Causal Therapy of Alkylphosphate Poisoning

We have designed to apply 2-pyridine aldoxime methiodide(PAM), considered to be a cholinesterase reactivator in vitro, both to the laboratory rabbits poisoned by parathion and to the patients of parathion poisoning, and obtained the following results: 1. With administration of PAM, a prompt and complete dispersion of symptoms of the poisoning can be realized. 2. Cholinesterase activity of red blood cell has instantly and completely recovered, and that of serum transiently. 3. The amount of serum mucoprotein and the activity of active protein-SH-radical of serum varied in direct proportion to the activity of serum cholinesterase. 4. Generally, an intravenous injection of 1g. PAM is sufficient even in the severe case and it may be increased when necessary. 5. The ill effect has not been encountered in the PAM administration. 6. PAM exerts no influence on the cholinesterase activity of normal blood. 7. PAM is expected to play an important role as a prophylactic agent of alkylphosphate poisoning. From these results it seems clear that PAM is a specific and effective antidote against alkylphosphate intoxication.</p

Motor endplate cholinesterase in human skeletal muscle.

The activity and properties of cholinesterase (ChE) of the motor endplate and its fractions were studied in isolated human skeletal muscle. This preparation was used since the ChE activity of the membrane preparation was localized only in the motor endplate. The endplate ChE was stable in the isolated membrane for 4 weeks at 4 degrees C. The specific activity of the extracted ChE of human muscle membrane was 29.6% higher than that of the original membrane. Studies with specific substrates and ChE inhibitors indicated that most of the ChE of human muscle membrane and its fractions was acetylcholinesterase, and that the minor component was pseudocholinesterase. A Michaelis-Menten constant of 3.82 mM was estimated in the endplate ChE, and 0.88 mM in the extracted ChE of the endplate. The extracted human endplate ChE was separated into three fractions by Sephadex G-200 chromatography, and into two fractions by acrylamide gel electrophoresis.</p

Influences of Organ Extracts as well as Serum of Blood Disease Patient on the Nucleic Acid Metabolism of a Rabbit 3rd Report: Cytochemical Studies

1) The nucleic acid amount that has been estimated in view to chemical determination in the previous 2 reports, have here been laid under the observation cytochemically, according to Feulgen reaction (DNA) and thionine staining (RNA). 2) Having maintained some investigations on Ketoenol substances (KES), i.e., oligonucleotide of DNA, the bone marrow KES has proved to rise in amount on occasions when slpeen extracts, essential hypochromic anemia serum, serum of Banti's syndrome have been applied. The liver KES, comparing in general to the controls, increases; above all, to a marked degree, in case of hypoplastic anemia or hookworm anemia serum is concerned. The spleen KES shows a rise in case extracts of liver and spleen, together with serum of Banti's syndrome and healthy men have been injected; also shows a great increase when serum of essential hypochromic anemia, esp., the bone-marrow extract has been employed. The kidndy KES quite increases when the bone-marrow extract, spleen extract as well as the serum of Banti's syndrome or healthy men have been applied

Influences of Organ Extracts as well as Serum of Blood Disease Patient on the Nucleic Acid Metabolism of a Rabbit 2nd Report: Influences of Serum of Patients of Blood Disease on the Nucleic Acid Quantity of Rabbit's Organs

By intravenous injection of serum of patients of blood disorder as well as control serum of healthy men, observed the nucleic acid appearing in its bone-marrow, liver, spleen, and kidney, which proved as: 1) In case healthy men's serum has been injected, bone-marrow nucleic acid and DNA in, liver, spleen, and kidney indicate a decrease; while RNA both in spleen and kidney increases slightly; and that of liver does so pretty much. If those results obtained will be put under comparison with those obtained under the use of healthy men's serum: 2) Under the administration of serum of hypoplastic anemia, bone-marrow nucleic acid increases in a marked degree, liver as well as kidney DNA do so in a moderate degree; RNA of liver and kidney decrease rather. As to spleen nucleic acid, no marked change occurs. 3) If the serum of leukemia is injected, a slight increase takes place to liver and spleen DNA, while liver and kidney RNA show an abatement quite: but as to the rest, no great changes appear. 4) When serum of Banti's syndrome has been injected, the increase of both the bone-marrow nucleic acidi prove most caundid: though the spleen DNA increases, liver nucleic acid as well as RNA of spleen and kidney show a slight decrease respectively. 5) On occasion serum of hookworm anemia has been injected, spleen nucleic acid proves a marked increase; bone-marrow DNA increases greatly, but RNA in liver and kidney decreases. 6) When serum of essential hypochromic anemia is injected, a remarkable increase in the bone-marrow nucleic acid happens; but, as to the rest, small change occurs, only a slight increase of liver and spleen DNA, along with a decrease of liver RNA

Cholinesterase of skeletal muscle and its subcellular components.

