Biomedical subjects

J P James

Publications and source records attributed to J P James.

11 recordsLinked to original sources

PubMed1992

Circulating von Willebrand factor in inflammatory bowel disease.

Raised circulating von Willebrand factor is a recognised marker of vascular injury. To evaluate the role of vascular injury in the pathogenesis of inflammatory bowel disease, serum von Willebrand factor in Crohn's disease, ulcerative colitis, confirmed bacterial diarrhoea, and healthy subjects was measured. von Willebrand factor values were raised in 9/14 patients (p = 0.007) with active Crohn's disease, 15/28 (p = 0.0004) with inactive Crohn's disease, 16/23 (p = 0.0003) with active ulcerative colitis, 9/27 (p = 0.04) with inactive ulcerative colitis, and 15/17 (p = 0.0001) patients with bacterial diarrhoea. Serum von Willebrand factor was unrelated to disease activity in Crohn's disease but was significantly raised in active (p = 0.02) compared with inactive ulcerative colitis. In contrast to controls, the detection of von Willebrand factor from inflammatory bowel disease sera and that from fractured endothelial cells was significantly inhibited by the reducing agent, dithiothreitol, suggesting the presence of an additional dithiothreitol sensitive form of the molecule derived from injured endothelial cells in inflammatory bowel disease. That serum von Willebrand factor is raised in quiescent as well as active Crohn's disease is compatible with the proposal that vascular injury is a fundamental abnormality in this disorder. The raised von Willebrand factor values in active inflammatory bowel disease and bacterial diarrhoea could be caused by either vascular injury, occurring secondary to bowel inflammation, or to an acute phase response resulting from endothelial cell stimulation by mediators released during the inflammatory process. Raised circulating von Willebrand factor could contribute to the increased risk of thrombosis associated with active inflammatory bowel disease.

Bacterial Infections↗

PubMed1991

Matrix-assisted UV-laser desorption/ionization mass spectrometric analysis of monoclonal antibodies for the determination of carbohydrate, conjugated chelator, and conjugated drug content.

The chemically averaged molecular weights of a variety of native and conjugated monoclonal antibodies, approximately 150,000, were measured by matrix-assisted UV-laser desorption/ionization mass spectrometry. The average mass of the carbohydrate present in a monoclonal antibody was estimated from the difference between the measured mass of the monoclonal antibody and the mass of the protein present in the monoclonal antibody computed from the amino acid translation of the DNA sequence. The loading of chelators and anticancer drugs conjugated to a monoclonal antibody was quantitated from the difference in the measured masses for the conjugated and untreated monoclonal antibody relative to the expected mass change upon conjugation of 1 mol of chelator or drug. The loading results obtained by mass spectrometry were consistent in most cases with measurements obtained by radioactivity trace assay or UV spectrometry. Similar matrix-assisted UV-laser desorption/ionization mass spectrometric studies were also made after reducing untreated and conjugated monoclonal antibodies with dithiothreitol to determine the distribution of carbohydrate and chelator between the light and heavy chains of the molecules. Matrix-assisted UV-laser desorption/ionization mass spectra were used to compute loading values for covalently bound drugs and proteins, while the loading values obtained by use of gel-filtration HPLC and UV spectrometry cannot distinguish between covalently and noncovalently bound drugs and proteins.

Antibodies, Monoclonal↗

PubMed1990

Factor VIII related antigen in connective tissue disease patients and relatives.

This study assayed serum levels of FVIII Rag as a marker of endothelial injury in patients not only with frank connective tissue disease but also in those presenting with Raynaud's phenomenon and in families of those with systemic sclerosis. Elevated levels of FVIII Rag were found in 62% of patients with systemic sclerosis (SS), 38% with systemic lupus erythematosus (SLE), 67% with mixed connective tissue disease (MCTD) and in 17% with primary Raynaud's phenomenon. Twenty per cent of first degree relatives of patients with SS also demonstrated high levels of FVIII Rag and certain antibodies, namely those reacting with U1RNP and the centromere. The association between elevated FVIII Rag and antibodies linked to Raynaud's and vasculitis lends support to antibody involvement in pathogenesis. High levels of FVIII Rag in family members may reflect an increased susceptibility of endothelium to injury particularly since relatives also have a higher frequency of clinical features such as Raynaud's phenomenon.

Antibodies↗

PubMed1989

Reconstitution of cytolytic alloreactivity with N-[4-[(4-fluorophenyl) sulfonyl]phenyl]acetamide (CL 259,763) in animals immunocompromised by cyclophosphamide.

A novel synthetic immunopotentiator, i.e. N-[4-[(4-fluorophenyl)sulfonyl]phenyl]acetamide (CL 259,763), was investigated for its potential in reconstituting the cell-mediated immune response of animals whose immunologic system had been severely depressed by cytoreductive agents. It was demonstrated that lymphocytes from mice which had received 300 mg/kg of cyclophosphamide (CY) immediately following antigen sensitization had a reduced capability of responding to alloantigens in mixed lymphocyte culture and failed to generate effective cytolytic T-lymphocytes (CTL) capable of destroying appropriate tumor target cells in a cytotoxicity assay. However, treatment of these immunocompromised animals with CL 259,763 produced a significant restoration of alloreactivity, as evidenced by an enhancement of the CTL response. Although effective doses of CL 259,763 ranged from 20 to 300 mg/kg, the optimal effect was observed at 75 mg/kg. Findings from a time course study indicated that the maximum restoration occurred when CL 259,763 was given to mice 2-5 days after, but not before or simultaneously with, CY treatment. Both the immunoimpairment by CY and its reversal by CL 259,763 appeared not to be antigen specific. The lessened immunoreactivity of CY-treated mice was explicable by the presence of suppressor cells in their spleens. These suppressors were able to adhere to plastic and resisted treatment with anti-Thy 1.2 antibody, indicating a macrophage characteristic. Flow cytometric analysis indicated a quantitative depletion of all T-lymphocytes, including Thy-1.2(+), Lyt-1(+), Lyt-2(+) and L3T4(+) subsets in the spleens of CY-treated mice; however, a population of Mac-1(+) cells was markedly expanded.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

PubMed1985