Experimentally induced infection with Helicobacter pylori in squirrel monkeys (Saimiri spp.): clinical, microbiological, and histopathologic findings.
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Animals↗
Biomedical subjects
J W Lawson
Publications and source records attributed to J W Lawson.
Use of electroejaculation to collect semen samples from wild seals.
Semen samples were obtained from 7 adult male gray seals (Halichoerus grypus) at a colony on Sable Island, Nova Scotia, Canada, using a portable electroejaculation system. Males were anesthetized with tiletamine-zolazepam. A probe was inserted in the rectum, and a progressive series of 10 to 15 stimulations (1 to 9 V, 25 to 750 mA) was applied. Males ejaculated after 15 to 29 minutes of stimulation and produced ejaculates with volumes of 4 to 17 ml that had vigorous, motile spermatozoa. Although trials were performed in winter conditions (0 to -15 C), simple storage methods (semen samples collected into plastic bags and placed in a warm pocket or an insulated cooler) kept spermatozoa motile for up to 4 hours after ejaculation. The procedure described here provides a means for collection of semen samples for genetic analyses and tests of reproductive competence in seals.
Animals↗
A new transient activator of phosphofructokinase during initiation of rapid glycolysis in brain.
The tissue contents of previously known allosteric effectors of brain phosphofructokinase (EC 2.7.1.11) (PFK) and the kinetic behavior of isolated PFK were investigated during the initiation of rapid glycolytic flux in freeze-blown rat brain. Comparing 0- with 5-s brains revealed that there was a 4-fold drop in total tissue content of Fru-6-P and a 5.6-fold increase in Fru-1,6-P2 consistent with activation of PFK. Additionally, analysis of brain content showed a 15-fold increase in AMP, a 3-fold decrease in ATP, a 3-fold decrease in Pi, and a 1.6-fold increase in NH4+. There was no change in Fru-2,6-P2, H+, citrate, or Glc-1,6-P2 or the kinetic profiles of isolated PFK for ATP inhibition or Fru-2,6-P2 activation. We concluded that the observed change in PFK activity could be accounted for only partially by changes in the concentrations of adenine nucleotides and other known effectors. High performance liquid chromatography fractions of extracts obtained from 5-s brains showed the activator with a mobility identical to ribose 1,5-P2 and gave 2 nmol/g (wet weight) at 0 s, 10 nmol/g at 5 s, and 2 nmol/g at 20 s. Assay of PFK in the presence of effectors determined to be in tissue at 5 s showed that addition of 10 nmol/ml ribose 1,5-P2 gave a 4-fold activation of PFK. Based on the rapidity of its formation, its potency of activation, and its similarity in chemical properties to authentic ribose 1,5-P2, we conclude that ribose 1,5-P2 served as the initial activator of PFK in brain.
Adenosine Monophosphate↗
Stimulation of the immune response by dimethylglycine, a nontoxic metabolite.
The immunomodulating capacities of dimethylglycine (DMG) were examined in a rabbit model. Female New Zealand white rabbits were immunized on day 0 and were given booster inoculations on day 9 with either killed influenza virus or Salmonella typhi vaccine. Experimental animals were force fed 20 mg/kg body weight of DMG daily beginning 14 days prior to the first inoculation and continuing throughout the experiment. Control animals were force fed daily only distilled water. Blood was obtained on day 0, day 9, and day 30. Hemagglutination inhibition assays showed a more than fourfold increase in mean antibody titer to influenza antigen in the DMG-treated animals (p = 0.0006) after the first inoculation, and a fourfold increase in mean titer after the booster inoculation (p = 0.1000). A standard agglutination test for Salmonella typhi O (somatic) and H (flagella) antigens was performed on all sera from animals receiving the typhoid vaccine. Mean antibody titers to the O antigen were significantly higher (more than threefold) after the first inoculation (p = 0.0302) and more than fivefold higher after the booster inoculation (p = 0.0047) in DMG-treated animals. Mean antibody titers to the H antigen were also higher in DMG-treated animals compared with controls after both the first and second inoculation. Lymphocyte transformation assays on cells taken from DMG-treated animals immunized with the influenza vaccine showed a tenfold increase in mean proliferative response (p = 0.0024). Lymphocytes from DMG-treated animals immunized with the typhoid vaccine showed a fourfold increase (mean values) in thymidine uptake (p = 0.0180). No toxicity or adverse effects were observed at any time during the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Observations on cell-wall deficient forms of Pseudomonas maltophilia.
