibitory effect of oxotremorine on release of 3H-NA, whereas laudanosine did not. These data suggest that atracurium possesses an antimuscarinic effect. Its metabolite, laudanosine, in concentrations which would be expected following prolonged administration of atracurium, produced a marked increase in release of 3H-NA. This effect of laudanosine may explain some of the unwanted effects seen following administration of atracurium.
Animals↗
[Plasma histamine release following the intravenous administration of atracurium in man].
The purpose of this study was to measure plasma histamine concentration following the intravenous bolus injection of atracurium in surgical patients and to clarify any correlation of resultant cardiovascular change with plasma histamine release. Twelve elective surgical patients of ASA-I were studied after the approved informed consent. Twenty of blood samples were collected for the assay of plasma histamine at 1 minute before as the control and 1, 3, 5, and 10 minutes after the administration of atracurium 0.6mg.kg-1 or 1.2mg.kg-1 intravenously. Plasma histamine was measured by utilization of the modified single isotope radioenzymatic assay. Blood pressure, heart rate, EKG and cutaneous signs were observed continuously during the study. Intravenous bolus administration of 0.6mg.kg-1 and 1.2mg.kg-1 atracurium which is larger than 2 times of ED95 demonstrated significant changes in heart rate, blood pressure and histamine release. A significant increase in plasma histamine, a decrease in blood pressure and an increase in heart rate occurred at 1 to 3 minutes after the injection of atracurium. Plasma histamine release and cardiovascular changes had strong correlation with the intravenous dose of atracurium.
Atracurium↗
[Effect of laudanosine on catecholamine release in dogs].
It is well established that a large dose of atracurium (more than twice ED95) produces significant release of histamine in the blood accompanying hypotension but recovery to control level within a few minutes after the administration of atracurium. We speculated that laudanosine, a metabolite of atracurium may play an important role in preventing this cardiovascular disaster due to histamine release. From this concept, we investigated the effect of laudanosine on the release of epinephrine and norepinephrine in dogs, anesthetized with halothane, nitrous oxide and oxygen. Two different doses of laudanosine (1 microgram.kg-1 and 10 micrograms.kg-1) were selected and serum catecholamine levels were measured with HPLC in six dogs. Intravenous injection of 1.0 microgram.kg-1 laudanosine increased NE level from 0.11 +/- 0.03ng.ml-1 to 0.13 +/- 0.04ng.ml-1 at 3 minutes after the injection. Blood pressure, heart rate, pulmonary arterial pressure, pulmonary wedge pressure and central venous pressure did not change significantly. The intravenous injection of 10 micrograms.kg-1 laudanosine increased NE level from 0.09 +/- 0.02ng.ml-1 to 0.14 +/- 0.02ng.ml-1 at 1 minutes after the injection, but there was no remarkable cardiovascular effect. From this study we conclude that the intravenous injection of laudanosine increased serum NE level, but there was no significant hemodynamic change in the dogs.
Animals↗
Inhibition of mobilization of acetylcholine: the weak link in neuromuscular transmission during partial neuromuscular block with d-tubocurarine.
The authors have demonstrated earlier, by direct measurement of acetylcholine (ACh), that d-tubocurarine (d-Tc) and other nondepolarizing muscle relaxants decrease the release of ACh from the indirectly stimulated mouse hemidiaphragm preparation. It was the purpose of the present study to determine whether the decrease of the stimulated release of ACh and the increase in the intensity of the partial neuromuscular block observed at higher stimulation rates is caused by the inhibition of mobilization of ACh from reserve depots to release sites or by inhibition of the release process itself. To attain our objective, the authors have investigated the influence of the progressive increase of the rate of stimulation from 0.1 to 1, 2, 3, and 5 Hz on the force of contraction on the in vitro phrenic nerve-hemidiaphragm and in vivo sciatic nerve-tibialis anterior preparation in the absence of drugs and after about 20% neuromuscular block produced by d-Tc or by Mg2+. The latter is known to inhibit the Ca2+ dependent release of ACh. In the absence of drugs increasing the stimulation rate increased the force of contraction, in vivo and in vitro, during both indirect and direct stimulation. In the phrenic nerve-hemidiaphragm preparation the increase was significant at 1, 2, 3, and 5 Hz (P less than 0.001) with both types of stimulation. In the sciatic nerve-tibialis anterior preparation the force of contraction was only higher at 3 and 5 Hz (P less than 0.01). The similar magnitude of the increase of the force of contraction during direct and indirect stimulation indicates that it is caused by facilitation of the contraction of the muscle fibers.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcholine↗
Amino acid sequence of ferredoxin isolated from Cyanidium caldarium strain RK-1.
