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Biomedical subjects

M J Dawson

Publications and source records attributed to M J Dawson.

70 records · Page 4Linked to original sources

Energy conservation in the terminal region of the respiratory chain of the methylotrophic bacterium Methylophilus methylotrophus.

Reduced + CO minus reduced difference spectra of respiratory membranes prepared from methanol-limited cultures of Methylophilus methylotrophus confirm the presence of three CO-binding cytochromes i.e. cytochromes aa3, o and cco. The kinetics of cyanide inhibition indicate that the respiratory chain of this organism is branched at the level of cytochrome c to two major terminal oxidases, viz. cytochromes aa3 and o; cytochrome cco is probably not a physiologically significant oxidase. Determination of proton and charge translocation stoichiometries (leads to H+/O and leads to K+/O quotients) during oxidation of ascorbate-N,N,N',N'-tetramethyl-p-phenylenediamine shows that the terminal oxidase system of this organism exhibits a net inward translocation of 2e-, but no net proton translocation, when a pair of electrons are passed from cytochrome c to oxygen. The use of appropriate concentrations of cyanide to selectively inhibit cytochrome o indicates that the overall translocation stoichiometries are achieved by the two oxidases, aa3 and o, functioning similarly. These and other results suggest that methanol oxidase is organised as a simple redox arm with the methanol oxidation site and oxygen consumption site(s) on the periplasmic and cytoplasmic faces of the inner membrane respectively.

Cell Membrane↗

Effects of spaced responding DRL on the stereotyped behavior of profoundly retarded persons.

Stereotypic responding and social behaviors of three profoundly retarded children were measured before and during application of a DRL contingency for stereotypic responding. A variant of the standard DRL procedure, spaced responding DRL, was used, in which reinforcement is delivered following a response if that response has been separated from the previous response by at least a fixed minimum time interval. Three children were treated by using a reversal design. Results showed that: (a) during baseline sessions, the children engaged in high rates of stereotypic responding and very low rates of appropriate social behavior; and (b) during DRL sessions, appropriate behavior increased markedly as stereotypic responding was reduced. The data suggest that spaced responding DRL may be effective in increasing appropriate social behavior as well as in reducing stereotypic responding.

Adolescent↗

Trimethoprim and co-trimoxazole in the treatment of acute urinary tract infections: patient compliance and efficacy.

Patient compliance and drug efficacy and side-effects were compared in two groups of patients with symptoms of acute lower urinary tract infections. One group was treated with trimethoprim, one tablet (300 mg) once a day, and the other with co-trimoxazole, two tablets (160 mg trimethoprim, 800 mg sulphamethoxazole) twice a day; both treatments were prescribed for seven days. Patient compliance was significantly greater with trimethoprim: corrected percentage compliance rates were 97.5 per cent for trimethoprim and 79.1 per cent for co-trimoxazole (p<0.05). Trimethoprim and co-trimoxazole were of equivalent effectiveness in the control of symptoms. Side-effects were more frequent with co-trimoxazole, but the difference was not significant.

Acute Disease↗

Studies of the biochemistry of contracting and relaxing muscle by the use of 31P n.m.r. in conjunction with other techniques.

When n.m.r. is applied to suitable chosen biological problems it yields a wealth of fundamental information unmatched by any other technique. By means of 31P n.m.r. we have studied intact living muscle at rest, during contraction and during recovery from contraction. Phosphocreatine, ATP, inorganic phosphate, phosphorylated intermediaries of glycolysis, pH and the binding of Mg2+ to ATP are observed directly in the spectra. From the spectra can be calculated the concentration of free ADP, the free energy change of ATP hydrolysis, the production of lactic acid and the total ATP turnover. Changes in these quantities can thus be followed continuously in vivo and we have shown how they are related to the decline in force development and to the slowing of relaxation that occur during fatigue. Similar methods have been applied to study the control of glycolysis.

Adenine Nucleotides↗

Self-injury in the profoundly retarded: clinically significant versus therapeutic control.

