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Biomedical subjects

D M Barnes

Publications and source records attributed to D M Barnes.

At least 55 records · Page 3Linked to original sources
PubMed1999

Overexpression of c-erbB2 is an independent marker of resistance to endocrine therapy in advanced breast cancer.

The present study investigated the interaction between c-erbB2 overexpression and the response to first-line endocrine therapy in patients with advanced breast cancer. The primary tumours of 241 patients who were treated at first relapse with endocrine therapy were assessed for overexpression of c-erbB2 by immunohistochemistry. c-erbB2 was overexpressed in 76 (32%) of primary breast cancers and did not correlate with any other prognostic factor. The overall response to treatment and time to progression were significantly lower in patients with c-erbB2-positive tumours compared to those that were c-erbB2-negative (38% vs 56%, P = 0.02; and 4.1 months vs 8.7 months, P < 0.001, respectively). In multivariate analysis, c-erbB2 status was the most significant predictive factor for a short time to progression (P = 0.0009). In patients with ER-positive primary tumours treated at relapse with tamoxifen (n = 170), overexpression of c-erbB2 was associated with a significantly shorter time to progression (5.5 months vs 11.2 months, P < 0.001). In conclusion, overexpression of c-erbB2 in the primary tumour is an independent marker of relative resistance to first-line endocrine therapy in patients with advanced breast cancer. In patients with ER-positive primary tumours, the overexpression of c-erbB2 defines a subgroup less likely to respond to endocrine therapy.

Adult↗
PubMed1999

Research on the probable cause of an outbreak of field rickets in turkeys.

An outbreak of field rickets in turkeys prompted studies on the cause. In Experiment 1, there were four treatments with two replicate pens of 10 poults per pen. The treatments consisted of poults fed newly manufactured feed (control), poults fed a diet containing control feed and 5% clean litter, poults fed control feed and 5% litter from the pens of affected poults, and poults challenged with an intestinal homogenate by gavage. Field rickets did not develop with these treatments. The feed was suspect, and, in Experiment 2, poults were either fed the suspect feed or newly manufactured feed. There were four replicate pens of 25 poults per pen. Poults fed the suspect feed had a decrease (P < or = 0.05) in BW at 1, 2, 3, and 4 wk of age; an increase in the relative weight of the liver, pancreas, kidney, and bursa of Fabricius; and a decrease in bone ash. There were changes in clinical chemistries. In the third study, there were five dietary treatments with two replicate pens of 25 poults per treatment. The treatments consisted of poults fed newly manufactured feed; new feed mixed with 25, 50, or 75% suspect feed; or 100% suspect feed. Body weights of poults fed 100% suspect feed were decreased at 2, 3, and 4 wk as was the relative weight of the liver, pancreas, and bursa of Fabricius. The relative weight of the kidney increased. Lameness, a decrease in bone ash, and changes in hematology and blood chemistry were observed in the poults consuming 100% suspect feed. These data demonstrate that feed from the original outbreak could induce field rickets and was toxic. Because the feed contained adequate vitamin D, calcium, and phosphorus, the cause of this outbreak of field rickets is thought to be a toxic feed contaminant affecting bone development.

Alkaline Phosphatase↗
PubMed1999

Use of Internet-based resources to support an introductory animal and poultry science course.

This article describes the development and implementation of a World Wide Web page to support a team-taught introductory animal and poultry science course. The objectives were to examine the capabilities of this type of instructional resource, determine students' willingness to use this type of resource, create opportunities for interactive learning, and improve students' enthusiasm for the subject area. A variety of course materials were made available through the Internet, including the class syllabus, lecture notes, and practice questions to support and augment class lectures. Additional on-line resources included a bulletin board for instructor announcements, a list-serve for student discussions concerning administrative and educational issues arising during the semester, a class E-mail list, and a page with links to other sites of agricultural interest. Materials were accessible from a variety of computer resources, including campus computing laboratories, dial-up access, and access via other Internet service providers. Use of the materials was evaluated by analysis of log files from the server. Effectiveness of the resources was determined from surveys of students conducted before and after implementation of the on-line resource. Students indicated that the most useful components of the Web page were the class notes and practice/review questions. Effectiveness of the site was related to the amount of material available through the site, the level of interaction, whether the task was required, and the ease of access to computers and the Web site. Student evaluations indicated that this form of instructional supplement is a viable method for enhancing the learning experience in the introductory animal sciences.

Animal Husbandry↗
PubMed1998

Immunohistochemical expression of BRCA2 protein and allelic loss at the BRCA2 locus in prostate cancer. CRC/BPG UK Familial Prostate Cancer Study Collaborators.

