Ontario Research Foundation Research Articles

Methacrylic acid- containing beads modulate macrophage polarization in a vascularizing subcutaneous mouse model

Event Abstract Back to Event Methacrylic acid- containing beads modulate macrophage polarization in a vascularizing subcutaneous mouse model Kongyu Zhang1 and Michael Sefton1, 2* 1 University of Toronto, Institute of Biomaterials and Biomedical Engineering, Canada 2 University of Toronto, Chemical Engineering and Applied Chemistry, Canada Previously, polymeric beads containing methacrylic acid (MAA) have been used to accelerate vascularization in mice. However, the mechanism(s) of this highly beneficial phenomenon are unclear. Studies in a diabetic wound healing model in vivo showed augmented vessel formation and accelerated wound closure, despite no apparent increase in macrophage infiltration. Vascularization has been linked to macrophage polarization and function[1],[2], suggesting that perhaps an advantageous shift in macrophage polarization may be the impetus for this favorable response. Given this, we hypothesized that MAA beads shift the dynamic sequence in macrophage polarization towards the vascular reparative phenotype to promote vessel formation. To test our hypothesis, we subcutaneously injected MAA beads and control methyl methacrylate (MM) beads into CD1 mice for 1-7 days (using PEG avg. wt. 1450 as a vehicle). The beads and surrounding tissue were explanted and analyzed for the infiltration of inflammatory cells and the formation of vessels by flow cytometry and histology, respectively. MAA beads induced a polarization bias towards MHCII-CD206+ (“M2”) macrophages (Fig. 1); which was accompanied by significantly more CD31+ vessels (Fig. 2), compared to controls. To fully demonstrate that the newly formed MAA-mediated vessels were perfusable and anastomosed with the host vasculature, we injected fluorophore-conjugated mouse GSL-1 lectin into mice 7 days after bead injection and visualized the mouse vasculature using confocal microscopy following CLARITY, a tissue preparation technique that enabled high-resolution imaging of intact tissues[3]. Fluorophore staining was observed surrounding MAA beads but not MM beads in CLARITY-processed tissues, suggesting that vessels were anastomosed to host vessels and perfusable (Fig. 2). These data support the hypothesis that macrophage polarization is a key element of MAA-mediated vessel formation. This information is expected to facilitate the development of advanced therapeutic biomaterials with vascular regenerative properties. Ontario Research Foundation; Natural Sciences and Engineering Research Council (NSERC); NSERC Collaborative Research and Training Experience (CREATE) in Manufacturing Materials and Mimetics (M3) training program; Province of Ontario; University of Toronto

Impact of electricity tariffs on optimal orientation of photovoltaic modules

The authors acknowledge the support by the Ontario Research Foundation—Research Excellence Grant, the Natural Sciences and Engineering Research Council of Canada and the Canada Research Chair program.

595 Evaluation of [18F]PyKYNE-losartan in rats using pet imaging

595 Evaluation of [18F]PyKYNE-losartan in rats using pet imaging

A functional single nucleotide polymorphism in PTPN22 contributes to diabetes susceptibility in the BioBreeding Rat (49.4)

Abstract The C1858T polymorphism in the Ptpn22 gene is associated with increased susceptibility to several autoimmune disorders including Type 1 Diabetes (T1D). This produces a gain-of-function R620W variant with diminished binding affinity to Csk, which, like PTPN22 is an inhibitor of antigen receptor signaling. In the T1D-prone BioBreeding (BB) rat, this gene is located in the Iddm3 locus on chromosome 2, making it a likely candidate gene. Sequencing revealed a non-synonymous SNP causing an A629T substitution C-terminal to the PTPN22 P1 domain that binds to Csk. Co-immunoprecipitations examining the PTPN22-Csk interaction have shown a 2-fold reduction in binding affinity of the BB compared to the ACI variant. Importantly, a genome-wide segregation analysis of an F2(BBxACI.1u.lyp) cohort revealed the dominant effect of the BB allele to confer a 3-fold increased T1D risk compared to the allele carried by the T1D-resistant ACI strain. Homozygosity for the BB allele is also associated with phenotypes indicative of immune dysregulation including increased proportions of activated CD4 T cells in the periphery. Reminiscent of the phenotypes observed in T1D patients carrying the R620W variant, BB-derived T and B cells exhibit hyporesponsiveness to antigen receptor engagement, with a concomitant decrease in IL-2 production by CD4 T cells. Banting and Best Diabetes Centre, Genome Canada, Ontario Research Foundation and CIHR

RADIUM IN DRINKING WATER AND BONE CANCER RISK IN ONTARIO YOUTHS

*Ontario Ministry of Labour;**Ontario Cancer Treatment and Research Foundation, Toronto, Ontario, Canada.

