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Biomedical subjects

C J Wallace

Publications and source records attributed to C J Wallace.

At least 19 recordsLinked to original sources
PubMed2001

Conserved tryptophan in cytochrome c: importance of the unique side-chain features of the indole moiety.

The absolute conservation of tryptophan at position 59 in cytochrome c is related to the unique chemical nature of its indole moiety. The indole side chain of Trp-59 possesses three salient features: bulk, hydrophobicity and the ability of its indole nitrogen to act as a hydrogen-bond donor. Crystallographic evidence identifies the indole nitrogen of Trp-59 as having a stabilizing hydrogen-bonding interaction with the buried carboxylate group of haem propionate 7. Side-chain bulk is also likely to be important because a Phe or Leu residue can replace Trp to give an at least partly functional protein, whereas the smaller Gly or Ser cannot. Semisynthetic analogues were designed to test the importance of the side-chain features of tryptophan by using a recently developed method for stereoselective fragment religation in yeast cytochrome c. Three yeast iso-1 cytochrome c analogues were produced in which Trp-59 was replaced by a non-coded amino acid: p-iodophenylalanine, beta-(3-pyridyl)-alanine or beta-(2-naphthyl)-alanine. Replacement of Trp-59 with these non-coded amino acids allows the reasons for its conservation to be analysed, because they vary with respect to size, hydrophobicity and hydrogen-bond potential. Our results show that decreasing the bulk and hydrophobicity of the side chain at position 59 has a profound but different impact on physicochemical and biological parameters from those of abolishing hydrogen-bond donor potential. This suggests that Trp-59 has both a local and a global stability effect by solvating a buried charge and by having a key role in the packing of the cytochrome c hydrophobic core.

Cytochrome c Group↗
PubMed2001

CASIG: a consumer-centered assessment for planning individualized treatment and evaluating program outcomes.

This paper reports the psychometric characteristics of a measure that assesses the treatment outcomes of individuals with serious and persistent mental illness. Unlike other outcome measures, this one is designed to be embedded in the clinical process of planning and evaluating treatment. It collects individualized data, structures how the data are used to plan and evaluate a client's treatment, and produces aggregate information relevant for research and program purposes. Two parallel versions were developed: one for the client's self-report, and one for an informant's report. The self-report measure was administered by peer-interviewers to 244 community interviewees, and by inpatient peer-interviewers to 93 inpatient interviewees. The community interviewees also completed the BASIS-32 and SF-36. Informants for 103 of the community interviewees completed the informant version of the measure, and the CCAR. Inpatient staff completed the informant version for 161 inpatient residents without regard for matching the 93 inpatient interviewees. The two versions had acceptable internal consistency, test--retest, and interrater reliabilities. Correlations of the community interviewees' and informants' results with the BASIS-32, SF-36, and CCAR provided evidence of convergent and discriminant validity, as did contrasts between community and inpatients interviewees. The usefulness of the instrument for clinical, program and research purposes is discussed, with emphasis on the characteristics that enhance its value in clinical practice --- assessment of meaningful outcomes, operationalization of client empowerment, comprehensiveness, easy administration, and continuity across time and provider. Also discussed is a computer-based program to summarize and present the results in a rapid, clinically meaningful manner.

Activities of Daily Living↗
PubMed2001

Protein matrix and dielectric effect in cytochrome c.

The effect of the protein matrix on the standard potential of a buried redox center has been investigated by using a selection of mutants and chemical derivatives in Saccharomyces cerevisiae cytochrome c isoform 1. Assuming only local structural perturbation and no alteration of the iron-ligation chemistry, Delta E(m)(0)' can be regarded as a measure of the difference in polypeptide solvation of the heme charge, which reflects the dielectric properties of the protein. The evaluation of an apparent dielectric constant (U(exp)/U(theo)) yields variable, and sometimes even negative, values if U(exp) = Delta G(0)redox. However, some consistent result are observed if U(exp) = Delta H(0)redox, with a measured epsilon(Delta Delta)(H)(redox) = 19 +/- 6. The variability is thus attributed to an entropic factor (epsilon(Delta Delta)(S)(redox)) that is investigated using a series of substitutions of Asn(52) and/or Tyr(67). In double mutants Y67F/N52I Y67F/N52V, where most of the hydrogen bond network in the heme crevice is eliminated, Delta S(redox) compares to the wild type. This indicates that a fully consistent hydrogen bond network has a similar polarizability as an apolar matrix. We therefore argue that the variability in net dielectric susceptibility arises from conformational polarizability, a factor that is not a function of atomic properties and coordinates and is therefore hard to predict using conventional physical relationships.

