Semi-quantitative assessment of tibial blood flow and distribution in response to surgical intervention using first pass radionuclide angiography and intravascular vital dye

The acute vascular response in bone to surgical trauma was investigated utilizing a sheep model. Blood flow and distribution were determined using two methods; perfusion of the vasculature with an intravascular vital dye (Disulphine blue) prior to euthanasia and by radionuclide angiography (RNA) before and after each surgical intervention. The pattern of Disulphine blue distribution provided a good indication of local perfuslon and response to surgical trauma (drilling holes). Radionuclide angiography provided a dynamic image of the vascular response to surgical trauma. The generation of time activity curves of the first pass of radionuclide bolus enabled calculation of the relative blood flow through selected regions.

For both techniques areas of ischaemia were apparent which were directly related to the location of screw holes. We conclude that factors other than bone plate contact influence the ischaemia that develops in bone subsequent to the application of bone plates.     

Interleukin 3 enhances cytotoxic T lymphocyte development and class I major histocompatibility complex "re-presentation" of exogenous antigen by tumor-infiltrating antigen-presenting cells.

We show that interleukin 3 (IL-3) enhances the generation of tumor-specific cytotoxic T lymphocytes (CTLs) through the stimulation of host antigen-presenting cells (APCs). The BALB/c (H-2d) spontaneous lung carcinoma line 1 was modified by gene transfection to express ovalbumin as a nominal "tumor antigen" and to secrete IL-3, a cytokine enhancing myeloid development. IL-3-transfected tumor cells are less tumorigenic than the parental cell line, and tumor-infiltrating lymphocytes isolated from these tumors contain increased numbers of tumor-specific CTLs. By using B3Z86/90.14 (B3Z), a unique T-cell hybridoma system restricted to ovalbumin/H-2b and implanting the tumors in (BALB/c x C57BL/6)F1 (H-2d/b) mice, we demonstrate that the IL-3-transfected tumors contain an increased number of a rare population of host cells that can process and "re-present" tumor antigen to CTLs. Electron microscopy allowed direct visualization of these host APCs, and these studies, along with surface marker phenotyping, indicate that these APCs are macrophage-like. The identification of these cells and their enhancement by IL-3 offers a new opportunity for tumor immunotherapy.     

Diabetic foods and the diabetic diet: A British Diabetic Association Discussion Paper

The role of special ‘Diabetic’ foods in the diabetic diet is considered and the following conclusions are drawn.

• 1 Most diabetic foods provide slightly, but not substantially, less energy than comparable non-diabetic products.
• 2 Many diabetic foods have a higher fat content than their non-diabetic equivalents. This is contrary to the requirements of the 1984 Food Labelling Regulations.
• 3 Many diabetic products have a relatively high content of protein.
• 4 In percentage terms, the greatest difference between diabetic and non-diabetic foods remains that of carbohydrate content, particularly carbohydrate other than fructose or sorbitol. On a per portion basis (for instance per teaspoon of jam) the difference is relatively small and likely to be of minimal practical significance.
• 5 Diabetic foods cost between 1.5 and 4 times as much as their non-diabetic equivalents.
• 6 Some ordinary reduced-sugar/low-calorie products are preferable to diabetic products in terms of fat and energy content and cost.
• 7 The promotion and widespread availability of diabetic foods tend to delude patients into believing that these products are advantageous, or even necessary. Their existence also undermines current dietary teaching by implying that diabetics cannot eat normal foods.
• 8 Diabetic foods offer no significant physiological or psychological benefits to diabetic patients and can even be counterproductive to good diabetic control. There is no longer a need for special diabetic foods in the modern dietary management of diabetes.

     

Beta2 integrin/ICAM-1 adhesion molecule interactions in cutaneous inflammation and tumor promotion

The beta2 integrin (CD 18/CD 11 a, b, c) family of proteins mediate adherence of leukocytes to vascular endothelium and the associated ligand, intercellular adhesion molecule-1 (ICAM-1; CD 54), interacts with beta2 integrin proteins to allow transendothelial migration of leukocytes into sites of inflammation. The present study examines the function of these proteins in a murine model of acute cutaneous inflammation induced following topical application of 12-O- tetradecanoylphorbol-13-acetate (TPA) to the dorsal epidermis of SENCAR mice and in a model of skin multistage carcinogenesis. At 24 h following topical application of TPA to the dorsal epidermis of mice, dermal leukocytes expressed higher levels of beta2 integrin protein compared with the lower levels of beta2 integrin protein expression by peripheral blood leukocytes. ICAM-1 protein was localized to epidermal keratinocytes and vascular endothelium in TPA-treated skin and to proliferating papilloma cells. Intravenous (i.v.) injection of either 50 microg anti-beta2 integrin antibody alone or in combination with anti-ICAM-1 antibody significantly inhibited both TPA-stimulated neutrophil infiltration into the dermis (P < 0.001) and myeloperoxidase (MPO) activity (P < 0.03 anti-beta2 integrin antibody; P < 0.01 anti- beta2 integrin + ICAM-1 adhesion molecule antibodies), but had no effect on TPA-induced epidermal hyperplasia. In addition, injection of either anti-ICAM-1 adhesion molecule antibody alone (P < 0.004) or in combination with anti-beta2 integrin antibody (P < 0.001) significantly inhibited TPA-induced production of 7,8-dihydroxy-2'-deoxyguanosine (8- OHdG) immunoreactive proteins by epidermal keratinocytes. Beta2 integrin/ICAM-1 adhesion molecules work in concert to regulate migration, retention and functional activation of leukocytes within the dermis during TPA-induced skin inflammation and within stromal tissue of papillomas that form during multi-stage carcinogenesis. Agents that inhibit these receptor/ligand interactions may be useful in defining the roles of specific cell populations in cutaneous inflammation and multistage carcinogenesis and may also have potential as anti-promoting and anti-progression agents.      

Angiogenesis is an early event in the development of chemically induced skin tumors

In this study we have analyzed the vascular response induced in the two- stage carcinogenesis model in SENCAR mice. The role of angiogenesis has not been explored in this model, which is the paradigm of multistage carcinogenesis and a model for neoplastic lesions derived from exophytic premalignant lesions (e.g. colon carcinoma, bladder papilloma). We investigated if angiogenesis is involved in the formation of papillomas and in the progression from papilloma to carcinoma. To this end we analyzed the vasculature of normal and hyperplastic skin, focal epidermal hyperplasias that are precursors of papillomas, papillomas at different stages and squamous cell carcinomas. We also analyzed the vascularization of papillomas induced in two strains of mice that differ in their susceptibility to malignant progression. We show here that angiogenesis is turned on in the earliest stages of papilloma formation. In late stages, regardless of state of progression, the predominant response is an increase in the size of blood vessels. Thus, in the SENCAR mouse model, representative of exophytic tumors, the angiogenesis switch is a very early event, probably mechanistically related to the development of the primarily exophytic lesions. Therefore, the density of blood vessels cannot be used as a predictor of malignant progression in this model.