Anti-canine distemper virus antibodies in common and grey seals.
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Animals↗
Biomedical subjects
D D Clarke
Publications and source records attributed to D D Clarke.
Evidence of steric factors in the fungitoxic mechanisms of 8-quinolinol and its 5- and 7-halogenated analogues.
Antifungal studies were made of mixtures of minimal inhibitory concentrations (MICs) of 8-quinolinol and its 5- and 7-halo analogues against six fungi: Aspergillus niger, A. oryzae, Trichoderma viride, Myrothecium verrucaria, Mucor cirinelloides, and Trichophyton mentagrophytes. Mixtures of 8-quinolinol with 5- or 7-fluoro-8-quinolinol and of 5- and 7-fluoro-8-quinolinol showed additive activity, and their respective toxicities were reversed by L-cysteine. These results suggested a common mechanism of activity for the three toxicants. Potentiation of the fungitoxicity of mixtures of 8-quinolinol and its 5- and 7-chloro, bromo, and iodo analogues, as well as mixtures of 5- and 7-chloro, 5- and 7-bromo, and 5- and 7-iodo-8-quinolinols, along with the absence of protection of the fungi by L-cysteine from the toxicities of these compounds was observed. This suggested that the modes of action of these compounds were different from each other and from 8-quinolinol and the 5- and 7-fluoro analogues. The geometry of 8-quinolinol as influenced by substituents in the 5- and 7- positions of the molecule determines its site(s) of fungitoxicity.
Antifungal Agents↗
Fluoroacetate and fluorocitrate: mechanism of action.
The concept of lethal synthesis as suggested by Peters is reviewed in the light of the more recent work in this area. It is suggested that fluorocitrate is a "suicide" substrate for aconitase rather than a competitive inhibitor as originally suggested. The use of these substances to study glial-neuronal relationships is considered.
Aconitate Hydratase↗
Synergistic antifungal action of 8-quinolinol and its bischelate with copper(II) and with mixed ligand chelates composed of copper(II), 8-quinolinol, and aromatic hydroxy acids.
Antifungal studies were made of mixtures of minimal inhibitory concentrations (MICs) of 8-quinolinol and its bischelates with copper(II), zinc(II), and manganese(II) and with mixed ligand chelates composed of 8-quinolinol, copper(II) and a second ligand including salicylic acid, 3-hydroxy-2-naphthoic acid, 3,5-diiodosalicylic acid, and 4-bromo-3-hydroxy-2-naphthoic acid. Mixtures of the MICs of the bischelates of 8-quinolinol with copper(II) and zinc(II) and copper(II) and manganese(II), as well as 7-iodo-8-quinolinol and its bischelate with copper(II), and 8-quinolinol and 5-iodo-8-quinolinol were also studied against six fungi: Aspergillus niger, Aspergillus oryzae, Trichoderma viride, Myrothecium verrucaria, Mucor cirinelloides, and Trichophyton mentagrophytes. With the exceptions of the mixtures of 8-quinolinol and (8-quinolinolato)(3,5-diiodosalicylato)copper(II) and (8-quinolinolato)(4-bromo-3-hydroxy-2-naphthoato)copper(II) against M. cirinelloides, all of the test organisms were inhibited by 40% or less of each mixture containing 8-quinolinol. Bischelates of 8-quinolinol with copper(II) and zinc(II) and copper(II) and manganese(II) inhibited five fungi at 50% of the mixtures of the MICs. Mucor cirinelloides was not inhibited by bis(8-quinolinolato)copper(II), bis(8-quinolinolato)zinc(II), or by bis(7-iodo-8-quinolinolato)copper(II).(ABSTRACT TRUNCATED AT 250 WORDS)
Antifungal Agents↗
Studies of transketolase abnormality in Alzheimer's disease.
The partially purified transketolase from each of eight well-nourished patients with Alzheimer's disease contained significantly less heat-stable component with a significantly longer half-life of heat inactivation than that from eight controls. Immunochemical studies utilizing antibodies to the purified human liver transketolase did not distinguish between red blood cell transketolases of patients with Alzheimer's disease and those of controls. However, three brains from patients with Alzheimer's disease that were deficient in transketolase activity lacked a 69-kilodalton form on immunoblots. Subtle structural abnormalities of transketolase appear to occur in a high proportion of patients with Alzheimer's disease.
Alzheimer Disease↗
Acetylation of synaptosomal protein: effect of Na+.
In a previous study it was shown that the acetyl moiety can be incorporated into the protein of purified synaptosomes (1). This process was inhibited by veratridine and the inhibitory effect was counteracted by tetrodotoxin. This suggested that the flux of Na+ may be related to the acetylation process. We now report that in a sodium free medium the amount of acetylation is increased and the inhibitory effect of veratridine (veratrine) is no longer evident. The addition of Na+ leads to a decrease in acetylation in the presence of veratrine. The presence of scorpion toxin has an effect similar to that of veratrine and the two are not additive. Hence, they appear to act on a common site. Molecular sieve chromatography shows four radioactively labeled peaks, two of which are particularly affected by veratrine. We also show that [3H]acetate incorporated into synaptosomal protein can be recovered as acetyldansylhydrazide. In addition, the concentration of free and bound acetate was measured in whole brain as well as in synaptosomes.
