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Biomedical subjects

I Hemingway

Publications and source records attributed to I Hemingway.

9 recordsLinked to original sources
PubMed1998

Serum concentrations of soluble adhesion molecules in patients with colorectal cancer.

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 48 patients with colorectal cancer before treatment, and their relation to clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with colorectal cancer in comparison with a group of healthy subjects (P < 0.00001). Levels of circulating ICAM-1 and VCAM-1 were increased both in patients with local and those with metastatic disease. Although elevated in some patients soluble E-cadherin and E-selectin concentrations were not significantly elevated compared with the control group (P = 0.71 and P = 0.052 respectively). The levels of circulating ICAM-1 were significantly correlated with those of VCAM-1 and E-selectin. A correlation was also found between the serum concentrations of E-selectin and ICAM-1 and alkaline phosphatase, total white cell count and platelet count. VCAM-1 was positively correlated with age and negatively with degree of tumour differentiation and haemoglobin concentration. The biological implications and possible clinical relevance of these findings are discussed.

Adult↗
PubMed1998

Adhesion molecule expression in the lung: a comparison between normal and diffuse interstitial lung disease.

Cellular adhesion molecules are crucial determinants of the migration of immune effector cells to the tissues. In chronic inflammatory diseases, upregulation of the expression of these molecules may contribute to the persistent inflammatory process. The aim of this study was to determine whether there is evidence of adhesion molecule expression in chronically inflamed lung. Soluble adhesion molecules in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunoassay in 54 patients with chronic interstitial lung diseases and 16 normal controls. Adhesion molecule expression in fibrosing alveolitis (FA) lung and in control lung was assessed using immunohistology and reverse transcription-polymerase chain reaction (RT-PCR) amplification. Soluble intercellular adhesion molecule-1 (ICAM-1) was detected in all but two subjects. There was no difference in ICAM-1 concentration between disease groups and normal subjects. In contrast, soluble E-selectin was detected in 17 of the 70 subjects and was significantly associated with the presence of lung disease (p=0.0173). Furthermore, the presence of soluble E-selectin was associated with a raised lymphocyte percentage in BALF (p=0.0069). Soluble VCAM was only detected in five of the 70 subjects (two normals, three patients). There was no difference in adhesion molecule expression in lung parenchyma between FA and controls assessed by immunohistology and RT-PCR. The most striking finding of our study was the universal expression of intercellular adhesion molecule-1 in both normal and diseased lung, emphasizing the important role of the lung in immune function. Upregulation of E-selectin may contribute to inflammatory cell accumulation in chronic interstitial lung diseases.

Adolescent↗
PubMed1997

Circulating soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in patients with gastric cancer.

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 45 patients with gastric cancer before treatment and their correlation with clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology, survival and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with gastric cancer in comparison with the group of healthy subjects (P < 0.00001 and P < 0.0001 respectively). Increased serum concentrations of VCAM-1 were associated with locally advanced and metastatic disease whereas ICAM-1 was significantly elevated both in local and in advanced/metastatic disease. Soluble E-cadherin and E-selectin concentrations did not show any significant elevation in gastric cancer patients. Concentrations of soluble adhesion molecules showed significant correlation with each other (except E-selectin and VCAM-1) and with alkaline phosphatase. Soluble ICAM-1 and VCAM-1 were significantly associated with an elevated total white cell count. Patients with elevated VCAM-1 had significantly poorer survival in comparison with patients with normal serum levels (P = 0.0361).

Adult↗
PubMed1994

Soluble intercellular adhesion molecule-1 (ICAM-1) is released into the serum and ascites of human ovarian carcinoma patients and in nude mice bearing tumour xenografts.

We have demonstrated that patients with ovarian carcinoma have higher levels of soluble intercellular adhesion molecule-1 (ICAM-1) in their serum and ascitic fluids than serum from normal individuals and non-neoplastic gynaecological disease or ascites from patients with cirrhosis. In order to investigate the source of the ICAM-1, and to study the mechanisms which regulate ICAM-1 release in ovarian carcinoma, we have employed the nude mouse model system. Three different human ovarian carcinoma (HOC) cell lines were grown as ascitic tumours in the peritoneal cavity of nude mice. HOC xenografts harvested from nude mice expressed comparable levels of ICAM-1 on their cell surface. Human ICAM-1 was detected, with a species-specific ELISA, in serum and ascitic fluid of tumour-bearing mice, confirming that the tumours were the source of the ICAM-1. The three HOC xenografts showed different levels of ICAM-1 release, but within each xenograft model the level of ICAM-1 in serum and ascitic fluid correlated with the tumour burden. The level of ICAM-1 released by the HOC xenografts could be increased by in vivo treatment with interferon gamma (IFN-gamma). Interleukin 1 (IL-1), tumour necrosis factor (TNF) and IFN gamma increased the cell surface expression of ICAM-1 and caused the release of soluble ICAM-1 from HOC cells established in vitro. The nude mouse provides a useful system in which to study the effects of modulating ICAM-1 release on the progression of ovarian carcinoma and suggests that measuring ICAM-1 levels in the blood or ascites of patients may provide an indication of tumour burden.

Animals↗
PubMed1994

Increased circulating adhesion molecule concentrations in patients with the systemic inflammatory response syndrome: a prospective cohort study.