The cholinesterase activity of skeletal muscle and its subcellular components, including motor endplates, was compared chemically in human, mouse and rat. The total cholinesterase activity of muscle per unit protein was in the descending order of human, mouse and rat. Cholinesterase was present in all subcellular components fractionated by differential centrifugation, and was greatest in the microsome fraction followed, in descending order, by the mitochondria, myofibril, and supernatant fractions. Each of these fractions had greater cholinesterase activity in human muscle than in mouse muscle, and in mouse muscle than in rat muscle. The ratio of the activity of the microsome fraction to the activity of muscle homogenate was 11.1 in human, 4.6 in mouse and 3.4 in rat. Because of its relatively greater proportion, the myofibril fraction seems to contribute most to the total cholinesterase activity of muscle. Muscle membrane contained high cholinesterase activity of motor endplates, and the activity was greater than the activity of the microsome fraction in rat. Cholinesterase activity per motor endplate was in the descending order of rat, human and mouse, and the variation was less than the variation in the total muscle cholinesterase activity among these species.</p

Cholinesterase Activity of the Motor Endplate in Rat Intercostal Muscle

Cholinesterase activity was localized solely in the motor endplate of the membrane in rate intercostal muscle. The diameter of rat motor endplates in the gradient dimension was 31.9 micrometers. The cholinesterase activity per unit protein of the soluble fraction of rat muscle membrane was 35.6% higher than the original membrane. From studies with specific substrates and cholinesterase inhibitors, the cholinesterase activity of rat muscle membrane and its soluble fraction consists of more than 90% acetylcholinesterase and less than 10% pseudocholinesterase.</p

Inhibition of human motor endplate cholinesterase by anticholinesterase compounds.

The inhibition of human motor endplate cholinesterase by anticholinesterase compounds was studied using isolated muscle membrane preparation. Ambenonium was most potent, and edrophonium was least potent in inhibiting motor endplate cholinesterase. The slope of the regression line for inhibition of motor endplate cholinesterase was greatest for ambenonium, and smallest for neostigmine and edrophonium. These compounds were less potent inhibitors of plasma cholinesterase. Ambenonium was more specific, and other compounds were less specific inhibitors of motor endplate cholinesterase. In myasthenic patients, these compounds produced adequate inhibition of motor endplate cholinesterase even in the presence of relatively mild plasma cholinesterase inhibition.</p

Influences of Organ Extracts as well as Serum of Blood Disease Patient on the Nucleic Acid Metabolism of a Rabbit 1st Report: Influences of Organ Extracts on the Amount of Rabbits' Organ Nucleic Acid

After having injected intraperitoneally, such substances as extracts of the bone-marrow, liver, spleen as well as skeletal muscle, once a day, and in determining quantitatively, the nucleic acid contained in rabbit's bone marrow, liver, spleen, and kidney, in pursuit of the lapse of time, from 6 hours to 9 days, obtained results as follows: 1) The amount of organ nucleic acid (mg/100g) for a healthy rabbit proved: bonemarrow: DNA 728, RNA 45.7. liver: DNA 36.6, RNA 88.9. spleen: DNA 100.2, RNA 65.3. kidney. DNA 38.4, RNA 56.3. 2) By injection of bone marrow extract, the bone marrow DNA, after having decreased for a time, increased; so did RNA too. The liver DNA showed an increase, while, RNA decreased. The spleen DNA increased, after having decreased; RNA, ambiguous. Kidney nucleic acid proved variable, but in general showed increase in DNA. 3) By injection of liver extract, the bone-marrow nucleic acid proves increase in both the constituents, through a temporal decrease; while, RNA increases, The nucleic acid amount in the liver is indefinite but in general, proves certain decrease; kidney nucleic acid, whereas it is lacking in general in DNA, having once abated, newly increases. 4) In injection of liver extract, in general, bone marrow-DNA proves increase, while RNA increases after a decrease. In the liver, DNA shows an increase after a little time of decrease, while, RNA seen to have kept increasing in all. In the spleen, both DNA and RNA have a tencency to increase after having shown a slight decrease. As to kidney, there was observed a marked decrcase of RNA. 5) In case skeletal muscle extract has been injected, bone marrow RNA indicates more remarkable increase than with other extracts; in the liver both nucleic acids, esp. RNA increases; as to spleen, there RNA has generally been fixed; but DNA proves decrease in proprotion to the frequency of injection; while, the kidney nucleic acid show little change