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Biomedical subjects

J R Price

Publications and source records attributed to J R Price.

At least 19 recordsLinked to original sources

Role of the LIM domains in DNA recognition by the Lhx3 neuroendocrine transcription factor.

LIM homeodomain transcription factors regulate many aspects of development in multicellular organisms. Such factors contain two LIM domains in their amino terminus and a DNA-binding homeodomain. To better understand the mechanism of gene regulation by these proteins, we studied the role of the LIM domains in DNA interaction by Lhx3, a protein that is essential for pituitary development and motor neuron specification in mammals. By site selection, we demonstrate that Lhx3 binds at high affinity to an AT-rich consensus DNA sequence that is similar to sequences located within the promoters of some pituitary hormone genes. The LIM domains reduce the affinity of DNA binding by Lhx3, but do not affect the specificity. Lhx3 preferentially binds to the consensus site as a monomer with minor groove contacts. The Lhx3 binding consensus site confers Lhx3-dependent transcriptional activation to heterologous promoters. Further, DNA molecules containing the consensus Lhx3 binding site are bent to similar angles in complexes containing either wild type Lhx3 or Lhx3 lacking LIM domains. These data are consistent with Lhx3 having the properties of an architectural transcription factor. We also propose that there are distinct classes of LIM homeodomain transcription factors in which the LIM domains play different roles in modulating interactions with DNA sites in target genes.

AT Rich Sequence↗

Implicit/explicit memory versus analytic/nonanalytic processing: rethinking the mere exposure effect.

In studies of the mere exposure effect, rapid presentation of items can increase liking without accurate recognition. The effect on liking has been explained as a misattribution of fluency caused by prior presentation. However, fluency is also a source of feelings of familiarity. It is, therefore, surprising that prior experience can enhance liking without also causing familiarity-based recognition. We suggest that when study opportunities are minimal and test items are perceptually similar, people adopt an analytic approach, attempting to recognize distinctive features. That strategy fails because rapid presentation prevents effective encoding of such features; it also prevents people from experiencing fluency and a consequent feeling of familiarity. We suggest that the liking-without-recognition effect results from using an effective (nonanalytic) strategy in judging pleasantness, but an ineffective (analytic) strategy in recognition. Explanations of the mere exposure effect based on a distinction between implicit and explicit memory are unnecessary.

Humans↗

Cognitive behaviour therapy for adults with chronic fatigue syndrome.

OBJECTIVES: 1. To systematically review all randomised controlled trials of cognitive-behaviour therapy (CBT) for adults with chronic fatigue syndrome (CFS); 2. To test the hypothesis that CBT is more effective than orthodox medical management or other interventions in adults with CFS. SEARCH STRATEGY: 1. Electronic searching of bibliographic databases, including Medline, PsycLIT, Biological Abstracts, Embase, SIGLE, Index to Theses, Index to Scientific and Technical Proceedings, and Science Citation Index, using multiple search terms in order to perform a highly sensitive search. 2. Electronic searching of the Trials Register of the Depression, Anxiety and Neurosis group. 3. Citation lists of relevant studies and reviews were perused for other relevant trials. 4. Contact with the principal authors of relevant studies, and with researchers in the field. SELECTION CRITERIA: All randomised controlled trials were included in which - adult patients with CFS; - received CBT or a control intervention, being either orthodox medical management or another intervention; - and whose outcomes were assessed in an appropriate way. CBT could be either type 'A' (encouraging return to 'normal' levels of rest and activity) or type 'B' (encouraging rest and activity which were within levels imposed by the disorder). DATA COLLECTION AND ANALYSIS: The two reviewers worked independently throughout the selection of trials and data extraction, comparing findings only when there was disagreement. Relevant trials were allocated to one of three quality categories. Full data extraction, using a standardised data extraction sheet, was performed on studies which were of high or moderate quality. Trials of low quality were excluded from the review. The comparisons made to test the review hypothesis were of type 'A' CBT versus other intervention(s), and of type 'B' CBT versus other intervention(s). Functional outcome was used as the main outcome for comparison, but other appropriate outcomes were compared where possible. Results were synthesised using the Review Manager software. For dichotomous data, the odds ratio was calculated for each study. For continuous data, effect sizes were obtained and the standardised mean difference, with 95% confidence intervals, was calculated. MAIN RESULTS: Only three relevant trials of adequate quality were found. These trials demonstrated that CBT significantly benefits physical functioning in adult out-patients with CFS when compared to orthodox medical management or relaxation. It is necessary to treat about two patients to prevent one additional unsatisfactory physical outcome about six months after treatment end. CBT appeared highly acceptable to the patients in these trials. There is no satisfactory evidence for the effectiveness of CBT in patients with the milder forms of CFS found in primary care or in patients who are so disabled that they are unable to attend out-patients. Additionally, there is no satisfactory evidence for the effectiveness of group CBT. REVIEWER'S CONCLUSIONS: Cognitive behaviour therapy appears to be an effective and acceptable treatment for adult out-patients with chronic fatigue syndrome. CFS is a common and disabling disorder. Its sufferers deserve the medical profession to be more aware of the potential of this therapy to bring lasting functional benefit, and health service managers to increase its availability. Further research is needed in this important area. Trials should conform to accepted standards of reporting and methodology. The effectiveness of CBT in more and less severely disabled patients than those usually seen in out-patient clinics needs to be assessed. Trials of group CBT and in-patient CBT compared to orthodox medical management, and of CBT compared to graded activity alone, also need to be conducted.