Supportive care needs of women undergoing breast diagnostics and their families: A focus for nursing interventions

This article reviews the literature regarding the supportive care needs of women undergoing breast diagnostics. The experience of undergoing a diagnostice work-up for a breast abnormality is extremely stressful for most women, when fears of breast cancer are either allayed or realized. If their needs are not identified and addressed, individuals and their families rish experiencing psychosocial distress. Nurses are in an excellent position to provide supportive care services which meet the needs of women during this time. The Supportive Care Framework (Ontario Cancer Treatment and Research Foundation, 1994) directs the review of supportive care needs and resulting nursing interventions. Conclusions are drawn for nursing practice and future research.

IL-8 induces calcium mobilization in interleukin-2-activated natural killer cells independently of inositol 1,4,5 trisphosphate.

Annals of the New York Academy of SciencesVolume 766, Issue 1 p. 292-295 IL-8 Induces Calcium Mobilization in Interleukin-2-activated Natural Killer Cells Independently of Inositol 1,4,5 Trisphosphatea ALA AL-AOUKATY, ALA AL-AOUKATY Northeastern Ontario Regional Cancer Centre Department of Chemistry-Biochemistry Laurentian University Sudbury, Ontario, P3E 5J1 and Department of Medicine Faculty of Medicine University of Ottawa Ottawa, Ontario KIN 6N5 and Montreal General Hospital Montreal, Quebec, Canada H3G 1A4Search for more papers by this authorADEL GIAID, ADEL GIAID Northeastern Ontario Regional Cancer Centre Department of Chemistry-Biochemistry Laurentian University Sudbury, Ontario, P3E 5J1 and Department of Medicine Faculty of Medicine University of Ottawa Ottawa, Ontario KIN 6N5 and Montreal General Hospital Montreal, Quebec, Canada H3G 1A4Search for more papers by this authorAZZAM A. MAGHAZACHI, Corresponding Author AZZAM A. MAGHAZACHI41 Ramsey Lake Road, Sudbury, Ontario P3E 5J1, Canada.Search for more papers by this author ALA AL-AOUKATY, ALA AL-AOUKATY Northeastern Ontario Regional Cancer Centre Department of Chemistry-Biochemistry Laurentian University Sudbury, Ontario, P3E 5J1 and Department of Medicine Faculty of Medicine University of Ottawa Ottawa, Ontario KIN 6N5 and Montreal General Hospital Montreal, Quebec, Canada H3G 1A4Search for more papers by this authorADEL GIAID, ADEL GIAID Northeastern Ontario Regional Cancer Centre Department of Chemistry-Biochemistry Laurentian University Sudbury, Ontario, P3E 5J1 and Department of Medicine Faculty of Medicine University of Ottawa Ottawa, Ontario KIN 6N5 and Montreal General Hospital Montreal, Quebec, Canada H3G 1A4Search for more papers by this authorAZZAM A. MAGHAZACHI, Corresponding Author AZZAM A. MAGHAZACHI41 Ramsey Lake Road, Sudbury, Ontario P3E 5J1, Canada.Search for more papers by this author First published: September 1995 https://doi.org/10.1111/j.1749-6632.1995.tb26680.xCitations: 3 a This work was supported by a Grant from the Northern Cancer Research Foundation. Dr. A. A. Maghazachi is a Career Scientist of the Ontario Cancer Treatment and Research Foundation. Dr. A. Giaid is supported by the Heart and Stroke Foundation of Canada. ‡41 Ramsey Lake Road, Sudbury, Ontario P3E 5J1, Canada. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume766, Issue1Receptor Activation by Antigens, Cytokines, Hormones, and Growth FactorsSeptember 1995Pages 292-295 RelatedInformation

Chemotherapy waste reduction through shelf-life extension.

