| 1. |
- Lindmark, G, et al.
(författare)
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Stromal expression of platelet-derived growth factor beta-receptor and platelet-derived growth factor B-chain in colorectal cancer.
- 1993
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Ingår i: Laboratory Investigation. - 0023-6837 .- 1530-0307. ; 69:6, s. 682-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The importance of growth factors, such as platelet-derived growth factor (PDGF), for stromal activation in colorectal cancer is unclear.EXPERIMENTAL DESIGN: The expression of beta-receptors for PDGF, and PDGF B-chain (PDGF AB and PDGF BB) was investigated by immunohistologic techniques in full-thickness biopsies from 210 colorectal cancers. These antigens were detected by the monoclonal antibodies PDGFR-B2 and PDGF 007, respectively.RESULTS: All tumors contained granular clusters of PDGF beta-receptor expressing stromal cells, whereas tumor epithelium was invariably negative. The staining was most prominent in vascular cells. There were several cells in the tumor stroma that expressed PDGF AB/BB. Double immunofluorescence stainings in specimens from four patients performed in order to characterize PDGF beta-receptor- and PDGF AB/BB expressing cells showed that cells expressing PDGF beta-receptors did not express PDGF AB/BB. About 20% of cells in the stroma expressing PDGF AB/BB were macrophages (CD68-positive cells), whereas the nature of the remaining stromal cells expressing PDGF AB/BB could not be disclosed. Furthermore, about 30% of CD68-positive macrophages expressed PDGF AB/BB, but not PDGF beta-receptors. The extent of clusters of PDGF beta-receptor expressing cells varied considerably between tumors, and its prognostic value was considered in the entire tumor material. The number of clusters did, however, not correlate to tumor differentiation, tumor stage according to Dukes', or outcome.CONCLUSIONS: The presence of cells expressing PDGF beta-receptor and PDGF AB/BB respectively, i.e., expression of the receptor and its ligand, fulfills two of the prerequisites for a role of PDGF in the activation of stromal cells in colorectal cancers. The data suggest that stromal activation, characterized by clusters of PDGF beta-receptor expressing cells, is of importance for the formation of tumor stroma per se. However, the expression of the PDGF beta-receptor has no potential as a prognostic marker.
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| 2. |
- Mekjavić, I. B., et al.
(författare)
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Perception of thermal comfort during narcosis
- 1994
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Ingår i: Undersea & Hyperbaric Medicine. - 1066-2936. ; 21:1, s. 9-19
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Tidskriftsartikel (refereegranskat)abstract
- We examined the perception of thermal comfort in six male subjects immersed in water at 28 degrees C (study I) and 15 degrees C (study II), breathing either room air (AIR) or a normoxic mixture containing 30% N2O (N2O). Immersions were terminated if esophageal temperature (Tes) decreased by 2 degrees C from resting levels or to 35 degrees C. At regular intervals, subjects rated their perception of thermal comfort on a 21-point scale (thermal comfort vote, TCV; +10 = very, very hot, 0 = neutral, -10 = very, very cold). For similar decreases in Tes from resting preimmersion values (mean +/- SD = -0.90 degrees +/- 0.13 degrees C and -0.92 degrees +/- 0.15 degrees C during the AIR and N2O trials in study I, and -0.90 degree +/- 0.22 degree C and -0.89 degree +/- 0.27 degree C during the AIR and N2O trials in study II), subjects perceived the immersions as less cold during the N2O trials. The median TCVs for the AIR condition of -5 in study I and -7.75 in study II, were significantly lower than those reported by the subjects for the respective N2O conditions (1.75 in study I and -5.5 in study II). It is concluded that behavioral adjustments required for maintaining thermal balance may be diminished during narcosis due to the altered perception of thermal discomfort. Assuming that the effect of inert gas narcosis on thermoregulatory responses is similar to that of N2O, then combined with the significant attenuation of heat gain mechanisms by anesthetic gases, the attenuation of the perception of thermal comfort may represent a significant factor in the etiology of hypothermia observed in compressed air divers.
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| 3. |
- Reuterdahl, C, et al.
(författare)
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Tissue localization of beta receptors for platelet-derived growth factor and platelet-derived growth factor B chain during wound repair in humans
- 1993
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 91:5, s. 2065-2075
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Tidskriftsartikel (refereegranskat)abstract
- The expression and localization of PDGF beta receptors and PDGF-AB/BB in human healing wounds was evaluated by immunohistochemical techniques and in situ hybridization. Expression of PDGF beta receptor protein and PDGF-AB/BB were analyzed in wound margin biopsies using the PDGFR-B2 and PDGF 007 antibodies. PDGF beta receptor expression was minor in normal skin. An increased expression of PDGF beta receptor protein was prominent in vessels in the proliferating tissue zone in wounds as early as 1 d after surgery and was apparent < or = 4 wk after surgery. There was also a concordant increase in PDGF beta receptor mRNA detected by in situ hybridization. PDGF-AB/BB was present in healing wounds as well as in normal skin. In normal skin, expression of PDGF-AB/BB was confined to peripheral nerve fibers and to solitary cells of the epidermis and of the superficial dermis. In wounds, infiltrating mononuclear cells also stained for PDGF-AB/BB. To identify cell types expressing PDGF AB/BB and PDGF beta receptors, respectively, we performed double immunofluorescence stainings. PDGF beta receptors were expressed by vascular smooth muscle cells and cells in capillary walls; the receptor protein could not be detected in neurofilament containing structures, T lymphocytes, or CD68 expressing macrophages. PDGF-AB/BB colocalized with neurofilaments, it was present in Langerhans cells of the epidermis and in HLA-DR positive cells located in the epidermal/dermal junction area. Of the macrophages infiltrating the wound, 43 +/- 18% stained positively for PDGF AB/BB. Since PDGF-AB/BB and PDGF beta receptors are expressed in the healing wound, two essential prerequisites for a role of PDGF in wound healing are fulfilled.