Ferredoxin was isolated from ther eukaryotic alga Cyanidium caldarium strain RK-1 and its amino acid sequence was determined. The ferredoxin is composed of 97 amino acid residues, and its molecular weight is 10,599 excluding the iron-sulfur cluster. The amino acid sequence differs from that of C. caldarium strain 1355/1, by 24 amino acid substitutions plus one deletion at the amino terminus.
Amino Acid Sequence↗
Lasting nutritional imbalance following abstinence in patients with alcoholic cirrhosis.
The dietary intake of eight alcoholic patients with liver cirrhosis following complete abstinence was compared with that of non-alcoholic cirrhotics. Protein and lipid amounts actually ingested were much lower, even following abstinence, in alcoholic cirrhotics than in non-alcoholic cirrhotics, suggesting that dietary customs of alcoholics with liver disease do not change easily. Therefore, dietary education is necessary for abstaining alcoholics and should be aggressively applied in the out-patient clinic.
Adult↗
Liver fibrosis in obese patients with fatty livers.
Liver fibrosis was observed in non-alcoholic, non-diabetic obese patients with fatty liver. The extent of fibrosis was more severe in patients who were obese for a long time and had severe fatty deposition in the liver. Laboratory data were not useful for differentiating between fatty livers with and without liver fibrosis. The results suggested that fatty liver in obese patients should be treated by weight reduction in order to prevent the progression of liver fibrosis.
Adolescent↗
Species variation in the site and mechanism of the neuromuscular effects of diadonium in rodents.
The unusually wide, 80-fold species variation observed by others (1,2) in the neuromuscular (NM) potency of diadonium, a nondepolarizing muscle relaxant (MR), between cat and man suggested that the site and mechanism of its NM effect may vary in different species. To obtain information on this question, the NM potency of diadonium and the reversibility of its NM effect by neostigmine and/or 4-aminopyridine (4AP) was investigated on the in vitro phrenic nerve--hemidiaphragm preparations of rats, mice and guinea pigs. The concentration of diadonium that caused 90% NM block (IC90) was much greater in guinea pigs, 1.74 +/- 0.02 and 1.28 +/- 0.01 mu, when the preparations were stimulated with single stimuli at 0.1 Hz or with 0.1 s trains of 50 Hz tetani every 10 s, respectively, than in rats (IC90 = 62.4 +/- 0.89 and 52.1 +/- 1.00 microM) or mice (IC90 = 51.9 +/- 0.98 and 44.4 +/- 0.22 microM). In guinea pigs, the NM blocking effect of diadonium could be antagonized by neostigmine. This indicates that in this species the NM blocking effect of diadonium is primarily caused by inhibition of the interaction of acetylcholine (ACh), released by the nerve impulse, with the cholinergic receptors (cholinoceptors) of the postjunctional membrane (p.j.m.). By contrast, in rats and mice diadonium was not antagonized by neostigmine but was reversed by 4-aminopyridine. This suggests that in these species, in contrast to other nondepolarizing MR, diadonium does not inhibit NM transmission postsynaptically, but by inhibiting the positive nicotinic feedback mechanism of mobilization of ACh from reserve depots to release sites, causes a presynaptic NM block.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcholine↗
The influence of aminopyridines on Ca2+-dependent evoked release of acetylcholine from rat cortex slices.
