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Biomedical subjects

A Clark

Publications and source records attributed to A Clark.

At least 307 records · Page 17Linked to original sources

The interaction of calcium transport and ADP phosphorylation in brain mitochondria.

Brain mitochondria respiring on glutamate plus malate had a respiratory control index (RCI) for the addition of ADP of 5.5 and P:O ratio of 2.9. These mitochondria also had a Ca2+:O ratio of approximately 5.2, and the ratio of oxygen uptake in the presence of external Ca2+ to that in its absence was 4.0. The reversible transition of respiration to State 3 on the addition of ADP in phosphate media could be blocked by the prior accumulation of 50--200 nmoles/mg of Ca2+. The inhibition was reversible, and on the release of the accumulated Ca2+ by Na+/Ca2+ exchange, the mitochondria became responsive to ADP. The decreased response to ADP following the addition of Ca2+ is probably associated with Ca2+ ions complexing adenine nucleotides within the mitochondria, thus reducing the exchangeable pool and the amount of ADP available to the F1-ATPase.

Adenosine Diphosphate↗

Immunity to influenza in ferrets. XIV: Comparative immunity following infection or immunization with live or inactivated vaccine.

Immunization by live influenza virus induced a greater protective effect against subsequent challenge by the homologous virus than by the corresponding killed virus vaccine. Furthermore, tracheas excised from 11-day and 28-day influenza-virus-infected ferrets were more resistant to reinfection than tracheas excised from ferrets immunized by killed influenza vaccine, despite equivalent serum antibody titres at these times. Histological examination of trachea sections taken from vaccinated and virus-infected animals showed an increased cellular inflammatory infiltrate in the latter at Days 11 and 28 after immunization. The amount of IgG detected in these sections, measured by a fluorescent antibody technique, correlated with the extent of cellular infiltration, the fluorescence being both intra- and extracellular for sections from virus-infected animals, but only extracellular in sections from Day-28 vaccinated animals. In contrast there was little or no cellular infiltration into lung tissues, the levels of IgG detected being comparable to those in sections taken from control animals. These results provide further evidence that live influenza vaccines induce local antibody in the upper respiratory tract of ferrets, in contrast to killed influenza vaccines, and that this local induction may play a significant role in the greater protective efficacy of live influenza vaccines.

Animals↗

Two additional examples of non-transfusion-stimulated anti-Kell.

We have recently encountered two additional examples of non-red cell-stimulated naturally occurring anti-Kelly antibodies in ther sera of two apparently healthy male blood donors. Neither of these donors was previously transfuse. Both antibodies were initially detected using a low ionic medium. Additionally, these two antibodies decreased in reactivity within a seven month period of time. Further documentation of these unusual cases may assist in the understanding of the Kell blood group system.

Adult↗

Inhibition of Neisseria gonorrhoeae by normal human saliva.

Saliva was found to be a powerful and specific inhibitor of Neisseria gonorrhoeae. Although 28 other species of bacteria were tested, including Neisseria meningitidis, Neisseria pharyngis var flava, Neisseria lactamica, and Neisseria catarrhalis, we failed to find any others sensitive to saliva under similar conditions. The physical properties of the inhibitory substance indicated that it might be salivary alpha-amylase. To test this hypothesis alpha-amylase was extracted from saliva and was shown to have a high antigonococcal activity. Hog pancreas alpha-amylase also showed strong antigonococcal activity, thus the observations indicate that for the strains we tested alpha-amylase is inhibitory to gonococci. This observation indicates that either the gonococcal outer cell wall contains some unique lipopolysaccharides or that the gonococcus is unusually dependent on the integrity of these moieties. Whichever speculation proves to be true it indicates a need for a careful study of the gonococcal cell wall.

Adult↗

Salicylate intoxication and influenza in ferrets.

A model of salicylate intoxication was developed in ferrets to permit the evaluation of the interaction with viruses isolated from patients with Reye's syndrome. Salicylate intoxication produced a mild elevation of the serum glutamic oxaloacetic transaminase and fatty changes in the liver, but these changes differed from those seen in Reye's syndrome on light and electron microscopy. Salicylates were associated with decreased activity of hepatic phosphorylase and a slight depression of activity or ornithine transcarbamylase, a mitochondrial urea cycle enzyme. Infection with influenza viruses produced mild fatty changes in the liver, but did not significantly potentiate the effects of salicylate intoxication on the over-all mortality, the degree of fatty changes, or the hepatic enzymes. Influenza infection alone was not associated with decreased hepatic phosphorylase activity, but was associated with decreased activity of ornithine transcarbamylase. Influenza A was isolated from the livers of two of four animals cultured in embryonated eggs.

Animals↗

Reactogenicity and immunogenicity of whole and ether-Tween-split influenza A virus vaccines in volunteers.

Two separate, double-blind studies were carried out in volunteers to compare the reactogenicity of, and serum antibody responses to, whole or ether-Tween-split inactivated influenza virus vaccines. In both studies the ether-Tween-split vaccines induced a lower rate of reactions. The serum hemagglutination-inhibiting (HAI) antibody response of volunteers to the A/Scotland/74 component of the split vaccine used in the first study was significantly greater than that following inoculation of A/Scotland/74 whole-virus vaccine. The neuraminidase-inhibiting (NI) antibody responses of the volunteers to each vaccine were similar. In the second study, a markedly better NI antibody response to the influenza A virus component was seen following immunization with split-virus vaccine, but the HAI antibody response to both split and whole vaccines was the same. In both studies the serum HAI antibody responses to the B/Hong Kong/73 component of the vaccines were similar. Challenge of the volunteers with attenuated influenza viruses homologous to the influenza A component of the vaccines showed both types of vaccines to be protective.