Amino Acid Substitution↗
PubMed2001

ATP induces a conformational change in lipid-bound cytochrome c.

Resonance energy transfer studies using a pyrene-labeled phospholipid derivative 1-palmitoyl-2-[10-(pyren-1-yl)decanoyl]-sn-glycero-3-phosphoglycerol (donor) and the heme (acceptor) of cytochrome c (cyt c) have indicated that ATP causes changes in the conformation of the lipid-bound protein (Rytömaa, M., Mustonen, P., and Kinnunen, P. K. J. (1992) J. Biol. Chem. 267, 22243-22248). Accordingly, after binding cyt c via its so called C-site to neat phosphatidylglycerol liposomes (mole fraction of PG = 1.0) has commenced, further quenching of donor fluorescence is caused by ATP, saturating at 2 mm nucleotide. ATP-induced conformational changes in liposome-associated cyt c could be directly demonstrated by CD in the Soret band region (380-460 nm). The latter data were further supported by time-resolved spectroscopy using the fluorescent cyt c analog with a Zn(2+)-substituted heme moiety. A high affinity ATP-binding site has been demonstrated in cyt c (Craig, D. B., and Wallace, C. J. A. (1993) Protein Sci. 2, 966-976) that is compromised by replacing the invariant Arg(91) to norleucine. Although no major effects on conformation and function of cyt c were concluded due to the modification, a significantly reduced effect by ATP on the lipid-bound [Nle(91)]cyt c was evident, implying that this modulation is mediated via the Arg(91)-containing binding site.

Adenosine Triphosphate↗
PubMed2001

Social functioning and quality of life comparisons between obsessive-compulsive and schizophrenic disorders.

Treatment of obsessive-compulsive disorder has focused almost exclusively on symptom reduction; however, deficits in social functioning and quality of life of individuals with this disorder may contribute more to their "burden," suffering, and disability. To gauge the significance of social dysfunction and quality of life of persons with obsessive-compulsive disorder (OCD), we made comparisons with a group of persons with schizophrenia matched for age and gender. Thirty-one patients with OCD participating in a partial hospital treatment program were compared with 68 schizophrenic outpatients participating in a day rehabilitation program. The Independent Living Skills Survey (ILSS) and Lehman Quality of Life Scale (QOL) were administered before and after treatment for both cohorts. QOL scores were significantly lower for the OCD patients both before and after treatment, but improved significantly during treatment. OCD and schizophrenic patients had similar scores on almost every domain of the ILSS at pretreatment. The OCD patients improved significantly on many of the domains of social and independent living skills as a result of treatment and acquired significantly greater skills by post-treatment than did their counterparts with schizophrenia; however, the performance of social and independent living skills by OCD patients remained less than satisfactory even in domains where they improved. In the areas of job and leisure skills, there were significant group-by-time interactions. We concluded that patients with severe OCD and patients with schizophrenia are equally socially impaired. However, OCD patients experience greater significant functional improvement with multimodal treatment.

Activities of Daily Living↗
PubMed2001

Cortical excitability is not depressed in movement-modulated stretch response of human thumb flexor.

There is strong evidence that the predominant pathway of the long-latency stretch reflex for flexor pollicis longus crosses the motor cortex. This reflex response is diminished during active thumb movements. We tested the hypothesis that this could be due to a decrease in the excitability of the transcortical component during movement. During isometric, concentric and eccentric thumb movements, transcranial magnetic stimulation (TMS) of the motor cortex was given at a time when the reflex signal was traversing the motor cortex. TMS was also given earlier in separate runs when the signal was traversing the spinal cord under each of the three contractile conditions. The electromyogram was analysed for non-linear summation between stretch responses and the potential evoked by the cortical stimulus. The response to TMS alone was uniform across the three types of contraction, and the lack of cortical involvement in the short-latency reflex was confirmed. The TMS-evoked response summed in a non-linear manner with the long-latency reflex response, confirming that the excitability of the motor cortex was increased as the reflex signal passed through it. The long-latency response was markedly depressed during isotonic compared with isometric contractions. However, the non-linear summation was not greater during the isometric contractions. Thus, the depressed reflex responses during isotonic movements do not stem from reduced motor cortical responsiveness or afferent input to the transcortical pathway, and may instead reflect modulation of cutaneous reflexes during isotonic contractions.