Adult↗

Managing physical symptoms: the clinical assessment as treatment.

Physical symptoms are a common cause of attendance at general hospital out-patient clinics. There is good evidence that cognitive therapy is effective in the management of such physical symptoms. This narrative review suggests that the assessment itself, without formal psychological therapy, may be used as a treatment, regardless of whether relevant pathology is absent or present. Changing patients' beliefs about their symptoms may improve a broad range of outcomes, including symptoms, disability, distress, and health-care resource use. The evidence for investigations as treatment is reviewed, along with potential for further development and possible pitfalls. A rationale is presented for a brief psychoeducational intervention that can be delivered in the clinic. This would be a logical extension of the kind of simple explanation and reassurance that occurs routinely today, but which is not explicitly used as, or regarded as, treatment. The dearth of relevant evidence is emphasized, and recommendations are made for future research.

Adult↗

Characterization of the porcine Lhx3/LIM-3/P-Lim LIM homeodomain transcription factor.

Lhx3/LIM-3/P-Lim is a LIM homeodomain transcription factor which is essential in mice for the development of anterior and intermediate lobes of the pituitary gland. We report the cloning and characterization of porcine Lhx3. The porcine Lhx3 protein exhibits strong similarity to murine Lhx3 within the amino terminal LIM domains and the homeodomain, however, it is diverged in regions outside these motifs. Expression vectors for porcine Lhx3 activated murine and porcine alpha-glycoprotein reporter genes in transfection assays, and recombinant porcine Lhx3 protein specifically bound to a target site within the porcine alpha-glycoprotein gene upstream sequence. In addition, porcine Lhx3 synergistically induced transcription from prolactin enhancer/promoter reporter genes in cooperation with the Pit-1 pituitary transcription factor. Porcine Lhx3 protein interacted with Pit-1 protein in solution and also with the LIM domain-binding protein NLI/Lbd1/CLIM. Together, these data indicate that many aspects of Lhx3 function in the mammalian pituitary are conserved and that Lhx3 may be involved in the activation of trophic hormone genes during early and late stages of pituitary organogenesis. Divergence in the Lhx3 amino acid sequence between mammalian species may suggest distinct activities for this protein in some species and may help identify important functional domains of this key developmental transcription factor.

Amino Acid Sequence↗

Adult reading assessment: are we doing the best with what we have?

This article describes a survey completed by 728 neuropsychologists for the purpose of gathering information about the assessment of reading in adults as part of neuropsychological examinations. The survey information gathered addressed (a) the general frequency of assessing adult reading, (b) the assessment tools used, (c) the general purposes for the assessment of reading, (d) the need for a review describing available adult reading norm-referenced tests, and (e) the need for the development of criterion-referenced reading tests appropriate for determining functional reading abilities. Survey findings are reported and discussed. A list and description of reading tests appropriate for assessing reading in adults also is provided in the Appendix.

Achievement↗

Novel isoprenylated proteins identified by an expression library screen.

Isoprenylated proteins are involved in eukaryotic cell growth and signal transduction. The protein determinant for prenylation is a short carboxyl-terminal motif containing a cysteine, to which the isoprenoid is covalently attached via thioether linkage. To date, isoprenylated proteins have almost all been identified by demonstrating the attachment of an isoprenoid to previously known proteins. Thus, many isoprenylated proteins probably remain undiscovered. To identify novel isoprenylated proteins for subsequent biochemical study, colony blots of a Glycine max cDNA expression library were [3H]farnesyl-labeled in vitro. Proteins identified by this screen contained several different carboxyl termini that conform to consensus farnesylation motifs. These proteins included known farnesylated proteins (DnaJ homologs) and several novel proteins, two of which contained six or more tandem repeats of a hexapeptide having the consensus sequence (E/G)(G/P)EK(P/K)K. Thus, plants contain a diverse array of genes encoding farnesylated proteins, and our results indicate that fundamental differences in the identities of farnesylated proteins may exist between plants and other eukaryotes. Expression library screening by direct labeling can be adapted to identify isoprenylated proteins from other organisms, as well as proteins with other post-translational modifications.

