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Biomedical subjects

D Barnes

Publications and source records attributed to D Barnes.

At least 91 records · Page 5Linked to original sources

Cyclin D1 and prognosis in human breast cancer.

We have used immunohistochemical staining to assess the expression of cyclin D1 in formalin-fixed sections of 345 breast carcinomas, dating back 20 years. Clinical follow-up data were available on all patients. Approximately 50% of the tumours showed excessive nuclear staining for cyclin D1 as compared with normal epithelium. Some tumours showed strong cytoplasmic staining in the absence of nuclear staining, and around 25% of the tumours were judged to be negative for nuclear cyclin D1. Contrary to expectations, moderate/strong staining for cyclin D1 was associated with improved relapse-free and overall survival relative to patients whose tumours stained weakly or negatively. Conversely, tumours that were considered negative for cyclin D1 staining had an adverse prognosis, and the poor outcome was further accentuated if the tumours were also oestrogen receptor-negative. A possible explanation for our findings is that tumours in which cyclin D1 levels are abnormally low may have sustained mutations in other genes, such as RBI and that it is this abnormality that has the more significant impact on survival from breast cancer.

Adult↗

Patterns of disease activity in multiple sclerosis patients: a study with quantitative gadolinium-enhanced brain MRI and cytokine measurement in different clinical subgroups.

In this study we assessed the subclinical disease activity in 45 patients with primary progressive, secondary progressive or relapsing-remitting multiple sclerosis (MS). The patients had gadolinium-enhanced brain MRI scans, which were analysed using a semiquantitative method both for lesion load and for degree of enhancement. At the same time cerebrospinal fluid (CSF) and serum samples were collected and, from these, cytokine levels were measured in most cases by enzyme-linked immunoassay using commercially available kits. Enhancing lesions on MRI were found in 73% of the patients. The sensitivity of this test was greatly increased by our method of analysis as far as the primary progressive patients are concerned (70% vs 40% for conventional evaluation). CSF interleukin-1 beta (IL-1 beta) levels were above the normal range in 22% and IL-6 levels in 13% of patients, while tumour necrosis factor alpha (TNF-alpha) was undetectable or below the upper normal limits in all the samples tested. Serum IL-1 beta was above the normal limits in 40%, IL-6 in 42% and TNF-alpha in 7% of patients. No significant differences in cytokine profiles were found between the clinical subgroups. This study confirms the high sensitivity of gadolinium-enhanced MRI in detecting MS activity, which was further increased by our method of analysis. Longitudinal studies performed with more sensitive immunological techniques are needed to define better the relationship between cytokine, clinical and MRI data in MS patients.

Adult↗

Microalbuminuria as a marker of silent myocardial ischaemia in IDDM patients.

Insulin-dependent diabetic (IDDM) subjects with microalbuminuria have an increased long-term risk of overt cardiovascular disease; however, the early exposure to cardiovascular risk factors may increase their predisposition to current silent myocardial ischaemia. The frequency of silent myocardial ischaemia detected by stress echocardiography and electrocardiography was significantly greater in 32 asymptomatic IDDM patients with microalbuminuria compared to 32 normoalbuminuric IDDM patients (25% [n = 8] vs 6.3% [n = 2]; p = 0.03, odds ratio [95% CI] 6.3 [1.2, 37.8]). Elective coronary artery bypass grafting was required in 1 patient with microalbuminuria and silent myocardial disease. Microalbuminuria and poorer autonomic function were independently associated with silent myocardial ischaemia in multivariate analysis (p = 0.03 and p = 0.02, respectively). Screening for silent myocardial ischaemia using these non-invasive tests may be warranted in microalbuminuric IDDM which patients could be of considerable clinical importance.

Adolescent↗

Emergent simple discriminations and conditional relations in children, intellectually impaired adults, and normal adults.

Previous research has shown that when, under non-reinforced conditions, stimuli are added to S+ and S- stimuli in simultaneous discrimination tasks, transfer between paired stimuli is likely to occur. The present study examined whether this procedure also leads to the formation of conditional relations between paired stimuli. In Experiments 1, 2, and 3, normal pre-school children were trained on a simultaneous discrimination task with A1 reinforced and A2 not reinforced (A1+/A2-). Then they received two tests (no programmed consequences): one with B stimuli superimposed on the A stimuli (A1B1/ A2B2), and one with B stimuli only (B1/B2). Subjects who selected A1B1 and B1 also received conditional discrimination tests: one with B1 or B2 as samples and A1 and A2 as comparisons (B-A), and one in which the functions of these stimuli were reversed (A-B). Intellectually impaired adults and normal adults served in Experiments 4 and 5, respectively. These experiments were basically the same except that the subjects were also given the opportunity to demonstrate transfer from B to C via BC (B1C1/B2C2 and C1/C2 tests). Most children (75%) and intellectually impaired adults (75%) treated the conditional discrimination probe tasks as simple discriminations and typically selected the trained and derived S+ stimuli. The remaining children, intellectually impaired adults, and all normal adults related all directly and indirectly linked stimuli of the same functions conditionally to one another (A-B, B-C, A-C, and vice versa). The present findings suggest that, as humans develop, conditional stimulus relations may emerge from tasks and stimulus configurations that are increasingly remote from traditional conditional discrimination tasks.