Adolescent↗
PubMed2001

Resolving the individual components of a pH-induced conformational change.

This communication introduces a simple method to determine the pKs of microscopic ionizations from complex titration curves. We used this approach to study the alkaline transition (pH-dependent ligand exchange) of mitochondrial cytochrome c. The linearization of titration curves permitted resolution of two to three limiting microscopic ionizations. By combining these data with studies of the temperature dependence of ligand-exchange equilibria, we found evidence that the alkaline transition comprises two chemically distinct processes: the deprotonation of the alternative ligands and the break of the iron-methionine ligation bond. We also noted that, in the horse and untrimethylated S. cerevisiae iso-1 cytochromes c, the permissible deprotonation of the epsilon-amino group of Lys(72) allows formation of an alkaline isomer at lower pH, with lesser stability, which leads to hysteresis in the titration curves. The linearization of the titration curves for different cytochromes c thus brings insight on the microscopic contributions to conformational stability.

Animals↗
PubMed2001

Computerized decision support for mechanical ventilation of trauma induced ARDS: results of a randomized clinical trial.

BACKGROUND: Variability and logistic complexity of mechanical ventilatory support of acute respiratory distress syndrome, and need to standardize care among all clinicians and patients, led University of Utah/LDS Hospital physicians, nurses, and engineers to develop a comprehensive computerized protocol. This bedside decision support system was the basis of a multicenter clinical trial (1993-1998) that showed ability to export a computerized protocol to other sites and improved efficacy with computer- versus physician-directed ventilatory support. The Memorial Hermann Hospital Shock Trauma intensive care unit (ICU) (Houston, TX; a Level I trauma center and teaching affiliate of The University of Texas Houston Medical School) served as one of the 10 trial sites and recruited two thirds of the trauma patients. Results from the trauma patient subgroup at this site are reported to answer three questions: Can a computerized protocol be successfully exported to a trauma ICU? Was ventilator management different between study groups? Was patient outcome affected? METHODS: Sixty-seven trauma patients were randomized at the Memorial Hermann Shock Trauma ICU site. "Protocol" assigned patients had ventilatory support directed by the bedside respiratory therapist using the computerized protocol. "Nonprotocol" patients were managed by physician orders. RESULTS: Of the 67 trauma patients randomized, 33 were protocol (age 40 +/- 3; Injury Severity Score [ISS] 26 +/- 3; 73% blunt) and 34 were nonprotocol (age 38 +/- 2; ISS 25 +/- 2; 76% blunt). For the protocol group, the computerized protocol was used 96% of the time of ventilatory support and 95% of computer-generated instructions were followed by the bedside respiratory therapist. Outcome measures (i.e., survival, ICU length of stay, morbidity, and barotrauma) were not significantly different between groups. Fio2 > or = 0.6 and Pplateau > or = 35 cm H2O exposures were less for the protocol group. CONCLUSION: A computerized protocol for bedside decision support was successfully exported to a trauma center, and effectively standardized mechanical ventilatory support of trauma-induced acute respiratory distress syndrome without adverse effect on patient outcome.

Adult↗
PubMed2001

Contribution of leucine 85 to the structure and function of Saccharomyces cerevisiae iso-1 cytochrome c.