Alkyl and Aryl Transferases↗

Effects of case management after severe head injury.

OBJECTIVES: To examine the effects of early case management for patients with severe head injury on outcome, family function, and provision of rehabilitation services. DESIGN: Prospective controlled unmatched non-randomised study for up to two years after injury. SETTING: Four district general hospitals and two university teaching hospitals, each with neurosurgical units, in east central, north, and north east London and its environs. SUBJECTS: 126 patients aged 16-60 recruited acutely and sequentially after severe head injury. All received standard rehabilitation services in each of the six hospitals and districts: case management was also provided for the 56 patients admitted to three of the hospitals. MAIN OUTCOME MEASURES: Standard measures of patients' physical and cognitive impairment; disability and handicap; and affective, behavioural, and social functioning and of relatives' affective and social functioning. Relatives' perception of burden; changes in patients' and relatives' housing, financial, vocational, recreational, and medical needs; and ongoing requirements for care and support; and the amount and type of paramedical input provided were assessed with structured questionnaires. RESULTS: For a given severity of injury, case management increased the chance and range of contact with inpatient and outpatient rehabilitation services. However, duration of contact was not increased by case management, and there was no demonstrable improvement in outcome in the case managed group. Any trends were in favour of the control group and could be accounted for by group differences in initial severity of injury. CONCLUSIONS: Widespread introduction of early case management of patients after severe head injury is not supported, and early case management is not a substitute for improvement in provision of skilled and specialist rehabilitation for patients.

Activities of Daily Living↗

Raising doubts about claims of malingering: implications of relationships between MCMI-II and MMPI-2 performances.

Test results from 90 personal injury claimants were used to explore the relationship between personality disorders (Dependent, Histrionic, Compulsive, Schizoid, Schizotypal, Paranoid, Narcissistic, Borderline, Antisocial, Avoidant, and Passive-Aggressive) as assessed by the MCMI-II and response style measured by MMPI-2 validity scales (F, K, L, F-K, O-S, Es, and FBS). With the exception of the Dependent and Narcissistic scales, all personality disorder scales were found to have a significant relationship with validity indicators in the direction of faking bad. These results suggest that the presence of characterological factors (i.e., a personality disorder), rather than malingering, contributes to exaggerated results in a forensic setting. Implications for future research are addressed.

Adult↗

Selection and the competitive standing of health plans in a multiple-choice, multiple-insurer market.

Previous studies have determined that biased selection occurs in multiple-choice, multiple-insurer programs. To the extent that health plans are affected by biased selection, efficiency becomes less important since adverse selection may raise a particular plan's costs relative to those of its competitors. This study finds that both favorable and unfavorable selection deteriorate over time. Thus, not only may selection harm the competitive standing of individual plans, but it may also force these plans to withdraw from the market. With free entry, no plan is immune from fatal adverse selection.

Community Participation↗

Biased selection in the Federal Employees Health Benefits Program.

The existence of biased selection in health insurance markets has long been assumed by economic theorists as well as seen between classes of health plans. In this paper, we use a model of the premium rate that takes into consideration the effects of moral hazard to make empirical estimates of the extent of selection in the Federal Employees Health Benefits Program. We find that biased selection has raised the premium of the Blue Cross Plan high-option coverage by 21% and lowered the premium of the low-option coverage by 29%, both relative to premiums that would have been charged in the absence of selection.

Blue Cross Blue Shield Insurance Plans↗

Stability in the Federal Employees Health Benefits Program.

Recently the Federal Employees Health Benefits Program has been the subject of much discussion in Washington as a result of the rather large premium increases in 1982 and 1983, the delayed open season of 1981, and the benefit reductions. Enrollees responded in May 1982 to the changes; a record number switched plans. It appears that enrollees were simply responding to the new premiums and benefits. In this paper we describe the economic incentives faced by enrollees in the FEHBP. We find that, due to the strong incentives for enrollees to leave certain high-cost plans, continued instability should be expected. In fact, the disparity between expected benefits and premium is so great for some plans (e.g. the Blue Cross high-option) that their survival is questionable. This lack of stability raises important questions about the viability of some pro-competition proposals involving multiple-insurer systems.

Actuarial Analysis↗