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Biomedical subjects

J Cason

Publications and source records attributed to J Cason.

51 records · Page 3Linked to original sources

An antigen chimera of poliovirus induces antibodies against human papillomavirus type 16.

It has been established that the surface of poliovirus type 1 can be extensively modified to incorporate antigenic domains from other poliovirus serotypes and from unrelated viruses. The fact that the modified (chimeric) viruses exhibit dual antigenicity and immunogenicity led us to explore the possibility of using the Sabin vaccine strain of poliovirus type 1 as a vector for the presentation of antigenic domains from human papillomavirus type 16 (HPV-16), a virus associated with the development of cervical carcinoma. We report here the construction and characterization of a chimeric poliovirus containing a 16-residue sequence derived from the major capsid protein (L1) of HPV-16. This virus chimera stimulated the production in rabbits of antibodies which recognized the HPV-16-derived peptide and an L1 fusion protein synthesized in Escherichia coli and detected HPV-16 in human biopsy material by immunoperoxidase staining. The possibility that poliovirus-HPV chimeras could be used as vaccines against HPV-16 is discussed.

Amino Acid Sequence↗

Identification of immunogenic regions of the major coat protein of human papillomavirus type 16 that contain type-restricted epitopes.

We have identified regions of the major capsid protein, L1, of the human papillomavirus (HPV) type 16 (HPV-16 L1), that are recognized by five monoclonal antibodies (MAbs) raised to a bacterial fusion protein containing residues 172 to 375 of HPV-16 L1. All five MAbs recognized HPV-16-infected tissue sections by immunohistochemistry, but not sections infected with HPV-1a (cutaneous warts), HPV-6b or -11 (genital warts). MAbs 3D1, 5A4 and 1D6 also recognized HPV-2-infected sections (cutaneous warts); MAb 8C4 recognized only sections containing HPV-16. Four MAbs (8C4, 3D1, 1D6 and 5A4) recognized a synthetic peptide corresponding to residues 269 to 284 of HPV-16 L1; within this region a minimum antibody binding site was identified, a tripeptide 276 to 278. However the complete epitope appears to extend beyond these residues and beyond HPV-16 L1 (269 to 284). The fifth MAb, 1C6, recognized bacterial fusion proteins containing HPV-6b L1, -16 L1 or -18 L1 using immunoblots, yet appeared HPV-16-specific when tested on infected tissue sections. This MAb recognized five amino acids within a different region of HPV-16 L1 (residues 299 to 313).

Amino Acid Sequence↗

Zinc status in inflammatory bowel disease.

1. The zinc contents of plasma, erythrocytes, polymorphonuclear leucocytes and mononuclear leucocytes from 18 normal control subjects, 31 patients with Crohn's disease and 15 patients with ulcerative colitis were measured. 2. Plasma zinc levels were low in Crohn's disease, particularly in malnourished patients, and related to plasma albumin concentrations, but were normal in ulcerative colitis. 3. Erythrocyte zinc levels were normal in both Crohn's disease and ulcerative colitis. 4. Mean polymorphonuclear leucocyte zinc levels were normal in Crohn's disease and ulcerative colitis. Ten per cent of Crohn's disease patients had subnormal levels, which were associated with inactive disease, while 10% had elevated levels, which were associated with active disease. Seven per cent of ulcerative colitis patients had subnormal levels. Mononuclear leucocyte zinc levels were normal in Crohn's disease and in ulcerative colitis. 5. Tissue zinc depletion occurs in only a few patients with Crohn's disease and ulcerative colitis.

Adolescent↗

Polymorphonuclear leucocytes in Crohn's disease and ulcerative proctocolitis: association between enhanced adherence to nylon fibre and disease variables.

The adherence of polymorphonuclear leucocytes (PMN) to nylon fibre was investigated in patients with Crohn's disease, ulcerative proctocolitis, and anorexia nervosa, and compared with changes of circulating PMNs, C reactive protein concentrations, erythrocyte sedimentation rates, and clinical assessment of disease activity. PMN adherence was in excess of the maximum value detected for healthy subjects in 14 of 25 patients with Crohn's disease and two of 10 with proctocolitis, but it was within the normal range for all eight with anorexia nervosa. High adherence in Crohn's disease, however, was not associated with quantitative or qualitative changes of PMN populations, absolute concentrations of C reactive protein, erythrocyte sedimentation rates, disease severity, drug regimens, malnutrition, or zinc deficiency. High PMN adherence in Crohn's disease may therefore reflect the activation in vivo of normal PMN by humoral factors.

Adolescent↗

Analysis of human lymphocyte transformation responses to graded doses of T cell mitogens by curve fitting.