Two experiments investigated the effects of behavioural interventions on the self-injurious behaviour of two profoundly retarded girls who had a long history of such behaviour. In the first experiment, response-contingent aromatic ammonia was used as the aversive stimulus to reduce the high frequency of face-slapping and face-hitting in a deaf and blind girl. In the second experiment an overcorrection procedure was used to control jaw-hitting in another girl. In both cases, the treatments resulted in near-zero levels of self-injury. However, complete suppression of self-injury was not achieved. The results are discussed in terms of clinically significant versus therapeutic control of self-injurious behaviour in institutionalised profoundly retarded persons.

Adolescent↗

Mechanical relaxation rate and metabolism studied in fatiguing muscle by phosphorus nuclear magnetic resonance.

1. We have used phosphorus nuclear magnetic resonance (31P NMR) to study muscular fatigue in anaerobic amphibian muscle. In this paper the biochemical and energetic changes that result from a series of tetani are related to the decrease in rate constant (1/tau) for the final, exponential, phase of relaxation. 2. Using 31P NMR we have measured the concentrations of phosphocreatine (PCr), inorganic phosphate (Pi) and ATP as well as the internal pH. From our measurements we have calculated [creatine], [free ADP], the free-energy change (more precisely, the affinity A = -dG/d xi) for ATP hydrolysis and the rates of lactic acid production and of ATP hydrolysis. 3. We have found that 1/tau, the rate constant of relaxation, is correlated with each of the following, independently of the pattern of stimulation: isometric force production, all of the measured or calculated metabolite levels, pH and dG/d xi. 4. There is a clear dependence upon the pattern of stimulation of the relation between 1/tau and each of the following: total duration of the experiment, number of contractions, rate of lactic acid production and rate of ATP hydrolysis. 5. The rate of relaxation is linearly related to [PCr], [creatine], [Pi] and dG/d xi. It is nonlinearly related to isometric force, [ATP], [H+] and rate of ATP hydrolysis. 6. We conclude that the change in 1/tau, like that of isometric force, depends upon metabolic factors, and not upon any independent changes in the activation or deactivation of contraction. We suggest that 1/tau may depend upon the free-energy change for ATP hydrolysis which in turn may be related to the rate of Ca2+ uptake into the sarcoplasmic reticulum.

Adenosine Diphosphate↗

Muscular fatigue investigated by phosphorus nuclear magnetic resonance.

Muscular fatigue has been studied using 31PNMR to measure the levels and rates of utilisation of several key metabolites and the free-energy change for ATP hydrolysis. Force development is closely correlated with metabolite levels and is proportional to the rate at which ATP is hydrolysed.

Adenosine Triphosphate↗

Contraction and recovery of living muscles studies by 31P nuclear magnetic resonance.

1. Phosphorus nuclear magnetic resonance ((31)P NMR) can be used to measure the concentrations of phosphorus-containing metabolites within living tissue. We have developed methods for maintaining muscles in physiological condition, stimulating them and recording tension while at the same time accumulating their (31)P NMR spectra. Experiments were performed on frog sartorii and frog and toad gastrocnemii at 4 degrees C.2. The NMR signals from (31)P (the naturally occurring phosphorus) is weak, and signal averaging is required. In order to follow the time course of reactions it is necessary to maintain the muscles in a steady state for many hours while they are undergoing repeated contractions. Signals were accumulated in separate computer bins according to time after initiation of contraction. By these means spectra were obtained which corresponded to the different intervals during the contraction and recovery cycle.3. In the absence of stimulation, the spectra of frog sartorius muscles and of their extracts indicated concentrations of adenosine triphosphate (ATP), phosphoryl creatine (PCr), inorganic orthophosphate (P(i)) and sugar phosphates (sugar P) which are in reasonable agreement with the values obtained by chemical analysis.4. We have confirmed that unidentified resonances representing unknown compounds appear in the spectra of both frog and toad muscle; one of these is much larger in spectra from toad than from frog. We have found an additional small, unidentified resonance which appears to be specific to toad muscle.5. Spectra accumulated during actual contractions (1 s tetani every 2 min) did not differ dramatically from those accumulated throughout the 2 min cycle of contraction and partial recovery.6. Following 25 s tetanii, approximately 20% of the PCr had been hydrolysed; it was then rebuilt exponentially with a half-time of about 10 min. The increase in [P(i)] immediately after contraction and the time course of its disappearance corresponded to the changes in [PCr]. During the later half of the recovery period the concentration of P(i) was reduced to below that in resting muscle. The [sugar P] remained very high ( approximately 4 mmol kg(-1)) throughout the 56 min interval between contractions.7. When frog sartorii were tetanized for 1 s every 2 min, the changes in [PCr] and [P(i)] between contractions could not be observed because too little signal was obtained from these small muscles. However, when toad gastrocnemii were similarly stimulated, the changes in these compounds could be readily detected and were even greater than expected.8. The position of the P(i) resonance can be used to monitor intracellular pH and changes in pH. Under the conditions of our experiments the average intracellular pH in unstimulated frog sartorius muscles was 7.5. After a 25 s tetanus this was observed to move in the acid direction by a few tenths of a pH unit and to return to its pre-stimulation value before the end of the recovery period. After a 1 s contraction of toad gastrocnemius the environment of P(i) became slightly more alkaline for the first few seconds.

