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Biomedical subjects

J Turnbull

Publications and source records attributed to J Turnbull.

At least 19 recordsLinked to original sources

An evaluation of a training course in the short-term management of violence.

Few comprehensive studies have been carried out regarding the nature and extent of violence towards staff in the caring professions. Scarcer still are studies which have thoroughly evaluated the impact of training in the management of violent and aggressive behaviour. Against this background, the following paper describes an evaluation of a 10-day in-service education course in the short-term management of violence. Set within an AB design, a combination of questionnaires and video rated role plays were used to investigate the impact of the training on the knowledge, effect and behaviour of course participants in two groups (N = 25). Results in most areas indicate that positive and significant changes have been brought about. Directions for future research in this area are identified and discussed.

Adult

Religious affiliation and major depression.

Data from the Duke Epidemiologic Catchment Area survey were used to examine the relationship between religious affiliation and major depression among 2,850 adults in the community. Religious affiliations were categorized into six groups: mainline Protestant (27 percent), conservative Protestant (59 percent), Pentecostal (4.2 percent), Catholic (2.4 percent), other religions (2.6 percent), and no affiliation (4.4 percent). The six-month prevalence of major depression among Pentecostals was 5.4 percent, compared with 1.7 percent for the entire sample. Even after psychosocial factors such as gender, age, race, socioeconomic status, negative life events, and social support were controlled for, the likelihood of major depression among Pentecostals was three times greater than among persons with other affiliations. Carefully designed studies are needed to understand the complex interactions of religion and mental health.

Adolescent

pH dependency of the reactions catalyzed by chorismate mutase-prephenate dehydrogenase from Escherichia coli.

The variation with pH of the kinetic parameters associated with the mutase and dehydrogenase reactions catalyzed by chorismate mutase-prephenate dehydrogenase has been determined with the aim of elucidating the role that ionizing amino acid residues play in binding and catalysis. The pH dependency of log V for the dehydrogenase reaction shows that the enzyme possesses a single ionizing group with a pK value of 6.5 that must be unprotonated for catalysis. This same group is observed in the V/Kprephenate, as well as in the V/KNAD, profile. The V/Kprephenate profile exhibits a second ionizing residue with a pK value of 8.4 that must be protonated for the binding of prephenate to the enzyme. For the mutase reaction, the V/Kchorismate profile indicates the presence of three ionizing residues at the active site. Two of these residues, with similar pK values of about 7, must be protonated, while the third, with a pK value of 6.3, must be unprotonated. It can be concluded that all three groups are concerned with the binding of chorismate to the enzyme since the maximum velocity of the mutase reaction is essentially independent of pH. This conclusion is confirmed by the finding that the Ki profile for the competitive inhibitor, (3-endo,8-exo)-8-hydroxy-2-oxabicyclo[3.3]non-6-ene-3,5-dicarboxylic acid, shows the same three ionizing groups as observed in the V/Kchorismate profile. By contrast, the Ki profile for carboxyethyldihydrobenzoate shows only one residue, with a pK value of 7.3, that must be protonated for binding of the inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites

Kinetic studies on chorismate mutase-prephenate dehydrogenase from Escherichia coli: models for the feedback inhibition of prephenate dehydrogenase by L-tyrosine.

Kinetic studies have been undertaken to elucidate the mechanism of the allosteric inhibition by tyrosine of the prephenate dehydrogenase activity of the bifunctional dimeric enzyme chorismate mutase-prephenate dehydrogenase. The effect of tyrosine on the initial velocity of the reactions in the presence of both prephenate and the alternative substrate, 1-carboxy-4-hydroxy-2-cyclohexene-1-propanoate, have been determined. In addition, investigations have been made of the effect of tyrosine on the inhibition of the reaction by the inhibitory analogues of prephenate, (4-hydroxyphenyl)pyruvate, and (carboxyethyl)-1,4-dihydrobenzoate. The results of the double inhibition experiments indicate clearly that the enzyme possesses a distinct allosteric site for the binding of tyrosine. The initial velocity data obtained with both substrates have been fitted to the rate equations that describe a wide range of models. From a comparison of the results obtained from studies with the two substrates, and with a knowledge of the value for the dissociation constant of the tyrosine-enzyme complex, definitive conclusions have been reached about the mechanism of the allosteric inhibition. It is concluded that tyrosine combines twice at allosteric sites and in an antisynergistic fashion, while prephenate reacts at both active sites of the dimeric enzyme as well as weakly at one of the allosteric sites. It appears that the latter is simple competition reaction that affects neither the binding of prephenate at the active site nor the rate of product formation. The model also predicts the formation of an active tyrosine-enzyme-prephenate complex that yields product at a much slower rate than does the enzyme-prephenate complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Allosteric Regulation

Etiologic factors for unitemporal vs bitemporal epileptiform discharges.