Pseudomonas maltophilia cell-wall deficient forms were induced using a medium containing carbenicillin and polyvinyl pyrrolidone. Scanning electron microscopy proved to be a very effective method of demonstrating the various phases. It is suggested that the rapid rate of reversion to bacterial forms could have been due to plasmids.
Carbenicillin↗
Isozymes of fructose 6-phosphate,2-kinase:fructose-2,6-bisphosphatase in rat and bovine heart, liver, and skeletal muscle.
The distribution of Fructose 6-P,2-kinase:Fructose 2,6-bisphosphatase in rat and bovine heart, liver, and skeletal muscle tissues was examined. With DEAE-cellulose chromatography, two peaks (I and II) of Fru 6-P,2-kinase activity were detected in all tissue extracts. Peak I was the predominant form both in rat and bovine heart tissue, while peak II was the major form in liver and skeletal muscle. Antibodies to heart enzyme reacted specifically with peak I, and antibodies to liver enzyme reacted with peak II from both liver and skeletal muscle. All the isozymes were bifunctional. All the tissues examined contained other isozymes in minor amounts.
Animals↗
Effects of insulin and work on fructose 2,6-bisphosphate content and phosphofructokinase activity in perfused rat hearts.
The effects of insulin and increased cardiac work on glycolytic rate, metabolite content, and fructose 2,6-bisphosphate (Fru-2,6-P2) content were studied in isolated perfused rat hearts. Steady-state rates of glycolysis increased 5-fold with the addition of insulin to the perfusate or by increasing cardiac pressure-volume work and correlated well in most conditions with changes in substrate concentration (Fru-6-P) and with concentration of the activator, Fru-2,6-P2. There was no correlation with changes in other well known regulators including citrate, ATP, AMP, Pi, or cytosolic phosphorylation potential. Using phosphofructokinase purified from hearts perfused under identical conditions, allosteric kinetic experiments were performed using the metabolite and effector concentrations determined from in vivo experiments. Reaction rates for phosphofructokinase calculated in vitro agreed well with the glycolytic rates measured in vivo and correlated with changes in Fru-6-P but not with other effectors. However, higher Fru-2,6-P2 levels were more effective in maintaining phosphofructokinase activity at high ATP and citrate levels. Kinetic experiments did not indicate a covalent modification of phosphofructokinase. These data indicate that control of cardiac phosphofructokinase and glycolysis may be accomplished by changes in the availability of substrate, Fru-6-P, and activator, Fru-2,6-P2, rather than by citrate, adenine nucleotides, or cytosolic phosphorylation potential as previously suggested.
Allosteric Regulation↗
Hypertrophic cardiomyopathy: current views on etiology, pathophysiology, and management.
Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease of unknown cause that is characterized by a hypertrophied, nondilated, hypercontractile left ventricle. Its etiology and pathogenesis remain undefined but the three principal factors implicated are a genetic predisposition, a hypersensitivity to catecholamines, and an abnormal calcium metabolism. The hypertrophy typically involves the intraventricular septum to varying degrees, but may also involve the apex or free wall and even be concentric. The disease occurs in either an obstructive or a nonobstructive form depending on whether an intraventricular pressure gradient can be demonstrated at rest or on provocation. The gradient and obstruction to outflow is usually seen in patients with asymmetric septal hypertrophy (ASH) and anterior motion of the mitral valve during systole (SAM). Abnormal left ventricular diastolic function characterized by inadequate filling and impaired relaxation has been shown to be very important in both the obstructive and nonobstructive forms of the disease. In addition, inadequate coronary vasodilator reserve as a result of small vessel disease, microvascular spasm, and/or low capillary density per unit myocardial mass has been implicated as an important cause of ischemia in patients without coronary artery disease. HCM is a disease of young adulthood with relatively slow progression; young patients are often asymptomatic, whereas older patients are more limited by dyspnea, angina, dizziness, or syncope. Supraventricular tachyarrhythmias occur in 30% of patients, and high-grade ventricular arrhythmias occur in over 75%. The annual mortality is 3-5%. The common mode of demise is sudden cardiac death. Therefore, the primary objectives of treatment are the amelioration of symptoms, the control of arrhythmias, and the prevention of sudden death. Beta-adrenoreceptor blocking agents decrease myocardial contractility and oxygen demands and increase ventricular volume; therefore, they are most useful in patients with the obstructive form of HCM. Calcium channel antagonists enhance left ventricular relaxation, relieve microvascular spasm, and improve coronary filling and therefore are the agents of choice in patients with diastolic dysfunction. The ability of the calcium channel antagonists to decrease contractility makes them valuable in patients with obstructive HCM. Arterial vasodilators, diuretics, nitrates, and inotropic agents should be avoided because they can increase the intraventricular gradient. Myomyectomy is reserved for those patients with the obstructive form of HCM whose symptoms are refractory to medical therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
Cardiomyopathy, Hypertrophic↗
Inhibition of quinidine-propranolol elevation of the ventricular fibrillation threshold by bilateral stellectomy+vagotomy in the anesthetized dog.