Many epidemiological studies have reported an association between breast and prostate cancer. BRCA2 functions as a tumour-suppressor gene in about 35% of large familial breast-cancer clusters; its role in the pathogenesis of sporadic breast cancer is less clear. We have evaluated immunohistochemical expression of BRCA2 protein and allelic loss of markers at the BRCA2 locus in tissue derived both from sporadic and from familial cases of prostate cancer. Immunohistochemical analysis was performed in 167 paraffin-embedded archival specimens. Normal prostate and 75% (120/160) of prostate-cancer tissue did not express BRCA2 protein. However, 25% (40/160) of cancer cases did express patchy staining; of these, 17% (2711 60) expressed positive nuclear staining in normal glandular tissue adjacent to tumour (either in addition to, or, independent of tumour). Allelic loss is the hallmark of a tumour-suppressor gene. Markers flanking (D13S267, D13S260) and within (D13S171) the BRCA2 gene indicated allelic loss in at least one locus in 23% (17/73) of tumours analyzed. There was no difference in the rates of allelic loss between sporadic and familial tumours, nor was there any association between immunohistochemical staining and allelic loss. Although immunohistochemical staining provided no useful prognostic information, allelic loss at BRCA2 was shown in univariate analysis to be associated with poorer survival (log-rank test, p = 0.046).

BRCA2 Protein↗
PubMed1998

Characterization of p53 oligomerization domain mutations isolated from Li-Fraumeni and Li-Fraumeni like family members.

p53 is a tumour suppressor gene which functions as a transcription factor to upregulate genes for growth arrest and apoptosis following DNA damage. p53 mutations are associated with Li-Fraumeni and Li-Fraumeni like syndromes. Recently mutations of the oligomerization domain have been isolated from an LFS and an LFL family affecting respectively codon 344 (Leu to Pro) and 337 (Arg to Cys). The present study was designed to determine the affect of these mutations on the function of p53 protein. p53 344 Leu to Pro existed only in a monomeric form and could not bind to DNA. It was inactive at inducing apoptosis, transactivating luciferase from a bax promoter and inhibiting cell growth. In contrast, p53 337 Arg to Cys could form tetramers and could bind to DNA. However, p53 337 Arg to Cys was not fully active and could only induce apoptosis, transactivate luciferase from a bax promoter and inhibit cell growth with approximately 60% of the ability of wild-type p53. Both mutant proteins had reduced ability to bind to MDM2, p53 337 Arg to Cys being more reduced than p53 344 Leu to Pro. These results indicate that point mutations in the oligomerization domain can disrupt p53 function. In addition, the value of LFS and LFL families for the further understanding of the biological and biochemical properties of p53 is demonstrated.

Apoptosis↗
PubMed1998

Retinoblastoma and p16 proteins in mammary carcinoma: their relationship to cyclin D1 and histopathological parameters.

The cell cycle-associated retinoblastoma protein (pRb) and p16 protein were demonstrated using immuno-histochemistry on paraffin sections from 192 cases of invasive breast carcinoma. Abnormal expression of pRb was defined as negative staining and was seen in 17% of tumours. Such abnormal expression was significantly more frequent in tumours with negative oestrogen receptor (ER) status. There was also a trend for tumours which were negative for pRb to be grade III ductal carcinomas. There was no association between p16 staining and any histopathological parameter, though, surprisingly, log-rank analysis showed that strong staining was associated with a poor outcome. There was a significant inverse relationship between pRb and p16 expression and a significant positive association between pRb and cyclin D1. In a Cox multivariate analysis, which included cyclin D1, neither pRb nor p16 was an independent predictor of patient outcome.

Breast Neoplasms↗
PubMed1998

Cyclin D1 and associated proteins in mammary ductal carcinoma in situ and atypical ductal hyperplasia.

Experimental studies suggest that cyclin D1 is a potential oncogene but in clinical studies of invasive breast cancer, overexpression of cyclin D1 is found to be associated with oestrogen receptor (ER) expression and low histological grade, both markers of good prognosis. Immunohistochemistry has been used to examine the relationship between cyclin D1 expression and differentiation in 36 cases of ductal carcinoma in situ (DCIS) and the interrelationship between expression of cyclin D1, its associated protein product of the retinoblastoma gene (pRb), and ER, in this group of cases. The expression of these markers has also been examined in nine cases of atypical ductal hyperplasia (ADH) and these results have been compared with the levels of expression seen in DCIS. Cyclin D1 overexpression was found in 23/36 (64 per cent) cases of DCIS and, in contrast to invasive carcinoma, there was no relationship with either differentiation or ER expression. The level of pRb expression was significantly associated with cyclin D1 expression (rS = 0.49, P = 0.001) and only two cases (6 per cent) were pRb-negative. There was no association between pRb and differentiation of DCIS or ER status. In contrast to DCIS, only one case of ADH showed overexpression of cyclin D1 (Mann-Whitney U-test, P = 0.02). All cases of ADH were ER-positive and showed moderate pRb staining, similar to that seen in well-differentiated DCIS. These results provide further evidence that overexpression of cyclin D1 plays a role early in carcinogenesis.

