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Biomedical subjects

J C Mason

Publications and source records attributed to J C Mason.

At least 37 records · Page 2Linked to original sources
PubMed1999

Induction of decay-accelerating factor by cytokines or the membrane-attack complex protects vascular endothelial cells against complement deposition.

Vascular endothelium is continuously exposed to complement-mediated challenge, and this is enhanced during inflammation. Although the complement-regulatory proteins decay-accelerating factor (DAF), CD59, and membrane cofactor protein (MCP) protect endothelial cells (ECs) against complement-mediated injury, the control of their expression and relative contributions to vascular protection is unclear. We explored the hypothesis that mechanisms exist which induce upregulation of complement-regulatory proteins on ECs to maintain vascular function in inflammation. Tumor necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma) each increased DAF expression but not CD59 or MCP expression, and a combination of these cytokines was more potent than either alone. Cytokine-induced expression depended on increased DAF mRNA and de novo protein synthesis and was maximal by 72 hours. In addition, assembly of the membrane-attack complex (MAC) on ECs induced a 3-fold increase in DAF expression, and this was enhanced by cytokines. DAF upregulation was not inhibited by protein kinase C (PKC) antagonists. The increase in DAF was functionally relevant since it reduced complement 3 (C3) deposition by 40%, and this was inhibited by an anti-DAF monoclonal antibody. These observations indicate that upregulation of DAF expression by cytokines or MAC may represent an important feedback mechanism to maintain the integrity of the microvasculature during subacute and chronic inflammatory processes involving complement activation.

Antigens, CD↗
PubMed1999

NSAIDs and the oesophagus.

There have been many studies documenting the deleterious effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the gastrointestinal tract, and it is widely accepted that these agents cause mucosal damage in the stomach, duodenum, jejunum, ileum and colon. The mechanism of this toxicity is at least partly due to inhibition of endogenous prostaglandin synthesis. Prostaglandins, especially PGE2, PGI2 and the synthetic PGE1 analogue misoprostol, protect the stomach from these harmful effects. There is good theoretical evidence that the opposite is the case in the oesophagus, with prostaglandins causing relaxation of the lower oesophageal sphincter, increasing acid reflux and acting as mediators of the inflammatory response. NSAIDs have beneficial effects in some models of oesophagitis and have even been proposed as treatment for oesophagitis. In spite of these theoretical benefits, there are many reports implicating NSAIDs in the pathogenesis of oesophagitis, oesophageal ulceration and stricture formation.

Animals↗
PubMed1999

Anti-Kaposi's sarcoma and antiangiogenic activities of sulfated dextrins.

Delivery of the sulfated polysaccharide dextrin 2-sulfate by the intraperitoneal route to the lymphatic circulation resulted in a clinically significant improvement in Kaposi's sarcoma in three patients. Our in vitro studies show that although sulfated dextrins do not interfere with the growth of isolated human umbilical vein endothelial cells, they do inhibit the morphological differentiation of endothelial cells into tubes as well as reduce new vessel formation in a placental angiogenesis assay. The antiangiogenic effect of dextrin 6-sulfate is greater than that of dextrin 2-sulfate and is independent of their anti-human immunodeficiency virus type 1 activities.

Anti-HIV Agents↗
PubMed1999

Pulmonary granulocyte kinetics in relation to endothelial and granulocyte activation.

