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Biomedical subjects

D A Gilbert

Publications and source records attributed to D A Gilbert.

At least 19 recordsLinked to original sources
PubMed2006

Temporal variation in the expression of the p53 protein in proliferating and differentiating murine erythroleukaemia cells.

Temporal changes in the expression of p53 were investigated during hexamethylene bisacetamide (HMBA)-induced differentiation of murine erythroleukaemic (MEL) cells. Cell preparations were analysed by SDS-PAGE and western immunoblotting, which detected an immunospecific band of molecular mass 53 kDa. This analysis provided semi-quantitative information. Cell extracts were analysed further by means of ELISA techniques, using a p53-specific antibody, to provide quantitative data. In time series experiments in which cells were isolated at 15, 30 and 60 min intervals, dynamic variations in the expression of the p53 protein were detected in both the untreated and the HMBA-treated MEL cells. In all cases, the effects were complex with variations in amplitude, frequency and phasing of the rhythms. The available evidence suggests that the observed patterns, like periodic variations in other systems, are modified in rhythmic fashion with respect to period and amplitude. The results add further support for our view that it is essential to consider the dynamics when interpreting the role of p53 and cellular processes in general.

Acetamides↗
PubMed2005

Temporal changes in the expression of protein phosphatase 1 and protein phosphatase 2A in proliferating and differentiating murine erythroleukaemia cells.

Rhythmic changes in the expression of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) were investigated during hexamethylene bisacetamide (HMBA) induced differentiation of murine erythroleukaemic (MEL) cells. Cell extracts were analysed by SDS-PAGE and western immunoblotting using specific antibodies. An immunospecific band of molecular mass 36 kDa (catalytic subunit) was detected for PP1. For PP2A, two immunospecific bands of 32 kDa (proteolytically cleaved catalytic subunit) and 36 kDa (catalytic subunit) were observed. Comparisons of proliferating and differentiating cells using only one time point showed no significant differences between mean values for the expression of the PP1 or PP2A enzyme proteins. This kind of analysis, implying that HMBA had little effect, proved misleading, as comparisons using multiple time points showed rhythmic patterns of protein expression which were modulated by the differentiating agent. The effects were complex affecting both the frequency and phasing of rhythms. The results add further support for the view that live cells are multi-oscillators and for the concept that differentiation depends on changes in temporal organization of complex autodynamic feedback loops and multiple interactions between control circuits performing in parallel. In particular, modulation of the dynamics of key proteins, such as PP1 and PP2A, may be a possible mechanism for controlling cellular function and reversing transformation in accordance with long standing theoretical and other experimental data.

Acetamides↗
PubMed2001

Markers for mapping by admixture linkage disequilibrium in African American and Hispanic populations.

Population linkage disequilibrium occurs as a consequence of mutation, selection, genetic drift, and population substructure produced by admixture of genetically distinct ethnic populations. African American and Hispanic ethnic groups have a history of significant gene flow among parent groups, which can be of value in affecting genome scans for disease-gene discovery in the case-control and transmission/disequilibrium test designs. Disease-gene discovery using mapping by admixture linkage disequilibrium (MALD) requires a map of polymorphic markers that differentiate between the founding populations, along with differences in disease-gene allele frequencies. We describe markers appropriate for MALD mapping by assessing allele frequencies of 744 short tandem repeats (STRs) in African Americans, Hispanics, European Americans, and Asians, by choosing STR markers that have large differences in composite delta, log-likelihood ratios, and/or I*(2) for MALD. Additional markers can be added to this MALD map by utilization of the rapidly growing single-nucleotide-polymorphism databases and the literature, to achieve a 3-10-cM scanning scale. The map will be useful for studies of diseases, including prostate and breast cancer, diabetes, hypertension, and end-stage renal disease, that have large differences in incidence between the founding populations of either Hispanics or African Americans.

Black or African American↗
PubMed2000

Problems associated with the study of cellular oscillations.

Data from the article by Brodsky et al. (2000) have been examined in order to confirm that the fluctuations they report are not random but have a rhythmic basis, thereby verifying their conclusions regarding the existence of periodicity in protein synthesis. Reasons are outlined why oscillations should be expected in all cellular biochemical studies. Associated practical problems are briefly discussed together with comments on the validity and value of less rigorous methods of analysis. The subject of aliasing is raised as justification for doubting the validity of much published data, especially where periodicity has not been suspected. The existence of oscillations indicates the need for a thorough re-evaluation of our understanding of cell biochemistry.

Animals↗
PubMed2000

Transient chaos in intracellular dynamics?

Periodogram analyses of the temporal variations of several cellular oscillations occasionally reveal the existence of short duration bands containing a wide range of frequencies. The possibility is considered that these are due to the transient compliance with chaotic conditions.

Animals↗
PubMed1999

Medication treatment for the severely and persistently mentally ill: the Texas Medication Algorithm Project.