OBJECTIVE: To investigate the relationship between the soluble derivatives of endothelial adhesion molecules liberated by activated vascular endothelium and the development of the systemic inflammatory response syndrome and organ dysfunction in septic patients. DESIGN: Prospective cohort study with controls. SETTING: University hospital intensive care unit. PATIENTS: Healthy volunteers (controls, n = 85), patients with the systemic inflammatory response syndrome (n = 21), patients with systemic inflammatory response syndrome and organ dysfunction (n = 14), and miscellaneous, severely ill patients (n = 5). INTERVENTIONS: Plasma samples were collected from consecutive patients who satisfied the criteria for inclusion in the groups listed above. MEASUREMENTS AND MAIN RESULTS: The plasma was assayed by enzyme-linked immunosorbent assay (ELISA) for each of the three soluble adhesion molecules: sE-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1. There were low basal amounts of these adhesion molecules in the healthy volunteers, while plasma concentrations of all three adhesion molecules were increased in the sepsis groups. The median soluble E-selectin concentration was higher in those patients with organ dysfunction compared with the concentrations in patients with uncomplicated sepsis (p < .01 at first and p < .001 when comparing peak values attained). No patient survived when the amount of soluble E-selectin was > 30 units/mL. CONCLUSIONS: Concentrations of circulating vascular endothelial adhesion molecules, especially soluble E-selectin, are increased in patients with systemic inflammatory response syndrome and these concentrations are more increased in patients with organ dysfunction. High plasma concentrations of soluble E-selectin were closely associated with multiple-organ dysfunction and death. Measurement of adhesion molecules, especially soluble E-selectin, might be used to advantage in the management of patients with sepsis.

Adult↗
PubMed1994

Activation dependent and independent VLA-4 binding sites on vascular cell adhesion molecule-1.

Vascular cell adhesion molecule-1 (VCAM) is a cytokine-inducible member of the immunoglobulin superfamily which binds to the integrin VLA-4. VCAM is expressed predominantly on the vascular endothelium where it is involved in the recruitment of mononuclear cells and lymphocytes to sites of inflammation. Two forms of VCAM containing six and seven Ig domains (VCAM-6d; VCAM-7d) are generated by alternative splicing but the physiological significance of this is unknown. We have utilised VCAM deletion mutants, VCAM-transfected cell lines and monoclonal antibodies to assess the functional importance of the individual VCAM domains. We have identified two binding sites on VCAM-7d located in domains 1 and 4 that are involved in the adhesion of the U937 human myelomonocytic cell line. Adhesion to domain 1 is temperature-independent, inhibited by the anti-VCAM mAbs 4B2 or lE10, and insensitive to PMA activation. In contrast, adhesion to domain 4 is temperature sensitive, unaffected by mAbs 4B2 or lE10 and augmented by PMA. Adhesion to both domains can be totally inhibited by the anti-VLA-4 mAb, 2B4. The anti-VCAM mAb 4B2 inhibits adhesion of U937 cells to stably transfected VCAM-7d-CHO cells at 4 degrees C, but, at 37 degrees C the effect of 4B2 on adhesion is modest with incubation times of less than 60 minutes duration. With longer incubation times, its effectiveness gradually increases, so that by 2 hours > 75% of the response can be blocked. Co-incubation with PMA prevents this time-dependent enhancement of 4B2 efficacy but has no significant effect on the inhibitory activity of the anti-VLA-4 mAb 2B4. These data can be explained by postulating a two stage ligand-receptor interaction that involves activation-induced changes in the avidity of VLA-4 for domain 4 of VCAM.

Alternative Splicing↗
PubMed1992

Soluble intercellular adhesion molecule 1 is released by human melanoma cells and is associated with tumor growth in nude mice.

We have studied the cytokine regulation of cell surface and soluble intercellular adhesion molecule 1 (ICAM-1) expression on the human melanoma cell line A375M. Unstimulated cells express ICAM-1 on their cell surface but do not secrete significant levels of soluble ICAM-1. Interleukin 1, interleukin 6, tumor necrosis factor, and gamma-interferon all increased cell surface expression of ICAM-1. Tumor necrosis factor, interleukin 1, and gamma-interferon also caused the release of soluble ICAM-1. The serum of melanoma patients has been reported to contain elevated levels of soluble ICAM-1; however, the source of this ICAM-1 is unclear. The serum from nude mice bearing s.c. human melanoma tumors was found to contain soluble human ICAM-1. ICAM-1 levels showed a positive correlation with tumor weight. The release of ICAM-1 from melanoma tumors, in response to host-derived cytokines, may have relevance to immune recognition of the tumor.

Animals↗
PubMed1990

Hydrolytic enzyme production by Clostridium difficile and its relationship to toxin production and virulence in the hamster model.

Thirty isolates of Clostridium difficile expressing different degrees of toxigenicity and virulence in an animal model were assayed for the production of chondroitin-4-sulphatase, hyaluronidase, heparinase, collagenase and protease. All strains demonstrated some hydrolytic enzyme activity. There was no direct correlation between toxigenic status, or virulence, and hydrolytic enzyme production. However, all five strains known to be highly virulent in the hamster model had hyaluronidase, chondroitin-4-sulphatase and collagenase activity whereas only three of five toxigenic but poorly virulent strains had these activities, the collagenase activity being weak in all three cases. The only two proteolytic strains are also highly virulent. The potential tissue damaging properties of these hydrolytic enzymes may help to explain the differences in virulence of C. difficile strains seen in the Syrian hamster model of antibiotic-associated colitis, and may contribute to the spectrum of disease seen in man. It is also possible that chondroitin-4-sulphatase, hyaluronidase and collagenase activity may release essential nutrients, promoting establishment of C. difficile in the gut.

Animals↗