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F Burns

Publications and source records attributed to F Burns.

29 records · Page 2Linked to original sources

Localization and imaging of radiolabeled monoclonal antibodies against colorectal carcinoma in tumor-bearing nude mice.

Four monoclonal antibodies (MoAbs) (35, 115, 17-1A, and B72.3) directed towards human carcinoma surface antigens have been studied in athymic nude mice with LS174T, CO112, or SW948 colon carcinoma xenografts or negative control melanoma (MEL-1), lymphoma (Namalwa), and breast (MCF-7) carcinoma xenografts to evaluate the effects of antigenic heterogeneity and time after administration on localization and imaging. 125I-labeled 115 showed the highest uptake of any antibody in LS174T tumors. MoAbs 35 and B72.3 showed similar but lower levels of uptake in LS174T and CO112 tumors, but B72.3 concentrated less in SW948 tumors. 17-1A showed the highest degree of accumulation in SW948 tumor xenografts. No specific uptake of the four anti-carcinoma MoAbs was observed in MEL-1, Namalwa, or MCF-7 xenografts. The specificity of the in vivo tumor localization of the four anti-carcinoma MoAbs was confirmed by the low degree of accumulation of a control MoAb against influenza virus in LS174T tumors. Imaging studies with 131I-labeled colorectal cancer MoAbs showed specific uptake and retention in LS174T tumors, with progressive clearance from the whole body. The colorectal cancer MoAbs were compared for immunohistochemical binding against biopsies from patients with colorectal cancer and adjacent normal colonic tissue. Most colorectal cancer specimens showed moderate to strong staining with the four MoAbs. The percentage of positive cells varied within and between tumors demonstrating antigenic heterogeneity. Absent to slight focal staining was seen with normal colon tissue. B72.3 showed the highest degree of staining specificity. This study indicates a difference in the immunohistochemical binding of a panel of MoAbs against biopsies of colon adenocarcinoma and a dependence of in vivo localization on the human colon cancer cell line used as target. This has important implications for future clinical diagnostic and therapeutic studies.

Animals↗

Pseudopapilledema and macrocephaly in a child.

A seven-year old female with primary megalencephaly and pseudopapilledema has been followed for over four consecutive years. Physical examinations of the patient and her family, funduscopic photography, and fluorescein angiography have failed to identify the etiology of her pseudopapilledema. Macrocephaly and pseudopapilledema have been seen in association in only one previous report to our knowledge. The importance of distinguishing pseudopapilledema from true papilledema in children with large heads is reviewed.

Brain↗

Expression of long terminal repeat (LTR) sequences in carcinogen-induced murine skin carcinomas.

RNA sequences homologous to the Long Terminal Repeat (LTR) sequence of Moloney Murine Leukemia Virus proviral DNA are expressed in murine squamous cell carcinomas of the skin induced by chemical carcinogens. These transcripts range in size from 8.2 to less than 2.4 kb but their size profile varies between individual tumors. These RNAs are not detected in the poly A+ RNA fraction obtained from the epidermis of control mice or carcinogen induced skin papillomas. The poly A+ RNAs from the livers and spleens of some of the mice with skin carcinomas also revealed LTR related sequences, whereas these RNAs were not detected in the livers and spleens of control mice or of carcinogen-treated mice that did not develop carcinomas. Thus, chemical carcinogenesis in mouse skin is associated with constitutive expression of endogenous retrovirus related sequences in the carcinomas as well as in certain apparently normal host tissues.

9,10-Dimethyl-1,2-benzanthracene↗

Systolic properties of normal and septic isolated rat hearts. The effect of branched chain amino acids.

Systolic properties and coronary flow were studied in Langendorff preparations of normal and septic rat hearts paced at 100, 200, 300, and 400 beats per minute. In addition, the effects of amino acid formulations differing in their branched chain amino acid (BCAA) concentration in normal and septic rat hearts were investigated. Our experiments demonstrated the following: in the normal isolated rat heart, Krebs plus glucose and Krebs plus glucose plus 42% BCAA are most effective in maintaining systolic properties, while Krebs plus glucose plus 15% or 100% BCAA were considerably less effective. Sepsis results in a significant decrease in the systolic properties of the isolated rat heart, and in a loss of the negative linear correlation between contractility and heart rate, probably the result of a diminishing intracellular load of contractile calcium. In the isolated septic rat heart, mechanical washout during perfusion has a beneficial effect, suggesting the presence of a myocardial depressant substance in sepsis. The use of a balanced amino acid mixture containing 42% BCAA exerts the greatest benefit in maintaining systolic properties and in improving coronary flow in the isolated septic rat heart.

Amino Acids, Branched-Chain↗

Approach to risk assessment for genotoxic carcinogens based on data from the mouse skin initiation-promotion model.

Tumor induction data in the mouse skin initiation-promotion system were found to be consistent with a quadratic function where the coefficient of the linear term depended on the dose of the promoter. The model implies that the existence of promoters may be more important at low doses of the carcinogen than at high doses where most testing is performed. Experiments are described showing that the initiating effect of carcinogenic chemicals, such as benzo(a)pyrene, 7,12-dimethyl-benz(a)anthracene, nitroquinoline oxide and beta-propiolactone, accumulates in a linear, irreversible manner at low doses. Even when 7,12-dimethylbenz(a)anthracene was applied intragastrically to pregnant females, initiating activity was found in the skins of exposed offspring about in proportion to dose applied and number of cells at risk. The initiated cells essentially represent a potential for cancer that has a high probability for expression in the presence of a promoter. Risk then can be interpreted in terms of the accumulated dose of initiator which alone presents a small risk of cancer. However, a promoter may substantially expand the overall risk, possibly by clonally expanding the initiated cells. Promotion needs to be sustained since there is a reduction of cancer risk if promotion is ended early. Some tissues, such as mouse bladder, may be intrinsically promoted more than others so that comparisons between tissues and between species are best made when the combination of intrinsic promotion and response to extrinsic promotion are comparable.

Animals↗

Dose-dependent size increases of aortic lesions following chronic exposure to 7,12-dimethylbenz(a)anthracene.

The prevalence, size, and patterns of distribution of arterial lesions (plaques) were investigated in cockerels exposed chronically to 7,12-dimethylbenz(a)anthracene (DMBA). Animals, from 5 to 20 weeks of age, received weekly i.m. injections of 5, 10, or 20 mg of DMBA per kg, dissolved in dimethyl sulfoxide. Control animals received weekly injections of dimethyl sulfoxide. All animals were sacrificed at 21 weeks of age. The entire aorta from each animal was cut transversely into 5-mm segments starting at the iliac trifurcation. The cross-sectional area of plaques was determined by light microscopic analysis of sections taken from the face of each segment. Plaque frequency was similar in DMBA-treated and control groups. However, mean plaque cross-sectional area was 7- to 11-fold higher for the treatment groups than for the controls. The distribution of plaque areas in both treated animals and controls was consistent with a log normal distribution. Median cross-sectional area and plaque volume index each increased in a linear fashion with DMBA dose. Small plaques were present in all groups. Large plaques were present only in DMBA-treated animals. Labeling indices of plaques, although low, were 2.3- to 26-fold higher than for underlying medial smooth muscle cells. The data indicate that the primary response to chronic DMBA exposure is a dose-dependent size increase of spontaneous aortic lesions and not the induction of new lesions.

9,10-Dimethyl-1,2-benzanthracene↗