Antibodies, Viral↗

The management of drug induced gingival hyperplasia in mentally retarded patients with hemophilia: a report of two cases.

Two cases of hemophilia in severely mentally retarded patients with drug-induced gingival hyperplasia are presented. The method of management in each case is described. A conservative approach is recommended in which tissue removals and only selected extractions are performed. It is also suggested that the sequela of dilantin hyperplasia be considered when dilantin is used in patients with hemophilia or severely mentally retarded patients whose oral hygiene may be difficult to maintain. If feasible, as in the first case reported, discontinuance of the drug should be considered. In case 2 the patient is presently being weaned from dilantin therapy. It should be understood that the authors are concerned with the immediate clinical management of drug-induced gingival hyperplasia in mentally-retarded patients with hemophilia. Although this method of management has proved successful in the hands of the authors, we do not have data to show that it is the best form of treatment for these patients.

Adult↗

Immune-mediated reactions to althesin (alphaxalone).

Measurements of complement conversion and white cell variations were made on sequential blood samples obtained from a single volunteer following repeated administration of Althesin. The results suggest a mechanism by which a clinically significant hypersensitivity reaction to the drug might be mediated. Studies of patients receiving routine anaesthesia revealed a very high incidence of subclinical "hypersensitivity" reaction, some of which appear to be immune-mediated. These reactions occurred irrespective of whether the patients were induced with Althesin, methohexitone or propanidid.

Adult↗

Identification of the pace-maker current in frog atrium.

1. The nature and interactions of the membrane currents underlying induced pace-maker activity in frog atrial muscle have been investigated using a double sucrose gap technique. 2. The membrane current which controls the speed of the atrial pacemaker depolarization (the pace-maker current, ip), is shown to be an outward current activated within the plateau potential range of a normal action potential. The subsequent deactivation of ip at more negative potentials unmasks the depolarizing action of time-independent inward membrane currents so that a pace-maker potential can result. 3. The deactivation of ip over a limited potential range (between about -30 and -60 mV) can be reliably recorded by switching on the voltage clamp during an induced pace-maker depolarization. 4. Investigation of the time and voltage-dependent behaviour of ip over a much wider potential range is less straightforward. How ip can be separated from other components of outward current present in the decay tails following square voltage clamp depolarizations is described. 5. The majority of such current decay tails contain three components of outward current. It appears that two of these components, one of which is ip, are true Hodgkin-Huxley conductance systems chiefly carrying potassium ions. 6. The nature of the third current, which decays very slowly at moderate membrane potentials (about -40 mV), is discussed and reasons are briefly given for considering it to result from the accumulation of potassium ions in extracellular spaces. Preliminary evidence that potassium depletion occurs at potentials negative to the resting potential of the trabeculum is also presented. 7. Because of the obvious complexities involved, a quantitative analysis of the atrial outward currents is not attempted here but forms the subject of a following paper (Brown, Clark & Noble, 1976a).

Animals↗

Analysis of pace-maker and repolarization currents in frog atrial muscle.

1. A quantitative analysis of the time-dependent component of outward membrane current in atrial wall trabeculae from Rana catesbeiana and Rana ridibunda has been carried out using a double sucrose gap technique. 2. Separation of the different components of delayed outward current was hampered by the sigmoid onset of one of the outward current systems ixfast and by the development of potassium ion accumulation which prevented current activation from reaching a steady state at positive membrane potentials. Semilogarithmic analysis of positive current decay tails recorded immediately following square voltage clamp depolarizations was therefore used to separate the two membrane conductance components ixfast and ixslow and the third component, attributable to potassium ion accumulation, which was almost invariably present in the tails. 3. It is shown that inaccuracies in this method of semilogarithmic separation of components caused by visual assessment of the i3 (accumulation) line are minor compared with the large changes in the time constants of ixfast and more especially of ixslow which would result from ignoring the potassium accumulation component. 4. Such semilogarithmic separation of the three components of outward current gave separate activation curves for each of the two membrane conductance components, ixfast and ixslow. 5. Measurement of 'total' activation curves in which all components of outward current were represented could be made more easily and fairly reliably. The position and shape of these activation curves on the voltage axis were found to closely resemble those obtained by three component separation. It is therefore suggested that such a simplified analysis reflects the properties of the individual currents sufficiently well for it to be of use in preliminary studies of, for example, drug action. 6. The kinetic properties of the atrial outward currents have been investigated over a wide potential range. Because of the presence of potassium ion accumulation, an indirect method of obtaining the average value of 1/gamma for outward current decay at negative potentials had to be employed. 7. It is shown that some degree of inward-going rectification is associated with the outward current systems of frog atrium. 8. The possible reasons for the differences between the analysis presented here and those presented earlier by us (Brown & Noble, 1969a, b) and by Ojeda & Rougier (1974) are discussed.

Animals↗