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B Gerdin

Publications and source records attributed to B Gerdin.

At least 37 records · Page 2Linked to original sources
PubMed1997

Dynamic role of hyaluronan (HYA) in connective tissue activation and inflammation.

An increased tissue accumulation of HYA occurs in several human and experimental inflammatory conditions. Such is the case in sarcoidosis, idiopathic pulmonary fibrosis and farmer's lung in man, and experimental bleomycin-induced lung damage in rats. Graft rejection in man and rats, experimental myocarditis in mice and myocardial infarction in rats follow the same pattern. Increased amounts of HYA also appear in gut luminal perfusion fluid in human inflammatory bowel disease. A transient accumulation of HYA is seen in wound healing, which is more sustained in fetuses. An increased accumulation of water and presentation of ligands for receptors on inflammatory cells are two consequences of the HYA accumulation.

Animals↗
PubMed1997

Tumor cell and connective tissue cell interactions in human colorectal adenocarcinoma. Transfer of platelet-derived growth factor-AB/BB to stromal cells.

Mechanisms underlying stimulation of platelet-derived growth factor (PDGF) beta-receptors expressed on connective tissue cells in human colorectal adenocarcinoma were investigated in this study. PDGF-AB/BB, but not PDGF receptors, was expressed by tumor cells in situ, as well as in tumor cell isolates of low passage from human colorectal adenocarcinoma. In an experimental co-culture system, conditioned medium from tumor cells only marginally activated PDGF beta-receptors expressed on fibroblasts. In contrast, co-culturing of the two cell types led to a marked PDGF beta-receptor activation. Functional PDGF-AB/BB was found to be associated with heparinase-I-sensitive components on the tumor cell surface. PDGF-AB/BB, isolated from heparinase-I-sensitive cell surface components, induced a marked activation of PDGF beta-receptors. Furthermore, co-culturing tumor cells together with fibroblasts led to a sustained activation of PDGF beta-receptors expressed on fibroblasts. Double immunofluorescence staining of tissue sections from human colorectal adenocarcinoma, combined with computer-aided image analysis, revealed that nonproliferating tumor cells were the predominant cellular source of PDGF-AB/BB in the tumor stroma. In addition, PDGF-AB/BB-expressing tumor cells were found juxtapositioned to microvascular cells expressing activated PDGF beta-receptors. Confocal microscopy revealed a cytoplasmic and cell-membrane-associated expression of PDGF-AB/BB in tumor cells situated in the stroma. In contrast, epithelial cells situated in normal or tumorous acinar structures revealed only a cell-membrane-associated PDGF-AB/BB expression. The is vitro and in situ results demonstrate that tumor cells not only facilitate but also have the ability to modulate connective tissue cell responsiveness to PDGF-AB/BB in a paracrine fashion, through direct cell-cell interactions in human colorectal adenocarcinoma.

Adenocarcinoma↗
PubMed1996

Recruitment of type I collagen producing cells from the microvasculature in vitro.

We have previously suggested that microvascular pericytes can differentiate into fibroblast-like, type I collagen-producing cells during excessive dermal scarring in vivo (Sundberg, C., Ivarsson, M., Gerdin, B., and Rubin, K., Lab. Invest. 74, 454-468, 1996). Here we have investigated to what extent pericytes derived from microvessels of full-term human placenta exhibited this capacity in vitro. Vascular fragments of human term placenta were isolated by enzymatic digestion and separation in Percoll. Their microvascular origin was ascertained by confocal microscopy using antibodies specific for endothelial cells (PAL-E) and pericytes (high-molecular-weight-melanoma-associated antigen). When vascular fragments were cultured in vitro, large cells with irregular edges migrated out from the fragments. After 4-6 days in culture, these cells started to proliferate and reached near confluence after approximately 8 days. The cultures were not overgrown by clones of cells with a high proliferative capacity, as demonstrated by cell membrane fluorescence staining and Ki67 expression. Expression of PAL-E, high-molecular-weight-melanoma-associated antigen, smooth muscle alpha-actin, desmin, and collagen synthesis (prolyl-4-hydroxylase and type I procollagen, as well as collagen pro-alpha1(I) mRNA) were followed during a culture period of 8 days. The cells were PAL-E negative but expressed high-molecular-weight-melanoma-associated antigen, smooth muscle alpha-actin, and desmin. Based on morphology and expression of the various markers, the outgrowing cells were identified as pericytes. With time in culture the cells decreased their expression of all these markers and increased their expression of prolyl-4-hydroxylase, type I procollagen, and collagen pro-alpha1(I) mRNA. Metabolic labeling and SDS-PAGE analysis of labeled proteins revealed that type I collagen was the major collagen species synthesized in the cultures. Our results support the hypotheses that pericytes can leave the vasculature and differentiate into collagen-producing cells and that cultured "fibroblasts" are derived from pericytes.