Cytochrome c is a small electron-transport protein whose major role is to transfer electrons between complex III (cytochrome reductase) and complex IV (cytochrome c oxidase) in the inner mitochondrial membrane of eukaryotes. Cytochrome c is used as a model for the examination of protein folding and structure and for the study of biological electron-transport processes. Amongst 96 cytochrome c sequences, residue 85 is generally conserved as either isoleucine or leucine. Spatially, the side chain is associated closely with that of the invariant residue Phe82, and this interaction may be important for optimal cytochrome c activity. The functional role of residue 85 has been examined using six site-directed mutants of Saccharomyces cerevisiae iso-1 cytochrome c, including, for the first time, kinetic data for electron transfer with the principle physiological partners. Results indicate two likely roles for the residue: first, heme crevice resistance to ligand exchange, sensitive to both the hydrophobicity and volume of the side chain; second, modulation of electron-transport activity through maintenance of the hydrophobic character of the protein in the vicinity of Phe82 and the exposed heme edge, and possibly of the ability of this region to facilitate redox-linked conformational change.

Chromatography, High Pressure Liquid↗
PubMed2001

A tale of two charges: distinct roles for an acidic and a basic amino acid in the structure and function of cytochrome c.

Cytochrome c is a small electron transport protein found in the intermembrane space of mitochondria. As it interacts with a number of different physiological partners in a specific fashion, its structure varies little over eukaryotic evolutionary history. Two highly conserved residues found within its sequence are those at positions 13 and 90 (numbering is based on the standard horse cytochrome c); with single exceptions, residue 13 is either Lys or Arg, and residue 90 is either Glu or Asp. There have been conflicting views on the roles to be ascribed to these residues, particularly residue 13, so the functional properties of a number of site-directed mutants of Saccaromyces cerevisiae iso-1 cytochrome c have been examined. Results indicate that the two residues do not interact specifically with each other; however, residue 13 (Arg) is likely to be involved in interactions between cytochrome c and other electrostatically oriented physiological partners (intermolecular), whereas residue 90 (Asp) is involved in maintaining the intrinsic structure and stability of cytochrome c (intramolecular). This is supported by molecular dynamics simulations carried out for these mutants where removal of the negative charge at position 90 leads to significant shifts in the conformations of neighboring residues, particularly lysine 86. Both charged residues appear to exert their effects through electrostatics; however, biological activity is significantly more sensitive to substitutions of residue 13 than of residue 90.

Animals↗
PubMed2000

The independent living skills survey: a comprehensive measure of the community functioning of severely and persistently mentally ill individuals.

The research reported in this article investigated the psychometric characteristics of the Independent Living Skills Survey (ILSS), a comprehensive, objective, performance-focused, easy-to-administer measure of the basic functional living skills of individuals with severe and persistent mental illness (SPMI). Two versions were developed, one for informants and one for self-report. Data from three research projects were analyzed to determine the versions' internal consistency, stability, interrater reliability, sensitivity to the effects of skills training, and concurrent and predictive validity. The results indicated that the two versions have acceptable psychometric characteristics, and suggestions are offered for their use in planning individualized treatment, evaluating programmatic services, and determining eligibility for benefits.

Activities of Daily Living↗
PubMed2000

Identifying and using reinforcers to enhance the treatment of persons with serious mental illness.

Successful engagement of clients with serious and persistent mental illnesses in the planning and implementation of treatment requires the identification of individualized reinforcers through motivational analyses. Reinforcer surveys are interviews or questionnaires that list numerous objects, persons, activities, and settings, and then assess the client's perception of the value of each item. Such surveys help identify the type of reward that might be useful for motivating the client. If properly assessed and delivered, reinforcers can increase clients' skill acquisition, attainment of goals, and feelings of self-efficacy.

Humans↗
PubMed2000

Enlisting indigenous community supporters in skills training programs for persons with severe mental illness.

OBJECTIVE: This study evaluated the generalization of skills training for severely and persistently mentally ill individuals who were paired with indigenous supporters. The supporters monitored the individuals' environments and prompted them to use their skills. METHODS: A total of 85 individuals with severe and persistent mental illness received six months of skills training. Forty-five of the participants received support from an individual of their choosing. The other 40 participants did not have supporters. At the end of the six-month skills training period, the supporters' participation was officially terminated, although they were encouraged to remain in their role for as long as both parties felt comfortable. The effects of the support were measured in terms of interpersonal functioning, acquisition and retention of the skills, psychopathology, global functioning, and satisfaction. Several process measures were also collected. RESULTS: The support procedures were evaluated favorably by both patients and supporters. The interpersonal functioning of the group with supporters was found to be significantly better than that of the nonsupported group at six- and 12-month follow-ups. No differences were found between the groups in symptoms-which were minimal during the entire training period-or skills learning and retention. CONCLUSIONS: The effects of support are likely applicable for a variety of individuals, supporters, and facilities. Indirect evidence suggested the importance of providing support for the supporters.

