Search PubMed⌕ Search

Biomedical subjects

M Sullivan

Publications and source records attributed to M Sullivan.

At least 271 records · Page 15Linked to original sources
PubMed1991

D1 dopamine receptors can interact with both stimulatory and inhibitory guanine nucleotide binding proteins.

Pretreatment of striatal membranes with N-ethylmaleimide in the presence of a D1-specific agonist inactivated endogenous guanine nucleotide binding proteins (G proteins), but not D1 dopamine receptors, resulting in a loss of high-affinity agonist binding sites. Such D1 receptors were solubilized, mixed with exogenous G proteins from cells not containing D1 receptors, and reconstituted into phospholipid vesicles. These reconstituted receptors were able to couple to the exogenous G proteins, and the proportion of agonist high-affinity sites of the receptor (40-57%) was similar to levels obtained with naive receptors coupling to endogenous G proteins (40%) upon solubilization and reconstitution. These hybrid high-affinity sites were fully modulated by guanine nucleotides. Pretreatment of cells with pertussis toxin prior to extraction of G proteins resulted in a 50% decrease in the proportion of high-affinity sites; these sites remained sensitive to guanine nucleotides. When D1 receptors were reconstituted with extracts of cyc- cells, which lack stimulatory G proteins, the proportion of high-affinity sites was reduced to 31% of the total. Pertussis toxin treatment of the cyc- cells completely abolished the formation of high-affinity sites. These results demonstrate that D1-dopaminergic receptors are able to couple to not only stimulatory G proteins (Gs), but also to inhibitory G proteins (Gi).

Animals↗
PubMed1991

Polyomavirus large T mutants affected in retinoblastoma protein binding are defective in immortalization.

To clarify the relationship between the various activities of the polyomavirus large T antigen and the contribution of this oncogene to neoplastic transformation, we constructed a series of mutants with small deletions or single-amino-acid substitutions in two separate regions of the protein. These sequences were targeted because they showed considerable similarity to conserved regions 1 and 2 of adenovirus E1A which are thought to be binding sites for the retinoblastoma gene product (pRB). The pRB-binding properties of the large T mutants were assessed with an in vitro coimmunoprecipitation assay. pRB binding was readily detected with wild-type large T, but coprecipitation was completely abolished by as little as a single amino acid substitution (Asp-141----Glu or Glu-146----Asp) in region 2 of the polyomavirus large T antigen. Mutants defective in pRB binding were unable to immortalize primary rat embryo fibroblasts, suggesting that association with pRB is an important component of immortalization mediated by polyomavirus large T. The mutations in region 1 affected pRB binding only marginally, yet some of them severely impaired immortalization, indicating that pRB binding may be essential but not sufficient for immortalization.

Amino Acid Sequence↗
PubMed1991

Investigating the proxy effect and the saliency principle in household based postal questionnaires.

STUDY OBJECTIVE: The aim was to investigate two possible sources of bias inherent in using a household based postal questionnaire, the "proxy effect", inaccurate reporting about characteristics of others, and the "saliency principle", reporting of only the most salient features. This is of importance in surveys concerned with screening the population to identify individuals with certain characteristics, and so possibly relying on one member of the household to reply on behalf of all others. DESIGN AND SETTING: A two stage survey of disablement in the population was undertaken. A first phase postal questionnaire was sent to 25,168 households in Calderdale, West Yorkshire, England, to ascertain the prevalence of physical disability and of troubles with the joints. The second phase comprised in depth interviews with a sample of individuals identified in the first phase as being disabled. RESPONDENTS: A total of 21,889 postal questionnaires were returned (87%) representing households containing 42,826 people aged 16 years and over. A disproportionately stratified random sample of 950 respondents reporting disability was taken in the second phase. Of these 891 were still available, and 838 (94%) were interviewed. MEASUREMENTS AND MAIN RESULTS: The postal questionnaire found that almost 29% of those who lived "alone" (without another adult) reported some level of disability, compared to only 10% of those who lived with others. The difference remained significant after standardisation. This apparent underreporting or "proxy effect" was present for reporting about disability overall, but not for severe disability (dependence on help of others), which suggests the operation of the "saliency principle". Reporting on joint troubles appeared to be affected by the proxy effect both for any joint problems, and when more than five joints were affected. Analysis of a small set of postal questionnaires from respondents who reported joint problems only at interview and where we could identify who had completed the postal questionnaire supports the hypothesis of a proxy effect; two thirds of the original postal questionnaires had been completed by a proxy. The results were further complicated by an interaction between reporting of disability and joint troubles: the greater the level of disability, the less likely the reporting of joint troubles. CONCLUSIONS: The findings have general implications for studies involving postal household screening questionnaires, and raises additional concerns about those that are multitopic in content. In surveys of symptoms and minor disability, a proxy effect is likely to be operative. This effect is not apparent for obvious and long standing problems such as dependence on others for help. However the interaction between the reporting of disability and joint symptoms carries important implications for the development of multitopic postal screening questionnaires.