Minimization of total drug expenditures within the health care system, without affecting patient outcome has become a rational goal in today's economic, environment. The objective of this study was to observe the effect of extending the shelf-life for three chemotherapy medications, [doxorubicin, epirubicin and mitoxantrone] on wastage of these medications. Prior to and following the introduction of new, longer, shelf-lives for these three medications, prospective, non-randomized, unblinded four-month chemotherapy wastage audits for all chemotherapy medications were completed at 18 institutional sites within Ontario (six Ontario Cancer Treatment and Research Foundation clinics, ten Ontario hospitals and two preparation sites in a large cancer treatment centre). Data were provided by 18 sites in 1989 but from only 12 sites in 1990. Ten of the 12 sites extended their shelf-lives for each of doxorubicin, epirubicin and mitoxantrone, and on average, waste at these sites was reduced to less than 1% of the 1989 total for epirubicin, less than 15% for doxorubicin and 35% for mitoxantrone. Many sites eliminated waste entirely for these drugs. For sites which did not extend their shelf-lives, the waste remained unchanged. We conclude that appropriate extension of the shelf-life for chemotherapy medications can reduce waste, and is a relatively simple method of reducing expenditures without affecting health outcomes or adding additional complications to IV chemotherapy.

A NOVEL TRANSFORMING GROWTH FACTOR IS PRESENT IN MALIGNANT ASCITES FROM HUMAN OVARIAN CARCINOMA

Ontario Cancer Treatment and Research Foundation, Hamilton Regional Cancer Centre, and McMaster University, Hamilton, Ontario, Canada

REVERSAL OF SUPPRESSION OF LYMPHOKINE- ACTIVATED KILLER CELLS BY TRANSFORMING GROWTH FACTOR-BETA (TGF-β) IN OVARIAN CARCINOMA ASCITIC FLUID REQUIRES INTERLEUKIN-2 (IL-2) COMBINED WITH ANTI-CD3 ANTIBODY

(Ontario Cancer Treatment and Research Foundation—Hamilton Regional Cancer Centre, and Department of Medicine, McMaster University, Hamilton, Ontario, Canada).

In vivo evaluation of hydrophobic and fibrillar microporous polyetherurethane urea graft

Mitrathane® hydrophobic and fifarillar microporous prosthesis was implanted as infrarenal arterial substitute in dogs; it was evaluated in terms of patency rates, healing characteristics and biostability. Segments of grafts were implanted in duplicate for a period of implantation of 24 h, 1 wk, 1month and 6 month. Two control grafts from the Ontario Research Foundation were implanted: one for 1 month, the other for six month. All except the two Mitrathane grafts implanted for 6 month were patent at death. The Mitrathane grafts showed kinking at one and 6 month post-implantation. The ORF graft implanted for 1 month was found crinkled in its mid-section and the external capsule was ruptured in the graft implanted for 6 month, without crinkling. Histological studies showed fibrin deposits on the flow surface and infiltration of blood elements into the wall of the Mitrathane grafts implanted for 24 h and 1wk. A thin internal capsule was present on the graft flow surface of both types of graft tested 1month post-implantation; scanning electron microscopy revealed the presence of endothelial-like cells on the luminal surface, particularly in the vicinity of the anastomoses. At 6 month, the Mitrathane grafts were occluded by a thick thrombus originating from the anastomoses, while the ORF graft showed infiltration of collagen through the polyurethane fibrillar structure of the wall with an endothelial-like lining covering the flow surface in the vicinity of both anastomoses.

Experimental Glass Failure Data and Equivalent One‐Minute Loads

The paper examines the extent to which a procedure for calculating equivalent one-minute loads on glass panels developed by the National Bureau of Standards (NBS) is consistent with results of destructive tests recently reported by the Ontario Research Foundation (ORF). The ORF tests were conducted on 107 annealed float glass panels with dimensions 1.52m × 2.43m × 6mm, simply supported on four sides. The loading rates ranged from about 0.0025kPa/s to about 25kPa/s, and the times to failure ranged from about 920s to about 0.1s. To check the validity of the NBS procedure, it is noted that if the ORF panels had been tested to failure under constant loads with one minute duration, one should expect the means and the standard deviations of the loads to be the same for various samples—to within sampling errors consistent with the sample sizes. The same should therefore be true of calculated values. Results of statistical tests are presented, from which it can be concluded with high confidence that the validity of the NBS procedure is confirmed by the ORF tests.

