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M Sullivan

Publications and source records attributed to M Sullivan.

At least 55 records · Page 3Linked to original sources
PubMed1997

Tissue-specific inhibition of apolipoprotein B mRNA editing in the liver by adenovirus-mediated transfer of a dominant negative mutant APOBEC-1 leads to increased low density lipoprotein in mice.

APOBEC-1 is a catalytic subunit of an apolipoprotein B (apoB) mRNA editing enzyme complex. In humans it is expressed only in the intestine, whereas in mice it is expressed in both the liver and intestine. APOBEC-1 exists as a spontaneous homodimer (Lau, P. P., Zhu, H.-J., Baldini, A., Charnsangavej, C., and Chan, L. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 8522-8526). We tested the editing activity and dimerization potential of three different mouse APOBEC-1 mutants using in vitro editing activity assay and immunoprecipitation in the presence of epitope-tagged APOBEC-1. One catalytically inactive mutant, mu1 (H61K/C93S/C96S), that retains its capacity to dimerize with wild-type APOBEC-1 was found to inhibit the editing activity of the latter and was thus a dominant negative mutant. Two other inactive mutants that dimerized poorly with APOBEC-1 failed to inhibit its activity. Intravenous injection of a mu1 adenovirus, Admu1, in C57BL/6J mice in vivo resulted in liver-specific expression of mu1 mRNA. On days 4 and 9 after virus injection, endogenous hepatic apoB mRNA editing was 23.3 +/- 5.0 and 36.8 +/- 5.7%, respectively, compared with 65.3 +/- 11 and 71.3 +/- 5.2%, respectively, for luciferase adenovirus-treated animals. Plasma apoB-100 accounted for 95 and 93% of total plasma apoB in Admu1 animals on days 4 and 9, respectively, compared with 78 and 72% in luciferase adenovirus animals. Plasma cholesterol on day 9 was 98 +/- 17 mg/dl in the mu1-treated animals, substantially higher than phosphate-buffered saline-treated (57 +/- 9 mg/dl) or luciferase-treated (71 +/- 12 mg/dl) controls. Fast protein liquid chromatography analysis of mouse plasma showed that the intermediate density/low density lipoprotein fractions in the animals treated with the dominant negative mutant adenovirus were much higher than those in controls. We conclude that active APOBEC-1 functions as a dimer and its activity is inhibited by a dominant negative mutant. Furthermore, apoB mRNA editing determines the availability of apoB-100, which in turn limits the amount of intermediate density/low density lipoprotein that can be formed in mice. Liver-specific inhibition of apoB mRNA editing is an important component of any strategy to enhance the value of mice as a model for human lipoprotein metabolism.

APOBEC-1 Deaminase↗
PubMed1997

Receptor-mediated stimulation of lipid signalling pathways in CHO cells elicits the rapid transient induction of the PDE1B isoform of Ca2+/calmodulin-stimulated cAMP phosphodiesterase.

Chinese hamster ovary cells (CHO cells) do not exhibit any Ca2+/calmodulin-stimulated cAMP phosphodiesterase (PDE1) activity. Challenge of CHO cells with agonists for endogenous P2-purinoceptors, lysophosphatidic acid receptors and thrombin receptors caused a similar rapid transient induction of PDE1 activity in each instance. This was also evident on noradrenaline challenge of a cloned CHO cell line transfected so as to overexpress alpha 1B-adrenoceptors. This novel PDE1 activity appeared within about 15 min of exposure to ligands, rose to a maximum value within 30 min to 1 h and then rapidly decreased. In each case, the expression of novel PDE1 activity was blocked by the transcriptional inhibitor actinomycin D. Challenge with insulin of either native CHO cells or a CHO cell line transfected so as to overexpress the human insulin receptor failed to induce PDE1 activity. Reverse transcriptase-PCR analyses, using degenerate primers able to detect the PDE1C isoform, did not amplify any fragment from RNA preparations of CHO cells expressing PDE1 activity, although they did so from the human thyroid carcinoma FTC133 cell line. Reverse transcriptase-PCR analyses, using degenerate primers able to detect the PDE1A and PDE1B isoforms, successfully amplified a fragment of the predicted size from RNA preparations of both CHO cells expressing PDE1 activity and human Jurkat T-cells. Sequencing of the PCR products, generated using the PDE1A/B primers, yielded a novel sequence which, by analogy with sequences reported for bovine and murine PDE1B forms, suggests that the PDE1 species induced in CHO cells through protein kinase C activation and that expressed in Jurkat T-cells are PDE1B forms.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

Dietary intake in relation to restrained eating, disinhibition, and hunger in obese and nonobese Swedish women.