Actins↗
PubMed1996

Prognostic significance of the microvascular count in colorectal cancer.

PURPOSE: To investigate the potential correlations between a high microvascular count and the survival rate in colorectal cancer. MATERIALS AND METHODS: Three markers for endothelial cells--Ulex Europaeus Lectin (UEA), a polyclonal anti-von Willebrand factor (vWF) antibody, and a monoclonal anti-CD31 antibody (all from Dakopatts, Glostrup, Denmark)--were used for immunohistochemical detection of microvessels in whole-mount sections from 15 colorectal cancers. Areas with higher microvascular density were homogeneously distributed in the sections, regardless of the marker used. The anti-vWF antibody was subsequently used for quantification of microvessels in full-cross tumor biopsies collected from 212 consecutive surgical specimens. The correlations between the mean number of microvessels in areas with the highest microvascular density and tumor differentiation, tumor stage according to Dukes', and survival time were investigated. RESULTS: A significantly longer survival time was shown for patients who had tumors with a mean of more than 10 anti-vWF-positive microvessels, as compared with those who had < or = five. Tumors with a microvascular count between six and 10 microvessels behaved in-between. There was no correlation between the number of microvessels and tumor differentiation or Dukes' stage. CONCLUSION: The number of microvessels measurable in tumor biopsies seems to be a prognostic predictor independent of Dukes' stage in colorectal cancer. However, our results are opposite to the findings in other tumor types investigated so far; we found that a high microvascular count predicted a longer survival time, rather than a shorter one. Determination of the microvascular count can be of importance in therapy selection even before, or immediately after, surgery, ie, before Dukes' stage is known.

Adult↗
PubMed1996

Anastomotic healing of small bowel with or without chronic radiation damage in protein-deficient malnourished rats.

OBJECTIVE: To assess the influence of protein malnutrition on anastomotic healing in rat small bowel with or without chronic radiation damage. DESIGN: Controlled laboratory study. SETTING: University hospital, Sweden. MATERIAL: 60 male Sprague-Dawley rats. INTERVENTION: A short segment of the distal ileum was exteriorised and irradiated (n = 30) or only exposed (n = 30), and 20 weeks later an anastomosis was made within this segment. Two weeks before anastomosis half of the animals in each group received rat chow in which the protein content had been reduced to 25%; standard rat chow was given to the remaining animals. MAIN OUTCOME MEASUREMENTS: Weight changes, anastomotic bursting strength, amount of perianastomotic hydroxyproline, and number of anastomotic complications. RESULTS: 13 animals in the irradiated group and 11 animals in the non-irradiated group died of intestinal obstruction or respiratory distress leaving 17 and 19 animals that could be evaluated. Body weight was significantly reduced in animals with protein restriction (p < 0.001). A two way ANOVA showed an association between bursting strength and irradiation (p = 0.02) but not bursting strength and protein restriction. Anastomotic complications were more common in irradiated than in non-irradiated animals irrespective of the nutrition given (8/8 and 8/9 compared with 2/9 and 2/10, p = 0.0006). CONCLUSION: Protein malnutrition had no influence on anastomotic healing in rat intestine with or without chronic radiation damage.

Anastomosis, Surgical↗
PubMed1996

Pericytes as collagen-producing cells in excessive dermal scarring.

