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Biomedical subjects

M Johnston

Publications and source records attributed to M Johnston.

At least 289 records · Page 16Linked to original sources
PubMed1980

Relationship between pre-operative anxiety and post-operative state.

Janis (1958) has proposed a curvilinear relationship pre-operative anxiety and post-operative emotional state. While other hypotheses share the prediction of a poor outcome for patients with pre-operative high anxiety, Janis' theory is unique in predicting a poor outcome for those with low anxiety. Subsequent research has failed to confirm Janis' hypotheses, perhaps because the designs have been insensitive to the predictions for low anxiety patients. The current study tests the hypothesis more directly and finds some support for a linear relationship between pre-operative anxiety and post-operative negative affect, with no support for Janis' curvilinear hypothesis. On the whole, pre-operative anxiety was a poor predictor of other measures of recovery but, on one measure, patients with low anxiety showed a slower recovery than those with moderate anxiety, i.e. supporting the prediction of a poor outcome for low anxiety patients. The implications of these results for pre-operative preparation of surgical patients and the development of theories of anxiety are discussed.

Adult↗
PubMed1979

Suicide inactivation of bacterial cystathionine gamma-synthase and methionine gamma-lyase during processing of L-propargylglycine.

L-Propargylglycine, a naturally occurring gamma, delta-acetylenic alpha-amino acid, induces mechanism-based inactivation of two pyridoxal phosphate dependent enzymes of methionine metabolism: (1) cystathionine gamma-synthease, which catalyzes a gamma-replacement reaction in methionine biosynthesis, and (2) methionine gamma-lyase, which catalyzes a gamma-elimination reaction in methionine breakdown. Biphasic pseudo-first-order inactivation kinetics were observed for both enzymes. Complete inactivation is achieved with a minimum molar ratio ([propargylglycine]/[enzyme monomer]) of 4:1 for cystathionine gamma-synthase and of 8:1 for methionine gamma-lyase, consistent with a small number of turnovers per inactivation event. Partitioning ratios were determined directly from observed primary kinetic isotope effects. [alpha-2H]Propargylglycine displays kH/kD values of about 3 on inactivation half-times. [alpha-3H]-Propargylglycine gives release of tritium to solvent nominally stoichiometric with inactivation but, on correction for the calculated tritium isotope discrimination, partition ratios of four and six turnovers per monomer inactivated are indicated for cystathionine gamma-synthase and methionine gamma-lyase, respectively. The inactivation stoichiometry, using [alpha-14C]-propargylglycine, is four labels per tetramer of cystathionine gamma-synthase but usually only two labels per tetramer of methionine gamma-lyase (half-of-the-sites reactivity). Two-dimensional urea isoelectrofocusing/NaDodSO4 electrophoresis suggests (1) that both native enzymes are alpha 2 beta 2 tetramers where the subunits are distinguishable by charge but not by size and (2) that, while each subunit of a cystathionine gamma-synthase tetramer becomes modified by propargylglycine, only one alpha and one beta subunit may be labeled in an inactive alpha 2 beta 2 tetramer of methionine gamma-lyase. Steady-state spectroscopic analyses during inactivation indicated that modified cystathionine gamma-synthase may reprotonate C2 of the enzyme--inactivator adduct, so that the cofactor is still in the pyridoxaldimine oxidation state. Fully inactivated methionine gamma-lyase has lambda max values at 460 and 495 nm, which may represent conjugated pyridoximine paraquinoid that does not reprotonate at C2 of the bound adduct. Either species could arise from Michael-type addition of an enzymic nucleophile to an electrophilic 3,4-allenic paraquinoid intermediate, generated initially by propargylic rearrangement upon a 4,5-acetylenic pyridoximine structure, as originally proposed for propargylglycine inactivation of gamma-cystathionase [Abeles, R., & Walsh, C. (1973) J. Am. Chem. Soc. 95, 6124]. It is reasonable that cystathionine gamma-synthase is the major in vivo target for this natural acetylenic toxin, the growth-inhibitory effects of which are reversed by methionine.

Alkynes↗
PubMed1979

Mechanistic studies with vinylglycine and beta-haloaminobutyrates as substrates for cystathionine gamma-synthetase from Salmonella typhimurium.

Cystathionine gamma-synthetase (EC 4.2.99.9), a key enzyme in bacterial methionoine biosynthesis, has been found to use L-vinylglycine (2-amino-3-butenoate) and L-beta-haloaminobutyrates (X = F, Cl) as substrates in addition to the physiological gamma-substituted substrate O-succinyl-L-homoserine (OSHS). Vinylglycine is a substrate both for alpha-ketobutyrate formation (the normal product from gamma elimination with OSHS) and for cystathionine formation (the normal gamma-replacement product with OSHS) in the presence of cysteine. This behavior substantiates that the stabilized vinylglycine--pyridoxal phosphate (PLP) alpha carbanion is the key partitioning species in this enzyme's catalysis. The Vmax values for ketobutyrate production and cystathonine formation from vinylglycine are equivalent at approximately 45 U/mg, whereas the corresponding Vmax values from OSHS are 20 and 200 U/mg, respectively, suggesting different rate-determining steps with these two substrates. The beta-haloaminobutyrates undergo catalyzed HX elimination to yield bound aminocrotonate--PLP directly as a an initial intermediate and as a precursor of ketobutyrate. Little or no cystathionine formation is detectable when these substrates are incubated with enzyme and the normal cosubstrate cysteine, strongly indicating that the aminocrotonate--PLP intermediate is not in rapid, reversible equilibrium with the stabilized vinylglycine--PLP carbanion; in normal catalysis, the prototropic shift from alpha carbanion to aminocrotonate appears functionally unidirectional. The HX-elimination step from beta-chloroaminobutyrate is nonconcerted as demonstrated by a 3H2O in equilibrium chloroaminobutyrate exchange reaction. Further suggestion for discrete beta-halo-alpha-carbanionic intermediates derives from the observation that the haloaminobutyrates appear to a partition between ketobutyrate formation and enzyme inactivation. Since neither vinylglycine nor OSHS causes any detectable inactivation during turnover, it is likely that the inactivation species is not a common intermediate, i.e., the electrophilic aminocrotonate--PLP species (a potential Michael acceptor), but rather a species peculiar to the beta-haloaminobutyrate pathway. The beta-halo-alpha-carbanion--PLP intermediate has beta-halo-alpha-iminodihydropyridine character in the p-quinoid resonance contributor and is a good candidate for an alkylating agent by an SN2--displacement mechanism. Spectroscopic analyses of incubations with the various amino acid substrates show a number of long-wavelength absorbing species forming during turnover, tentative assignments are suggested.

