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Biomedical subjects

D M Barnes

Publications and source records attributed to D M Barnes.

At least 127 records · Page 7Linked to original sources
PubMed1991

A 5- and 8-year clinical evaluation of a posterior composite resin.

Class I and II posterior composite resin (Ful-Fil) restorations were placed and were clinically evaluated, according to the US Public Health Service criteria, at baseline, 6 months, 5 years, and 8 years. At 5 years/8 years, alpha scores were assigned to the following percentages of restorations: 16%/31% for color match; 65%/62% for marginal discoloration; 74%/54% for cavosurface marginal discoloration; 100%/100% for axial contour; and 81%/65% for anatomic form. At 5 years/8 years, 56%/33% of Class II restorations had tight proximal contacts; 45%/44% had light contacts; and 0%/22% had no contacts. Transient postoperative sensitivity was reported in 6% of the restorations. Indirect evaluation indicated that there was an average of 64 +/- 35 microns of wear at baseline (because of overfinishing), 105 +/- 67 microns at 6 months, 217 +/- 76 microns at 5 years, and 253 +/- 82 microns at 8 years. At 5 years, three of the restorations, and at 8 years, four additional restorations, were clinically unacceptable because of recurrent caries and/or excessive wear. Final success rates of 90% and 77% at 5 and 8 years, respectively, were calculated.

Adult↗
PubMed1990

Reproductive and neonatal losses associated with possible encephalomyocarditis virus infection in pigs.

A possible infection with encephalomyocarditis virus was investigated on two Minnesota pig farms which experienced an increase in stillborn and mummified fetuses, high pre-weaning mortality and reduced farrowing rates. The monthly averages for the numbers of piglets born dead per litter on farms A and B reached 4-6 and 3-6, the pre-weaning mortalities 50 per cent and 31 per cent, and the farrowing rates 52 per cent and 63 per cent, respectively. Serological and histopathological examinations supported a diagnosis of infection with encephalomyocarditis virus, but attempts to isolate the virus failed. Specific antibody to the virus was detected in both fetal and neonatal sera collected from abnormal litters. The predominant histopathological finding was myocarditis consisting of focal or diffuse mononuclear cell infiltration. The detection of specific antibody, and the myocardial lesions in stillborn fetuses, suggested that the problems were associated with infection by encephalomyocarditis virus.

Abortion, Veterinary↗
PubMed1990

Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms.

Proliferating cell nuclear antigen (PCNA) is a 36 kD nuclear protein associated with the cell cycle. A monoclonal antibody, PC10, that recognizes a fixation and processing resistant epitope has been used to investigate its tissue distribution. Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues. PCNA immunoreactivity is induced in lectin stimulated peripheral blood mononuclear cells in parallel with bromodeoxyuridine incorporation and the number of cells with PCNA immunoreactivity is reduced by induction of differentiation in HL60 cells. In non-Hodgkin's lymphomas a linear relation between Ki67 and PCNA staining was demonstrated. These data suggest that in normal tissues and lymphoid neoplasms, PCNA immunolocalization can be used as an index of cell proliferation. However, in some forms of neoplasia, including breast and gastric cancer and in vitro cell lines, the simple relation between PCNA expression and cell proliferation is lost. In some breast and pancreatic tumours there is apparent deregulation of PCNA with increased expression in tissues adjacent to the tumours. The over-expression in some tumours and in adjacent morphologically normal tissue may represent autocrine or paracrine growth factor influence on PCNA gene expression.

Adult↗
PubMed1990

Immunohistochemical demonstration of c-erbB-2 protein in mammary ductal carcinoma in situ.

