Biological aspects of inorganic polyphosphates.
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Polyphosphates↗
Biomedical subjects
J E Clark
Publications and source records attributed to J E Clark.
Rhabdomyolysis associated with cocaine intoxication.
A case of a patient who had an acutely toxic reaction to cocaine ingestion and later developed acute renal failure secondary to rhabdomyolysis is described. Evidence of rhabdomyolysis was noted by the combination of myalgia, urine discoloration, and elevated serum concentrations of muscle enzymes. Although the mechanism of the rhabdomyolysis is unknown, the clinical presentation resembled that of a norepinephrine-induced vasoconstrictive effect that alters the metabolic demands of the muscle in such a way that the muscle is damaged.
Adult↗
Irreversible opiate agonists and antagonists. IV. Analgesic actions of 14-hydroxydihydromorphinone hydrazones.
Several phenylhydrazone derivatives of oxymorphone [phenylhydrazone and p-nitrophenylhydrazone (OxyPNPH)] as well as oxymorphonazine produce a wash-resistant inhibition of radiolabeled opioid binding, suggesting nonequilibrium binding to opiate receptors. All are agonists and, in an effort to correlate their prolonged inhibition of binding with their pharmacology, we examined their analgesic actions in vivo. Dose-response curves at 1 hr revealed similar potencies of oxymorphone and the derivatives, with the exception of OxyPNPH which was significantly less potent. After 10 hr, oxymorphone at doses up to 50 mg/kg did not demonstrate any effect. In contrast, OxyPNPH at 25 mg/kg elevated tail-flick latencies from 2 to over 8 sec after 10 hr. The 50-mg/kg dose elevated latencies to approximately 5 sec after 24 hr. Oxymorphonazine and oxymorphone phenylhydrazone also produced a prolonged analgesia, although not as effectively as OxyPNPH. The prolonged analgesic actions of OxyPNPH were highly dependent upon a critical period of 2 to 3 h immediately after injection. Blockade of receptors during this period with naloxone prevented analgesia at all time points examined. If the long duration of action of OxyPNPH resulted simply from a long half-life and persistent-free compound within the brain, analgesia should have returned by 8 hr, at which time naloxone has been eliminated. The absence of analgesia 8 hr after both OxyPNPH and naloxone argues against simple pharmacokinetic mechanisms for the prolonged analgesia and is consistent with persistent receptor occupation. OxyPNPH (25 mg/kg) administered in vivo lowered radiolabeled opioid binding effectively in brain membranes despite extensive washing. OxyPNPH lowered mu1 binding by approximately 60% and mu2 binding by 35% whereas delta binding was not lowered significantly.
Analgesia↗
Polyphosphate kinase from Propionibacterium shermanii. Demonstration that polyphosphates are primers and determination of the size of the synthesized polyphosphate.
Polyphosphate kinase from Propionibacterium shermanii was purified to 70% homogeneity and shown to be a monomeric enzyme of molecular weight 83,000 +/- 3,000. It was demonstrated that short chains of polyphosphate serve as primers by using [32P]polyphosphate, 6-80 residues in length for synthesis of long-chain polyphosphate glucokinase, the radiolabel was found to be at the end of the polymer, proving that the mechanism of elongation of polyphosphate by polyphosphate kinase is strictly processive. Only 1 out of 3-8 of the polyphosphate chains contained the primer, indicating that there is a second unknown pathway of initiation which does not involve the polyphosphate primer. The termination of polyphosphate synthesis was investigated. With polyphosphate as a primer, the majority of the synthesized polyphosphate was 750 residues in length. With phosphate, in place of the polyphosphate primer, the major portion was about 2,000 residues in length but there was a large span of chain lengths down to 300. Termination is influenced by pH, temperature, and the concentration of the polyphosphate primer, with the chain length decreasing as either the temperature or the concentration of primer is increased.
Adenosine Triphosphate↗
Preparation of standards and determination of sizes of long-chain polyphosphates by gel electrophoresis.
Procedures are presented for isolating fractions of long-chain polyphosphates which have a narrow range of sizes and for determining their chain lengths. The polyphosphates are isolated by elution from preparative polyacrylamide gels. Then, the lengths of these polymers are determined by a method of successive approximations of length from data obtained by electrophoresis on several different gels of varying polyacrylamide concentrations. Once sized, these isolated polyphosphates may be used as electrophoresis standards, making it possible to rapidly and accurately ascertain the size of other samples having unknown chain lengths. By comparison with two other procedures for sizing polyphosphates, it is shown that the method is definitely valid to a length of 450 and most likely to a length of at least 900. This electrophoresis procedure allows, for the first time, the determination of the range of sizes present and the average chain length with only 2-20 micrograms of polyphosphate.
DNA↗
The step cycle organization of infant walkers.