The aim of the study was to measure the peripheral blood levels of soluble E-selectin in patients with systemic inflammation and compare them with in vivo granulocyte activation, pulmonary intravascular granulocyte pooling, pulmonary extravascular granulocyte migration and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) aerosol clearance, an index of lung injury. The level of soluble E-selectin was measured by capture ELISA. Granulocytes were labelled with 111In and 99mTc for quantification of pulmonary granulocyte kinetics. The pulmonary vascular granulocyte pool (PGP) was expressed as a fraction of the total blood granulocyte pool. Pulmonary granulocyte migration was quantified on 24-h images using the 111In signal. Granulocyte activation was quantified as the percentage of circulating cells showing shape change ('primed'). Lung injury was assessed from the clearance rate of inhaled 99mTc-DTPA aerosol. Eighteen patients with systemic inflammation were studied: five with inflammatory bowel disease, eight with systemic vasculitis, four with graft versus host disease and one with a recent renal transplant. The peripheral blood levels of soluble E-selectin were significantly elevated in patients with systemic inflammation. The level of soluble E-selectin showed a significant association with granulocyte migration (Spearman rank correlation coefficient, Rs=0.53; P<0.05) but not with PGP or with the percentage of cells showing shape change (P>0.05 for both). Granulocyte migration was bimodal: patients were therefore subdivided into 'migrators' and 'non-migrators'. Soluble E-selectin level, 99mTc-DTPA clearance and PGP, but not the percentage of cells showing shape change, were significantly higher in migrators than in non-migrators. We conclude that pulmonary intravascular granulocyte pooling is increased in the presence of increased numbers of circulating primed granulocytes but increased pooling does not by itself promote granulocyte migration into the lung interstitium. Insofar as an elevated level of E-selectin in peripheral blood reflects vascular endothelial activation, the data are consistent with the notion that pulmonary endothelial activation is required, in addition to granulocyte activation and an expanded PGP, for granulocyte migration into lung parenchyma and, therefore, for lung injury to occur.

Adult↗
PubMed1997

Systemic lupus erythematosus, thrombocytopenia, microangiopathic haemolytic anaemia and anti-CD36 antibodies.

Thrombocytopenia in patients with acute systemic lupus erythematosus (SLE) frequently presents the clinician with considerable diagnostic and therapeutic difficulties. In this Grand Round, we present a 48-yr-old woman with a 7 yr history of lupus, who presented with acute proliferative glomerulonephritis and nephrotic syndrome, pneumonia, profound hypocomplementaemia and a severe microangiopathic haemolytic anaemia with associated thrombocytopenia. Her thrombocytopenia proved initially refractory to conventional immunosuppressive therapy, and corticosteroids, and resolved only with plasma exchange and repeated fresh frozen plasma infusions. Serological testing revealed high-titre antinuclear antibodies (ANA) and markedly raised antibodies to double-stranded (ds) DNA, but no significant elevation in anticardiolipin antibodies. Platelet-associated IgG and IgM and antibodies to the CD36 glycoprotein antigen, expressed on platelets and endothelium, were detected in the serum. We address some of the difficult diagnostic and management issues raised by this complex patient and the possible immunopathological links between antibodies to CD36, immune-mediated red cell destruction, thrombocytopenia and thrombotic microangiopathic haemolytic anaemia.

Anemia, Hemolytic, Autoimmune↗
PubMed1997

Human umbilical vein and dermal microvascular endothelial cells show heterogeneity in response to PKC activation.

Changes in endothelial cell (EC) phenotype are central to the function of endothelium in inflammation. Although these events mainly occur in the microvasculature, previous studies have predominantly used large-vessel EC. Using enzyme-linked immunosorbent and flow cytometric assays, we compared the responses of human umbilical vein endothelial cells (HUVEC) and dermal microvascular endothelial cells (DMEC) to the activation of protein kinase C (PKC). Stimulation with phorbol 12,13-dibutyrate and more selective PKC agonists, including 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), induced morphological changes and proliferation in both EC types. PKC activation induced a marked increase in Thy-1 expression on DMEC and only a moderate rise on HUVEC. Furthermore, heterogeneity in the induction of the adhesion molecules intercellular adhesion molecule 1, vascular cell adhesion molecule 1 IVCAM-1), and E-selectin between the two EC types following activation of PKC was demonstrated. In particular, E-selectin and VCAM-1 were significantly upregulated on HUVEC but not DMEC. The data indicate that the PKC pathway is unlikely to be important for E-selectin and VCAM-1 expression in the microvasculature but are consistent with a role for PKC in angiogenesis. This diversity in signaling in response to PKC activation may depend on differential utilization of PKC isozymes and may facilitate specialized endothelial responses.

Cell Adhesion Molecules↗
PubMed1996

Human Thy-1 is cytokine-inducible on vascular endothelial cells and is a signaling molecule regulated by protein kinase C.