Adult↗
PubMed1998

Tumour grade does not change between primary and recurrent mammary carcinoma.

The primary tumour grade in 115 patients with infiltrating ductal carcinoma of the breast was compared with the type of the ductal carcinoma in situ (DCIS) component and with the grade of 169 locally recurrent and metastatic lesions. 102 patients had axillary lymph node metastases at the time of primary surgery, 49 had subsequent recurrences and 36 had both. There was concordance of grade between the primary tumour and axillary lymph node metastases and with subsequent locally recurrent and metastatic lesions. The type of the DCIS component was also significantly associated with the grade of the infiltrating component. No evidence of progression of tumour grade between these phases of mammary carcinoma was found.

Breast Neoplasms↗
PubMed1998

Increased use of immunohistochemistry for oestrogen receptor measurement in mammary carcinoma: the need for quality assurance.

This paper outlines the changes which have occurred over the last 25 years in the methods employed for the measurement of oestrogen receptors to aid the management of women with breast cancer. Immunohistochemistry is now the method of choice and knowledge of oestrogen receptor status is being used with increasing frequency for the selection of adjuvant treatment as well as for the treatment of metastatic disease. It is essential that good quality assurance procedures are established so that results are reproducible and can be used with confidence in individual centres as well as being comparable with those produced elsewhere. A retrospective study of 170 women with metastatic breast cancer provides the basis for a discussion on the advantages and pitfalls of the immunohistochemical assay. Particular emphasis is paid to the choice of cut-off and how the results may be applied in patient management.

Breast Neoplasms↗
PubMed1998

Cyclin D1 in breast cancer.

Cyclin D1 protein plays an important part in regulating the progress of the cell during the G1 phase of the cell cycle. The cyclin D1 gene, CCND1, is amplified in approximately 20% of mammary carcinomas, and the protein is over-expressed in approximately 50% of cases. This has led to intensive study to ascertain whether cyclin D1 is a biological marker in breast cancer; however, the clinical work has produced unexpected results. Work in cell lines and in transgenic mice indicate that CCND1 is a weak oncogene and it was expected that, like c-erbB-2, over-expression of cyclin D1 protein would be associated with a poor prognosis. Early immunohistochemical prognostic studies produced equivocal results but we, and others, have recently shown that strong staining for cyclin D1 is more likely to be seen in well differentiated, estrogen receptor positive carcinomas. Furthermore, we have found that over-expression of cyclin D1 is actually associated with a good outcome, both in terms of prognosis and response to endocrine treatment. Cyclin D1 is frequently over-expressed in ductal carcinoma in situ but not in benign breast disease, including atypical ductal hyperplasia; hence its expression appears to be closely linked with carcinogenesis. In order to help explain the apparent beneficial effects of cyclin D1 over-expression, a number of closely associated cell cycle proteins have also been evaluated, including the cyclin dependent kinase inhibitor p27, which blocks the activating effects of cyclin D1. Initial reports show that high levels of p27 are associated with a good prognosis and we have shown a positive association between p27 and cyclin D1 expression. These clinical results of cyclin D1 are an example of how information obtained from basic cell biology studies needs to be complemented by clinical studies to ascertain the true worth of a prognostic marker.

Animals↗
PubMed1998

Cell proliferation measured by MIB1 and timing of surgery for breast cancer.

We have investigated the use of the antibody MIB1 as a proliferative and prognostic marker in breast cancer and whether changes in proliferative activity could account for differences in prognosis of premenopausal women operated on during different phases of the menstrual cycle. MIB1 expression was strongly correlated with S-phase fraction and histological grade. There was no difference in MIB1 scores between different phases of the menstrual cycle. Both MIB1 score and timing of surgery correlated significantly with duration of survival, while the two together were even stronger predictors of overall survival. Women with slowly proliferating tumours surgically removed in the luteal phase had a very good prognosis, whereas women with rapidly proliferating tumours excised at other times of the cycle had a worse prognosis.

Adult↗
PubMed1998

Family history and survival in premenopausal breast cancer.