Immunohistochemistry and image analysis were performed on sections from excessive dermal scar formation to investigate the potential of pericytes to differentiate into collagen-producing cells. Expression of the prolyl-4-hydroxylase beta-subunit (P-4-H) was used as a marker for collagen synthesis as the distribution of this protein was identical to the distribution of procollagen type I C-propeptide and similar to the distribution of cells expressing pro alpha 1(I) collagen mRNA. Double immunofluorescence stainings using combinations of monoclonal antibodies specific for activated pericytes in vivo (high molecular weight-melanoma associated antigen (HMW-MAA)), P-4-H, smooth muscle alpha-actin (SMA), endothelial cells (PAL-E), platelet-derived growth factor (PDGF) beta-receptor, and the integrin alpha 5 subunit were performed. Stained sections were analyzed by computerized image analysis allowing for a quantification of the degree of colocalization between pairs of antigens on the same tissue section. Four different subpopulations of HMW-MAA expressing cells were discerned. The first subpopulation corresponded to intramural pericytes, juxtapositioned to the endothelium, that expressed HMW-MAA, SMA, integrin alpha 5 subunit and the PDGF beta-receptor, but not P-4-H. The second subpopulation was partly dissociated from the microvascular wall and exhibited a similar antigen expression except for a decrease in expression of SMA. Cells in the third subpopulation were located in the perivascular space and expressed P-4-H, integrin alpha 5 subunit, the PDGF beta-receptor and, albeit less pronounced, HMW-MAA, but not SMA. The fourth subpopulation expressed integrin alpha 5 subunit, HMW-MAA and the PDGF beta-receptor, no expression of SMA and a strong expression of P-4-H. Moreover, an in vitro analysis of cells derived from isolated microvascular fragments from human dermis revealed a similar pattern of phenotypical change. Taken together the data suggest that a population of intramural pericytes migrate into the perivascular space and develop into collagen-synthesizing fibroblasts during fibrosis.

Basement Membrane↗
PubMed1995

Regional rectal perfusion: a new in vivo approach to study rectal drug absorption in man.

BACKGROUND: In vivo permeability measurements of drugs in the colonic/rectal region in humans are difficult. A new instrument for the perfusion of a defined and closed segment in the colon/rectum was developed. The objective of this study was to evaluate its use for studying drug absorption mechanisms in the human rectum and to investigate the effect of transmucosal water absorption on drug permeability. Six healthy subjects participated at 2 separate occasions by using a modified system for segmental rectal perfusion. The system consisted of a multichannel tube with inflatable balloons and was endoscopically introduced into the rectum. The technique was considered acceptable by the following criteria; (a) high and reproducible recovery of PEG 4000, (b) stable residence time of the solution within the test segment, (c) flux of electrolytes that agrees with previous reports, (d) mass-balance absorption of antipyrine across the rectal barrier, (e) and good acceptability to the subjects. The permeability of antipyrine in the rectal region was increased by inducing net water absorption. D-glucose was not absorbed during any study periods. The present technique is valuable for studying drug absorption from the human rectum.

Antipyrine↗
PubMed1995

Hepatic extraction of hyaluronic acid in porcine peritonitis.

The hepatic extraction of hyaluronic acid (HA) was studied in porcine fecal peritonitis in two groups of animals given various amounts of volume substitution. There was a progressive decrease in hepatic blood flow (QH) and a corresponding increase in the plasma concentration of HA in arterial blood over a 5-hour observation period, less pronounced in animals given more volume substitution. While hepatic clearance of HA decreased, the extraction ratio over the liver was not altered. The extracted amount of HA, which at steady state reflects the turnover of HA, was also unchanged. There was a significant correlation between QH and arterial HA concentration (r = 0.57; p < 0.05). The data suggest that the arterial HA concentration in sepsis reflects QH rather than an altered ability of the liver to eliminate HA.

Animals↗
PubMed1995

Anastomotic breaking strength and healing of anastomoses in rat intestine with and without chronic radiation damage.

OBJECTIVE: To assess the influence of chronic radiation damage on anastomotic healing in the small bowel in rats. DESIGN: Controlled laboratory study. SETTING: University hospital, Sweden. MATERIAL: 90 male Sprague-Dawley rats. INTERVENTIONS: A short segment of the distal ileum was exteriorised and irradiated with a single dose (experimental group, n = 45) or exposed only (control group, n = 45). Twenty weeks later resection and anastomosis were done within this segment using 7/0 polypropylene. MAIN OUTCOME MEASURES: The anastomotic breaking strength, the amount of perianastomotic hydroxyproline, and the number of anastomotic complications. RESULTS: The breaking strength and the amount of perianastomotic hydroxyproline were higher in the irradiated than in the non-irradiated group. In contrast, anastomotic complications were significantly more common in irradiated animals. CONCLUSION: Anastomotic complications in irradiated intestine are not related to the amount of perianastomotic collagen or to breaking strength.

Anastomosis, Surgical↗
PubMed1995

Mucosal synthesis and release of prostaglandin E2 from activated eosinophils and macrophages in ulcerative colitis.