To walk independently, the human infant must coordinate its multisegmented body to achieve both postural stability and forward mobility. In this experiment, we sought evidence of the form this coordination takes in infants who have been walking 3 to 10 months. Using the Philippson phases to represent the step cycle, we analyzed film records of infants and adults walking at speeds from 2 to 4 km/hr. Our results reveal a clear relationship between walking speed and the F and E(3) Philippson phases of the step cycle in both the young walkers and the adults. Indeed, across all four phases of the step cycle, the infants exhibited an organization that was almost identical to that of the mature walkers.
Journal Article↗
The effects of videogame playing on the response selection processing of elderly adults.
Within an information processing framework, age-related declines in speeded responding are attributed to one or more stages of processing. It was the purpose of this experiment to demonstrate the potential reversibility of this decline in at least one processing stage, response selection. Two groups of elderly participants (57 to 83 years) were pretested on a two-choice reaction time (RT) task under two levels of spatial stimulus-response (S-R) compatibility, a task demand shown to affect response selection. Following the pretest, one group participated in 7 weeks of videogame play, whereas a second group did not. All participants were posttested on the same two-choice RT task. The results of the analysis of covariance revealed that those elderly individuals who played videogames were faster than the control participants under both levels of S-R compatibility. The effect of videogame play, however, was greater for low compatibility. These results are taken as support for a potential to improve response selection through videogame play.
Aged↗
Error in equation for predicting warfarin dosage.
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Humans↗
Purification of 5,10-methenyltetrahydrofolate cyclohydrolase from Clostridium formicoaceticum.
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Aminohydrolases↗
Purification and properties of 5,10-methylenetetrahydrofolate reductase from Clostridium formicoaceticum.
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5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
Isolation of intact chains of polyphosphate from "Propionibacterium shermanii" grown on glucose or lactate.
A procedure is presented for the isolation of intact polyphosphate (poly P) from "Propionibacterium shermanii." It is demonstrated, by including [32P]poly P during the extraction, that this procedure does not hydrolyze the poly P, and it is shown that two other widely used procedures do cause breakdown of the poly P. The procedure presented allows isolation of three fractions, short-chain poly P which is soluble in trichloroacetic acid, long-chain poly P which is soluble at neutral pH, and long-chain poly P which is present in volutin granules. Cells which had been grown on lactate did not contain short-chain poly P but did contain a high amount of long-chain poly P, which accumulated to 3% of the cell dry weight. At least 70% of this poly P was present in volutin granules. The poly P ranged in length from 250 to 725 phosphate residues and was the same average size as that synthesized in vitro by the poly P kinase from "P. shermanii". This indicates that the poly P kinase is responsible for catalyzing the synthesis of the poly P. In contrast to cells grown on lactate, those which had been grown on glucose did not contain volutin granules, did contain short-chain poly P and had 100-fold less long-chain poly P than lactate-grown cells. We propose that during the fermentation of glucose, the amount of poly P is lower than during growth on lactate because it is continuously utilized as a substrate in the phosphorylation of glucose.
Cell Fractionation↗
Purification and properties of 5,10-methylenetetrahydrofolate reductase, an iron-sulfur flavoprotein from Clostridium formicoaceticum.
Methylenetetrahydrofolate reductase in Clostridium formicoaceticum has been purified to a specific activity of 140 mumol min-1 mg-1 when assayed at 37 degrees C, pH 7.2, in the direction of oxidation of 5-methyltetrahydrofolate with benzyl viologen as electron acceptor. The purified enzyme is judged to be homogeneous by polyacrylamide disc-gel electrophoresis and gel filtration. The enzyme which is an octamer has a molecular weight of about 237,000 and consists of four each of two different subunits having the molecular weights 26,000 and 35,000. The octameric enzyme contains per mol 15.2 +/- 0.3 iron, 2.3 +/- 0.2 zinc, 19.5 +/- 1.3 acid-labile sulfur, and 1.7 FAD. The UV-visible absorbance spectrum has a peak at 385 nm and a shoulder at 430 nm and is that of a flavoprotein containing iron-sulfur centers. The reductase, which is sensitive to oxygen, must be handled anaerobically and is stabilized by 2 mM dithionite. It catalyzes the reduction of methylene blue, menadione, benzyl viologen, rubredoxin, and FAD with 5-methyltetrahydrofolate and the oxidation of reduced ferredoxin and FADH2 with 5,10-methylenetetrahydrofolate. No activity was observed with pyridine nucleotides. It is suggested that the physiologically important reaction catalyzed by the enzyme is the reduced ferredoxin-dependent reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate.
5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
Properties of purified carbon monoxide dehydrogenase from Clostridium thermoaceticum, a nickel, iron-sulfur protein.
