Search PubMed⌕ Search

Biomedical subjects

R T Jones

Publications and source records attributed to R T Jones.

At least 217 records · Page 12Linked to original sources

Immunochemical and physicochemical characterization of commercial Alternaria extracts: a model for standardization of mold allergen extracts.

To develop a model for mold allergen extract standardization, we studied eight commercial Alternaria extracts from various suppliers by a variety of immunochemical and physicochemical techniques, including measurement of Alt-I, a purified allergenic fraction of Alternaria. Wide variations were noted in the allergenic and antigenic potencies of these extracts. Estimates of Alt-I content measured by Alt-I RAST inhibition and by radioimmunoassay correlated significantly (p less than 0.05), but Alt-I activity by either method could not be correlated with allergenic potency as measured by RAST inhibiton using solid-phase Alternaria. Each test extract produced unique and differing patterns of Coomassie blue-stained bands in isoelectrofocusing gels and in crossed immunoelectrophoresis gels using rabbit antibodies to Alternaria. The optimal method for mold allergen standardization involves a combination of RAST inhibiton, isoelectrofocusing, and crossed immunoelectrophoresis techniques, and, if possible, quantitation of individual allergens.

Allergens↗

Shared allergenic and antigenic determinants in Alternaria and Stemphylium extracts.

Alternaria and Stemphylium extracts were compared by means of various immunochemical and biologic methods. Skin-test responses to Alternaria and Stemphylium in allergic patients were positively correlated, and RAST binding values with the sera of 30 patients utilizing solid-phase Alt-I, Alternaria (70% ammonium sulfate--precipitable fraction), and Stemphylium allergens showed significant correlation, giving evidence for the presence of common allergenic determinants among these three extracts. In RAST inhibition assays, Alternaria and Stemphylium extracts exhibited dose-related inhibiton with solid-phase Stemphylium, Alternaria, and Alt-I, confirming the presence of Alt-I as the major shared allergenic fraction in the two extracts. In repetitive absorption experiments, both Alt-I and Alternaria solid-phase allergens absorbed Stemphylium-specific IgE antibodies from a 12-person serum pool. Similarly, Stemphylium solid-phase allergen absorbed both Alternaria- and Alt-I--specific IgE antibodies. Double-antibody radioimmunoassay for Alt-I showed higher Alt-I activity in Stemphylium than in Alternaria extract. In double-immunodiffusion experiments with rabbit anti--Alt-I antibodies, both Stemphylium and Alternaria extracts produced precipitin lines of identity with Alt-I. The antigenic relationship of the two crude extracts was further confirmed by crossed and crossed-line immunoelectrophoresis experiments. Our results showed that Alternaria and Stemphylium extracts contain multiple shared allergenic and antigenic determinants, including Alt-I.

Absorption↗

Identification of a cholinergic-specific antigen Chol-1 as a ganglioside.

An antiserum specific for cholinergic terminals was used to identify an antigen conserved between Elasmobranchs and mammals. Immunohistochemistry and a cytotoxicity test were used to assay the binding of antibody to mammalian terminals. Torpedo electric organ gangliosides totally abolished antibody binding. The highest inhibitory activity was associated with a single polysialoganglioside band on TLC plates. Neuraminidase altered the migration of the inhibitory activity on TLC plates. Antibody binding was inhibited by ganglioside fractions derived from chicken and mammalian brains. A summary of those tissues in which the antigen has been detected is presented. The possible function of the antigen is discussed.

Animals↗

Functional properties of Hb Pasadena, alpha 2 beta 2 75(E 19) Leu replaced by Arg.