OBJECTIVE: To study the synthesis and release of prostaglandin E2 (PGE2) in diseased and healthy areas of the colon in ulcerative colitis/proctitis (UC) patients. METHODS: Perfusate fluid from rectal and sigmoid segments in patients with UC was analyzed for PGE2, eosinophil cationic protein, myeloperoxidase, and tumor necrosis factor-alpha concentrations. To further elucidate the cell-specific origin of mucosal PGE2 synthesis, double immunofluorescence staining as well as imaging analysis using antibodies reactive with prostaglandin H-synthase and cell-specific antigens were used on surgical colonic specimens from patients with active UC and from controls. RESULTS: The concentrations of PGE2 were, on average, 10-fold higher in perfusates from diseased areas in patients with UC than in perfusates from healthy areas in patients and controls. The PGE2 values correlated well with the released concentrations of eosinophil cationic protein, myeloperoxidase, and tumor necrosis factor-alpha. In the tissue specimens, there was a prominent colocalization in the expression of prostaglandin H-synthase on the one hand and CD 68 (a macrophage marker) and EG1/EG2 (eosinophil cationic protein markers) on the other hand, in both UC patients and controls. This did not apply to prostaglandin H-synthase and antibodies against B and T lymphocytes, neutrophils, or epithelial cells. CONCLUSION: The increased PGE2 production found in the inflamed mucosa in active UC may be caused by a fraction of activated eosinophils and macrophages.

Adult↗
PubMed1995

Intestinal mucosal injury during porcine faecal peritonitis.

OBJECTIVE: To assess the incidence of intestinal mucosal injury during faecal peritonitis in pigs, the relation of such lesions to haemodynamic variables, intramucosal pH (pHi), and endothelial adherence of polymorphonuclear leucocytes (PMNs). DESIGN: Experimental laboratory study. SETTING: University department of surgery, Sweden. SUBJECTS: 57 Juvenile pigs. INTERVENTIONS: Pigs had faecal peritonitis induced (n = 39) or a sham procedure (n = 18). In addition, 15 animals were pretreated with the monoclonal CD18 receptor antibody IB4 before induction of peritonitis with the aim of preventing tissue accumulation of PMNs. MAIN OUTCOME MEASURES: Development of mucosal lesions and correlation with haemodynamic variables. RESULTS: 17/18 (94%) of control animals had normal mucosa. The incidence of mucosal lesions in animals with faecal peritonitis was 56%. Animals with severe mucosal injury (grade 4-5) had significantly lower mean arterial pressure, cardiac index, and pHi during the last hour of the experiment compared with animals without mucosal lesions. Pretreatment with IB4 did not prevent the development of intestinal mucosal injuries. Intramucosal pH decreased during sepsis and was not affected by IB4. CONCLUSIONS: Severe intestinal mucosal injury is associated with arterial hypotension, low cardiac index, and low pH. Neither the mucosal injury nor the reduction in pHi seen during porcine faecal peritonitis seemed to be leucocyte-related phenomena.

Animals↗
PubMed1994

Effects of a novel 21-aminosteroid or methylprednisolone in experimental total intestinal ischemia.

OBJECTIVE: To investigate whether tirilazad mesylate, a 21-aminosteroid, protects the small intestinal mucosa from injury following total warm or cold ischemia and reperfusion. DESIGN: Randomized vehicle-controlled experimental study. SETTING: A university department of surgery. ANIMALS: Wistar rats. The warm ischemia series preceded the cold ischemia series. Animals were randomized within each series. Microscopic evaluation was performed on coded tissue slides. INTERVENTIONS: Warm ischemia was induced by a hydrostatic pressure cuff inflated to 10 mm Hg above the systolic arterial pressure for 60 minutes. Cold ischemia was studied after small intestinal transplantation. The transplant was stored for 5 hours in University of Wisconsin solution at 8 degrees C. Ischemia was followed by 60 minutes of reperfusion. In both series, tirilazad mesylate (3 mg/kg) or methylprednisolone sodium succinate (30 mg/kg) was given. Controls were given tirilazad vehicle or saline solution. MAIN OUTCOME MEASURE: Microscopic grade of small intestinal mucosal injury. RESULTS: Mucosal injury was evident in all groups of animals that were subjected to warm or cold ischemia. Reperfusion following cold ischemia induced a significant reperfusion injury. Neither tirilazad nor methylprednisolone protected the small intestinal mucosa during ischemia or reperfusion. CONCLUSION: Mucosal injury following warm or cold intestinal ischemia and reperfusion is caused by factors other than or in addition to lipid peroxidation, which is preventable by use of a 21-aminosteroid.

Animals↗