The aims of this study were to: describe dietary intakes of obese and nonobese middle-aged women using a validated food frequency questionnaire; to assess dietary restraint, disinhibition, and hunger by the three factor eating questionnaire (TFEQ) in obese and nonobese samples and determine which of the factors are independently associated with obesity; and to examine correlations between selected nutritional variables and the TFEQ factors. Subjects studied included 179 obese Swedish women (BMI > 32) and 147 nonobese population-based controls (BMI < 28). Age-adjusted mean energy intake was significantly higher in obese women (2730 +/- 78 vs. 2025 +/- 85 kcal, p < 0.0001). In absolute and relative terms, fat intake was higher and alcohol intake was lower in the obese subjects. Disinhibition was the strongest TFEQ factor independently differentiating the obese and nonobese states, i.e., after adjustment for restraint and hunger. Within the obese sample, strong associations were seen between energy intake and disinhibition (p = 0.0005) and hunger (p = 0.0004). The association between energy intake and restrained eating was negative and weaker (p = 0.04). No such associations were seen in nonobese women. Thus, using a dietary instrument that is valid and unbiased with respect to obesity, strong psychological correlates, possibly causal, of variability in energy intake were detected in middle-aged women with obesity. Disinhibition is associated with both obesity and high-energy intakes and is therefore an important factor to consider in the treatment of women with obesity.

Adult↗
PubMed1997

Quality of life after gastrectomy for gastric carcinoma: controlled study of reconstructive procedures.

The choice of reconstruction after gastrectomy and the significance of remaining reservoir function is a matter of controversy. To broaden the criteria for choice of treatment, we conducted a prospective randomized clinical trial to determine the impact of various gastrectomy procedures on quality of life. Consecutive patients (n = 64) eligible for curative gastric cancer surgery were randomized to have either a total (n = 31) or subtotal (n = 13) gastrectomy or a jejunal S-shaped pouch (n = 20) implanted as a gastric substitute. The quality-of-life evaluation was based on a battery of questionnaires covering both general and specific aspects of life. The patients were rated by one of two psychiatrists who were blinded to the patients' group affiliation. Assessments were made on three occasions: during the week prior to surgery and 3 and 12 months after the surgical intervention. The postoperative complication and mortality rates were similar in all treatment groups, with few serious complications recorded. Irrespective of type of treatment, the patients suffered from alimentary symptoms and functional limitations in everyday life, whereas their mental well-being improved after surgery. Patients who underwent subtotal gastrectomy had the best outcome, especially with respect to complaints of diarrhea. Patients given a gastric substitute after gastrectomy showed no difference from those who had only a total gastrectomy. We conclude that despite significant unfavorable consequences that follow gastrectomy, patients recover with an improved mental status. A pouch reconstruction after total gastrectomy does not improve quality of life, but a subtotal gastrectomy has advantages that must be considered when the procedure is clinically feasible.

Adult↗
PubMed1997

Quality of life in patients with prostatic cancer: results from a Swedish population study.