The between-group comparison of complete lymphocyte transformation dose-response curves is complex. We have therefore derived a mathematical model of the dose-response characteristics of human mononuclear cells to stimulation by concanavalin A (ConA) and purified phytohaemagglutinin (PHA), in order to simplify such analyses. This model describes dose-response curves in terms of the magnitude of the peak response, the dose of mitogen that elicits the peak and an estimate of the range of mitogen doses which induce a response. Responses to ConA were described by the model more precisely than those to PHA. Furthermore, use of the model revealed differences between anorexia nervosa patients and healthy subjects in terms of the dose of mitogen necessary to elicit a peak response and the range of mitogen concentrations producing a response. It is proposed that this form of mathematical treatment may be of use for the comparison of lymphocyte transformation dose-response curves and for the valid rejection of suspect results.

Anorexia Nervosa↗

Characterization of the C3 receptor induced by herpes simplex virus type 1 infection of human epidermal, endothelial, and A431 cells.

Herpes simplex virus type 1 (HSV-1) infection induces the appearance of viral analogues of human Fc IgG and C3 receptors on the surface of human cells. The virally induced C3 receptor(s) has been broadly defined as a C3b receptor, but its ligand binding characteristics have not been rigorously defined. In this study, human epidermal cells, A431 cells, and human umbilical vein endothelial cells infected with HSV-1 demonstrated rosetting with sheep erythrocytes (E) coated with IgG (E-IgG) or the complement components C3b (EAC3b) or iC3b (EAC3bi), but not with E-IgM, C4 (EAC14), C3d (EAC3d), or E alone. Rosetting was markedly enhanced by pretreatment of HSV-1-infected cells with neuraminidase. Unlike human C3 receptors, the HSV-1-induced C3 receptor was found to be trypsin resistant. To determine whether HSV-1 induced CR1-like receptors or CR3-like receptors, infected cells were pretreated with EDTA, which is known to inhibit native CR3 function. EDTA failed to prevent rosetting with EAC3bi. Furthermore, blocking studies using monoclonal antibodies against CR1 and CR3 revealed that the anti-CR1 antibody 5C11 consistently blocked EAC3b and EAC3bi rosetting with HSV-1-infected cells in a dose dependent manner, but monoclonal antibodies against CR3 did not. This study indicates that the HSV-1-induced C3 receptor is an analogue of CR1.

Antibodies, Monoclonal↗

Interleukin 1 in Crohn's disease.

A number of the activities currently ascribed to the mediator interleukin 1 (IL-1) are relevant to chronic inflammatory bowel disease. Using the mouse thymocyte stimulation assay, lymphocyte-activating factor (LAF) activity was measured in plasma samples and supernatants from cultures of peripheral blood mononuclear cells from 16 patients with Crohn's disease, six with ulcerative colitis, and 10 healthy subjects. Results were compared with disease activity, drug therapy, granulocyte count, and plasma levels of zinc and C-reactive protein (CRP). Very low levels of LAF were detected in a few plasma samples from each of the subject groups. Mononuclear cells from healthy subjects produced LAF only when cultured with lipopolysaccharide, but stimulated cells from patients produced greater amounts. Moreover, cells from six patients with Crohn's disease, not receiving steroids, produced LAF spontaneously. Crohn's disease patients also had low plasma zinc but elevated levels of CRP and granulocytes. This enhanced production of LAF in vitro may reflect a primary cellular defect in Crohn's disease, or a secondary consequence of monocyte activation.

Adult↗

Cell-mediated immunity in anorexia nervosa.

Twelve patients with anorexia nervosa were studied for cell-mediated immunity in terms of delayed hypersensitivity reactions to recall antigens, lymphocyte transformation responses to T-cell mitogens, and numbers of circulating leucocytes and T-cell subpopulations. Compared to controls, all patients had reduced cutaneous reactions and four were anergic. There was a mild leucopenia in patients and both T4+ and T3+ numbers were slightly reduced. Mean peak transformation responses for patients were slightly lower than controls for phytohaemagglutinin, but not for concanavalin A; however, patients required greater doses of mitogens to elicit peak transformation responses. Plasmas from patients did not contain inhibitors of transformation responses. We conclude that there are functional cellular abnormalities associated with the under-nutrition of anorexia nervosa.

Adult↗

Polymorphonuclear leukocyte function in ulcerative colitis and Crohn's disease.