Adolescent↗
PubMed1991

Nonlymphoblastic lymphoma in children--histology and stage-related response to therapy: a Pediatric Oncology Group study.

From May 1979 to March 1983, 93 eligible patients with nonlymphoblastic lymphoma (NLBL) were treated by members of the Pediatric Oncology Group (POG) with Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine, prednisone, cyclophosphamide, and mercaptopurine (ACOP+); CNS prophylaxis with intrathecal (IT) methotrexate, hydrocortisone, and cranial irradiation (2,400 rads), and radiation therapy to the primary disease were administered in stages I and II, and to residual disease in stages III and IV. Duration of treatment was 2 years for stages I, II, and III and 3 years for stage IV disease. Of the 93 patients entered onto the study, 47 had diffuse small noncleaved-cell lymphoma (DSNCL), 38 had diffuse large-cell lymphoma (DLCL), and eight had other histologies. Localized disease (stages I and II) was present in 51 patients, and 42 had advanced (stages III and IV) disease. The study confirmed previously reported importance of stage with a 4-year event-free survival (EFS) of 78% (SE +/- 7%) for patients with localized disease as compared with 44% (SE +/- 9%) in patients with advanced disease (P less than or equal to .001). In localized disease, seven of 11 adverse events occurred in patients who were off therapy and more than 30 months after the initial diagnosis (relapse, three; second malignancy, two; death in remission, two). Large-cell histology proved to be an important prognostic factor in patients with stages III and IV disease with EFS at 4 years of 67% (SE +/- 11%) for DLCL versus 17% (SE +/- 11%) for DSNCL (P less than or equal to .001). We conclude that it is important to distinguish histologically between small noncleaved-cell and large-cell types of NLBL as a basis for further controlled clinical trials.

Adolescent↗
PubMed1991

Quality of life during chemotherapy for small cell lung cancer. I. An evaluation with generic health measures.

The Sickness Impact Profile (SIP) and the Hospital Anxiety and Depression scale (HAD) were used for assessment of physical and psychosocial functioning and emotional distress in patients with small cell lung cancer (SCLC) receiving chemotherapy. Treatment schedules extended over 12 months. Before treatment sixty-two patients, 36-80 years of age, completed the questionnaires and a selection of lung cancer symptom items. Approximately 50% of the patients reported clinically significant physical dysfunction, while emotional distress was reported by 25% and social restraints by 40%. Self-reported overall dysfunction, as assessed by SIP total index, was clinically significant in 60% of the patients. SIP physical and total indices were strongly related to WHO performance status (grade 0-4). The assessment was subsequently repeated every third month during the treatment period. Overall tumour response rate was 82%. The changes of physical and psychosocial functioning, as assessed by SIP, were significantly related to tumour response, although a persistent substantial overall dysfunction was shown among 50% of the responders after 3 months and among c. 40% after 6 months. In addition to tumour response, pain and appetite changes correlated with the change of overall SIP in multivariate analysis, implying the importance of pain control and appetite stimulating measures for patients with advanced cancer. Anxiety and depression, as measured by HAD, were reduced in 21 patients who completed 12 months chemotherapy, but only anxiety co-varied with tumour response. The results lend support to the use of the generic SIP and HAD as outcome measures in clinical research with SCLC patients receiving chemotherapy.

Adult↗
PubMed1991

Use of database management software in a management information system.

If information is to play a useful role in the decision making process, an organization must design a system for capturing, organizing and presenting information from daily activities to its managers. Use of relational database management software to design a custom application as part of a management information system is both practical and cost effective. Designing a database management application is very challenging but well worth the effort, asserts the author of this case study.

Data Display↗
PubMed1991

Cyclosporin A and FK-506 both affect DNA binding of regulatory nuclear proteins to the human interleukin-2 promoter.

The structurally unrelated immunosuppressive drugs cyclosporin A (Sandimmun) and FK-506 both interfere with the process of T-cell proliferation by blocking the transcription of the T-cell growth factor interleukin-2 (IL-2). Here we demonstrate that the transcriptional activation of this gene requires the binding of regulatory nuclear proteins to a promoter element with sequence similarity to the consensus binding site for NF-kappa B-related transcription factors. We present evidence that the binding by regulatory nuclear proteins to the kappa B element of the IL-2 promoter is affected negatively by cyclosporin A and FK-506 at concentrations paralleling their immunosuppressive activity in vivo. The decrease in DNA-protein complex formation induced by the immunosuppressive drugs correlates with a decrease in IL-2 production. FK-506 is 10 to 100 times more potent than cyclosporin A in its ability to inhibit sequence-specific DNA binding and IL-2 production. Our findings suggest that the actions of both drugs converge at the level of DNA-protein interaction.