We compared the etiologic factors and clinical characteristics of 30 patients with unitemporal vs those of 30 patients with bitemporal independent (minimum 20% from one side) interictal epileptiform discharges on extracranial electroencephalograms. Febrile seizures occurred significantly more frequently in the unitemporal (40%) than in the bitemporal (17%) group. Mass lesions were more common in the bitemporal group, and seven of 10 patients with mass lesions showed bitemporal interictal epileptiform discharges. There were no statistically significant differences in age at onset, frequency of seizures, duration of epilepsy, and history of central nervous system infection or trauma between the two groups. A history of febrile seizures or central nervous system infection that may be expected to cause diffuse cerebral injury does not appear to be the major factor predisposing to the development of bitemporal interictal epileptiform discharges.

Adolescent

Outcome of psychogenic seizures in children and adolescents compared with adults.

We compared outcome of psychogenic seizures documented by video-EEG in 18 nonepileptic children and adolescents (ages 8 to 18; median, 14.5 years old) and 20 adults (ages 25 to 56; median, 34.0 years old). Outcome was significantly better for the younger patients at 1 year, 2 years, and 3 years after diagnosis. At these follow-up times, the percentages of children and adolescents free of psychogenic attacks were 73%, 75%, and 81%; at the same follow-up times, the percentages of adults free of psychogenic attacks were only 25%, 25%, and 40%. Factors leading to better outcome for younger patients may have been different psychological mechanisms at different ages of onset and greater effectiveness with earlier intervention.

Adolescent

Chorismate mutase-prephenate dehydrogenase from Escherichia coli. 1. Kinetic characterization of the dehydrogenase reaction by use of alternative substrates.

The bifunctional enzyme involved in tyrosine biosynthesis, chorismate mutase-prephenate dehydrogenase, has been isolated from extracts of a plasmid-containing strain of Escherichia coli K12 and purified to homogeneity by a modified procedure that involves chromatography on both Matrex Blue A and Sepharose-AMP. Detailed studies of the dehydrogenase reaction have been undertaken with analogues of prephenate that act as substrates. The analogues, which included two of the four possible diastereoisomers of 1-carboxy-4-hydroxy-2-cyclohexene-1-propanoate (deoxodihydroprephenate) as well as D- and L-arogenate, were synthesized chemically. As judged by their V/K values, all analogues were poorer substrates than prephenate. The order of their effectiveness as substrates is prephenate greater than one isomer of 1-carboxy-4-hydroxy-2-cyclohexene-1-propanoate greater than L-arogenate greater than other isomer of 1-carboxy-4-hydroxy-2-cyclohexene-1-propanoate greater than D-arogenate. Thus the dehydrogenase activity is dependent on the degree and position of unsaturation in the ring structure of prephenate as well as on the type of substitution on the pyruvyl side chain. With prephenate as a substrate, the reaction is irreversible because it involves oxidative decarboxylation. By contrast, 1-carboxy-4-hydroxy-2-cyclohexene-1-propanoate undergoes only a simple oxidation, and thus, with this substrate, the reaction is reversible. Steady-state velocity data, obtained by varying substrates over a range of higher concentrations, suggest that the dehydrogenase reaction conforms to a rapid equilibrium, random mechanism with 1-carboxy-4-hydroxy-2-cyclohexene-1-propanoate as a substrate in the forward reaction or with the corresponding ketone derivative as a substrate in the reverse direction. The initial velocity patterns obtained by varying prephenate or 1-carboxy-4-hydroxy-2-cyclohexene-1-propanoate over a range of lower concentrations, at different fixed concentrations of NAD, were nonlinear and consistent with a unique model that is described by a velocity equation which is the ratio of quadratic polynomials. An equilibrium constant of 1.4 x 10(-7) M for the reaction in the presence of 1-carboxy-4-hydroxy-2-cyclohexene-1-propanoate indicates that the equilibrium lies very much in favor of ketone production.

Bacterial Proteins

Chorismate mutase-prephenate dehydrogenase from Escherichia coli. 2. Evidence for two different active sites.