Acetylation↗
Effect of secoverine on colonic myoelectric activity in diverticular disease of the colon.
The effect of secoverine on colonic smooth muscle was measured in patients with diverticular disease and in healthy subjects. The frequency of slow wave activity was determined using the fast Fourier transform (FFT) and peak identification analysis (SWSA). The mean slow wave frequency was similar (6 cycles/minute) in healthy subjects using both analytic methods. The slow wave frequency in patients with diverticular disease was similar to that in healthy subjects. The peak frequency measured with SWSA was uniformly higher than that measured with FFT. Secoverine, a muscarinic antagonist, did not affect the slow wave frequency. Eating a 1000-kcal meal initiates an increase in colonic spike activity (22 +/- 2 spike potential/30 min) (P less than 0.001) in healthy subjects during the immediate postprandial period. The gastrocolonic response in patients with diverticular disease was prolonged for 60 min. Secoverine inhibited the gastrocolonic response in patients with diverticular disease. These studies suggest patients with diverticular disease have a similar slow wave frequency as healthy subjects, the gastrocolonic response is prolonged in patients with diverticular disease, and secoverine inhibits the colonic response.
Aged↗
Acetate and fluoroacetate as possible markers for glial metabolism in vivo.
[3H]Acetate has been shown by light autoradiographic methods to label the neuropil but not the perikarya in brain and retina. [3H]Fluoroacetate behaves similarly. The study provides anatomical data which support the concept of metabolic compartmentation of glutamic acid and associated metabolites previously derived from biochemical studies. It is suggested that these may be markers of non-neuronal metabolism, probably mostly glial, and may be used to develop procedures which will provide complementary data to that obtained with 2-deoxyglucose on regional metabolism in brain.
Acetates↗
Outcome of surgery for laryngeal paralysis in four cats.
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Animals↗
The subcellular localization of glutamate dehydrogenase (GDH): is GDH a marker for mitochondria in brain?
Glutamate dehydrogenase (GDH, EC 1.4.1.2) has long been used as a marker for mitochondria in brain and other tissues, despite reports indicating that GDH is also present in nuclei of liver and dorsal root ganglia. To examine whether GDH can be used as a marker to differentiate between mitochondria and nuclei in the brain, we have measured GDH by enzymatic activity and on immunoblots in rat brain mitochondria and nuclei which were highly enriched by density-gradient centrifugation methods. The activity of GDH was enriched in the nuclear fraction as well as in the mitochondrial fraction, while the activities of other "mitochondrial" enzymes (fumarase, NAD-isocitrate dehydrogenase and pyruvate dehydrogenase complex) were enriched only in the mitochondrial fraction. Immunoblots using polyclonal antibodies against bovine liver GDH confirmed the presence of GDH in the rat brain nuclear and mitochondrial fractions. The GDH in these two subcellular fractions had a very similar molecular weight of 56,000 daltons. The mitochondrial and nuclear GDH differed, however, in their susceptibility to solubilization by detergents and salts. The mitochondrial GDH could be solubilized by extraction with low concentrations of detergents (0.1% Triton X-100 and 0.1% Lubrol PX), while the nuclear GDH could be solubilized only by elevated concentrations of detergents (0.3% each) plus KCl (greater than 150 mM). Our results indicate that GDH is present in both nuclei and mitochondria in rat brain. The notion that GDH may serve as a marker for mitochondria needs to be re-evaluated.
Animals↗
Purification and characterization of a soluble and a particulate glutamate dehydrogenase from rat brain.
Glutamate dehydrogenase (GDH) activity was determined in high-speed fractions (100,000 g for 60 min) obtained from whole rat brain homogenates after removal of a low-speed pellet (480 g for 10 min). Approximately 60% of the high-speed GDH activity was particulate (associated with membrane) and the remaining was soluble (probably of mitochondrial matrix origin). Most of the particulate GDH activity resisted extraction by several commonly used detergents, high concentration of salt, and sonication; however, it was largely extractable with the cationic detergent cetyltrimethylammonium bromide (CTAB) in hypotonic buffer solution. The two GDH activities were purified using a combination of hydrophobic interaction, ion exchange, and hydroxyapatite chromatography. Throughout these purification steps the two activities showed similar behavior. Kinetic studies indicated similar Km values for the two GDH fractions for the substrates alpha-ketoglutarate, ammonia, and glutamate; however, there were small but significant differences in Km values for NADH and NADPH. Although the allosteric stimulation by ADP and L-leucine and inhibition by diethylstilbestrol was comparable, the two GDH components differed significantly in their susceptibility to GTP inhibition in the presence of 1 mM ADP, with apparent Ki values of 18.5 and 9.0 microM GTP for the soluble and particulate fractions, respectively. The Hill plot coefficient, binding constant, and cooperativity index for the GTP inhibition were also significantly different, indicating that the two GDH activities differ in their allosteric sites. In addition, enzyme activities of the two purified proteins exhibited a significant difference in thermal stability when inactivated at 45 degrees C and pH 7.4 in 50 mM phosphate buffer.