The aim of this study was to determine whether polymorphonuclear leukocyte chemotaxis, adhesion, and electrophoretic mobility were altered in inflammatory bowel disease and whether such alterations could be related to prior ingestion of immune complexes. Polymorphonuclear leukocytes from patients with ulcerative colitis and Crohn's disease showed significantly impaired stimulated migration (P less than 0.05), increased adhesiveness (P less than 0.01 in ulcerative colitis, P less than 0.001 in Crohn's disease), and reduced electrophoretic mobility (P less than 0.02 in ulcerative colitis, P less than 0.001 in Crohn's disease) compared with healthy controls. The disease control of patients with rheumatoid arthritis demonstrated reduced stimulated migration (P less than 0.025) but normal adhesion. Preincubating normal cells in inflammatory bowel disease sera suggested that the altered migration and adhesion were due to circulating serum factors. Circulating immune complexes, detected by the C1q PEG binding assay, were present in 12.5% of patients with ulcerative colitis and 30% with Crohn's disease. Direct immunofluorescence of polymorphonuclear leukocytes suggested binding and/or ingestion of complexes in 57% of patients with ulcerative colitis, and 67% with Crohn's disease. There was a direct correlation between positive immunofluorescence and impaired cell migration in ulcerative colitis (P less than 0.05), but no such relationship was found in the other parameters of polymorph function.

Antigen-Antibody Complex↗

IgA-containing circulating immune complexes in patients with igA nephropathy.

The role of circulating immune complexes in the pathogenesis of IgA nephropathy (Berger's disease) is controversial. Previous studies have shown that a minority of these patients have immune complexes, but the methods used have been able to detect only IgG- or IgM-containing circulating immune complexes. Using a sensitive specific Raji cell radioimmunoassay for IgA-containing circulating immune complexes, we have examined serum specimens from 12 patients with IgA nephropathy for the presence of IgA-containing circulating immune complexes. In addition, the Raji cell IgG assay and the 125I-C1q binding assay were used for the detection of IgG- or IgM-containing circulating immune complexes. Purified monoclonal antibodies against human IgA1 and IgA2 were used to determine the subclass of IgA present in renal biopsy specimens from five of these patients. Six of 12 (50 percent) patients had IgA-containing circulating immune complexes, whereas only two of 12 (17 percent) had positive results in the Raji IgG assay and one of 12 (8 percent) in the 125I-C1q binding assay. There was no correlation between serum IgA, C3 C4, or factor B levels and the presence or level of IgA-containing circulating immune complexes. None of the three patients with renal failure had circulating immune complexes of any type. Of the seven patents with disease duration of two years or less, five (71 percent) had IgA-containing circulating immune complexes and three (43 percent) had IgG- or IgM-containing complexes. In all five renal biopsy specimens examined for IgA subclass, diffuse heavy, mesangial deposits of IgA1 were seen, whereas IgA2 staining was absent or present in only trace amounts. These findings suggest that IgA1 is the predominant antibody in renal biopsy specimens from patients with IgA nephropathy. The finding of IgA-containing circulating immune complexes in these patients--and their more frequent occurrence in patients with early stages of the disease--suggests that IgA-containing circulating immune complexes may play a role in the pathogenesis of IgA nephropathy.

Adolescent↗

Ultrasound has no anti-inflammatory effect.

The use of therapeutic ultrasound within the Health Service is widespread and growing. The most common indication is to reduce inflammation. We have tested the influence of ultrasound on a model of acute inflammation in the rat, and we have found a complete absence of any anti-inflammatory action.

Animals↗

Prolonged reduction in polymorphonuclear adhesion following oral colchicine.

Polymorphonuclear leucocyte (PMN) function was studied in 7 healthy subjects before and after 5 mg of colchicine taken in divided doses over 24 hours. Mean adherence to nylon fibre colums fell from a pretreatment level of 51% to 33.6% by day 1, remained low (31.8%) at day 5, and returned to pretreatment levels only by about day 9. Random motility (agarose plate method) fell from 932 micrometers to 688 micrometers by day 1, but had returned to normal by day 5. Directed migration and the phagocytic index (opsonised Candida albicans method) were not affected by colchicine treatment. In this marked and prolonged reduction in PMN adhesion implies an influence on maturing PMN precursors in bone marrow. Adherence to nylon fibres may reflect in-vivo properties of PMN which are important in the pathogenesis of acute gouty arthritis.

Administration, Oral↗

High risk genital papillomavirus infections are spread vertically.

It is well recognised that high-risk human papillomaviruses (HPVs) are spread by sexual activity, but the possibility of non-sexual transmission remains controversial. We present evidence for vertical transmission from at least 30% HPV positive mothers to their infants, resulting in persistent infection in children. That the mother is the source of infant infection has been confirmed by DNA sequencing. We also discuss the evidence for oral HPV-16 infection in children. In our own studies, HPV-16 DNA was detected in buccal cells from 48% children, aged 3-11 and transcriptionally active infection was confirmed in some children. Other studies have reported prevalences of 19%-27% among children less than 11 years of age. Studies that have failed to detect high-risk HPVs in children have used techniques which were insufficiently sensitive to detect the low levels of virus present. Serological studies also suggest that < or = 45% prepubertal children have acquired HPV-16. Thus, convincing evidence is now available for vertical transmission of high risk HPVs, which probably results in widespread infection among children. The consequences of such infections remain to be elucidated.

Antibodies, Viral↗