Adult↗

International population and development: the United Nations' Cairo Action Plan for women's health.

The report of the International Conference on Population and Development (Cairo Action Document) was sponsored by 180 national governments and 1,200 nongovernmental organizations during the United Nations' conference on women, population, and development in Cairo, Egypt 1994. Many international conferences preceded the one in Cairo but it was there that women participated at an unprecedented level in shaping the debate. The resulting document represents a quantum leap for women's health. Nurses can play a major role in using the principles in the Cairo Action Document by empowering women and enhancing their health care. To invite dialogue, the authors provide an analysis of the Cairo Plan from a nursing perspective and identify three paradoxes that may hinder progress: Universal values and local cultures, global policy and local implementation, and national development and women's empowerment. Clinicians, scholars, and members of professional organizations are asked to consider the assumptions that underlie the recommendations for action and to propose ways to resolve the problems that may evolve during implementation.

Egypt↗

IFNB in MS.

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Humans↗

Amplification of chromosome band 11q13 and a role for cyclin D1 in human breast cancer.

In this paper we describe how research on the mouse mammary tumor virus model of breast cancer resulted in the identification of an amplified region of DNA on human chromosome 11 band q13. This amplification occurs in approximately 15% of primary breast cancers. Several candidate oncogenes map within the amplicon but by analysing expression of these genes a strong case can be made for a role for cyclin D1 in tumorigenesis. Immunohistochemical staining indicates that cyclin D1 is expressed at elevated levels in around 40% of breast cancers, including those with the 11q13 amplification. The potential function of cyclin D1 as a regulator of early cell division cycle events would be consistent with a role in neoplasia.

Blotting, Southern↗

Matching versus cultural competence in research: methodological considerations.

Researcher/participant matching has been used in nursing research as a strategy for the development of culturally competent knowledge. In this manuscript, the complexities inherent in matching in nursing research are discussed. In raising and discussing issues and questions related to matching, we argue that although matching may be one of the strategies used to generate culturally competent knowledge, it is frequently too complex for operationalization. Therefore, we propose that researchers reflect on questions related to their knowledge of culture, their cultural sensitivity, and the nature of collaboration during every phase of the research. Reflecting on and responding to these questions in every research project may facilitate the development of more culturally competent knowledge.

Cultural Diversity↗

Expression of ras p21, p53 and c-erbB-2 in advanced breast cancer and response to first line hormonal therapy.

Several oncogenes and tumour-suppressor genes have been identified that may have an important role in the development of human breast carcinoma. Furthermore, some of these gene alterations may be linked to the development of invasion and subsequent metastasis. Alterations in the expression of ras p21, p53 and c-erbB-2 have all been linked to tumours with rapid cellular proliferation, but the evidence that they are of prognostic importance in patients with breast cancer is conflicting. This study explores the relationship between expression of these oncoproteins and clinical outcome in 92 patients with either locally advanced or metastatic breast cancer treated with primary endocrine therapy. Specimens of the primary carcinoma were available for analysis of hormone receptor, Ki67 labelling index, epidermal growth factor receptor (EGFR), c-erbB-2, p53 and ras p21. Clinical response was measured according to UICC criteria after 6 months of treatment and all patients were followed for time to progression and overall survival. As shown previously, oestrogen receptor (ER) negativity, high Ki67 labelling index and EGFR overexpression were associated with a shorter time to progression and overall survival. However, no statistically significant relationship existed between expression of ras p21, p53 or c-erbB-2 and response to treatment, time to progression or overall survival. We conclude that staining for these three oncoproteins has no role in therapeutic decision-making in patients with advanced breast cancer. The negative finding implies that while abnormal expression of these genes may have an important role in the development of breast cancer, the variations in growth characteristics of advanced breast cancer may be influenced by other factors.

Adult↗

The Effect of Follow-up on Reporting Success for Obesity Surgery.

BACKGROUND: Much is written about the importance of follow-up in determining the effect of surgical treatment for obesity upon weight loss. When patients are lost to follow-up, it has been suggested that these patients should be considered as failures. This study was undertaken to determine the effect of incorporating patients not followed in a definition of success for weight loss at one year. METHODS: Data from 34 surgical practices were used to study the effect of using two different denominators, patients followed (Df) or patients eligible (De), to define success. The numerator used in both methods was the number of patients with </= 50% EW at 1 year. RESULTS: One-year follow-up was 61% (5091/8356). Success was 67% (3423/5091) when calculated using the denominator patients followed (Df). No correlation was found between success and follow-up when data within each surgical practice were averaged and used in a correlation analysis. CONCLUSIONS: This study does not support the thesis that patients who fall to return for follow-up should be considered as having failed in weight control.