PURPOSE: We evaluated a prostate cancer-specific module in an unselected patient population. MATERIALS AND METHODS: A population study design was used to confirm the psychometric properties and clinical relevance of a prostate cancer-specific module, supplementing the standardized EORTC QLQ-C30 in Sweden. The study sample comprised 1,138 patients (81% response rate) examined by a mailout/mailback procedure 1.5 to 3.5 years after diagnosis. The standardized multitrait analysis method estimated the internal consistency and convergent and discriminant validity of 3 multi-item scales on sexuality, urinary symptoms and bowel symptoms. Confirmation of prostate-specific scales by disease stage and treatment used principal components analysis. The clinical relevance was tested by correlation analysis including disease and treatment-related parameters. RESULTS: Convergent and discriminant validity of all 3 prostate-specific scales was confirmed. The internal consistency was satisfactory for the sexuality and urinary scales (alpha 0.92 and 0.76, respectively), while the bowel scale failed to reach the alpha level of 0.70 required for group comparisons. The former scales showed invariance over all principal components analyses of subgroups (disease stage and treatment). The latter scale comprised differing numbers of items in the subgroup analyses, suggesting the use of single items at present. Descriptive data of the core and module questionnaires by disease and treatment-related parameters confirmed their interpretability and thus their clinical usefulness. CONCLUSIONS: The presented self-report questionnaire technique has great potential to inform clinicians about the quality of life in patients suffering from prostate cancer.

Aged↗
PubMed1997

Predictors of physician frustration in the care of patients with rheumatological complaints.

Recent studies of the doctor-patient relationship have shown that certain patients are perceived as frustrating or difficult by their doctors; however, little is known about the characteristics of these patients that elicit this dissatisfaction. As part of a larger study of rheumatology clinic patients with fibromyalgia or rheumatoid arthritis (N = 68) we used stepwise multiple regression to select the factors most associated with physician frustration while controlling for the effects of other variables. Variable domains included demographics, psychiatric diagnoses, personality factors, functional disability, disease state, and trauma history. These domains as well as individual variables within these domains were systematically evaluated for their unique contribution to the prediction of physician frustration as measured by the Difficult Doctor-Patient Relationship Questionnaire (DDPRQ). Initial bivariate correlates of physician frustration included marital status, current dysthymia and agoraphobia, lifetime panic disorder and obsessive-compulsive disorder, adult rape and physical abuse, somatization disorder, physical and social disability, the presence of fibromyalgia, as well as neuroticism, illness impact, and perceived loss of control. The best multivariable model for estimating frustration magnitude included somatization disorder, perception of lack of control over illness, and a lifetime history of obsessive-compulsive disorder. These factors explained 48% of the variance in DDPRQ score. Physicians in this study were most frustrated with patients who had ongoing preoccupation with multiple medically unexplained physical symptoms as well as the perception of greater impact and lack of control over their illness. These findings suggest that treatment of somatization in patients with chronic symptoms may decrease physician frustration.

Adult↗
PubMed1997

Prospective, longitudinal quality-of-life study of patients with head and neck cancer: a feasibility study including the EORTC QLQ-C30.

Despite modern advances in the treatment of head and neck cancer, the survival rate fails to improve. Considering the different treatment modalities involved, quality of life has been thought of as an additional end point criterion for use in clinical trials. A Nordic protocol to measure the quality of life of head and neck cancer patients before, during, and after treatment was established. Before the study, a pilot study was done with this protocol. The main purpose of this pilot study was to find out whether this cancer population would answer quality-of-life questionnaires repeatedly (six times) over a 1-year period and whether the chosen questionnaires-a core questionnaire (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30)), a tumor-specific questionnaire, and a psychological distress measure (Hospital Anxiety and Depression scale (HAD))-were sensitive for changes to functions and symptoms during the study year. The results presented in this article all refer to the pilot study. Forty-eight consecutive patients agreed to participate in the study. The most common tumor locations were the oral cavity (17) and the larynx (12). Almost all patients received combined treatment: 45 of 48 radiation therapy, 18 of 48 chemotherapy, and 17 of 48 surgery. After the primary treatment, 40 patients had complete tumor remission. Four of the 48 patients did not answer any questionnaires and were therefore excluded from the study. Of the remaining 44 patients, 3 died during the study year, and another 6 withdrew for various reasons. Thirty-five (85%) of the 41 patients alive at the 1-year follow-up answered all six questionnaires and thus completed the study. Mailed questionnaires were used throughout the study. All questionnaires were well accepted and found to be sensitive to changes during the study year. The greatest variability was found for symptoms and functions related specifically to head and neck cancer. The symptoms were swallowing difficulties, hoarse voice, sore mouth, dry mouth, and problems with taste. They all showed the same pattern, with an increase of symptoms during and just after finishing the treatment. The HAD scale revealed a high level of psychological distress, with 21% probable cases of psychiatric morbidity at diagnosis. In conclusion, it was shown that the study design and questionnaires were feasible for the forthcoming prospective quality-of-life assessment of Swedish and Norwegian head and neck cancer patients.

