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Biomedical subjects

C J Wallace

Publications and source records attributed to C J Wallace.

At least 109 records · Page 6Linked to original sources
PubMed1987

Multiple T cell antigenic determinants identified within a limited region of the horse cytochrome c molecule.

The antigen fine specificity of T cell hybridomas recognizing the horse apocytochrome c fragment 1-65, restricted to the I-Ab molecule, was determined to gain some insight into the molecular nature of T cell antigenic peptides. Two major groups of clones specific for distinct subsites, namely residues 1-38 and 39-65, could be identified. Hybridomas recognizing the latter determinant were further tested with different horse cytochrome c peptides and analogues. This analysis revealed the presence of at least two epitopes encompassed by residues 47-53 and 48-53. Furthermore, clones specific for the amino acid sequence 48-53 showed considerable heterogeneity in respect to the antigen concentration required to obtain 50% of the maximal interleukin 2 secretion. Most prominent was the heteroclitic response towards tuna cytochrome c which differs at positions 44, 46 and 47 from the horse cytochrome c molecule in the relevant region. Comparison of the conformation of the sequence 43-46 between the two cytochrome c suggests that this segment, which forms a 3(10) bend, may be important in maintaining the proper structure of the antigenic determinant. Moreover, the variations up to 180-fold in the concentrations of the cross-reacting cytochrome c and peptides required for stimulation were not always correlated with the maximal interleukin 2 secretion they induced. This indicates that the biological response, that is supposed to be an indication of the affinity of the T cell receptor for its ligand, is not necessarily a function of the antigen concentration.

Amino Acid Sequence↗
PubMed1986

A new non-covalent complex of semisynthetically modified tryptic fragments of cytochrome c.

We have prepared a semisynthetic analogue of fully acetimidylated horse cytochrome c, a complex in which the peptide bond between residues glycine-37 and arginine-38 is lacking. In contrast with the complex that we have previously described [Harris & Offord (1977) Biochem. J. 161, 12-25], in which the break in continuity is between residues arginine-38 and lysine-39, the new analogue has a nearly normal redox potential, and can more fully restore succinate oxidation to mitochondria depleted of cytochrome c. Studies of this and other analogues lead us to propose an explanation for the low biological activity of complex (1-38)-(39-104) and a role for the invariance of arginine-38.

Cytochrome c Group↗
PubMed1986

The oxidation-state-dependent ATP-binding site of cytochrome c. A possible physiological significance.

Cytochrome c binds certain physiological anions that are known to modulate the biological properties of the protein, although it is not known whether this effect is fortuitous or has physiological significance. We have examined the ability of the protein and its semisynthetic analogues to associate with certain of these anions, e.g. ATP, ADP, Pi and citrate. Our results show that specific residues or clusters of residues on the surface of horse heart cytochrome c are involved in the recognition sites for these anions. We also observed that binding at one site is linked to the oxidation state of the protein.

Adenosine Triphosphate↗
PubMed1986

Premorbid adjustment in adult male schizophrenics, as related to process vs. reactive, chronic vs. acute, age of onset, and neurologically impaired vs. non-impaired.

This study assessed premorbid functioning in 40 male, Caucasian schizophrenics, on the abbreviated Phillips Premorbid Adjustment Scale. Subjects with poorer premorbid adjustment tended to be process rather than reactive (p less than .01), early in age of onset (p less than .01), and neurologically impaired (p less than .01). Neurological impairment as a predisposing factor in early social incompetence was suggested after it was found that the subset of process vs. reactive, age of onset, and neurological impairment accounted for 46% of the variance in Phillips scores.

Acute Disease↗
PubMed1986

A holistic program for chronic schizophrenic patients.

A 10-week, inhospital holistic health program for male schizophrenic patients was compared with an equally intense social skills training program. The holistic program included training in the stress reduction techniques of exercise and meditation as well as education in stress management. Patients were also encouraged to explore the growth potential of their psychotic experiences and to develop positive beliefs about the outcome of their illness. Both groups showed similar significant decreases in psychopathology from admission to discharge, but the use of medication and a token economy milieu by all patients confounds the interpretability of this finding. After the holistic patients were discharged into the community, there was no maintenance of any of the holistic techniques. The 2-year relapse rate did not differ significantly between the two treatments. Findings from various studies associating schizophrenic relapse with stressful life events and familial tension make further experimentation with stress reduction techniques for the treatment of schizophrenia worthwhile.

Attitude↗
PubMed1986

Functional assessment in rehabilitation.