Functional properties of Hb Pasadena (beta 75[E19]Leu replaced by Arg) as well as correlations of its structure-function relationships with those of normal hemoglobin are presented. The homeotropic and heterotropic properties of the isolated variant were investigated by automatic recording oxygen equilibrium analysis. These studies indicate an increase of 02 affinity but normal cooperativity. The decrease of 02 affinity in response to organic phosphate (DPG and IHP) was found to be normal. However, the cooperativity of Hb Pasadena is less affected by IHP than is that of Hb A. The alkaline Bohr effect was found to be somewhat decreased, although the temperature effect is nearly normal. The autoxidation rate is increased by a factor of nearly 2 compared to normal. These observations are consistent with the conclusion that the beta (E19)75 leucyl hydrophobic residue of Hb A associates with beta (A8)11 Val, beta (A12)15 Trp and beta (H11)133 Val to form a hydrophobic cluster between the A, E and H helics which thereby stabilizes the heme of the beta chain in the deoxy ferrous state. The experimental results also suggest that the amino acid substitution in Hb Pasadena mainly disrupts the interior conformation of the beta subunit without affecting subunit interfaces. Thus it is predicted that Hb Pasadena should have a normal crystal structure in either the liganded (R) or unliganded (T) state. Its increased 02 affinity can be explained partially by a decrease of proton binding and partially by a shift of the R:T equilibrium towards the R conformation.

Female↗

The pathophysiology of septic shock: acute renal failure in rats following live E coli injection. A histochemical study of the proximal tubules.

Acute renal failure was induced in rats by injection of a lethal dose of live Escherichia coli. Enzyme activities of the proximal tubule were studied histochemically at three, six, and 12 hours following E coli injection. The enzymes examined were alkaline phosphatase (A1Pase), acid phosphatase (AcPase), adenosine triphosphatase (ATPase), succinate dehydrogenase (SDH), glucose-6-phosphatase (G6Pase), and glucose-6-phosphate dehydrogenase (G6PDH). At three hours, ATPase activity was slightly decreased, while other enzymes showed no changes in activities at this time. At six hours, a slight increase in AcPase activity was seen in the pars recta. At this time, although A1Pase showed no change in activity, other enzymes revealed slight decreases in activities: G6Pase and SDH in the pars convoluta, ATPase in the pars convoluta and pars recta, and G6PDH in pars recta. At 12 hours after treatment, all enzymes showed decreases in activities; however, no necrotic tubule changes were detectable by light microscopy. Since sodium reabsorption in proximal tubules requires a sodium pump consisting of Na-K ATPase, early histochemical changes in ATPase activity in proximal tubule following bacteremia may be related to early changes in sodium reabsorption causing polyuria and to the subsequent development of acute renal failure.

Acute Kidney Injury↗

The pathophysiology of septic shock: studies of reticuloendothelial system function and liver high-energy metabolism in rats following sublethal and lethal Escherichia coli injection.

Phagocytic indices and the hepatic energy charge (ATP + 1/2 ADP/ATP + ADP + AMP) were studied in rats after intravenous sublethal or lethal injection of live Escherichia coli (12--15 X 10(8) or 4--5 X 10(8) organisms/100 gm of body weight). Phagocytic indices as determined by carbon clearance test were progressively decreased in both groups from 0.063 of control to 0.028 or 0.022 (sublethal or lethal) at 12 hours (P less than 0.001). This was mainly due to marked decrease in carbon uptake in the liver even though a marked accumulation of carbon occurred in the lung. At 24 hours in the sublethal group, the phagocytic index was elevated (P less than 0.01). With regard to the spleen, carbon uptake in the sublethal group remained unchanged, in contrast to the decreased uptake in the lethal group, leading to a significant difference between sublethal and lethal groups (P less than 0.05 or less at six and 12 hours). On the other hand, the hepatic energy charge levels in the lethal group progressively decreased from 0.86 to 0.62 until death (P less than 0.001), while those in the sublethal group remained moderately decreased. Following carbon administration, the hepatic energy charges in the control and lethal groups were decreased, while those in the sublethal group remained unchanged. These results suggest a functional reserve of phagocytic activity in liver and spleen and activated high-energy metabolism in the liver for phagocytosis may play a role in determining survival from bacteremic shock.

Adenosine Triphosphate↗

The pathophysiology of septic shock: changes in hemodynamics in rats following live E coli injection. An application of the thermodilution method for measurement of cardiac output.