The antiarrhythmic potentiation that occurs with the coadministration of quinidine-propranolol has been attributed to propranolol-induced cardiac beta adrenergic receptor blockade. That this may not be the sole mechanism, however, is suggested by the finding that sotalol, pronethalol and practolol fail to potentiate quinidine in some antiarrhythmic tests. Thus, in the present experiments, the influence of bilateral stellectomy + vagotomy on quinidine-propranolol antiarrhythmic activity was studied in the anesthetized dog. Antiarrhythmic activity was determined as elevation of the electrical ventricular fibrillation threshold (VFT) when the left ventricle was stimulated directly with 60 Hz, 6 msec and varying mA for 2 sec. The increase in VFT produced by quinidine-propranolol (5 + 0.2 mg/kg, i.v.) was significantly reduced when the heart was subsequently denervated by bilateral stellectomy + vagotomy. The cardiac denervation did not significantly reduce the elevation of VFT that had been produced by prior administration of propranolol 0.4 mg/kg or sotalol. In other groups with prior bilateral stellectomy + vagotomy, the separate administration of propranolol 0.4 mg/kg or quinidine 5 mg/kg failed to significantly elevate the VFT although the VFT was increased by propranolol 0.8 mg/kg. The results indicate that the action of quinidine-propranolol to elevate the VFT may be dependent in part upon an intact nerve supply to the heart.
Anesthesia↗
Regulation of phosphofructokinase in perfused rat heart. Requirement for fructose 2,6-bisphosphate and a covalent modification.
Phosphofructokinase from rat heart perfused with epinephrine was purified to homogeneity and various allosteric properties were determined under conditions which approximate physiological concentrations of the substrates, effectors, and pH. The molecular weights of the protomer of the enzyme isolated from the hormone-stimulated and the control hearts are both approximately 83,000. The epinephrine-stimulated and the control enzymes contain 1.1 and 0.66 mol of phosphate/mol of protomer, respectively. Both enzymes can be fully phosphorylated by cAMP-dependent protein kinase indicating that the phosphorylation site is new and distinct from the known phosphorylation site of skeletal muscle phosphofructokinase. Pure phosphofructokinase isolated from the epinephrine-stimulated heart is significantly less sensitive to inhibition by ATP and citrate, and the K0.5 values for Fru-6-P (0.18 mM) and Fru-2,6-P2 (3 microM) are one-half those for the enzyme from control hearts. In the presence of in vivo concentrations of ATP, citrate, and Fru-6-P at pH 7.1, both enzymes are inactive in the absence of Fru-2,6-P2. Moreover, the K0.5 values for Fru-2,6-P2 of the hormone-stimulated and untreated enzymes are 3 and 6 microM, respectively. These differences in the allosteric properties of phosphofructokinases from the hormone-treated and the control hearts disappear when the enzymes are dephosphorylated by alkaline phosphatase. Determination of the glycolytic intermediates showed a 2-fold increase in Fru-6-P, Fru-2,6-P2, and AMP and 13-fold increase in Fru-1,6-P2. Partially purified Fru-6-P,2-kinase from epinephrine-stimulated and control hearts show KFru-6-P0.5 = 4 and 15 microM, respectively. These results indicate that rat heart phosphofructokinase in vivo requires Fru-2,6-P2 for its activity. Epinephrine stimulates phosphorylation of phosphofructokinase which results in a more active form. The hormone also increases Fru-2,6-P2 which appears to be the result of an activation of Fru-6-P,2-kinase by a covalent modification.