This article provides an overview of the issues involved in developing, using, and evaluating specific medication guidelines for patients with psychiatric disorders. The potential advantages and disadvantages, as well as the essential elements in the structure of algorithms, are illustrated by experience to date with the Texas Medication Algorithm Project, a public-academic collaboration. Phase 1 entailed assembling research findings on the efficacy of medications for schizophrenic, bipolar, and major depressive disorders. This knowledge was evaluated for its quality and relevance, integrated with expert clinical judgment as well as input by practicing clinicians, family advocates, and patients. Phase 1 (the design and development of the algorithms) was followed by a feasibility test (Phase 2). Phase 3 is an ongoing evaluation comparing the clinical and economic effects of using specific medication guidelines (algorithms) versus treatment as usual in public sector patients with severe and persistent mental illnesses.

Algorithms↗
PubMed1998

High-precision genotyping by denaturing capillary electrophoresis.

Genotyping, as applied to linkage mapping, human identification, or mapping of genetic traits, mandates electrophoretic separation systems that enable a user to identify alleles with high precision to obtain a correct genotype. For 2-bp microsatellites or short tandem repeats (STRs), standard deviations of +/-0.3 nucleotide are required to ensure with 99.7% probability the identity or dissimilarity of tested alleles. A complete system, consisting of commercially available laser-induced fluorescence capillary electrophoresis (ABI PRISM 310) and performance optimized polymer 4 (POP-4), was evaluated for microsatellite separations. POP-4 is a low viscosity polymer for use in uncoated fused microbore silica capillaries. It separates DNA fragments that differ in size by 1 nucleotide up to 250 nucleotides and that differ in size by 2 nucleotides for fragments up to at least 350 nucleotides in length in about 30 min. The presence of denaturants and, more importantly, operation at 60 degrees C was mandatory for high-precision and high-resolution sizing operation. Reproducible separation performance was achieved in excess of 100 injections per capillary with resulting standard deviations in the range of 0.04 to 0.17 nucleotide. Comparative sizing of known CEPH (Centre d'Etudes du Polymorphisme Humaine) samples performed at 22 independent test sites showed the usefulness of the system for genotyping with standard deviations of 0.24 nucleotide, or better.

Chromosome Mapping↗
PubMed1998

Texas Medication Algorithm Project: definitions, rationale, and methods to develop medication algorithms.

BACKGROUND: The Texas Medication Algorithm Project (TMAP), a public-academic collaborative effort, is a 3-phase project to develop, implement, and evaluate medication treatment algorithms for public sector patients with schizophrenia, major depressive disorders, or bipolar disorders. DISCUSSION: This paper, the first in a series describing the activities of the TMAP, focuses on the various definitions and reasons why guidelines have gained popularity. Also discussed are their strengths, the limitations of the various methods used to develop them, and potential barriers to their implementation.

Algorithms↗
PubMed1998

Relational message themes in nurses' listening behavior during brief patient-nurse interactions.

Using a relational message framework, this study examined themes communicated by nurses' listening behavior during brief patient-nurse interactions and whether the pattern of thematic scores reflected a positive patient-nurse relationship. A sample of 126 White college women individually viewed a videotape of six nurses listening to a patient-actress for 25 to 32 seconds. Participants reported what each nurses' listening behavior communicated on a 30-item instrument. Principal axis factoring using a seven-factor solution explained 57.7% to 65.0% of the common variance. Six of the factors proposed in the relational message framework were identified in each interaction: Trust/Receptivity, Depth/Similarity/Affection, Difference, Composure, Dominance or Power, and Formality. In four interactions the pattern of thematic scores suggested communication of a positive patient-nurse relationship. Thus it appears that the communication of positive patient-nurse relationships is not necessarily precluded by the time constraints in contemporary nursing practice.

Adolescent↗
PubMed1997

Developing clinical work processes in a state psychiatric hospital: a case study.

The Texas Department of Mental Health and Mental Retardation applied the continuous quality improvement (CQI) concept of work process to the delivery of clinical services in each of its eight state psychiatric hospitals. Two different clinical processes were involved: (1) individualized psychiatric treatment and (2) medical treatment. The processes were then benchmarked against national leaders in the delivery of public psychiatric hospital services. This case study demonstrates the applicability of the work process concept to a clinical environment where it can function as a management tool that can significantly improve the quality and efficiency of services provided to individual patients.

Hospitals, Psychiatric↗
PubMed1996

High frequency oscillations in the activity of phosphotyrosine phosphatase in murine erythroleukaemic cells: action of insulin and hexamethylene bisacetamide.

We have previously reported oscillations in the activities of the phosphoamino acid phosphatases in murine erythroleukaemic cells. In keeping with our predictions we now show that the phosphotyrosine phosphatase activity rhythm has a much shorter period than originally seemed the case, being of the order of 10 min and probably less. The periodic changes show evidence of rhythmic modulation of mean, period and amplitude as with all other cellular oscillations studied. Insulin decreases the frequency of the rhythm while the inducer of differentiation, hexamethylene bisacetamide (HMBA) decreases its amplitude. Current ideas on phosphorylation dynamics in relation to metabolism and mitosis may need to be revised in the light of the observations.