Carbon monoxide dehydrogenase from Clostridium thermoaceticum has been purified to homogeneity using a strict anaerobic procedure. The enzyme has a molecular weight of about 440,000 and it consists of three each of two different subunits giving the composition alpha 3 beta 3. The molecular weight of the alpha-subunit is 78,000 and that of the beta-subunit is 71,000. Pore limit gel electrophoresis gave a molecular weight of 161,000 indicating that the enzyme dissociates to form a dimer with an alpha beta structure. The dimer apparently contains per mol 2 nickel, 1 zinc, 11 iron, and 14 acid-labile sulfur. The anaerobic enzyme has an iron-sulfur type spectrum, which is changed in the presence of the substrate, CO. In the presence of oxygen, which destroys the activity or CO2, the spectrum is that of a typical iron-sulfur protein. Under acidic conditions a low molecular weight nickel factor separates from the enzyme. Viologens, methylene blue, ferredoxin, flavodoxin, and rubredoxin serve as electron acceptors. Of these rubredoxin is by far the most efficient. The enzyme has a pH optimum around 8.4. At this pH and 50 degrees C under 100% CO atmosphere, the apparent Km for methyl viologen is 3.03 mM and Vmax is 750 mumols of CO oxidized min-1 mg-1. Cyanide and methyl iodide inhibit the enzyme. CO reverses the cyanide inhibition but promotes the reaction with methyl iodide. The pure enzyme has no hydrogenase or formate dehydrogenase activity.
Aldehyde Oxidoreductases↗
Cardiac arrhythmias after phenylpropanolamine ingestion.
Physicians and pharmacists should be alerted to the potential adverse effects of phenylpropanolamine-containing products, which may include exaggerated hypertensive effects, arrhythmias (premature ventricular and atrial contractions together with paroxysmal ventricular or atrial tachycardia), psychotic reactions, and neurologic effects (grand mal seizures and intracerebral hemorrhage). A case of paroxysmal atrial tachycardia in a woman, after the ingestion of diet pills containing phenylpropanolamine and caffeine is reported.
Adult↗
Dyskeratosis congenita: two examples of this multisystem disorder.
Two brothers with the X-linked disorder, dyskeratosis congenita, are described. They showed the dermatologic triad of reticular hyperpigmentation, dystrophic nails, and leukoplakia oris as well as the other major feature of this disorder, aplastic anemia. Less common features observed included prenatal and postnatal growth retardation, mental retardation, elevated immunoglobulin levels, and gastrointestinal hemorrhage from mucosal ulceration. Previously unreported findings were intracranial calcifications and nutmeg-like cirrhotic changes of the liver. These brothers demonstrated that skeletal changes and bony fragility may predate anemia or steroid therapy. Although a DNA repair defect is postulated as a possible primary defect, cytogenetic studies revealed no evidence of increased chromosomal breakage.
Adolescent↗
Purification and properties of 5,10-methenyltetrahydrofolate cyclohydrolase from Clostridium formicoaceticum.
Methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9) from Clostridium formicoaceticum has been purified to a specific activity of 469 mumol min-1 mg-1 at 35 degrees C, pH 7.2. The purified enzyme is homogeneous as judged by polyacrylamide disc gel electrophoresis, sedimentation velocity, and gel filtration profiles. The molecular weight is 41,000 +/- 200 as determined by sedimentation equilibrium centrifugation. A subunit molecular weight of approximately 25,500 was obtained using sodium dodecyl sulfate-gel electrophoresis. The enzyme apparently is a dimer. The Stokes radius determined by gel filtration is 29.6 A. The apparent Km at pH 7.2 and 35 degrees C for 5,10-methenyltetrahydrofolate is 0.19 mM. The pure enzyme does not contain any 10-formyltetrahydrofolate synthetase or 5,10-methylenetetrahydrofolate dehydrogenase activities.
Amino Acids↗
Developmental differences in response processing.
Three age groups (kindergartners, fourth graders, and adults) were compared in their processing of response decisions in a two-choice reaction time task. Manipulation of spatial stimulus-response compatibility resulted in age-related differential effects on reaction time performance. For the younger children, selecting the appropriate response for an incompatibly paired stimulus light required proportionately longer processing time than for older subjects. Similar results were not found for performance under varying levels of response discriminability.
Journal Article↗
Concentrations of cefoxitin in gallbladder bile of cholecystectomy patients.
Cefoxitin was administered in a dose of 2 g intravenously to 17 patients scheduled for cholecystectomy. The concentrations of this agent in serum and gallbladder bile were measured simultaneously upon opening of the abdominal cavity. Concentrations of cefoxitin in excess of 10 microgram/ml were present in the gallbladder bile of 12 of the 13 patients from samples obtained between 35 and 165 min after cefoxitin infusion. Cystic or common duct obstruction did not preclude entry of the drug into gallbladder bile.
Adult↗