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| 4. |
- Sundberg, Christian, et al.
(författare)
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Microvascular pericytes express platelet-derived growth factor-beta receptors in human healing wounds and colorectal adenocarcinoma
- 1993
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Ingår i: American Journal of Pathology. - 0002-9440 .- 1525-2191. ; 143:5, s. 1377-1388
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Tidskriftsartikel (refereegranskat)abstract
- The expression of platelet-derived growth factor- beta (PDGF-beta) receptors in the microvasculature of human healing wounds and colorectal adenocarcinoma was investigated. Frozen sections were subjected to double immunofluorescence staining using monoclonal antibodies (MAbs) specific for pericytes (MAb 225.28 recognizing the high-molecular weight-melanoma-associated antigen, expressed by activated pericytes during angiogenesis), endothelial cells (MAb PAL-E), laminin, as well as PDGF-beta receptors (MAb PDGFR-B2) and its ligand PDGF-B chain (MAb PDGF 007). Stained sections were analyzed by computer-aided imaging processing that allowed for a numerical quantification of the degree of colocalization of the investigated antigens. An apparent background colocalization, varying between 23 and 35%, between markers for cells not expected to co-localize was recorded. This background could be due to limitations of camera resolution, to out-of-focus fluorescence, and to interdigitations of the investigated structures. In all six tumor specimens, co-localization of PDGF-beta receptors and PAL-E was not different from the background co-localization, whereas that of PDGF-beta receptors and high-molecular weight-melanoma-associated antigen was significantly higher with mean values between 57 and 71%. Qualitatively, the same pattern was obtained in the two investigated healing wounds. PDGF-B chain did not co-localize with either PAL-E or high-molecular weight-melanoma-associated antigen, but PDGF-B chain-expressing cells were, however, frequently found juxtaposed to the microvasculature. The expression of PDGF-beta receptors on pericytes in activated microvessels and the presence of PDGF-B chain-expressing cells in close proximity to the microvasculature of healing wounds and colorectal adenocarcinoma is compatible with a role for PDGF in the physiology of the microvasculature in these conditions.
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| 5. |
- Sundberg, DC, et al.
(författare)
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Morphology development of polymeric microparticles in aqueous dispersions. I. Thermodynamic considerations
- 1990
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Ingår i: Journal of Applied Polymer Science. - 0021-8995 .- 1097-4628. ; 41, s. 1425-1442
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Tidskriftsartikel (refereegranskat)abstract
- A thermodynamic analysis of polymer particle morphology highlights the role of interfacial tensions in controlling particle structure. The influence of the surfactant and the nature of the incompatible polymers is seen through their individual and collective effects upon these interfacial tensions. It has been found that by simply changing the type of surfactant used in the emulsion the particle morphology can change from core-shell to hemispherical, in agreement with thermodynamic predictions. Several apparently different morphologies (hemispherical, sandwich, multiple lobes) have been found to coexist at the same time within a single emulsion, suggesting that they may be simply different states of phase separation and not thermodynamically stable, unique morphologies. The thermodynamic analyses are independent of particle size and method of emulsion processing. Experimental evidence shows that the morphology of particles formed via in situ polymerization ( as in a synthetic latex) is controlled by interfacial tensions in the same manner as those particles formed via solvent evaporation from a solution of an incompatible polymer pair ( as in an artificial latex or microencapsulation).
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| 6. |
- Tomasini-Johansson, B R, et al.
(författare)
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Vitronectin in colorectal adenocarcinoma- : synthesis by stromal cells in culture
- 1994
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 214:1, s. 303-312
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the expression and cellular source of vitronectin in colorectal adenocarcinoma. Immunofluorescence staining of tissue sections revealed the presence of vitronectin in the stroma of the 11 tumors studied, but not in adjacent normal colon. A method was devised for the isolation from colorectal adenocarcinomas of fibroblast-like cells that stained positive for vimentin but negative for cytokeratin. These tumor-derived stromal cells synthesized and secreted vitronectin, as revealed by metabolic labeling and immunoprecipitation. This was confirmed by Southern blot analysis of polymerase chain reaction amplification products from reverse-transcribed RNA. Normal skin fibroblasts did not synthesize vitronectin. Immunofluorescence staining showed vitronectin deposited at focal contact sites in the tumor-derived cells, where it colocalized with vinculin and the alpha v integrin subunit. The deposition of vitronectin into focal contact sites was not dependent on the presence of serum. The finding that vitronectin can be synthesized and secreted by tumor-derived fibroblast-like cells in culture indicates that vitronectin expression can be promoted by as yet unknown signals provided in disease states, such as cancer.
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