Thy-1 is a glycosylphosphatidylinositol-anchored member of the Ig superfamily whose function, particularly in the human, remains unknown. We have demonstrated that human Thy-1 is expressed on endothelial cells (EC) both in situ and on the surface of cultured human umbilical vein EC and dermal microvascular EC (DMEC). The expression of the molecule decreased with serial passage but was restored by treatment of EC with PMA and phorbol-12,13-dibutyrate (PBu), which increased Thy-1 by up to 100-fold in a dose-dependent manner. This increase was first detectable at 12 h post-stimulation, peaked at 48 h, and was maintained at 72 h. In PBu-stimulated DMEC, Western blotting revealed Thy-1 to be a 29-kDa molecule, while Northern analysis demonstrated an increase in steady-state Thy-1 mRNA. Thy-1 expression was also induced on DMEC by treatment with TNF. Inhibition studies showed that the induction of Thy-1 by PBu and TNF was protein synthesis dependent. The up-regulation of Thy-1 by PBu, but not TNF, was inhibited by the protein kinase C inhibitor RO31-8220, suggesting the presence of protein kinase C-dependent and -independent pathways for Thy-1 expression. To investigate the function of Thy-1 on human EC, we studied changes in intracellular calcium concentration ([Ca2+]i) following cross-linking of Thy-1 on human umbilical vein EC. This resulted in a rapid transient rise of [Ca2+]i in EC. Our results demonstrate for the first time the presence of Thy-1 on cultured human EC. The expression on EC, the inducibility by TNF, and the ability to transmit signals suggest that Thy-1 may have an important role in inflammatory responses.

Antibodies, Monoclonal↗
PubMed1995

A rare mediastinal tumour presenting with systemic effects due to IL-6 and tumour necrosis factor (TNF) production.

Patients presenting with prolonged systemic illnesses with no specific clinical or serological defining features may be diagnosed as having atypical systemic vasculitides, but often turn out to have occult malignancies. Cytokines have been implicated in causing many of the systemic effects in such cases. In this study we describe a patient presenting after 2 years of a severe systemic illness with a marked acute phase response, due to an occult mediastinal angiomatoid malignant fibrous histiocytoma. Tumour resection was curative. We evaluated in detail the local and systemic production of cytokines induced by this tumour. Blood samples were taken pre- and post-operatively for cytokine studies. In vitro production of IL-2, IL-2R, IL-1 beta, IL-6 and TNF-alpha by cultured monocytes from the patient, as well as plasma cytokine levels, were measured by ELISA. Tumour cytokine production was also evaluated immunocytochemically, and by in situ hybridization with specific cDNA probes. Plasma IL-2R and IL-6, and IL-6 and TNF-alpha production by peripheral blood monocytes were markedly elevated before tumour resection, normalizing post-operatively. Most tumour cells and infiltrating lymphocytes stained with antibodies to IL-6, IL-6R and TNF-alpha, and expressed HLA class II. IL-6 and TNF-alpha mRNA production in the tumour was confirmed by in situ hybridization studies. We have described the first case of an occult angiomatoid malignant fibrous histiocytoma in the mediastinum. Studies of cytokine expression suggested that chronic TNF, IL-6, and IL-2 production by leucocytes and tumour cells in this patient was responsible for the severe systemic illness with which she presented.

Adult↗
PubMed1994

Familial polyarteritis nodosa.

Familial polyarteritis nodosa (PAN) is rare. We describe here two siblings who developed PAN 8 years apart. HLA typing showed that the affected family members shared a common haplotype with their unaffected mothers. Further study of the family history suggested the possibility of an inherited disorder of connective tissue predisposing to autoimmunity and aneurysm formation.

Adolescent↗
PubMed1993

Detection of increased levels of circulating intercellular adhesion molecule 1 in some patients with rheumatoid arthritis but not in patients with systemic lupus erythematosus. Lack of correlation with levels of circulating vascular cell adhesion molecule 1.

