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Biomedical subjects

C J Wallace

Publications and source records attributed to C J Wallace.

At least 127 records · Page 7Linked to original sources

The semisynthesis of analogues of cytochrome c. Modifications of arginine residues 38 and 91.

The arginine residues at positions 38 and 91 of horse cytochrome c are absolutely conserved throughout eukaryotic evolution. For studies of the functional roles of these residues, we have prepared, by semisynthetic techniques, analogues of cytochrome c in which one or the other of the arginine residues has been modified. The products of modification by adduct formation with pentane-2,4-dione were purified and extensively characterized. In biological tests, the arginine-91-modified cytochrome c showed little difference in behaviour from native horse cytochrome c. Modification of arginine-38, however, led to extensive changes in biological and chemical properties. We also prepared and tested adducts with cyclohexane-1,2-dione and camphorquinone-10-sulphonic acid. The same effects on biological properties were noted irrespective of the nature of the modifying group. We suggest reasons for the differences in sensitivity of the two sites.

Amino Acids↗

Ionization of tyrosine and lysine residues in native and modified horse cytochrome c.

1H-n.m.r. and 13C-n.m.r. spectroscopy of horse cytochrome c and 1H-n.m.r. spectroscopy of the lysine-modified proteins N epsilon-acetimidyl-, N epsilon-amidino-, N epsilon-trifluoroacetyl- and N epsilon-maleyl-cytochrome c have shown that, although the lysine modifications do not greatly perturb the protein structure at pH7 and 27 degrees C, at higher temperature or at alkaline pH some parts of the structure are markedly perturbed. At pH7 and 27 degrees C the region of the protein about Ile-57 is affected in all the modified proteins, though not all to the same degree. N epsilon-Maleylation most seriously affects the protein structure, and the fully maleylated protein is readily unfolded. At 27 degrees C all four of the tyrosine residues of native horse cytochrome c have pKa values above 11, but in N epsilon-acetimidyl-cytochrome c the pKa of one tyrosine residue is 10.2.

Animals↗

The incidence of minor physical anomalies in adult male schizophrenics.

The Waldrop anomaly score was used to assess the incidence of minor physical anomalies among 40 adult male Caucasian schizophrenics. This sample had a higher group mean anomaly score than that reported for the normal population (p less than .001). Those with higher anomaly scores evidenced poorer premorbid adjustment (p less than .05). A significant relationship also existed between anomaly scores and the subset of premorbid adjustment, Wechsler Adult Intelligence Scale Vocabulary scores, and the Neurological Impairment Index (p less than .05). These results suggest that first trimester developmental abnormalities, as reflected by the high incidence of anomalies, may parallel some form of central nervous system disturbance which may, in some cases, predispose toward the eventual development of schizophrenia. Implications of these findings, along with suggestions for further research, are considered.

Adult↗

Structural studies of eukaryotic cytochrome c modified at methionine-65.

1H n.m.r. spectra were recorded in both oxidation states for the following species: tuna cytochrome c, tuna [carboxymethylmethionine-65]cytochrome c, horse cytochrome c and horse [homoserine-65]cytochrome c. The experiments give the assignments of the singlet methyl resonances of methionine-65 and the N-terminal acetyl group. The modification at methionine-65 is shown to cause an extremely small structural perturbation to one part of the molecule close to the site of modification.

Animals↗

A review and critique of social skills training with schizophrenic patients.

The literature dealing with social skills training of schizophrenic patients indicates that topographical features and self-reports of anxiety and discomfort can be changed for the better by social skills training. Unfortunately, these changes do not occur for every patient and, when they do occur, often do not generalize to new situations. Research must be directed to determining the interaction between patient characteristics and training procedures as they affect outcome. The scope of the procedures must also be expanded if meaningful changes in patients' quality of life are to be effected.

Antipsychotic Agents↗

The semisynthesis of fragments corresponding to residues 66-104 of horse heart cytochrome c.