The instruments that assess the functional living skills of chronically mentally ill individuals are reviewed. The instruments range from those that provide relatively global assessments of major life roles such as wage earner and student, to those that provide relatively specific assessments of behaviors such as personal hygiene and money management skills. The content, format, psychometric characteristics, advantages, and disadvantages of each instrument are presented in detail so that the reader can select the instrument that best suits the purposes of the assessment.

Activities of Daily Living↗
PubMed1986

Training skills in the psychiatrically disabled: learning coping and competence.

Social skills training methods represent a major strategy for psychiatric rehabilitation. Building skills in patients with schizophrenic and other major mental disorders is based on the assumption that coping and competence can override stress and vulnerability in reducing relapses and improving psychosocial functioning. For maximum efficiency, skills training needs to incorporate procedures and principles of human learning and information processing. Several models for skills training have been designed and evaluated, each of which has proved to be effective in raising the social competence of chronic mental patients. The "basic" model involves role playing by the patient and modeling, prompting, feedback, and reinforcement by the therapist. A "problem-solving" model of training provides general strategies for dealing with a wide variety of social situations. This model uses role playing to enhance behavioral performance but also highlights the patient's abilities to perceive and process incoming social messages and meanings. It is essential that social skills training be imbedded in a comprehensive program of rehabilitation that features continuity of care, supportive community services, therapeutic relationships, and judicious prescription of psychotropic drugs.

Activities of Daily Living↗
PubMed1986

Social skills training for schizophrenic individuals at risk for relapse.

Two studies were conducted to evaluate the clinical efficacy of intensive social skills training in medicated schizophrenic inpatients at risk for relapse. In study 1, three patients were treated; two showed reductions in psychopathology and rehospitalization and improved social functioning 9 months following discharge. In study 2, social skills training was compared with holistic health treatment in 28 patients. Both groups showed reduced psychopathology 2 years after discharge; patients treated with social skills training had better social functioning, spent less time hospitalized, and had fewer symptomatic relapses. The results support the utility of social skills training as a psychosocial treatment for schizophrenia.

Adult↗
PubMed1985

Social skills training for patients with schizophrenia: a controlled clinical trial.

Twenty-eight schizophrenic male patients, diagnosed by the Present State Examination and Catego criteria, and from families high on "expressed emotion," were randomly assigned to either intensive social skills training or holistic health therapy. A multidimensional evaluation was conducted before and after 9 weeks of inpatient treatment and for 24 months in the community. Patients exposed to social skills training evidenced significantly greater acquisition, generalization, and durability of social skills; their social adjustment in the community was rated as better by significant others; and they experienced fewer relapses and rehospitalizations.

Adaptation, Psychological↗
PubMed1984

A case of spurious product formation during attempted resynthesis of proteins by reverse proteolysis. Some batches of 'pure' glycerol contain cross-linking agents.

In cases where enzyme-catalysed synthesis of a peptide bond is being used to re-form a protein from two large peptide fragments, the organic co-solvent chosen has so far been glycerol, for most solvents in use in small-molecule systems are potent protein denaturants. We have found, however, that impurities contaminating certain batches of glycerol are effective in cross-linking the complexes formed by these peptide fragments, thus mimicking the enzyme-catalysed process. In one such case, the reported re-formation of cytochrome c from a two-fragment complex system, cytochrome c-T, the extent and rate of conjugate formation duplicates that reported for enzymic resynthesis. We observed no difference between mixtures containing or lacking enzyme. We warn of the danger of confusion possible to those engaged in studies of resynthesis, and suggest a simple control of purchased glycerol to avoid it. We recommend similar caution to those (X-ray crystallographers and others) who seek to stabilize protein solutions by adding large quantities of glycerol.

Amino Acids↗
PubMed1984

The preparation of fully N-epsilon-acetimidylated cytochrome c.

We have re-examined the acetimidylation and subsequent deprotection of cytochrome c by published methods in the light of recent findings on the tendency of protein acetimidylation reactions to yield side products of differing net charges. We find that the protection methods do indeed yield a mixture of products, some of which have considerably diminished biological activity. Our observations support a postulated mechanism for the generation of side products, and we have been able to identify the major factor responsible for their formation by published methods. The deprotection method appears to be free of side reactions. We describe a new procedure for acetimidylation that will produce fully N-epsilon-acetimidylated cytochrome c. This derivative, lacking detectable side products and having good biological activity, is useful for structure-function studies and as an intermediate in the semisynthesis of cytochrome c analogues.

Chemical Phenomena↗
PubMed1984

The effect of complete or specific partial acetimidylation on the biological properties of cytochrome c and cytochrome c-T.