OBJECTIVE: To compare the levels of circulating intercellular adhesion molecule 1 (cICAM-1) and vascular cell adhesion molecule 1 (cVCAM-1) in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: Levels of cICAM-1 and cVCAM-1 were measured in both plasma and synovial fluid using monoclonal antibody sandwich enzyme-linked immunoassays. RESULTS: Levels of both cICAM-1 and cVCAM-1 were significantly increased (P < 0.001) in RA patients compared with normal controls. In contrast, only cVCAM-1, and not cICAM-1, was increased in patients with SLE. Levels of cICAM-1 and cVCAM-1 were significantly elevated in synovial fluid compared with plasma in paired samples from patients with RA. There was no correlation between levels of cICAM-1 and levels of cVCAM-1, in either plasma or synovial fluid. Whereas levels of cVCAM-1 correlated significantly with the erythrocyte sedimentation rate (ESR) and C-reactive protein level in RA patients and with the ESR in SLE patients, no significant correlations were found between cICAM-1 and either of these indices of disease activity. CONCLUSION: These observations indicate that levels of cICAM-1 and cVCAM-1 reflect separate pathophysiologic processes. Both may be useful markers for the diagnosis and management of patients with rheumatic diseases.

Adult↗
PubMed1993

Vertebral osteomyelitis due to Staphylococcus epidermidis.

Vertebral osteomyelitis due to Staphylococcus epidermidis is extremely rare and usually occurs in the context of immunosuppression in association with an adequate portal of entry for infection. This paper reports a case of vertebral osteomyelitis due to S. epidermidis in a man with no evidence of immunosuppression or obvious portal of entry. The patient presented with severe back pain but there were no clinical signs of infection. Radiographs and computerized tomographs showed destruction of thoracic vertebral bodies and an adjacent soft tissue mass. S. epidermidis was grown from multiple blood cultures. All isolates had identical antibiograms and biochemical profiles. There was evidence of healing of the vertebral bodies and resolution of the soft tissue mass after appropriate antistaphylococcal treatment.

Aged↗
PubMed1993

Detection of a circulating form of vascular cell adhesion molecule-1: raised levels in rheumatoid arthritis and systemic lupus erythematosus.

We have developed a panel of MoAbs against four separate but overlapping epitopes on endothelial cell (EC) vascular cell adhesion molecule-1 (VCAM-1). Two of the MoAbs (1G11 and 1E5) inhibited T cell adhesion to tumour necrosis factor (TNF)-activated EC, whilst two MoAbs (1.4C3 and 6D9) did not. Using these MoAbs we have identified a circulating form of VCAM-1 (cVCAM-1) which has identical epitope distribution to the EC form, and which is able to support the adhesion of the human lymphoblastoid cell line Jurkat J6 by a VLA-4- and VCAM-1-dependent mechanism when immobilized from plasma. cVCAM-1 isolated by immunoaffinity and size-exclusion chromatographies was shown by SDS-PAGE to have an apparent mol. wt of 85-90 kD. Levels of cVCAM-1 were significantly raised (P < 0.001) in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) compared with normal individuals. It is possible that cVCAM-1 may be a useful plasma marker for the diagnosis and management of patients with inflammatory diseases. Furthermore, detection of elevated cVCAM-1 levels may act as a guide to the importance of VCAM-1-dependent cell adhesion in different pathological settings.

Adolescent↗
PubMed1993

Spontaneous biloma in an elderly patient.

A previously well 84 year old man without prior history of abdominal trauma, instrumentation or surgery presented with localized biliary peritonitis (biloma). An associated bile duct stone was detected by abdominal ultrasound and endoscopic retrograde cholangiopancreatography and was successfully treated with systemic antibiotics and percutaneous and endoscopic stenting. The case is unusual in that the presentation was spontaneous.

Aged↗
PubMed1993

Acute renal failure treated by haemofiltration: factors affecting outcome.

Two hundred and fifty consecutive patients with acute renal failure treated by continuous haemofiltration on one intensive care unit (ICU) were studied prospectively to investigate the possibility of predicting outcome at the time of referral. Logistic regression analysis was used to identify important prognostic factors and the regression coefficients were used to weight a scoring system for the severity of illness of patients with acute renal failure. Overall survival was 53% with improvement over the course of the study. Multivariate analysis showed that outcome was related to age, need for artificial ventilation, use of inotropes, urine volume, serum bilirubin, arterial base deficit and serum creatinine. The scoring system based on the first five of these variables had a specificity of predicting death of 67% and a sensitivity of 76%.

Acute Kidney Injury↗