We describe the N epsilon-acetimidylation of horse heart cytochrome c with retention of biological activity, the cleavage of the modified protein by CNBr, the separation of the fragments, and their further side-chain protection. We describe the manipulation of the amino acid sequences of the fragments by stepwise semisynthetic methods. We have prepared fragments corresponding to residues 66-78 and 66-79 of the protein, as well as the [Asp66] analogue of fragment 66-79. We have prepared the natural sequence and the [o-fluoro-Phe82] analogue of the fragment corresponding to residues 81-104 of the protein, and the [N epsilon-trifluoroacetyl-Lys79], the [N epsilon-dinitrophenyl-Lys79] and the [S-acetamidomethyl-Cys79] analogues of fragment 79-104, and the [N epsilon-Cbz-Lys81] analogue of fragment 80-104. We have coupled back the fragments of natural sequence to form a semisynthetic fragment corresponding to residues 66-104 of the protein. Modified fragments were also coupled to give analogues of the 66-104-residue sequence. In every case the homoserine residue representing methionine-80 was removed from the C-terminus of the 66-80-residue fragment and replaced by methionine on the N-terminus of the 81-104 residue fragment during the preparation of the fragments for coupling. The semisynthetic fragments are ready for specific deprotection and further coupling. We have coupled one such fragment to the (1-65)-peptide to produce semisynthetic [Hse65]cytochrome c. The product has satisfactory characteristics on chemical analysis, and on assay of its biological activity.

Amino Acid Sequence↗

Behavioral observations before, during, and after brief isolation (time-out).

Four adult, chronic psychotic inpatients were observed before, during and after the contingent application of time-out. Time-out was a part of their individual treatment programs, and consisted of placement in a furnitureless room for 15 minutes. Observations were made of 16 behaviors grouped into seven categories; these categories included both consequated and nonconsequated behaviors. Observation sessions lasted for 15 minutes with interval recording of each behavior for the first 10 seconds of every 30-second block. Results for each subject were analyzed by means of three-way factorial ANOVAs, and indicated the following: a) three subjects exhibited significant differences in response frequency before, during, and after time-out that were consistent across all instances of their being placed in time-out; b) the particular behaviors that reliably varied with the observation conditions for one subject were not the same as those which reliably varied for another subject; c) two subjects significantly increased the frequency of their consequated responses during time-out in spite of the fact that time-out was effective as measured by a significantly lower emission rate after time-out compared to before time-out.

Adult↗

Generalization of behaviour therapy with psychotics.

Generalization of improvement in the behavioural treatment of psychotic patients must be planned in after-care settings, and for durability over time. The transfer of clinical gains is not an automatic by-product of treatment with severely and chronically impaired mental patients. Treatment strategies that facilitate generalization from hospital to community are illustrated in a case study using empirical data. Systematic and specific treatment programmes were co-ordinated between a state hospital ward and a community-based day hospital. Setting step-wise and limited goals is a feature of successful outcomes. Maintaining consistency in reinforcement contingencies from hospital to community settings, using natural reinforcers, pinpointing functional behaviours as therapeutic goals, over-learning, and training natural caregivers are methods that promote generalization.

Activities of Daily Living↗

Marital therapy in groups. A comparative evaluation of behavioral and interactional formats.

A comparative evaluation was conducted in a community mental health center between two types of brief, marital therapy in groups. The experimental group of four couples was exposed to behavioral methods based on social learning principles. The primary interventions were (1) training the spouses in discriminating and monitoring the occurrence of pleasing events and behaviors; (2) behavioral rehearsal of communication skills using prompting, modelling, feedback, and "homework" assignments; and (3) contingency contracting. The comparison group of five couples was led in an interactional format with the leaders encouraging ventilation of feelings, problem-solving through discussion, and mutual support and feedback. Both groups were led by the same three clinicians. Outcome was measured on multiple levels before, during and immediately after treatment. Follow-up assessments were conducted at one, two, and six months after treatment. Response measures included the self report by clients on marital satisfaction; on consumer satisfaction with the treatment experience; on their observations of pleasing behaviors given and received as recorded on wrist counters; and direct observation of client via "live" time-sampling and coding of videotapes of problem-solving discussions before and after treatment. Results showed few differences between groups on the self-report measures; however, there were significant improvements by both groups on these measures after treatment which were maintained into the follow-up evaluation. The direct observational data indicated that the members in the behavioral group displayed significantly more positive and mutually supportive verbal and nonverbal behaviors in their interaction as a result of treatment.

Behavior Therapy↗

It's the staff that keeps the patients talking.

This article is a critical look at the ingredients necessary to encourage chronic psychiatric patients to speak in a group setting. This study suggests that those chronically hospitalized patients with little speech can be encouraged to increase their verbalizations. Staff presence was the critical factor in the increase of patient speech. The opportunity to gain unusual privileges did not substantially increase the patient speech. In essence, this study indicates that as the amount of conversation from the nursing staff increases, a corresponding increase in patient verbalization occurs.

Chronic Disease↗