Adult↗
PubMed1997

A prospective quality of life study of patients with oral or pharyngeal carcinoma treated with external beam irradiation with or without brachytherapy.

The aim of this longitudinal quality of life (QL) study, was to study tumour-related symptoms and treatment side-effects of patients with oral or oropharyngeal cancer and to determine whether an increased local dose of irradiation (brachytherapy affected QL. The European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30), a tumour-specific Head and Neck questionnaire and the Hospital Anxiety and Depression scale (HAD) were used repeatedly during 1 year. There were 105 patients, with a cumulative response rate of 89%. Most symptoms and problems were at their peak 2 or 3 months after the start of treatment. Nutrition and pain were found to be the major problems, and as many as 19-40% reported psychiatric distress. Patients having received additional brachytherapy did not report any increase in QL problems (except for pain) compared with those having had external radiation only. Quality of life does not seem to be affected by the increased irradiation local dose given when brachytherapy is included in the treatment regimen.

Adult↗
PubMed1997

Spinal cord injuries: a shortened measure of function and mood.

A brief quality-of-life (QL) questionnaire was derived empirically from a cross-sectional study of 98 SCI-patients (83% men, median age 33.5 years, and median time after injury 2.3 years). A comprehensive general battery of well-established questionnaires (Sickness Impact Profile (SIP), Mood Adjective Check List (MACL), and Hospital Anxiety and Depression (HAD) scale) was combined with a study-specific set of questions to constitute patients' QL. A stepwise analysis model was used to define key areas and questions to be included in a brief SCI-adapted questionnaire. The central areas that independently mattered for SCI-patients' perception of good QL included mental health (no depressive feelings), physical and psychosocial dysfunction (no, or few and minor, limitations in mobility, body care and movement and social interaction), and SCI-related problems (no or little perceived difficulty with loss of independence due to injury). A 22-item questionnaire is suggested for routine clinical follow-up to assess more accurately when optimal treatment and services have been delivered.

Activities of Daily Living↗
PubMed1997

The efficacy of selective serotonin reuptake inhibitors for the management of chronic pain.

OBJECTIVE: To assess the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in the management of chronic pain. METHODS: Randomized, controlled trials of SSRIs in the management of chronic pain were identified by searching MEDLINE from 1966 to 1997 and by contacting the manufacturers of SSRIs available in the United States. MAIN RESULTS: Nineteen studies were identified, including 10 on the treatment of headache, 3 on diabetic neuropathy, 3 on fibromyalgia, and 3 on mixed-chronic pain. SSRIs were consistently helpful for mixed-chronic pain. Results were conflicting for migraine headache, tension headache, diabetic neuropathy, and fibromyalgia. CONCLUSIONS: SSRIs appear to be beneficial for mixed-chronic pain. It is unclear, from the available evidence, whether SSRIs are beneficial for migraine headaches, tension headaches, diabetic neuropathy, or fibromyalgia. For those patients it may be reasonable to reserve SSRIs for those who fall to respond to other medications or who are intolerant of their side effects.

Chronic Disease↗
PubMed1997

Cognition and social functioning in schizophrenia.

This article reviews three studies investigating the relationship between information processing and social functioning in schizophrenia. The most consistent finding is the association between vigilance performance on a hybrid continuous performance/span of apprehension task and various indices of social functioning (e.g., ward behavior). However, the nature of the information processing-social functioning relationships is mutable and appears dependent on a number of factors (e.g., cross-sectional versus longitudinal designs). This article concludes with a discussion of treatment implications and future research directions.

Adolescent↗
PubMed1997

Doctors, diagnosis, and disability: a disastrous diversion.

Patients and third party payers expect physicians to identify damage or disease as the cause of pain and disability, but often there is no damage or disease that can be identified. The process of disability determination requires physicians to make determinations that cannot be based on medical science and for which they have no specialized training. The combination of pseudodiagnosis and pseudodisability is likely to bankrupt countries that do not recognize this folly and design more productive health and disability systems. Physicians need much more education about human behavior and the highly variable relationships among disease, distress, and disability.