The presence of the c-erbB-2 protein, demonstrated immunohistochemically with antibody 21N, has been studied in 72 cases of pure mammary ductal carcinoma in situ. Sixty-one percent of cases showed positive staining. The protein was always present in large-cell comedo type of ductal carcinoma in situ, and never in small-cell cribriform/micropapillary type of ductal carcinoma in situ. When nuclear size was measured, staining was associated with tumors containing cells with large nuclei measuring up to 20 mu, and was never present in lesions containing cells with small nuclei measuring 10 mu or less. In tumors of mixed histopathologic type of ductal carcinoma in situ, variable staining was seen; the cells with small nuclei never stained, while the majority of cells with large nuclei reacted positively. The possible relevance of these findings to the biologic behavior of DCIS is discussed.

Breast Neoplasms↗
PubMed1990

Gene amplification on chromosome band 11q13 and oestrogen receptor status in breast cancer.

We have analysed DNA from 183 primary breast cancers for amplification or rearrangement of a number of cellular proto-oncogenes, focusing primarily on a cluster of markers on the long arm of chromosome 11. Two of these oncogenes, INT2 and HST1, both of which encode members of the fibroblast growth factor family, are implicated in the generation of virally induced mammary tumours in mice. Here we confirm earlier reports that the q13 region of chromosome 11, in which these genes are tandemly linked, is modestly amplified in approximately 15% of primary human breast cancers. This amplification is confined, with one exception, to cases in which the oestrogen receptor (ER) levels are in excess of 20 fmol/mg protein (P = 0.001). However, DNA amplification does not usually result in detectable expression of either the INT2 or HST1 gene. The data imply that some other gene in the vicinity must contribute to the development of a subset of ER-positive tumours and that assessing the amplification of this region of DNA may be of value in defining a separate category of ER-positive tumour.

Adult↗
PubMed1990

DNA index, S-phase fraction, histological grade and prognosis in breast cancer.

DNA index and S-phase fraction (SPF) were measured by flow cytometry on paraffin embedded tissue from 140 primary breast tumours. The results of DNA analysis were compared with the size, degree of axillary node involvement, histological grade and steroid receptor content of the tumours, as well as with the patients' subsequent clinical course. Forty-four (31.4%) of the 140 tumours were diploid. S-phase fraction was evaluable for 134 (95.7%). The median SPF of the whole population was 7.1%, with diploid tumours having a significantly lower median SPF (3.2%) than aneuploid (10.1%, P less than 0.001). Both aneuploidy (P = 0.002) and high SPF (P less than 0.001) were strongly associated with high histological grade. There was no significant association between either DNA ploidy or SPF and tumour size, nodal status or steroid receptor content. An SPF below the median was strongly associated with better relapse-free survival (P = 0.008), overall survival (P = 0.004) and survival after relapse (P less than 0.001). Ploidy did not correlate significantly with clinical course. Multivariate analysis using the Cox model suggested that, while SPF gave prognostic information independent of tumour size or nodal status, this independent significance was lost when histological grade was included in the analysis.

Adult↗
PubMed1990

Node-negative breast cancer: prognostic subgroups defined by tumor size and flow cytometry.

Adjuvant systemic therapy for women with node-negative breast cancer is most easily justified for those patients at highest risk of relapse. We have examined the impact of tumor size, histologic grade, estrogen receptor (ER) status, tumor ploidy, and S-phase fraction (SPF) on relapse-free survival (RFS) for 169 patients with node-negative breast cancer in order to identify groups of patients at high and low risk of relapse. Patients with small tumors (less than or equal to 1.0 cm) had a significantly better RFS than those with larger tumors (P = .005), with 96% remaining relapse-free at 5 years. Patients with tumors less than or equal to 1.0 cm were thus excluded from analysis when attempting to define a group with a poor prognosis. Within the group of patients with tumors greater than 1.0 cm, tumor ploidy (P = .63), ER status (P = .3), or progesterone receptor (PgR) status (P = .24) did not predict for RFS. Patients with grade 1 or 2 infiltrating ductal tumors had a significantly better prognosis than those with grade 3 tumors (P = .04). The prognostic factor that gave the widest separation between subgroups, however, was SPF. Patients whose tumors were greater than 1.0 cm with an SPF less than or equal to 10% had a 5-year RFS of 78% compared with a 5-year RFS of 52% for those with an SPF greater than 10% (P = .006). We have combined tumor size and SPF to identify three prognostic groups: (1) tumor less than or equal to 1.0 cm, 5-year RFS 96%; (2) tumor greater than 1.0 cm plus SPF less than or equal to 10%, 5-year RFS 78%; 3) tumor greater than 1.0 cm plus SPF greater than 10%, 5-year RFS 52%. These prognostic groupings may help identify patients most suitable for adjuvant therapy.