Adenosine Diphosphate↗
Gastric acid secretory function in preterm infants.
To establish normal values for gastric secretory function in preterm infants, we studied 34 healthy preterm infants once a week during hospitalization. Basal acid output, pentagastrin-stimulated acid output, fasting serum gastrin, and fasting serum pancreatic polypeptide were measured during each study. Basal acid output at 1 week of age was 12 mumol/kg/hr, increasing over the first 4 weeks to 30 mumol/kg/hr. Administration of pentagastrin 6 micrograms/kg subcutaneously increased acid output in all age groups. Pentagastrin-stimulated acid output at 1 week was 21 mumol/kg/hr, increasing over the first 4 weeks to 44 mumol/kg/hr. Acid secretion did not change significantly over the next 4 to 6 weeks. Fasting serum gastrin concentration was stable over the first 6 weeks of life, but doubled during the end of the second month. Pancreatic polypeptide was found at low levels throughout the study. These studies confirm that the majority of healthy preterm infants secrete acid in quantity sufficient to maintain the gastric pH less than or equal to 4, providing a barrier to bacteria and protein antigens.
Achlorhydria↗
Effect of age on contrast sensitivity function: uniocular and binocular findings.
Monocular and binocular contrast sensitivity function for a range of spatial frequencies was measured in two groups of subjects with normal vision. Statistically significant differences in performance between the younger group (age 20-30 years) and the older group (age 50-87 years) were found at all spatial frequencies sampled between 0.40 and 19 X 25 cpd. In the age range 50-87 years there was a linear decline in contrast sensitivity with age for medium and high spatial frequencies, but sensitivity for low spatial frequencies was independent of age.
Adult↗
Contrast sensitivity and visual disability in chronic simple glaucoma.
A battery of vision tests was used to quantify visual defect in a group of 50 patients with chronic simple glaucoma. The vision tests were near and distance visual acuity, visual fields, and contrast sensitivity to static and temporally modulated sinusoidal grating patterns. Of these, static contrast sensitivity function appears to be the most sensitive method of measuring visual defect in glaucoma patients. The visual disability experienced by the glaucoma patients was quantified by means of a questionnaire, and the relationship between perceived visual disability and visual defect was examined. It was found that results from a group of tests, near visual acuity, visual field, and contrast sensitivity measures, are the best predictors of the difficulty experienced by patients in performing visually dependent daily activities.
Activities of Daily Living↗
Acetylation of synaptosomal protein: inhibition by veratridine.
Incubation of synaptosomes with [3H]acetate results in rapid labeling of protein. Labeling is decreased in the presence of veratridine, and the effect of veratridine is blocked by tetrodotoxin. Most of the radioactivity can be removed by base or acid hydrolysis, and is probably incorporated as acetate; it is this fraction that is affected by the veratridine. The data suggest that veratridine stimulates deacetylation is involved in membrane function.
Acetates↗
Sample-size nomograms.
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Clinical Trials as Topic↗
Is acetylation of protein involved in membrane function?
[3H]-acetate is rapidly incorporated as the acetyl moiety into synaptosomal protein and the apparent rate appears to decrease after approximately 1-2 minutes. A second dose of labeled acetate given 6 minutes after the first shows the same time dependent process suggesting that the protein substrate is not depleted. The apparent fall-off in the rate may represent the approach to a steady state of the mixing of the added acetate with internal cold acetate. Veratridine or batrachotoxin appears to stimulate a deacetylation process and tetrodotoxin blocks the effect of veratridine. Several proteins are acetylated at least one of which appears to be a glycoprotein of relatively low molecular weight. The presence of cold pyruvate or glucose competes with the incorporation of labeled acetate; the implication is that glucose and pyruvate can serve as a source of acetyl CoA for protein acetylation. The studies suggest that acetylation-deacetylation processes may be involved in membrane function, possibly in ion and/or transmitter channels.
Acetates↗
Amino acid analogs IV:4-fluoroisoleucine.
4-Fluoroisoleucine was produced by ammonolysis of 2-bromo-4-fluoro-3-methylpentanoic acid, which resulted from the bromofluorination of 4-methyl-2-pentenoic acid. It did not inhibit Plasmodium berghei in mice at 640 mg/kg and was not toxic to the animals. The fluoroamino acid inhibited Aspergillus niger, Trichoderma viride, Myrothecium verrucaria, Trichophyton mentagrophytes, and Mucor mucedo in Czapek solution agar at a concentration between 10(4) and 10(3) microgram/ml. Growth of Escherichia coli was inhibited 25% at 900 microgram/ml in a defined medium.
Animals↗