Adult↗
PubMed2000

Site-specific independent double labeling of proteins with reporter atoms.

Many types of physical, spectroscopic, and biological studies of proteins and other macromolecules are facilitated by the incorporation of reporter groups. In many cases these are single atom substitutes, for example isotopes (13C for C), or light (F for H) and heavy (Se for S) atom homologs. In some circumstances the incorporation of two different labels in the same molecule would be greatly desirable. Commonly used protein engineering methods for incorporating them can rarely cope with differential double labeling, and have other limitations such as universal, non-specific, or random incorporation. Although de novo peptide synthesis has the power to achieve highly specific labeling, the difficulties inherent in creating long sequences lead us to propose protein semisynthesis as the most practical approach. By ligating combinations of natural and labeled synthetic fragments to reform holoproteins, we can overcome any of the limitations discussed. Using cytochrome c as a model protein we show that two reporter atoms, selenium and bromine, can be simultaneously and site-specifically incorporated without significant consequences to structure and (or) function. This capability opens up the prospect of advances in a number of areas in structural biology.

Animals↗
PubMed1999

Mental health consumers as peer interviewers.

Although consumers are increasingly hired as mental health workers, they typically fulfill demanding jobs such as case manager. This study examined the performance and job satisfaction of 18 consumers with serious mental illness who were hired for less demanding work--to conduct highly structured interviews with their peers. The consumers completed interviews with 243 peers. Only one interviewer was unable to perform the work. Ninety percent of the interviews were completed satisfactorily. Interviewers reported increased skills and knowledge, improved self-assurance, and feelings of pride. Results of the study suggest that a wide range of consumers can perform structured treatment tasks.

Adult↗
PubMed1999

The effect of earplugs on sleep measures during exposure to simulated intensive care unit noise.

BACKGROUND: Sleep deprivation may contribute to impaired immune function, ventilatory compromise, disrupted thermoregulation, and delirium. Noise levels in intensive care units may be related to disturbed sleep patterns, but noise reduction has not been tested in this setting. OBJECTIVE: To measure the effect of a noise reduction intervention on the sleep of healthy subjects exposed to simulated intensive care unit noise. METHODS: After digital audiotape recording of noise and development of the noise reduction intervention, 5 nocturnal 8-hour periods of sleep were measured in 6 paid, healthy volunteers at 7-day intervals in a sleep disorders center. Polysomnographic data were collected by experienced sleep disorders technicians and scored by certified raters. After the first 3 quiet nights, earplugs were randomly assigned to be worn on the fourth and fifth nights during exposure to the recorded noise. Sound pressure levels were measured during all 5 nights. RESULTS: Sleep architecture and sound measurements on quiet nights did not differ significantly. Sound levels were significantly lower on quiet nights than on noise nights. Exposure to the noise increased the number of awakenings, percentage of stage 2 sleep, and rapid eye movement latency and decreased time asleep, sleep maintenance efficiency index, and percentage of rapid eye movement sleep. Earplugs worn during exposure to the noise produced a significant decrease in rapid eye movement latency and an increase in the percentage of rapid eye movement sleep. CONCLUSION: The results provide a reasonable basis for testing the effects of earplugs on the sleep of critically ill subjects.

Adult↗
PubMed1999

MR imaging of neoplasms of the lumbar spine.

MR imaging has evolved as the primary modality for imaging spinal neoplasms; however, neoplasms must be distinguished from unusual appearances of degenerative lesions. This article reviews MR imaging findings of a variety of neoplastic lesions of the lumbar spine. For example, extradural, metastatic tumors are the most common; nerve sheath tumors are the most common intradural extramedullary tumors; and ependymoma accounts for most of the tumors arising from the filum terminale.

Cauda Equina↗