Breast Neoplasms↗
PubMed1990

Rates of metallothionein synthesis, degradation and accretion in a chicken macrophage cell line.

To understand the regulation of metallothionein (MT) accretion in a chicken-macrophage cell line, fractional rates of MT synthesis (FRS) and degradation (FRD) were measured by following decay kinetics of [35S]cysteine in MT. To obtain valid measurements, we added various amounts of cysteine to medium to ensure that the isotope tracer was adequately diluted after MT was labeled in the presence of various levels of zinc. We also demonstrated that the measured fractional rate of MT accretion closely approximated the difference between FRS and FRD. All fractional rates were similar for the two MT isoforms isolated. FRD did not change during the 27-hr decay period, but FRS and fractional rate of MT accretion changed over time. FRS of MT was 0.097 and 0.012 hr-1 from 0 to 9 and 9 to 27 hr, respectively, after cells were incubated in medium supplemented with 50 microM zinc. FRD of MT was 0.020 hr-1. Addition of 1100 microM unlabeled cysteine to medium supplemented with 50 microM zinc increased FRD and decreased FRS and fractional rate of MT accretion, as compared with not adding cysteine. Overall, these results indicate that rates of MT synthesis and degradation can both regulate MT accretion. Further experiments with various amounts of zinc and cysteine added to medium suggested that the effect of added cysteine on MT fractional rates was due to chelation of unbound zinc. Elimination of the cysteine effect on MT fractional rates was accomplished by adding more zinc to cysteine-supplemented medium. Thus, the concentration of unbound zinc affects the rates of MT synthesis and degradation.

Animals↗
PubMed1990

Absence of activating transmembrane mutations in the c-erbB-2 proto-oncogene in human breast cancer.

The rat neu proto-oncogene, which is a putative growth factor receptor closely related to the epidermal growth factor receptor, can be activated in vivo by a single point mutation in the sequence encoding its transmembrane region. The human homologue of neu, c-erbB-2, can be activated in vitro to an oncogenic form by point mutations in the same relative position in the gene. We have sought the presence of such activating mutations in a series of 100 cases of human breast cancer by polymerase chain reaction amplification and sequence-specific oligonucleotide hybridization, and also by a designed restriction fragment length polymorphism strategy in cases with Southern blot evidence of c-erbB-2 amplification. No evidence of activating point mutations in the c-erbB-2 protooncogene was found in any of these cases.

Base Sequence↗
PubMed1989

1-beta-D-arabinofuranosylcytosine and hydroxyurea production of cytotoxic synergy with cis-diamminedichloroplatinum(II) and modification of platinum-induced DNA interstrand cross-linking.

1-beta-D-Arabinofuranosylcytosine (ara-C) and hydroxyurea (HU) were investigated as possible inhibitors for the repair of cis-diamminedichloroplatinum(II) (DDP)-induced DNA damage. HU and ara-C were chosen for their known ability to inhibit DNA excision repair following UV irradiation. Work by several groups has suggested that the repair of DDP-induced DNA damage may involve an excision-repair mechanism. The cytotoxic effects of dose, exposure duration, and sequence for the three drugs was studied in a human colon cancer cell line (HT-29) by colony formation assays. Significant synergistic cytotoxicity was seen whether HU + ara-C were given prior to, or following DDP exposure. Cytotoxic synergy was also seen between HU + ara-C themselves. The effect of the combined antimetabolites on the level and persistence of DDP-induced DNA interstrand cross-links was assessed by DNA alkaline elution. These were measured as an indicator of DDP-DNA adduct formation and removal. When HU + ara-C exposure preceded or followed DDP treatment, higher levels of interstrand cross-linking were found at late time points than were seen with DDP alone, suggesting repair inhibition. We conclude that the combination of HU, ara-C, and DDP shows synergistic cytotoxicity, and that this effect may be due in part to inhibition of DDP-induced DNA adduct repair. The concentrations of drugs used in vitro are achievable in humans. On the basis of these results, a Phase I/II clinical trial of the three agents in combination has been initiated.