Acetamides↗
PubMed1996

Independent high-frequency oscillations in the amounts of individual isozymes of lactate dehydrogenase in HL60 cells.

Early studies, using kinetic methods, suggested that the isozyme pattern of lactate dehydrogenase in various cells oscillated with time. More recent electrophoretic studies on murine erythroleukaemic cells (which exhibit only one isozyme) indicated very high frequency variations (period 2 min or less) in the amount of the lone active isozyme. We now show that in HL60 cells, the activity stain intensities of the two major isozyme bands both oscillate but the temporal variations are distinct. As with other cellular rhythms, each of the two periodicities seem to be modulated in cyclic fashion with respect to period, amplitude and mean levels, the periods of both the primary and modulating rhythms being of the order of 10-15 min or probably much less.

Activity Cycles↗
PubMed1996

Distinct, very high frequency oscillations in the activity and amount of active isozyme of lactate dehydrogenase in murine erythroleukaemic cells and a cell-free system.

Electrophoretic and kinetic determinations of the activity of lactate dehydrogenase in murine erythroleukaemic (MEL) cells, sampled at 1 min intervals, reveal distinct oscillations in the activity and amount of active isozyme. Both oscillations have periods in the range of 2-6 min (probably less) and both appear to be rhythmically modulated with respect to period, amplitude and mean. The oscillations also occur in cell-free systems, a fact which throws doubt on the value of studies where it is assumed that such preparations have constant composition.

Activity Cycles↗
PubMed1996

The role of colpocleisis with urethral lengthening in transsexual phalloplasty.

OBJECTIVE: Transsexual surgery is an unique area of rarely performed surgery. This study examines factors that have significance in the prevention of major morbidity in this unusual surgery. The role of the gynecologist in the psychologic, endocrine, and operative management is presented. STUDY DESIGN: Initial operations were complicated by fistulas at the urethra-to-phallus anastomosis site. After reviewing these complications, we modified our approach to include a two-stage procedure allowing for healing before microsurgery and sparing of the anterior vaginal wall during vaginal hysterectomy and colpocleisis. By sparing the anterior vaginal wall, we were able to better extend the urethra for later phallus attachment. RESULTS: Using the two-stage procedure at colpocleisis allowed a significant reduction in the fistula rate. (p = 0.0087) with the effective elimination-fistulas, the use of stiffeners during phalloplasty for better functional results is possible. CONCLUSION: Extending the urethra during colpocleisis allows for better healing and significantly decreased fistula formation. Proper blood supply for microvascular surgery and adequate tissue for the anastomosis site contribute to better results.

Female↗
PubMed1996

QI as resolution to a major lawsuit.

BACKGROUND: In 1991, in response to a lawsuit filed in 1974, the Texas Department of Mental Health and Mental Retardation (TXMHMR) became the first major state agency in Texas to implement a systemwide effort to implement quality improvement (QI) in its Quality System Oversight (QSO) program. QSO: The QSO approach includes a uniform internal hospital management structure focusing on teams and data-based decision making; the development of uniform work processes for each of the issues cited in the lawsuit; and a uniform set of procedures for determining compliance, including the establishment of numeric targets for which each hospital is accountable. CASE STUDY: At one TXMHMR hospital, patient records in a monthly random sample were below the performance target. Data showed that approximately 40% of the patients leave the hospital (many for a community mental health center) before a treatment plan (at 14 days) is developed. Based on a team's recommendations, a uniform assessment package is being developed for use by all TXMHMR hospitals and community mental health centers. THE NEXT STEP: In 1994, again in response to external pressures to improve quality, TXMHMR used a simplified version of the Malcolm Baldrige National Quality Award criteria for organizational self-assessment. Two pilot sites have developed action plans for improving performance as indicated on the self-assessments. SUMMARY AND CONCLUSIONS: The QSO program, put into place as a result of a lawsuit, provides a structure and database for TXMHMR to efficiently and effectively manage the performance of all hospitals in the system. All but one of the eight hospitals have exited, or are close to exiting, the lawsuit.

Affective Symptoms↗
PubMed1995

Ageing, oscillations and efficiency.

The phenomenon of ageing still defies understanding. Theoretical studies have indicated that glycolysis is more efficient at maintaining a high ATP/ADP ratio when oscillating at its resonant frequency. Earlier, it was proposed that the differentiated state results from the establishment of a stable pattern of temporal organisation. It is now suggested that ageing involves a decrease in efficiency due to the detuning of oscillating glycolysis as a result of frequency locking with other cellular oscillations in the differentiated state.

Adenosine Diphosphate↗