The clinicopathological characteristics of breast cancer in 95 women between the ages of 24 and 45 years with a family history of breast cancer were compared with tumours from 329 women with sporadic disease matched for age and year of diagnosis. There was a trend for the family history patients to have slightly smaller tumours (mean size 2.49 cm) than the controls (mean 3.04 cm) (Mann-Whitney test, P = 0.09). A significantly greater proportion of the familial cases had grade III infiltrating ductal carcinoma than did the controls (40% vs 27%; chi2(1) = 5.64, P = 0.02). Despite this, there were more cases of operable node-negative disease among the study group than among the controls (48% vs 32%; chi2(1) = 8.2, P = 0.004). There was a highly significant survival advantage for patients with a family history (chi2 = 22.4, P < 0.001). Five- and 10-year survival rates were 92% and 87% for those with a family history compared with 70% and 54% for those in the control group. This survival advantage was maintained when patients with operable disease only were considered. In multivariate analysis, which included age, tumour size, stage, histological grade and family history, family history was an independent predictor of favourable prognosis and, in a Cox model, was associated with a relative risk of survival of 6.11 (95% CI 2.81-13.28). These results suggest that familial breast cancer has a more favourable clinical course than the more common sporadic forms of the disease.

Adult↗
PubMed1998

Informed consent in a multicultural cancer patient population: implications for nursing practice.

Obtaining informed consent, an ethical obligation of nurses and other health care providers, occurs routinely when patients make health care decisions. The values underlying informed consent (promotion of patients' well-being and respect for their self-determination) are embedded in the dominant American culture. Nurses who apply the USA's cultural values of informed consent when caring for patients who come from other cultures encounter some ethical dilemmas. This descriptive study, conducted with Latino, Chinese and Anglo-American cancer patients in a large, public, west-coast clinic, describes constraints on the informed consent process in a multicultural setting, including language barriers, the clinical environment, control in decision making, and conflicting desired health outcomes for health care providers and patients, and suggests some implications for nursing practice.

Asian↗
PubMed1998

The clinical longevity of porcelain veneers: a 48-month clinical evaluation.

The authors evaluated the clinical longevity of a brand of porcelain veneers and the accompanying cementation system. Fifty-nine porcelain veneers were prepared and placed in 12 patients by one practitioner and evaluated by two evaluators using modified Ryge criteria at baseline and 12 months. Fifty-three veneers were evaluated similarly at 48 months. Plaque index and gingival index scores were recorded as well. At 48 months, the veneers had stable color, all margins were clinically acceptable, there was no secondary caries and the patients reported no sensitivity.

Adhesives↗
PubMed1998

Clinical evaluation of a new 10% carbamide peroxide tooth-whitening agent.

NUPRO Gold Tooth Whitening System was evaluated for efficacy according to the proposed ADA guidelines for acceptance. Sixty participants with discolored anterior teeth participated in a 14-day, double-blind, clinical trial. The participants were matched for age, gender, and oral health status and were given either a placebo gel without the active agent or the NUPRO Gold active gel, which they wore in a custom-fabricated mouth guard for home use. The shade of each participant's maxillary anterior teeth was evaluated using a value-oriented Vita Lumin Vacuum Shade Guide before the study. The same shade guide was used to determine shade changes. Time of use of the agent and potential side effects, such as tooth and gingival hypersensitivity and tissue irritation, were assessed at all recall examinations and were recorded by participants in daily diaries. The average shade change for the placebo users was less than one shade. The average shade change for the NUPRO Gold users was 6.96 shades. Tooth hypersensitivity varied from none to severe. Tissue irritation was minimal. The results of these evaluations indicate that NUPRO Gold is effective as a tooth-whitening system, when administered properly under the supervision of a dentist, with commonly reported side effects of transient tooth sensitivity and minimal gingival sensitivity. Little or no change in tissue health was noted. This study was supported by Dentsply Preventive Care (York, Pennsylvania).

Adolescent↗
PubMed1997

p53 immunohistochemical staining and survival after adjuvant chemotherapy for breast cancer.

We have investigated the relationship between immunohistochemically determined p53 status and outcome in 277 women with node-positive primary breast cancer who, following tumour excision and axillary clearance, were randomised to receive either 6 cycles of cyclophosphamide/methotrexate/S-fluorouracil (CMF) (n = 130) or no such post-operative treatment (n = 147). Follow-up data (median = 9 years) were available on all patients. A significant association was found between p53 status and survival. Patients with p53-positive tumours had a less favourable outcome than those with p53-negative disease. Women receiving adjuvant CMF chemotherapy had a significantly more favourable outcome compared to those who did not. The effect was seen both in women with p53-positive and p53-negative tumours; multivariate analysis showed relative risks for overall survival attributable to chemotherapy of 2.3 (95% CI 1.2-4.3) for women with p53-positive tumours and of 2.1 (95% CI 1.4-3.0) for those with p53-negative tumours. Thus, adjuvant chemotherapy with CMF is associated with a survival benefit in women with node-positive breast cancer irrespective of immunohistochemically determined p53 status.

Adult↗