Aminobutyrates↗
PubMed1979

Clinical and laboratory diagnosis of hemostatic disorders in newborn infants.

We describe a microtechnology for the study of the coagulation system in newborn infants. Interpretation of results demands an understanding of the techniques used and the nature of the control population from which normal values are drawn. We have examined two syndromes which represent the majority of hemostatic disorders of sick newborn infants. The first is thrombocytopenia resulting from bacterial infections in which there are minimal changes in the levels of blood coagulation factors and little tendency to bleed. The second is a syndrome of disseminated intravascular coagulation in which there is a profound disturbance in the coagulation mechanism, relatively little change in platelet counts, a severe hemorrhagic diathesis, and widespread ischemic necrosis.

Bacterial Infections↗
PubMed1978

The work of a clinical psychologist in primary care.

The data presented suggest that general practitioners would be likely to refer a large number of patients with diverse problems to clinical psychologists working in health centres. Compared with a centrally organized clinical psychology service, the work of the primary care psychologist is likely to offer the following advantages:1. Access to psychological help for patients with a need for such help, but who could not attend a central clinic owing to problems associated with travel, work, physical disability, or even a presenting problem such as agoraphobia.2. Greater continuity of care of patients.3. Increased communication between the psychologist and members of the primary care teams.4. Possibility of the psychologist seeing the patient earlier, before the problems have become entrenched.5. Less need for referral to other agencies.6. Reduced stigma for the patient.7. Development of new therapeutic approaches relevant to problems presenting in primary care.8. More flexible and more relevant therapy due to seeing the patients in their home setting.9. Greater therapeutic involvement of the patient's family.10. Reduced costs and inconvenience for the patient's family.11. Reduced administrative and ambulance service costs.While these points do not overcome the need for a formal evaluation of the work of psychologists in primary care, they do suggest that there are advantages in this type of service over the services which are currently available and that a full evaluation would be worth undertaking.

Adolescent↗
PubMed1976

Responsiveness of delinquents and non-delinquents to social reinforcement.

A series of six experiments, involving 198 subjects, examined the hypothesis that delinquents are less responsive than non-delinquents to social reinforcement and punishment. The hypothesis received support (a) using two different experimental techniques, one in which the subjects' judgements of autokinetic movement were modified and one using the Taffel (1955) verbal conditioning paradigm; (b) with the female adult administering the reinforcement and with a peer; (c) when the contingent social cues were rewarding (Good or Fine) and when they were punishing ('No'). The hypothesis was not supported when the verbal reinforcement was varied. Control studies using no reinforcement and money reinforcement indicated that the social reinforcement did indeed have a specific reinforcement effect and that delinquents did not show a general learning deficiency.

Adolescent↗
PubMed1976

Disability: a model and measurement technique.

Current methods of ranking or scoring disability tend to be arbitrary. A new method is put forward on the hypothesis that disability progresses in regular, cumulative patterns. A model of disability is defined and tested with the use of Guttman scale analysis. Its validity is indicated on data from a survey in the community and from postsurgical patients, and some factors involved in scale variation are identified. The model provides a simple measurement technique and has implications for the assessment of individual disadvantage, for the prediction of progress in recovery or deterioration, and for evaluation of the outcome of treatment regimes.

Activities of Daily Living↗
PubMed1975

Pepstatin, an inhibitor of leukokinin formation and ascitic fluid accumulation.

Ascites fluid accumulation accompanying a mastocytoma or L1210 murine tumor is significantly retarded following the i.p. or s.c. injection of moderate quantities of pepstatin, a known acid protease inhibitor. No effect on cell count was noted by pepstatin treatment. The probable mechanism by which pepstatin acts is by inhigiting the enzymatic formation of chemical mediators known as leukokinins. These are pharmoacologically active peptiedes having potent permeability characteristics previously described by this laboratory. Leukokinins are formed by cathepsin D-like enzymes present in the invading cells and in the ascites fluid acting on a protein substrate, leukokininogen. present in the ascites fluid. Pestatin inhibits the action of these leukokinin-forming enzymes invitro but has no effect on kallikreins (bradykinin-forming enzymes) in vitro. Human ascites fluid from a patient with ovarian carcioma was found to have a paepstatin-inhibited, leukokinin-generating system, as does the mouse. A 'chemical mediator' theory is proposed for ascites fromation which broadens the previously held theory of lymphatic blockage (Holm-Nielsen) and may explain the recent findings of Hirabayashi and Graham of increased plasma-ascites exchange in peritoneal carcionmatosis. Pepstatin inhibition of chemical mediator formation may represent a new therapeutic approach to ascites fluid accumulation in neoplastic disease.

Animals↗