Behavior↗
PubMed1997

Health-related quality of life after epilepsy surgery: a Swedish multicenter study.

PURPOSE: To investigate health-related quality of life (HRQOL) in relation to seizure outcome as part of a multicenter follow-up of epilepsy surgery in Sweden. METHODS: A battery including the SF-36 Health Survey and the Hospital Anxiety and Depression scale (HAD) was distributed to all patients older than 16 years. Mean follow-up time was 4 years (range, 2-13 years) and response rate, 91% (103 of 113 patients). HRQOL data were related to seizure frequency and severity (Chalfont Seizure Severity Scale). RESULTS: Seventy-six percent considered their global health to be better than it was before surgery. Degree of improvement in seizure control correlated with improved satisfaction with health (Spearman's r = 0.44). Higher SF-36 scores (higher HRQOL ratings) correlated with percentage reduction of seizure frequency for all scales and was strongest for perception of general health (Spearman's r = 0.46). When the patients were divided into four categories [A, completely seizure free (n = 29); B, seizure free with aura (n = 18); C, > or =75% reduction in seizure frequency (n = 24); and D, <75% reduction in seizure frequency (n = 32)], a strong positive association was found between higher SF-36 scores (with the exception of physical functioning) and better seizure control. Health-related limitations in role performance differentiated best between the outcome categories. For patients with > or =75% reduction in seizure frequency, low seizure severity correlated with higher HRQOL ratings for scales measuring social function, vitality, and mental health. Depression levels (HAD scale scores) were on average low. Anxiety (HAD) increased significantly from A to D. CONCLUSIONS: HRQOL seems to be scored as a continuum in relation to seizure frequency. Seizure severity measures give complementary information.

Adaptation, Psychological↗
PubMed1997

Radiographic abnormalities in canine multicentric lymphoma: a review of 84 cases.

The thoracic and abdominal radiographs of 84 dogs with multicentric lymphoma were examined to identify the radiological abnormalities. The frequency of occurrence of individual changes, role of radiography in diagnosis, relationship of radiographic changes to hypercalcaemia and prognostic relevance of radiographic findings were assessed. Multiple abnormalities were more commonly seen than solitary changes. No radiographic abnormalities were seen in approximately one quarter of thoracic radiographs and one fifth of abdominal radiographs. Lymphoma could not be diagnosed on the basis of radiographs alone. Many of the features of lymphoma were non-specific, having numerous possible causes. Cranial mediastinal disease was neither a prerequisite for, nor a disproportionately common finding in, hypercalcaemic patients. The absence of radiological abnormalities may be a positive prognostic indicator for the individual patient. The differential diagnoses for the radiographic abnormalities seen in lymphoma are discussed.

Abdomen↗
PubMed1997

Protein model representation and construction.

Crystallographic studies play a major role in current efforts towards protein structure determination. However, despite recent advances in computational tools for molecular modeling and graphics, the task of constructing a protein model from crystallographic data remains complex and time-consuming, requiring extensive expert intervention. This paper describes an approach to automating the process of model construction, where a model is represented as an annotated trace (or partial trace) of the three-dimensional backbone of the structure. Potential models are generated using an evolutionary algorithm, which incorporates multiple fitness functions tailored to different structural levels in the protein. Preliminary experimental results, which demonstrate the viability of the approach, are reported.

Algorithms↗
PubMed1997

Pain and the choice to hasten death in patients with painful metastatic cancer.

Unrelieved pain has been cited as an important reason why cancer patients may seek to hasten their deaths. We interviewed 48 patients with painful metastatic cancer to ascertain their interest in various active and passive modes of hastening death. Ninety percent of these patients supported the general right of terminally ill patients to passive modes of hastening death and 80% supported the right to active modes such as assisted suicide and euthanasia. If they developed severe pain that could not be relieved, 80% would instruct their physician write a "do not attempt resuscitation" order, 40%-50% would want to receive suicide information or a lethal prescription from their physician, and 34% would request a lethal injection from their physician. Current pain and depression levels were not associated with interest in hastening death, but current somatic symptom burden was significantly associated with this interest.

Adult↗