Cell Survival↗
PubMed1989

Extended role for needle biopsy in the management of carcinoma of the breast.

Treatment choice in primary breast cancer is wide and still controversial; it seems likely that the optimum treatment for individual patients could be dictated by biological indicators of tumour behaviour. If biopsy could provide prognostic information as well as detailed tissue diagnosis then definitive treatment, with or without adjuvant systemic therapy, could be planned from the outset. We studied 140 patients with a clinical diagnosis of primary breast cancer to determine how much information could be obtained from Tru-Cut needle biopsies performed at the first clinic visit. Ten patients were found to have benign disease. Of 130 carcinomas, 123 (95 per cent sensitivity) were diagnosed correctly from the needle biopsies, with seven false negative and no false positive results (100 per cent specificity). Precise histopathology was predicted in 121 (93 per cent). Grade was correctly assessed in 77 of 112 (69 per cent), but needle biopsy was not accurate for assessment of lymphatic invasion nor elastosis. Steroid hormone receptors were assayed in 59 needle biopsies, and the incidence of oestrogen receptor positivity (34, 58 per cent) was similar to the resected tumours (35, 59 per cent), but the incidence of progesterone receptor positivity (26, 44 per cent) was lower (33, 56 per cent, P less than 0.04). Immunostaining with monoclonal antibody human milk fat globule membrane was accurate in the needle biopsies. DNA analysis by flow cytometry was performed in 37 tumours and the concordance between needle biopsies and resected samples was high. Tru-Cut needle biopsy obviates open biopsy and gives reliable detailed information.

Adult↗
PubMed1989

The expression of milk fat globule antigens within human mammary tumours: relationship to steroid hormone receptors and response to endocrine treatment.

The value of steroid hormone receptors for the management of advanced carcinoma of the breast is often limited by the lack of availability of fresh tissue. Differentiation antigens may be estimated on paraffin-embedded fixed material by immunostaining, and the aim of this study was to determine whether staining with the monoclonal antibody raised to human milk fat globule (HMFG-1) could replace receptor measurements. The indirect immunoperoxidase technique was used to stain formalin-fixed paraffin-embedded tumour samples from 168 patients. All received tamoxifen or ovarian ablation as first-line systemic therapy, and all were evaluable for response (UICC criteria). One hundred and sixty-seven had oestrogen (ER) and progesterone receptors (PR) estimated. HMFG-1 staining was assessed as the percentage of tumour cells stained, and by the site of stain. The proportion of cells stained was highly correlated with both ER (P less than 0.0001) and PR (P less than 0.0001) and with response. When greater than or equal to 30% cells stained, 53 of 69 (77%) responded; when 20-29% stained 10 of 19 (53%) responded, when 10-19% stained seven of 19 (37%) responded, and when less than or equal to 9% cells stained 16 of 61 (26%) responded (P less than 0.0001). The median survival of patients with tumours that stained greater than or equal to 30% cells was 36 months, and with no cells stained, 11 months (P less than 0.0001). ROC (receiver operator characteristic) curves found that the optimum threshold for sensitivity and specificity of response prediction was greater than or equal to 20% cells stained. Cox's multiple regression analysis of 42 variables indicated that PR was the most important predictor of survival (P less than 0.000001), but that after PR the percentage of cells stained with HMFG-1 was the most important (P less than 0.0001). We conclude that immunostaining for HMFG-1 gives similar information to receptor status, and has the advantage that fixed archival tissue may be used.

Adult↗