Adenosine Triphosphate↗

Restoration of potassium-stimulated respiration of glycerol-treated muscle.

Agent that produced contracture in skeletal muscle, such as caffeine or K-depolarization, also caused an increased rate of oxygen consumption. Both of these functions are calcium dependent. In this study the respiratory response to K-depolarization and to caffeine was monitored in glycerol-treated and normal frog sartorius muscles. Although glycerol-treated muscle does not contract in response to K-depolarization, it does develop normal caffeine contractures. The respiratory response to both potassium and caffeine is greatly inhibited in glycerol-treated muscles. Pretreatment with dibutyryl cyclic AMP restored the respiratory response to normal levels in glycerol-treated muscle. Pretreatment with low levels of caffeine that had no effect on oxygen uptake markedly enhanced oxygen uptake with higher concentrations of caffeine and resulted in a normal respiratory response to K-depolarization even though there was no tension development. Caffeine had no effect on adenyl cyclase activity even at concentrations that markedly stimulated oxygen uptake. The data suggest that potassium stimulation of oxygen uptake in glycerol treated muscle is uncoupled by a defect in the formation of a cyclic nucleotide cofactor, rather than a defect in calcium influx.

Animals↗

Cholinergic sensitivity: normal variability as a function of stimulus background.

The sensitivity of the normally innervated iris sphincter to its neuro-transmitter, acetylchloline, and to relatd agents varies inversely with the preexisting physiological stimulus background, that is, the environmental light intnsity. This normal variability suggests the existence of a negative feedback mechahnism whereby sensitivity of the effector cell is modutlated by a product of neuronal activity.

Acetylcholine↗

Thermotolerance in chicken red blood cells studied by 31P NMR spectroscopy.

Chicken red bloods cells (RBCs) were used as a model for cell survival following hyperthermia of differentiated cells, with rat RBCs serving as controls. The purpose was to investigate whether cells heated at 51.5 degrees C with or without prior heat shock exhibited discernible differences in phosphorus metabolites, intracellular pH or Mg2+ using 31P nuclear magnetic resonance spectroscopy. The biochemical differences that distinguished the heat-shocked from the non-heat-shocked chicken cells were: (1) a decrease in intensity of the low and wide (300 Hz) resonance that underlies the high resolution signals and which arises from the partially mobile membrane phospholipids, suggesting that membrane fluidity was decreased during the induction of thermotolerance; and (2) a time-dependent leftward shift of the peak representing the 4,6P of inositol pentaphosphate together with a broadening of all of the 31P peaks during heat-shock and heat challenge, which persisted after return to the control temperature. This is consistent with significant oxygen consumption in the heat-shocked but not the non-heat-shocked cells. We conclude that chicken RBCs are capable of specific metabolic and physiologic responses to heat shock, as expected in cells known to produce heat-shock proteins and to be capable of thermotolerance induction.

Animals↗