The inhibition of the bifunctional enzyme chorismate mutase-prephenate dehydrogenase by substrate analogues, by the end product, tyrosine, and by the protein modifying agent iodoacetate has been investigated. The purpose of the investigations was to determine if the two reactions catalyzed by the enzyme occur at a single active site or at two separate active sites. Evidence in support of the conclusion that the mutase and dehydrogenase reactions are catalyzed at two similar but distinct active sites comes from the following results: (1) A substrate analogue (endo-oxabicyclic diacid) that inhibits competitively the mutase reaction has no effect on the dehydrogenase reaction. (2) Malonic acid and several of its derivatives act as inhibitory analogues of chorismate in the mutase reaction and of prephenate in the dehydrogenase reaction. However, different dissociation constants for their interaction with the free enzyme are obtained from studies on the mutase and dehydrogenase reactions. (3) The kinetics of the inhibition by tyrosine of the mutase reaction in the presence of NAD differ from those of the dehydrogenase reaction. The results confirm that carboxymethylation with iodoacetate of one cysteine residue per subunit eliminates both mutase and dehydrogenase activities and show that the inactivation of the enzyme activities is due to iodoacetate functioning as an active site directed inhibitor.

Bacterial Proteins

Turn it around: short-term management for aggression and anger.

1. Although nurses are at considerable risk for assaults, there are few practical and specific guidelines for controlling anger and aggression. 2. A training course was developed to give staff the necessary skills and knowledge to cope with clients who have the potential to become angry and assaultive, or those who have already become violent. 3. Participants in the training course felt more confident in managing potentially violent situations, and they reported relying on methods to de-escalate the situation to halt a sequence that would ultimately lead to violence.

Aggression

Phorbol ester-induced synaptic facilitation is different than long-term potentiation.

The studies described here tested the hypothesis that the changes in synaptic efficacy produced by phorbol esters in hippocampal slices are equivalent to the long-term potentiation (LTP) induced by high-frequency stimulation. In contrast to the extremely stable synaptic potentiation induced by electrical stimulation, the facilitatory effects of phorbol 12,13-diacetate and phorbol 12,13-dibutyrate were transient: washout of the drugs restored normal responses in approximately 1-2 and 2-4 hr for phorbol diacetate and phorbol dibutyrate, respectively. It is noteworthy that the more liposoluble of the phorbol esters required longer washout periods. Robust LTP still occurred in response to high-frequency stimulation after washout of phorbol esters and to a lesser degree during their application. Treatment of slices with H-7, an inhibitor of protein kinase C, did not prevent LTP induction although it significantly affected neuronal excitability and produced effects opposite to those of phorbol esters. Finally, phorbol esters altered responses to repetitive stimulation in a way that could account for the reduced LTP elicited in their presence. These results indicate that the increases in synaptic responses caused by phorbol esters and high-frequency electrical stimulation are quite different and thus do not support the hypothesis that activation of protein kinase C, the presumed target of the phorbol esters, triggers LTP.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Anger control.

Anger is a poorly understood but very common emotion. When it is misdirected or uncontrolled it becomes dangerous. An analysis of anger and a treatment paradigm is presented, and we outline a research project in which we are using the approach with a group of mentally handicapped adults.

Aggression

Speculations on disease states induced by excitatory amino acids.

There is much current interest in excitatory amino acids and their receptors because of their postulated involvement in several disorders of the nervous system. They function as neurotransmitters, but can act as neurotoxins in some situations. They have been implicated in the pathogenesis of cerebral hypoxic/ischemic and hypoglycemic damage, in epilepsy, in some degenerative diseases, and in some forms of neurotoxin-induced cerebral dysfunction. These diseases may reflect abnormality in a system which has evolved to provide synaptic plasticity essential for learning and memory. The purpose of this paper is to explore the ramifications of such a hypothesis.

Amino Acids

Psychotherapy for bulimia: a controlled study.

A psychotherapy study for bulimia is described. The preliminary results of a random allocation control trial comparing cognitive behaviour therapy, behaviour therapy and group psychotherapy with a waiting list control are presented. The results of the first 60 subjects in active treatment are shown. They indicate that all three treatments are effective in dramatically reducing the behavioural symptoms of the bulimia syndrome. There is evidence that cognitive therapy has a greater effect on symptoms of depression and self-esteem. No evidence is yet available on the longterm outcome of the three treatments.

Adolescent