Organochlorine and PCB residues in Lake Erie mink populations

G. Proulx, 1 D. V. C. Weseloh, 2 J. E. Elliott, 3 S. Teeple, 4 P. A. M. Anghern, 5 and P. Mineau 6 134 Donjeux, Lorraine, Quebec, J6Z 3C5, Canada; 2Canadian Wildlife Service, Canada Center for Inland Waters, 867 Lakeshore Road, Burlington, Ontario, L7R 4A6, Canada; 3Canadian Wildlife Service, Toxic Chemicals Program Section, National Wildlife Research Center, 100 Gamelin Blvd., Hull, Quebec, KIA 0E7, Canada; 4Inland Waters Directorate, Ontario Region Water Resources Branch, 75 Farquhar St., Guelph, Ontario, NIH 3N4, Canada; 5Canadian Wildlife Service, Toxic Chemicals Program Section, National Wildlife Research Center, 100 Gamelin Blvd., Hull, Quebec, K1A 0E7, Canada; and 6Canadian Wildlife Service, Canada Center for Inland Waters, 867 Lakeshore Road, Burlington, Ontario, L7R 4A6, Canada PCB poisoning has been found in mink (Mustela vison) fed on Great Lakes fish (Aulerich et al. 1973) but is poorly known for wild mink populations (0'Shea eta]. 1981). The objective of this study was to determine whether mink from the Lake Erie basin were accummulating levels of PCB and organochlorine residues high enough to cause health effects. MATERIALS AND METHODS The skinned carcasses of 55 wild mink caught in November and December ]978 and 1979, and from January to March 1979, were obtained from trappers through the Ontario Ministry of Natural Resources (Fig. l). Carcasses were wrapped in aluminium foil and stored at -40~ Weights of the skinned carcasses were corrected by assuming the skin to be 17% of the body weight (Sherburne and Dimond 1969). The head, lower legs, tail and stomach contents were discarded and carcasses were homogenized in a Hobart chopper for 5 to 20 minutes. Homogenates were analyzed by the Ontario Research Foundation for DDT, DDD, DDE, dieldrin, heptachlor epoxide, HCH, chlorobenzenes, chlordane, mire“ and PCB. Procedures are described in Reynolds and Cooper (1975) and Norstrom et al. (1980). PCBs were quantified by capillary gas chromatography against a I:I standard mixture of Aroclor 1254:1260. Geometric means were calculated for all residue data as a measure of central tendency because of the logarithmic distribution of the data. The logarithmic means of the residues were compared to each other in analyses of variances and t-tests (Dixon and Massey 1969). RESULTS AND DISCUSSION Levels of PCB 1254/1260 detected in mink body homogenates varied from 0.06 to 7.37 ppm, on a wet weight basis, and from 0.8 to Send reprint requests to G. Proulx at The Alberta Environmental Centre, P.O. Bag 4000, Vegreville, Alberta, TOB 4LO, Canada. 939

The effect of socioeconomic factors on the early prognosis of cancer

Previous studies have suggested that cancer patients of low socioeconomic status (SES) have poorer short and long-term survival than cancer patients of higher SES. In this study male and female patients between the ages of 25 and 70, admitted to two Ontario Cancer Treatment and Research Foundation Clinics with newly diagnosed cancers of a number of common sites, were interviewed to obtain information on education and occupation, and chronic illnesses other than cancer. Information on stage of disease at diagnosis, exact pathologic diagnosis, date of diagnosis, and treatment before and after admission to the clinic was obtained from clinic charts. Using multiple logistic regression analysis to control for the effect of stage and other variables, there was no convincing evidence that cancer patients of low SES measured by either education or occupation had a less favourable outcome at one year after diagnosis from cancers of all sites combined or lung cancer specifically. The data suggested that any single measure of SES affects males and females differently.

Lung Cancer: The Past Twenty-Five Years

On the occasion of this Fourth World Conference on Lung Cancer, I am privileged to present the opening keynote address. This presentation has been sponsored by the Ontario Cancer Treatment and Research Foundation. In 1952, the Foundation established an annual lectureship in memory of one of their prominent physicians. Dr. Gordon Earle Richards was one of Canada's pioneer radiologists and radiotherapists who was appointed Director of the Institute of Radiotherapy at Toronto General Hospital at a time when radium and high-voltage x-rays were just coming into common use for the treatment of malignant disease. He established an international reputation for his contributions to clinical radiotherapy, and was subsequently appointed Professor of Radiology at the University of Toronto. He was Managing Director of the Ontario Cancer Treatment and Research Foundation between 1945 and 1949. I wish to thank the Foundation for the privilege of presenting the 33rd Gordon Richards Memorial Lecture. On the occasion of this Fourth World Conference on Lung Cancer, I am privileged to present the opening keynote address. This presentation has been sponsored by the Ontario Cancer Treatment and Research Foundation. In 1952, the Foundation established an annual lectureship in memory of one of their prominent physicians. Dr. Gordon Earle Richards was one of Canada's pioneer radiologists and radiotherapists who was appointed Director of the Institute of Radiotherapy at Toronto General Hospital at a time when radium and high-voltage x-rays were just coming into common use for the treatment of malignant disease. He established an international reputation for his contributions to clinical radiotherapy, and was subsequently appointed Professor of Radiology at the University of Toronto. He was Managing Director of the Ontario Cancer Treatment and Research Foundation between 1945 and 1949. I wish to thank the Foundation for the privilege of presenting the 33rd Gordon Richards Memorial Lecture.

