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Prostatic carcinomas vary in their biological potential, even when stratified by grade and stage. Measurement of cellular proliferation by various methods has been shown to correlate with outcome for several human cancers, including prostatic carcinoma. Uptake of bromodeoxyuridine (BrdUrd), a thymidine analogue, has been accepted as a measure of cellular proliferative rate. However, the technique is somewhat complex, requiring incubation with fresh tissue. We compared cellular proliferation as measured by BrdUrd uptake with two more simple immunohistochemical methods in 44 prostatic adenocarcinoma specimens and correlated the results with standard clinical parameters. The tissue was obtained via needle biopsy, channel transurethral resection, and radical prostatectomy. Specimens were incubated in vitro with BrdUrd and then fixed and paraffin embedded. Sections were immunohistochemically stained with antibodies to BrdUrd, proliferating cell nuclear antigen (PCNA), and Ki-67. At least 1,000 cells were scored, and a labeling index (LI) was calculated (number of positive cells/total number of cells). The mean LI determined by all three indices was low (BrdUrd = 3.0, PCNA = 7.0, Ki-67 = 3.4), consistent with the knowledge that prostatic tumors grow slowly. In 36 patients who had not been treated at the time of analysis, the LI as determined by all three methods correlated well with clinical stage and pathological grade. Furthermore, the LIs discriminated between those with tumor confined to the prostate and those with extension to the seminal vesicles, lymph nodes, or bone (P = 0.003, 0.004, 0.008 for BrdUrd, PCNA, and Ki-67, respectively). The LIs for PCNA and Ki-67 correlated well with that for BrdUrd (r = 0.84; r = 0.85), while the LIs for Ki-67 and PCNA correlated slightly less well with each other (r = 0.78). PCNA and Ki-67 expression appear to reflect essentially the same biological process as BrdUrd uptake. Either can substitute for BrdUrd as a measure of cellular proliferation, and Ki-67 seems to offer the fewest technical problems.

SummaryWe have developed a new micro-assay for lymphotoxin utilizing murine l-929 target cells prelabeled with technetium-99m, a high specific activity, metastable gamma emitter which is bound to living cells and not released in appreciable quantities by dead or injured cells. Target l-cells prelabeled with 99mTc were added to micro tissue culture plates at a concentration of 10,000 cells/well. Eighteen hr later lymphotoxin or control material was added and the cells were incubated for an additional 12–28 hr. A maximum cytocidal effect was observed after incubation of target cells for 28 hr with 100 CU of lymphotoxin. The number of surviving adherent cells as determined by gamma counting for 99mTc was in accord with that recorded by visual enumeration. The 99mTc microassay is a sensitive, easily performed, rapid test for lymphotoxin activity which appears to have a number of advantages over previously reported in vitro methods.We thank Mrs. L. Williams and S. Vaishnav for technical assistance and Mrs. K. ...

MRI has been shown as an adapted non-invasive modality for the detection of tumours in humans. The development of paramagnetic contrast agents could add to the MRI diagnosis. With an experimental model of human breast (MX-1) carcinoma developed in nude mice, two different classes of contrast medium were tested. The first class includes the well-known Gd-DTPA and a new nitroxide compound on going development, representing non specific contrast agents. The specific contrast agents are represented by a metalloporphyrin Mn-TPPS4. Non specific contrast agents can add to the differentiation between well vascularized viable tissue and necrotic areas of tumors. While specific contrast agents may specifically target tumorous tissue.

Lymphotoxin-sensitive L cells were prelabeled with isotopically marked leucine and exposed either to human alpha-lymphotoxin (alpha-LT) or control buffer. Plasma membranes were then isolated from these cells, and TCA-precipitable leucine was determined as a measure of membrane protein. Human alpha-LT caused a marked reduction of plasmalemmal protein in LT-sensitive target cells. This loss of protein was general, not restricted to specific fractions, as assessed by sodium dodecyl sulfate (SDS)--polyacrylamide gel electrophoresis. Since purified alpha-LT had no detectable proteolytic activity, the effect of the lymphokine is not readily explained by direct enzymatic action on plasma-membrane protein. In contrast, there was no plasma--membrane protein loss in LT-resistant target cells on exposure to alpha-lymphotoxin.

The built environment has evolved through a layering process of both human needs and aspirations. We as a society 'Worship' the remnants of these richly varied and complex environments. In the previous 100 years, however, our environment has become a battleground for survival on many levels: environmental health, societal boundaries and quality of life. The so-called haphazard mode of environmental development was proceeding so quickly that 'MAN', through organization and control, sought to harness rampant growth by providing a mechanism to, in essence, protect us from ourselves. This mechanism was development standardization. Zoning and subdivision standards initially had a very positive effect on residential districts. They achieved the desired objective of improving the health, safety and welfare of local citizens. To remain a successful regulatory mechanism, however, requires frequent review. (Generally government regulations are continually reviewed because of a need to respond to current reality - a typical example is tax reform laws). This is especially true for development regulation, which necessarily must respond to the rapidly changing and dynamic evolution of the North American city and its peoples. In the case of residential development standards, however, there has been a lack of policy review resulting in a back-water of no change to the standard. Development standards, that were a direct response to mass housing development in the early nineteen hundreds, in many instances are still in place in municipalities in the Greater Vancouver area and likely throughout many other North American cities as well. It is apparent that the very standards that were invoked to ensure residential quality are now preventing development from creating that quality. At the core of the issue of planning and design standards is the lack of understanding of these two disciplines - by each other and by the public. As a result, in many instances both planners and the public equate design with a simple problem solving process according to explicit rules - the standards. Herein lies the core of the problem. This misrepresentation of design and what it stands for in terms of environmental quality. This misunderstanding has greatly influenced the world we live in and this influence as of late is not of the positive nature. The thrust of this thesis is an exploration of the issue of design in the context of residential development standards. What are the standards which influence/impact residential development? What were the objectives for which these standards were originally implemented? How do the standards currently support the implementation of recognized design principles which lead to high quality environments? What kind of residential world is created by adherence to the standards and what opportunities are lost? It is evident from this study that while the mechanism and often the mathematical formula of development standardization have remained relatively constant during the past half century, the city and the city dweller have not. Most new neighbourhoods in today's North American city lack identity, character and quality environment due to a set of zoning and subdivision standards that are antiquated and often based on arbitrary numbers. The case study examples of Village Homes in California and Ashcroft subdivision in Richmond, illustrate that conventional development standards prevent adherence to established residential design principles and that the nature of development standards is such that they are unable to contend with important and often basic design issues that are not amenable to simple arithmetic formula and measurement. It is also clear that standards not only adversely effect the physical condition of the residential environment, but also the people involved in the process of designing, constructing and regulating residential development. The designer is disillusioned, the developer confused, and the planner misfocused. The result is poor design, poor development, and poor planning. The failure to adopt and implement consistent and up-to-date policies and objectives for residential development standards has lead to the creation of stale, un-inviting, un-interesting and characterless living environments. The lesson to be learned here is that planners must first become more in tune with the issues and principles of design and second they must not be afraid to question established planning mechanisms. We therefore must ensure that a) the best mechanism is being employed and b) that it is based on appropriate and current policies and objectives that are leading to a better residential environment.