Anti-Bacterial Agents↗
PubMed1991

Prediction of team care effects in outpatients with rheumatoid arthritis.

Predictive factors for the outcome of 1-year rheuma-team care were studied in 68 female rheumatoid arthritis (RA) outpatients (mean age 56 years, mean RA duration 15 years). Seventy-three background variables were analyzed in a 4-step statistical model including partial and multivariate correlations in order to disclose the best predictors of change scores of the outcome measures chosen. These concerned disease activity (C-reactive protein, Lansbury articular index), physical joint function (Keitel index), mood (Mood Adjective Check List, MACL), and overall health (Sickness Impact Profile). Between 14 and 47% of the variance of the 1-year outcome change scores was explained by combinations of 2 or 3 predictors out of 12 strong background variables. The lowest value of explained variance was noted for MACL, and the highest for C-reactive protein. Both clinical, social, and self-assessed health data were among the predictors. Our results can provide a guide in the selection of patients with RA for multidisciplinary team care, in the formulation of treatment goals, and the creation of cost-effectiveness schedules.

Adult↗
PubMed1991

[Psychosocial problems and needs of cancer patients].

A Swedish-American epidemiological study of the psychosocial problems and needs of cancer patients have shown that the personal needs of such individuals are frequently ignored. The Swedish patients requested psychological support more often than the Americans, who instead reported a need for financial assistance. Swedish patients were very rarely offered psychiatric or psychological counselling, while many Americans felt that they had received good support from physicians and other medical personnel. Fourteen per cent of the Swedes and 2.7 per cent of the American patients had no-one to whom to turn for help. The article gives concrete recommendations for better psychosocial care of cancer patients.

Counseling↗
PubMed1991

Disorders of bladder function in spinal cord disease.

Successful management of bladder function mandates a thorough knowledge of the neuroanatomy and physiology of micturition. Accurate urodynamic diagnosis of the exact vesicourethral dysfunction is a key to successful management. The primary concern for the urologist is preservation of renal function, taking into account the social needs of the patient.

Humans↗
PubMed1991

Absorption of oral ciprofloxacin in a patient with cardiogenic shock.

Congestive heart failure and cardiogenic shock can alter the absorption process of some drugs. The absorption of ciprofloxacin has been studied in several disease states, but the effect of cardiogenic shock on its absorption is unknown. A 63-year-old man had a large myocardial infarction complicated by cardiogenic shock. When he began taking ciprofloxacin for pneumonia, he had renal and cardiac failure. Ciprofloxacin 500 mg was administered every 24 hours by nasogastric tube. Blood samples were collected 5 minutes prior to the second dose (20 hrs after the initial dose) and then regularly until 11 hours after the dose. Samples were analyzed using high-performance liquid chromatography. The trough concentration 20 hours after the initial dose was 3.7 micrograms/ml, and the serum concentrations after the second dose went from 5.6 to 4.94 micrograms/ml over the 11-hour sampling period. The peak concentration of 5.6 micrograms/ml occurred within 30 minutes after ciprofloxacin administration. It can be concluded from this case study that ciprofloxacin was adequately absorbed in this patient with multiple organ failure.

Ciprofloxacin↗
PubMed1991

Nursing skills necessary for competency in the high-tech health care system.

Neighbors, Sullivan, and Eldred tell us how schools of nursing and institutions of nursing practice conform--or fail to conform--in regard to what constitutes basic nursing procedures. Are schools leaving the new graduate unprepared for everyday practice? A survey of association degree schools is revealing.

Clinical Competence↗
PubMed1991

Spinal cord injuries. Clinical, functional, and emotional status.

Ninety-eight patients with traumatic spinal cord injury, at a median age of 33.5 years (range, 16-72 years), with nonremarkable distributions of neurologic characteristics were investigated at a median of 2.3 years (range, 0.1-23 years) after injury. Functioning, mood disturbances, and overall quality of life were recorded with established self-assessment instruments. Physical dysfunction levels were moderate, being proportionate to neurologic impairment. Psychosocial functions, mood states, and quality-of-life perceptions did not differ from those of a control population sample. Psychosocial function and mood disturbances varied greatly during the first 4 years after injury, but patients' later recordings expressed predominantly a balanced emotional state and a rewarding social life. Progress in this direction consisted of clearly lessened physical dysfunction 1 year after injury and better psychosocial function and well-being after 2 years, whereas patterns of social activities and contacts became gradually less inhibited during a 4-year period after injury. Analysis of complications in patients' histories that affected function and mood showed severe pain to be the only complication that related to lower quality-of-life scores. Urinary incontinence and infection and autonomous dysreflexia related to inhibited self-care performance; spasticity related to impaired ambulation and feeding skills. Gainful employment was the only demographic factor linked to high quality-of-life scores.

Activities of Daily Living↗