The biological consequences of acetimidylation of all 19 epsilon-amino groups of horse cytochrome c are a slight decrease in both the redox potential of the protein and its ability to stimulate oxygen uptake in the cytochrome c-depleted-mitochondria assay. Examination of a number of specific partially acetimidylated analogues and acetimidylated cytochromes c of other species has shown that the changes in biological properties, which are associated with a slight structural change as monitored by n.m.r. spectroscopy [Boswell, Moore, Williams, Harris, Wallace, Bocieck & Welti (1983) Biochem. J. 213, 679-686], appear to stem from modification of residues in a restricted region of the sequence. The failure of the redox potential of Saccharomyces cerevisae cytochrome c to be affected by acetimidylation suggests that it is lysine-53, absent from that species, that is the sensitive residue.

Animals↗
PubMed1984

Modulation of the alkaline transition in cytochrome c and cytochrome c-T by full or specific partial acetimidylation.

Acetimidylated horse cytochrome c and related derivatives exhibit more or less marked changes, both upscale and downscale, in apparent pK of the alkaline transition. This transition occurs when the normal methionine-80 residue is replaced at the sixth haem co-ordination position by another strong-field ligand. Analysis of the relationship between structural change and pK shift in these derivatives supports the view that the replacement ligand is a lysine residue, probably 72 or 79, and contradicts an alternative hypothesis. The results add further detail to a comprehensive view of the mechanism of this isomerization.

Alkalies↗
PubMed1984

Community and interpersonal functioning in the course of schizophrenic disorders.

The purpose of this article is to evaluate the role of community and interpersonal functioning in the developmental course and outcome of schizophrenic disorders. Based on a review of the research literature, it appears that certain patterns of poor functioning may be characteristic of at least a subgroup of schizophrenic individuals, predate the onset of the disorder, and predict the outcome of the disorder. Thus, some patterns of poor community and interpersonal functioning may be seen as potential indicators of vulnerability to the development of schizophrenic episodes rather than solely as consequences of schizophrenic psychotic symptoms.

Adolescent↗
PubMed1984

Subjective response to antipsychotic drugs: failure to replicate predictions of outcome.

Twenty male schizophrenic patients were given a test dose of chlorpromazine and their subjective response, graded on a syntonic-dysphoric continuum, was recorded at 4, 24, and 48 hours following the test dose. All patients were subsequently treated with an optimal dose of chlorpromazine or thioridazine plus either social skills training or holistic health therapy for a fixed inpatient period of 10 weeks. Patients were maintained on neuroleptics for a 9-month follow-up period. Subjective response to the test dose was not found to be significantly correlated to any of the outcome measures. This study's failure to replicate previously published findings that subjective response to test doses of neuroleptics predict outcome may stem from differences in patients population, treatment milieu, and compliance with drug regimen.

Adult↗
PubMed1984

Cognitive factors in the social skills of schizophrenic patients: implications for treatment.

This chapter illustrates how changes have occurred in a clinical research program designed to develop and evaluate treatment techniques for improving the social skills of chronic schizophrenic patients. These changes have been primarily in the definition of a socially skilled response; rather than defining such responses solely in terms of motor behaviors, we have attempted to include several cognitive elements hypothesized to be critical aspects of the process of producing an effective social response. The inclusion of these cognitive elements suggests that the findings of experimental psychopathologists about the perceptual, attentional, and information-processing dysfunctions of schizophrenic individuals may be highly relevant to the development of more effective treatment techniques. For example, a patient may make an ineffective social response because of an attentional or perceptual dysfunction that results in inaccurate reception of critical social and situational stimuli. Similarly, an ineffective response may be produced because of an information-processing dysfunction that makes a patient generate a restricted number of alternative and evaluate them incorrectly. If these attentional, perceptual, and information-processing dysfunctions are not simply linked to variations in symptomatology but represent enduring deficiencies, then an effective treatment strategy may require either that these dysfunctions be remedied (if at all possible) or that an environment be created that compensates for them. Of course much more information is needed about the extent to which these dysfunctions might affect performance in the social situations patients commonly face. Certain situations may be relatively simple, requiring attention to only one or two critical stimuli and a response that is well within the social repertoires of most patients. Other situations may be far more complex, requiring a high degree of sustained attention and complex, "subtle" responses that are not within the social repertoires of most patients. For example, anecdotal observations made during the use of the techniques to teach friendship /dating skills suggest that ongoing conversations are particularly difficult for patients. These situations seem to require a high degree of sustained attention to keep track of shifts in topics, detect changes in the partner's emotions, and introduce planned changes in the stream of conversation. Other situations, such as asking for items from nurses, seem relatively simple and can be performed fairly well by patients, even those who are highly symptomatic.(ABSTRACT TRUNCATED AT 400 WORDS)

Assertiveness↗