Fifteen anesthetized rats, 273 +/- 9 gm (SEM), were monitored hemodynamically for six hours following an IV injection of a sublethal (4--5) X 10(8) organisms/100 gm body wt, n = 5) or lethal 12--15 X 10(8) organisms/100 gm body wt, n = 5) dose of live Escherichia coli or saline (control, n = 5). A transpulmonary thermodilution method was used for measurement of cardiac output. Changes in the arterial blood temperature and pressure were recorded on a polygraph. In a simulated hydraulic model system, the measured flow rate was well correlated ( r = 0.993, P less than 0.001) with various actual flow readings (30--130 ml/minute). A sublethal dose resulted in a transient hyperdynamic state in the early stage; the cardiac index was increased from the initial rate of 258.2 +/- 9.4 to 312.3 +/- 10.7 ml/minute/kg with a concomitant decrease in the total peripheral resistance from 0.497 +/- 0.019 to 0.367 +/- 0.022 mm Hg/ml/minute/kg which was sustained for 120 minutes after treatment. In contrast, a lethal dose caused a prolonged hyperdynamic state in the early stage followed by a hypodynamic state in the late stage. The cardiac index was increased from 2.54 +/- 4.5 to 306.0 +/- 10.8 ml/minute/kg and the total peripheral resistance was decreased from 0.513 +/- 0.024 to 0.337 +/- 0.015 mm Hg/ml/minute/kg in the early stage, while, in the late stage, the former decreased to 195.0 +/- 13.3 ml/minute/Kg and the latter increased to 0.615 +/0 0.054 m Hg/ml/minute/kg. The mean arterial blood pressure was decreased in both groups in the early stage but maintained above 100 mm Hg. Essentially, no hemodynamic changes were noted in the control group. These results confirm our hypothesis that an injection of live E coli can produce a hyperdynamic state in the early stage as well as hypodynamic state in the late stage, and that serial hemodynamic studies on bacteremia in rats can be done successfully using the thermodilution method.

Animals↗

A study of oxidative phosphorylative activity and calcium-induced respiration of rat liver mitochondria following living Escherichia coli injection.

Mechanisms of subcellular dysfunction of the liver in sepsis are still obscure. The present study investigates changes in oxidative phosphorylative activity and calcium-induced respiration of rat liver mitochondria following live Escherichia coli injection (E coli, Serotype: 0--18. A 1.25--1.5 X 10(9)/100 gm body wt inoculum of E coli bacteria was injected via the tail vein, causing a 100% mortality rate within 24 hours after injection. In order to determine alteration of liver mitochondrial membrane permeability, serum ornithine carbamoyltransferase activity was measured following E coli injection. This activity increased ten to 100-fold over that of controls with time following injection. However, the yield of liver mitochondria from treated rats, estimated by the amount of collected mitochondrial protein and the recovery rate of succinate dehydrogenase activity in the final mitochondrial suspensions, was not significantly different from that of controls. Mitochondrial oxidative phosphorylative activity measured using glutamate as a substrate was enhanced throughout all period to death (P less than 0.01 at three and six hours, P less than 0.05 in the fatal stage) and was associated with concomitant increases in respiratory control ratios. Similar results were obtained using beta-hydroxybutyrate as a substrate. This enhancement was accompanied by an increase in 2-4-dinitrophenol-stimulated ATPase activity (160% at three hours and 130% in the fatal stage). Calcium-induced stimulation of mitochondrial respiration as well as initial calcium uptake rate linked to respiration, using glutamate as a substrate, were higher in liver mitochondria from rats with E coli treatment than in those of controls throughout all periods (P less than 0.01 or less). These results suggest the coexistence of hyperfunctioning as well as deteriorated mitochondria following lethal treatment with E coli.

3-Hydroxybutyric Acid↗

Effects of benactyzine hydrochloride on dynamic vision functions.

We have investigated the effects of an anticholinergic drug, benactyzine HCl on vision and vision function. Our experiments assess the time course and severity of benactyzine effects on visual acuity for static and moving targets, amplitude and dynamics of accommodation, pupil response to light and the spatial contrast sensitivity function. A single dose of the drug (4.14 mg/70 kg body weight, which is within the therapeutic range) and placebo were administered intramuscularly to 12 subjects. Large and significant decrements in visual function were demonstrated after the administration of benactyzine, particularly for those functions performed at near focus. The drug effect was rapid in onset, beginning 7-10 min after injection, peaked at approximately 30-40 min, and declined to baseline values over the next 2 h. The drug increased pulse rate and blood pressure, and induced an intoxicated state involving loss of concentration, attention, and short-term memory.