Journal Article↗

A transformation of self-discrimination response functions in accordance with the arbitrarily applicable relations of sameness, more than, and less than.

In Experiment 1, 2 experimental subjects were given pretraining of nonarbitrary relations that brought their responses under the control of four contextual stimuli; same, opposite, more than, and less than. One control subject was not exposed to this pretraining. The 2 pretrained subjects and the 3rd nonpretrained subject then received training in six arbitrary relations, the following four relations being the most critical: same/A1-B1, same/A1-C1, less than/A1-B2, more than/A1-C2. All 3 subjects were then tested for seven derived relations, the following three relations being the most important: same/B1-C1, more than/B1-C2, less than/B1-B2. The 2 pretrained subjects, but not the nonpretrained subject, showed the derived relations. One of the stimuli (B1) from the relational network and two novel stimuli (X1 and X2) were then used to train three different self-discrimination responses on three complex schedules of reinforcement. That is, all 3 subjects were trained to pick X1 if they had not emitted a response, to pick B1 if they had emitted one response only, and to pick X2 if they had emitted two responses only. The 2 pretrained subjects, but not the nonpretrained subject, showed the predicted transformation of self-discrimination response functions in accordance with the relations of sameness, more than, and less than (i.e., no response, pick B2; one response only, pick C1; and two responses only, pick C2). In Experiment 2, 2 new subjects were employed, and the arbitrary relational training and testing phases were modified to control for a procedural artifact that may have contributed to the results of the first experiment. Experiment 2 replicated the findings of Experiment 1. The pattern of results support the utility of a relational frames approach to understanding derived stimulus relations.

Journal Article↗

Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining.

Immunohistochemical staining with a monoclonal antibody against human cyclin D1 can be used to identify breast cancers that have an amplification of the q13 region of chromosome 11. In general, the intensity of staining is directly proportional to the degree of DNA amplification. In two unusual tumors, in which the CCND1 locus is highly amplified but staining is relatively weak, it appears that the DNA has undergone rearrangement and that the amplified/rearranged CCND1 allele may have reduced transcriptional activity. More significantly, the immunohistochemical technique identifies additional tumors in which the cyclin D1 gene is overexpressed with only marginal or undetectable increases in copy number, implying that other mechanisms can lead to deregulated expression. These results suggest that the frequency of overexpression is much higher than previously concluded from DNA-based analyses and that more than one-third of human breast cancers may contain excessive levels of cyclin D1. The technique we describe should facilitate the detection of this abnormality in a clinical setting and clarify its prognostic significance.

Alleles↗

Enhancing multi-agency collaboration in the management of child sexual abuse.

Conflict naturally occurs when multiple organizations with different mandates interact to deliver services to children who have been sexually abused. In this article, the authors review the underlying sources of conflict that impair interorganization functioning, and dysfunctional techniques used to manage such conflict. As an alternative to dysfunctional conflict management strategies, the authors develop a model for managing conflict which builds on concepts from the operations and negotiations literature. The approach the authors advocate involves the three steps of problem characterization, acknowledgement of relevant goals and interests, and negotiation when interests are in conflict. The benefit of this approach, and difficulties encountered when employing it, are discussed.

Child↗

A transfer of self-discrimination response functions through equivalence relations.

The present study tested the idea that human self-discrimination response functions may transfer through equivalence relations. Four subjects were trained in six symbolic matching-to-sample tasks (if see A1, choose B1; A1-C1, A2-B2, A2-C2, A3-B3, A3-C3) and were then tested for the formation of three equivalence relations (B1-C1, B2-C2, B3-C3). Two of the B stimuli (B1 and B2) were then used to train two different self-discrimination responses using either detailed instructions (Subjects 1 to 3) or minimal instructions (Subject 4) on two complex schedules of reinforcement (i.e., subjects were trained to pick the B1 stimulus if they had not emitted a response, and to pick the B2 stimulus if they had emitted one or more responses on the previous schedule). All 4 subjects showed the predicted transfer of self-discrimination response functions through equivalence relations (i.e., no response on the schedule, pick C1; one or more responses on the schedule, pick C2). Subjects also demonstrated this transfer when they were required to discriminate their schedule performance before exposure to the schedule (i.e., "what I intend to do"). Four control subjects were also used in the study. Two of these (Subjects 5 and 6) were not exposed to any form of matching-to-sample training and testing (nonequivalence controls). The 2 remaining subjects (7 and 8) were exposed to matching-to-sample training and testing that incorporated stimuli not used during the transfer test; C1 and C2 were replaced by N1 and N2 during the matching-to-sample training and testing, but C1 and C2 were used for the transfer tests (equivalence controls). All 4 subjects failed to produce the self-discrimination transfer performances observed with the experimental subjects.

Journal Article↗