Animals↗
Effect of some beta adrenergic blocking agents and phenytoin on potentiation of quinidine antiarrhythmic activity in the mouse.
Quinidine coadministered with propranolol produces antiarrhythmic potentiation. The mechanism is uncertain although some in vitro electrophysiologic studies have suggested that it may be due to propranolol-induced cardiac beta receptor blockade. Other effects of propranolol, however, including a decrease in cardiac sympathetic nerve activity as well as some direct cardiac membrane effects might also contribute. The possible contributions of these effects were studied indirectly by coadministering quinidine with several compounds (d-propranolol, l-propranolol, d-practolol, practolol, pronethalol, and phenytoin) which have varying effects on these parameters. Antiarrhythmic activity was determined as protection against chloroform-induced ventricular arrhythmias and beta blockade as inhibition of isoproterenol-induced tachycardia. Only d- and l-propranolol and phenytoin potentiated quinidine. The d-isomer was only approximately 1/8th as potent as the l-isomer for inhibiting isoproterenol tachycardia, and the lowest dose of the d-isomer coadministered with quinidine produced antiarrhythmic potentiation but little if any inhibition of isoproterenol tachycardia. The results suggest that cardiac beta blockade alone does not adequately explain the potentiation of quinidine by propranolol in the mouse. Perhaps a decrease in cardiac sympathetic nerve activity and the direct membrane effects as occur with d-, l-, and d,l-propranolol and phenytoin may also contribute to the potentiation.
Animals↗
Necroscopic findings of pleomorphic, variably acid-fast bacteria in a fatal case of Kaposi's sarcoma.
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Aged↗
Comparative antiarrhythmic activity of quinidine combined with propranolol and with sotalol.
Quinidine combined with propranolol produces antiarrhythmic synergism. The mechanism is uncertain but has been suggested as possibly due to increased activity of quinidine made possible by myocardial beta adrenergic receptor blockade by propranolol. In the present study, identical doses of quinidine were coadministered with doses of propranolol and of sotalol that produced equivalent beta blockade. Antiarrhythmic activity was measured as decreased ventricular vulnerability to electrical fibrillation in the dog and prevention of chloroform-induced ventricular fibrillation in the mouse. The two drug combinations did not produce equivalent antiarrhythmic activity because only quinidine-propranolol produced antiarrhythmic synergism.
Adrenergic beta-Antagonists↗
Isolation of a stable cell wall-defective form of Neisseria gonorrhoeae from a case of untreated gonococcal urethritis.
A cell wall-defective form of Neisseria gonorrhoeae from an exudate of an untreated patient with gonococcal urethritis was isolated on medium containing 7% polyvinylpyrrolidone. Initial attempts to grow the organism by standard microbiological methods had failed. This isolate was incapable of reversion to a normal gonococcus even after numerous subcultures and appeared to be a stable cell wall-defective form.
Cell Wall↗
Effects of pH and free Mg2+ on the Keq of the creatine kinase reaction and other phosphate hydrolyses and phosphate transfer reactions.
The observed equilibrium constants (Kobs) of the creatine kinase (EC 2.7.3.2), myokinase (EC 2.7.4.3), glucose-6-phosphatase (EC 3.1.3.9), and fructose-1,6-diphosphatase (EC 3.1.3.11) reactions have been determined at 38 degrees C, pH 7.0, ionic strength 0.25, and varying free magnesium concentrations. The equilibrium constant (KCK) for the creatine kinase reaction defined as: KCK = [sigma ATP] [sigma creatine] divided by ([sigma ADP] [sigma creatine-P] [H+]) was measured at 0.25 ionic strength and 38 degrees C and was shown to vary with free [Mg2+]. The value was found to be 3.78 x 10(8) M-1 at free [Mg2+] = 0 and 1.66 x 10(9) M-1 at free [Mg2+] = 10(-3) M. Therefore, at pH 7.0, the value of Kobs, defined as Kobs = KCK[H+] = [sigma ATP] [sigma creatine] divided by ([sigma ADP] [sigma creatine-P] was 37.8 at free [Mg2+] = 0 and 166 at free [Mg2+] = 10(-3) M. The Kobs value for the myokinase reaction, 2 sigma ADP equilibrium sigma AMP + sigma ATP, was found to vary with free [Mg2+], being 0.391 at free [Mg2+] = 0 and 1.05 at free [Mg2+] = 10(-3) M. Taking the standard state of water to have activity equal to 1, the Kobs of glucose-6-P hydrolysis, sigma glucose-6-P + H2O equilibrium sigma glucose + sigma Pi, was found not to vary with free [Mg2+], being 110 M at both free [Mg2+] = 0 and free [Mg2+] = 10(-3) M. The Kobs of fructose-1,6-P2 hydrolysis, sigma fructose-1,6-P2 equilibrium sigma fructose-6-P + sigma Pi, was found to vary with free [Mg2+], being 272 M at free [Mg2+] = 0 and 174 M at free [Mg2+] = 0.89 x 10(-3) M.