Accommodation, Ocular↗

Effects of an anticholinergic drug, benactyzine hyrochloride, on vision and vision performance.

Benactyzine is an anticholinergic agent which has been used in past years in psychiatry, but is little used today. It has central and peripheral anticholinergic effects, and when administered intramuscularly, it has a rapid onset of action. This may make it useful as an antidote for organophosphate poisoning, in spite of side-effects such as deficits of short term memory, concentration, and attention. As an anticholinergic drug it could also be expected to produce vision changes by its action on the intraocular musculature controlling the pupil and lens accommodation. We tested the drug on six volunteer subjects to establish the visual side-effects of intramuscular administration. We found that it reduced static and dynamic visual acuity, increased pupil size, reduced amplitude of accommodation and contrast sensitivity, while having little or no effect on glare recovery, color vision, intraocular pressure, stereoacuity, oculomotor tracking, and distance heterophoria. Benactyzine produced reductions in visual performance for up to 3 h and had the greatest effects on functions which have significant cognitive components. The present results suggest that the drug is unsuitable for treatment for oganophosphate poisoning when continuous performance is required, although a definitive test of ths suggestion would require that performance should be tested when benactyzine and the organophosphate of interest were combined.

Adult↗

Puff volume increases when low-nicotine cigarettes are smoked.

Variables of smoking were measured when subjects smoked the first cigarette of the day after an eight- to 10-hour period of abstinence. The cigarettes smoked had high, medium, or low nicotine yields but the tar and carbon monoxide yields, taste, and draw characteristics remained constant. The number of puffs and interval between puffs did not differ between nicotine doses. The smokers took larger puffs, however, when smoking cigarettes delivering lower nicotine yields than their normal brands. This change in the size of puff must be attributed to the change in nicotine yield since all other characteristics of the cigarettes remained constant. Thus encouraging the smoking of low-nicotine cigarettes may increase exposure to combustion products and not appreciably decrease exposure to nicotine, since the smokers increased the size of their puffs in response to the decreased nicotine yield.

Adult↗

Immunohistochemical localization of cholinergic nerve terminals.

Most of the published light-microscopic methods for the localization of cholinergic nerve pathways present various difficulties of interpretation. The production and characterization of an antiserum that binds specifically to cholinergic terminals is described. The antiserum was raised to small synaptosomes prepared from the purely cholinergic electric organ of Torpedo marmorata. It was shown to lyse cholinergic synaptosomes in a mixed population derived from guinea-pig cortex. After partial purification by adsorption onto nonspecific antigens, It was used to label nerve endings in several tissues of Torpedo, rat and guinea pigs using indirect immunofluorescence histochemistry. The antiserum appears to provide a highly specific means of localizing cholinergic nerve endings in these tissues.

Acetylcholinesterase↗

Evidence that cannabidiol does not significantly alter the pharmacokinetics of tetrahydrocannabinol in man.

The pharmacokinetics of delta 9-tetrahydrocannabinol (THC) administered intravenously was evaluated in four subjects after oral administration of placebo and 1500 mg of cannabidiol (CBD) according to a crossover design. The cannabidiol pretreatment had no apparent effect on THC pharmacokinetics, yet there may have been minimal effect on the formation and excretion of metabolites. The total (metabolic) blood clearance of THC averaged 17.4 ml/min/kg without CBD and 20.9 ml/min/kg with CBD, and was probably hepatic blood flow limited. The apparent steady-state volume of distribution averaged 9.86 (with CBD, 10.54) liters/kg. Irrespective of CBD pretreatment, the renal clearance of THC metabolites ranged from 17 ml/min after approximately 1 hr to 1.13 ml/min 3.5 days after dosing with THC. The apparent terminal halflife for metabolites averaged 8.2 days.

Adult↗