The release of acetylcholine (ACh) elicited by electrical stimulation was investigated in rat brain cortical slices preloaded with 3H-choline. Decreasing the [Ca2+]o from 2.5 to 0.3 mM caused a progressive reduction of the evoked release of ACh. 4-Aminopyridine (4AP) or LF14 [(1,1-dimethyl-3-(4-amino-3-pyridyl)], 4 x 10(-5) M doubled the evoked release of ACh when the [Ca2+]o was 2.5 mM and quadrupled it when it was 0.3 mM, to levels higher than those obtained with 2.5 mM [Ca2+]o alone. This indicates that both 4AP and LF14 decrease the Ca2+ requirements for the evoked release of ACh. The findings of this study indicate that LF14 may be suitable for the symptomatic treatment of senile dementia of Alzheimer's type, presumably caused by dysfunction of cholinergic transmission in the brain.
4-Aminopyridine↗
A simple method for monitoring muscular relaxation during continuous infusion of vecuronium.
There is considerable individual variation in the dose of vecuronium required for the maintenance of surgical relaxation. Therefore to provide uninterrupted relaxation without overdosage it is advisable to regulate the IV infusion of vecuronium on the basis of appropriate monitoring. Monitoring with mechanomyography (MMG) or electromyography requires costly equipment and is too complex for routine clinical use. Visual observation of the adductor pollicis muscle contracting against zero resistance is not suitable for the reliable assessment of the degree of neuromuscular (NM) block. For clinical purposes satisfactory monitoring can be achieved with the simple device (Myoscan) described. The reliability of the Myoscan was tested in 30 patients by simultaneous monitoring of the force of contraction of the adductor pollicis on one side with the Myoscan and on the contralateral side with the MMG. Retrospective analysis of the MMG indicated that the conduct of anaesthesia would have been virtually the same if it would have been based on MMG monitoring.
Adult↗
Production of normal piglets from microsurgically split morulae and blastocysts.
The embryo splitting technique was applied to pig embryos, and the developmental ability of the split embryos was examined by means of in vitro culture and transfer. Morulae, early blastocysts and blastocysts were collected from Landrace x Large White F(1) gilts which had been mated to Duroc boars. The embryos were bisected with a fine glass or alloy (PtIr) needle after the softening of zonae pellucidae. The halved-embryos, which had either been placed in zonae pellucidae or not, were transferred to recipient gilts immediately after the micromanipulation (Experiment 1) or after cultivation for 15 to 20 h (Experiment 2). In Experiment 1, two fetuses were obtained from one of three recipients which had received 12 half-embryos. In Experiment 2, three of five recipients became pregnant, and in one recipient, seven piglets of a litter were obtained from 12 zona-free half-embryos produced from the original seven blastocysts. The results obtained indicate that a simple method not requiring the encasing of split embryos into zonae pellucidae is satisfactory to produce viable half-embryos.
Journal Article↗
Are fluorescent bodies of Y-spermatozoa detectable in common with mammalan species?
An attempt was made to detect the fluorescent bodies (F-body), using Quinacrine mustard (Q-M) staining in the spermatozoa from eight mammalian species (human, bull, boar, dog, rabbit, rat, mouse, and mastomys) as well as in the cock (used as negative control). Sperm suspension, prepared after rinsing by repeated centrifugation with phosphate buffered saline (PBS), was either stained with Q-M for 24 h or treated with protease and then stained with Q-M for 60 min. The final concentration of Q-M in the mixed staining sperm suspension was 0.025 mg/ml. The examination using a reflecting fluorescent microscope revealed that the F-body found in human sperm was also present in the sperm of all the mammals but not in the cock after 24 h of staining. The enzyme-treated specimens showed higher incidences of F-bodies than specimens stained for 24 h without enzymatic digestion. These findings strongly suggest that the F-body is commonly present in the spermatozoa of many mammalian species.
Journal Article↗