An Economic Evaluation of Methanol Blends in Canadian Markets

he use of methanol as a blending component in the production of gasoline has increased markedly in recent years. For example, a blend of 3 per cent methanol, 3 per cent cosolvent (higher alcohols) and 94 per cent gasoline is currently used to meet almost three-quarters of West Germany's gasoline requirements (Energy, Mines and Resources Canada, 1984). In addition, methanol blends are now sold in some US markets.1 This is in sharp contrast to the case of straight (or neat) methanol where the high vehicle conversion costs greatly diminish its attractiveness as a transportation fuel (see Dupont and Diener (1985) for an evaluation of neat methanol in a Canadian context). While a number of vehicle test programs to evaluate the performance of methanol blends under Canadian driving conditions have been undertaken and have produced excellent results (for example, see Ontario Research Foundation, 1984; Taylor, 1984), these fuels are not commercially available here at present. Yet, there would appear to be the potential for substantial benefits associated with this alternative. These in-

Quality assurance past and present in Canada

Quality assurance in any clinical field must involve the three components of clinical care: (a) diagnosis and evaluation of patients; (b) medical decision making and treatment; and (c) outcome analysis. Nationally, there have been five annual reviews of outcome from all cancer centers following radiation therapy for cancer at various sites. These reviews are voluntary and organized through the Canadian Association of Radiologists. The objective is to determine if there are any major differences in outcome across the country, and if so, can such differences be related to the population treated or technique used. So far no major differences have been noted, although the reviews have led to improved communication between centers and constructive discussions of dose and technique. There is a National Tumour Reference Centre funded by the National Cancer Institute of Canada (NCIC) to provide assistance in establishing diagnostic criteria in pathology. Ontario has been active through the Ontario Cancer Treatment & Research Foundation and the Ontario Cancer Institute in establishing UICC TNM staging and reporting, together with an evaluative program for this staging system. All other quality assurance programs take place at the level of local centers.

Dr. R. G. MacLaren, M.B., Ch.B., F.R.C.S.(E.), F.R.C.P.(C), D.M.R.T

Dr. Robert MacLaren, Director of Radiation Oncology at the Hamilton Clinic of the Ontario Cancer Treatment and Research Foundation, died on January 28, 1980 at the age of 56 as a result of injuries sustained in a traffic accident. Dr. MacLaren attended Glasgow Academy and received his undergraduate and postgraduate medical education at Westminster Hospital Medical School.

Variable effects of post-operative radiotherapy on disease-free survival in subgroups of patients with node-negative breast carcinoma

We report in this paper a retrospective cohort study of the effect of post-operative radiotherapy on 5-yr disease-free survival in 433 patients with carcinoma of the breast registered at two clinics of the Ontario Cancer Treatment and Research Foundation between 1961 and 1970. All patients had had surgical removal of the breast and axillary tissue and were free of axillary spread of their disease. The contribution of radiotherapy to survival was assessed with possible confounding by known prognostic factors controlled using the multivariate stratification method recently described by Miettinen. In addition, to give a quantitative indication of radiotherapy's relationship with survival, logistic function modelling, accounting for both confounding and effect-modification of the prognostic factors, was employed. In each of the analyses, it was found that radiotherapy was associated in one subgroup with better than expected survival and in another with poorer outcome. In general, the subgroups identified by the different techniques were similar. These results suggest that, in considering the role of post-operative radiotherapy in the management of patients with carcinoma of the breast, the possibility that this treatment has variable effects that can be predicted by commonly recorded prognostic factors should be taken into account.