Adenosine Diphosphate↗
Cytosolic phosphorylation potential.
The tissue contents of the reactants of the myokinase (EC 2.7.4.3) and the combined glyceraldehyde-3-phophate dehydrogenase (EC 1.1.1.29)-3-phosphoglycerate kinase (EC 2.7.2.3) reactions were measured in rapidly inactivated samples of human blood and rat brain, muscle, and liver. The tissue contents of the reactants of the creatine kinase (EC 2.7.3.2) reaction were measured in rat brain and muscle. In vitro the value of the expression: KG+G = [sigma3PG] . [sigmaATP] . [sigmalactate] KLDH = [sigmaHAP]/22] . [sigmaADP][sigmaPi] . [sigmaRUVATE] (1) was found to be 0.725 x 10(7) M-1 at I = 0.25, T = 38 degrees C, and free [Mg2+] = 0.15 mM and the value measured in vivo in red cell was 0.699 x 10(7) M-1. The value of the expression KMYK = ([sigma ATP] [sigma AMP]/[ADP2]) measured under the above conditions and at pH 7.2 was found to be 0.744 while the value found in red cell was 0.784 +/- 0.037. These reactions, therefore, appear to be in a state of near-equilibrium in the red cell and the measured tissue contents of ATP and ADP, which are common reactants in both reactions, approximate closely the activity of these reactants in vivo. In brain and muscle, the value of KG + G/KLDH calculated from the measured tissue contents of the reactants was a factor of 20 or more lower than that expected at equilibrium as was the measured value of the expression: KCK = [sigma ATP] [sigma creatine] divided by [sigma ADP] [sigma creatine-P] [H+] (2) Substitution of calculated free [sigma ADP] values in the expression of KG + G/KLDH gave values of 0.83 +/- 0.19 x 10(7) M-1 for brain and muscle, respectively, which agreed well with the value of 1.65 x 10(7) M-1 measured in vitro at I = 0.25, free [Mg2+] = 1 mM, T = 38 degrees C. This agreement between two highly active enzyme systems in the same compartment is taken as evidence of the existence of near-equilibrium in both these systems and suggests that free cytosolic [sigma ADP] is probably 20-fold lower than measured cell ADP content in mitochondrial-containing tissues.
Adenine Nucleotides↗
Cyclic adenosine 3', 5'-monophosphate in Neisseria gonorrhoeae.
Intracellular cyclic adenosine 3', 5'-monophosphate (cAMP) was measured in two laboratory strains of Neisseria gonorrhoeae. Decreasing the glucose content of a defined media from 33 mM to 5.5 mM glucose resulted in an 11-to 25-fold increase of intracellular cAMP.
Culture Media↗
Synthesis, toxicity, and cardiovascular properties of N-aralkyl- and N-acyl-5-aminoethylindans.
Secondary amines and amides of 5-aminoethyl-6-methoxyindan and 5-aminoethyl-6-methylindan were synthesized, and the blood pressure lowering effects and accompanying changes in heart rate were evaluated in the unanesthetized desoxycorticosterone acetate hypertensive rat. The acute toxicities of the compounds were determined in mice. The amines were significantly more potent than the amides as antihypertensive agents and also were more toxic. 5-(3,4-Dimethoxybenzyl)aminoethyl-6-methylindan produced the greatest depression in systolic blood pressure at the dose level studied. Structure-activity relationships relevant to blood pressure lowering, heart rate, and toxicity are discussed.
Animals↗