Effects of Injected Organochlorines on Naturally Incubated Herring Gull Eggs

Organochlorine contaminants were extracted from Lake Ontario herring gull (Larus argentatus) eggs and injected into relatively uncontaminated, unincubated gull eggs on Kent Island, New Brunswick. Synthetic mixtures of PCB's, DDE, mirex, photomirex and hexachlorobenzene were injected in a similar fashion. All eggs were incubated by their natural parents. No increases in embryonic or chick mortality were observed in any contaminant injected group when compared to the injected controls. The embryonic uptake of pollutants was similar in naturally contaminated eggs and injected eggs. The significance of these findings with regard to the reproductive failure of Lake Ontario herring gulls is discussed. J. WILDL. MANAGE. 42(3):484-493 Increased embryonic death has been reported in herring gull colonies having poor reproductive success in Lakes Michigan (Keith 1966, Ludwig and Tomoff 1966) and Ontario (Gilbertson and Hale 1974, Gilman et al. 1977). The levels of several organochlorine compounds contained in eggs from these colonies are amongst the highest levels found in the Great Lakes. Artificial incubation studies indicated that eggs from Lake Ontario were less likely to hatch than eggs from less contaminated areas (Gilman et al. 1977). These incubation studies provided conclusive evidence that some factor associated with the egg itself and not linked to parental incubation behavior was responsible for much of the egg failure observed on Lake Ontario colonies. Strong correlations have been established between high concentrations of organochlorines and poor reproductive success for many avian species (Jefferies 1973, Blus et al. 1974, Gilbertson 1974, Newton and Bogan 1974, Fyfe et al. 1976). Controlled laboratory feeding studies have indicated that some organochlorines can induce embryonic mortality, but there is considerable species variation (Peakall et al. 1972, Tumasonis et al. 1973). Injections of PCB's into chicken eggs have caused complete hatching failure (McLaughlin et al. 1963). The amounts injected (ca. 300 and 600 ppm on a whole egg basis) were approximately 2-4 times the amount presently found in Lake Ontario herring gull eggs (Gilman et al. 1977). Organochlorines other than PCB's have been found relatively nontoxic when injected into chicken eggs at levels below 250 ppm (Dunachie and Fletcher 1969). No report has been published on the effects of injecting organochlorine contaminants either individually or in combination into eggs of wild birds. The study reported in this paper was an attempt to establish whether a causal relationship existed between levels of organochlorine contaminants in the yolk 484 J. Wildl. Manage. 42(3):1978 This content downloaded from 157.55.39.43 on Fri, 30 Sep 2016 05:29:52 UTC All use subject to http://about.jstor.org/terms INJECTED ORGANOCHLORINES IN GULL EGGS* Gilman et al. 485 lipid and herring gull embryonic survival. We limited our study to the examination of the direct embryo-toxic effects of yolk-borne organochlorines and did not examine the possible effects of such contaminants on the egg during its formation. To test thoroughly this cause and effect relationship we attempted to simulate environmental conditions as closely as possible. We injected known quantities of contaminants extracted from Lake Ontario herring gull eggs and some laboratory mixtures of organochlorine contaminants into unincubated and relatively uncontaminated herring gull eggs in New Brunswick. We also permitted the adult New Brunswick herring gulls to incubate the injected eggs to eliminate the effects of either abnormal incubation (Fox et al. 1978) or artificial incubation. Our reasons for using unincubated eggs for injection were threefold. First, organochlorine contaminants of eggs are laid down during yolk formation and are present during ovulation, fertilization, oviposition, and incubation of the egg. Dunachie and Fletcher (1969) have found that chlorinated cyclodiene pesticides are more toxic when injected early in incubation than later. Second, the proportion of embryonic mortality in Great Lakes herring gulls occurring during the first 7 days of incubation was high and ranged from 26 percent in Lake Michigan (Keith 1966) to 89 percent in Lake Ontario (Gilbertson 1974). In addition, a high percentage of eggs from these heavily contaminated areas failed to show any embryonic development (Gilman unpublished, Keith 1966). Third, we hypothesized that the embryonic mortality resulting from the presence of injected contaminants that had been extracted from eggs from an area with an overall failure rate of 80 percent in 1975 (Gilman et al. 1977) would be greater than the possible 50 percent mortality induced by the trauma of injecting unincubated eggs (Khera and Lyon 1968). The authors wish to thank J. Ryder, Lakehead University, who assisted with the uptake study and C. Huntington who permitted us to use the facilities of Bowdoin Scientific Station on Kent Island, N.B. L. Reynolds, Ontario Research Foundation, performed the analyses required for the uptake study, and R. Norstrom and H. Won, Toxic Chemicals Division, CWS, Ottawa, provided valuable assistance in the extractions and analyses