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Biomedical subjects

R Penny

Publications and source records attributed to R Penny.

At least 145 records · Page 8Linked to original sources
PubMed1986

Immunological abnormalities in patients with untreated retinal vasculitis.

Peripheral blood immunological features were assessed in 21 patients with clinical and angiographic evidence of retinal vasculitis (RV). Abnormalities of humoral and cellular immunity were frequent in this group of patients. Lymphopenia was the most common immunological abnormality, being present in 76% of patients at presentation (p less than 0.05). Peripheral blood T and B cells were decreased with a normal helper (OKT4) to suppressor (OKT8) T cell ratio in 11 patients tested (five with Behçet's syndrome and six with idiopathic RV). Significantly increased concentrations of serum immune complexes were present in 55% of patients (p less than 0.05). Results of the present study indicate the frequent association of peripheral blood immunological abnormalities in patients with active RV and indicate the possible role of immunological mechanisms in its pathogenesis.

Adolescent↗
PubMed1986

Seroimmunology of AIDS retrovirus infection. I. Use of immunofluorescence assay to confirm sera with ELISA reactivity.

One thousand sera shown to be reactive by one of two commercial enzyme linked immunosorbent assays (ELISA) for antibodies to the AIDS virus were referred to the NSW State Reference Laboratory for confirmatory assays. Each serum was retested by two commercial ELISA systems (Abbott and ENI), the ENI exclusionary H9 ELISA and an immunofluorescence assay. Three hundred and twenty four sera were reactive by all 3 tests whereas 244 demonstrated concordant non-reactivity. Three hundred and seventy seven sera were reactive by Abbott EIA only and could not be confirmed positive by the ENI ELISA incorporating exclusionary testing, immunofluorescence or Western immunoblot of representative sera. Sera obtained from teaching hospital laboratories were more likely to be positive and less likely to be negative by all 3 tests, and were also less likely to be Abbott EIA reactive only compared with sera obtained from the blood transfusion service. Of the remaining 55 sera, 52 demonstrated a negative immunofluorescent reaction or a pattern of equal fluorescence on AIDS virus infected and control cells. Representative sera were shown to be negative on Western immunoblot analysis. Of the 3 sera which demonstrated immunofluorescence reactivity, one was positive and one was negative by Western immunoblot, and one could not be determined. We conclude that a combination of two ELISAs, one with an exclusionary ELISA test and an immunofluorescence assay is a reliable and simple means of confirming reactive sera for AIDS virus antibodies.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Mast cell granules cause proliferation of human microvascular endothelial cells.

To investigate the possible role of mast cells in blood vessel formation, rat mast cell granules were studied for their proliferative effect on human microvascular endothelial cells. It was found that granules had a marked proliferative effect and that most of this activity was restricted to a dialyzable fraction. The dialyzable mast cell granule constituent histamine was found to be mitogenic, an effect that was shown with the use of specific agonists and antagonists to be mediated through an H1 receptor. H1 antagonists reduced the proliferation caused by the untreated mast cell granules to the level of proliferation caused by dialyzed granules, suggesting that all the dialyzable mitogenic activity was due to histamine. Histamine was also shown to cause proliferation of cells that were growth arrested by serum deprivation, suggesting that it is an endothelial growth factor. The compound responsible for the undialyzable mitogenic activity could not be identified but was shown not to be mast cell heparin. This demonstration of mast cell granule-induced endothelial proliferation suggests that the mast cell may be of importance in the process of angiogenesis.

Animals↗
PubMed1986

Chlamydial antibody crossreactivity with peripheral blood mononuclear cells of patients with ankylosing spondylitis: the role of HLA B27.

We have previously reported the association of Chlamydia trachomatis with HLA B27+ related diseases. To investigate the possibility that chlamydial antibodies serve to localize the immune response in such diseases, we examined the crossreactivity of chlamydial antibodies (rabbit anti-D and anti-L2 serotypes) with peripheral blood mononuclear cells of patients with ankylosing spondylitis (AS) and anterior uveitis (AU) and with human and bovine ocular tissue and cells in culture. Our results indicate a significantly increased percentage binding of chlamydial antibody (D serotype) to the mononuclear cells of HLA B27+ patients with AS when compared with HLA B27- patients with AS (12.9% +/- 2.2 versus 5.4% +/- 2.2), B27+ controls (5.5% +/- 1.5) and B27- controls (6.1% +/- 1.0). There was no significant difference between controls and HLA B27+ patients with AU (6.6% +/- 1.9) and B27- patients with AU (8.7% +/- 1.1). This crossreactivity could not be blocked by monoclonal HLA B27 antibody. Chlamydial antibodies (D and L2) crossreact with human and bovine conjunctiva but not uvea, tissue culture derived iris fibroblasts or smooth muscle cells. Our results provide additional support for the concept of crossreactivity between antibodies to microbial agents and peripheral blood mononuclear cells of patients with HLA B27+ AS.

Adolescent↗
PubMed1985

Acute AIDS retrovirus infection. Definition of a clinical illness associated with seroconversion.

In the course of a prospective immunoepidemiological study of homosexual men in Sydney, seroconversion to the AIDS-associated retrovirus (ARV) was observed in 12 subjects. Review of the clinical files defined an acute infectious-mononucleosis-like illness in 11 subjects. The illness was of sudden onset, lasted from 3 to 14 days, and was associated with fevers, sweats, malaise, lethargy, anorexia, nausea, myalgia, arthralgia, headaches, sore throat, diarrhoea, generalised lymphadenopathy, a macular erythematous truncal eruption, and thrombocytopenia. In 1 subject an incubation period of 6 days after presumed exposure to ARV was determined and in 3 subjects seroconversion took place 19, 32, and 56 days after onset. Comparison of T-cell subsets before and after the acute illness showed inversion of T4:T8 ratio in 8 subjects, due to increased numbers of circulating T8+ cells. These findings support the notion of an acute clinical, immunological, and serological response to infection with ARV which should be considered in the differential diagnosis of mononucleosis-like syndromes in groups at high risk for the development of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Human dermal microvascular endothelial cells: an improved method for tissue culture and a description of some singular properties in culture.

Tissue culture of human large vessel endothelium is now routine in many laboratories but tissue culture of human microvascular endothelium remains a difficult procedure, preventing study of features of endothelial function that may be peculiar to the microvasculature. This report describes an improved method for tissue culture of human dermal microvascular endothelium derived from foreskin. The method is rapid, reproducible, avoids contamination with nonendothelial cells, and does not require the use of a tumor-conditioned medium. The major modifications over existing techniques are the use of a Percoll density gradient to remove the majority of nonendothelial cells followed by a simplified weeding procedure that removes residual nonendothelial cells and leaves large numbers of endothelial cells to grow rapidly to confluence. The cells are identified as endothelial by their morphology and by positive immunofluorescence for Factor VIII. Proliferation experiments demonstrate their requirement for an exogenous matrix and for a high concentration of human serum. Whole serum was required as platelet-poor plasma serum had poor growth stimulatory activity. Proliferation could be enhanced by dibutyryl cyclic AMP or endothelial cell growth substance and was maximal with the combination of endothelial cell growth substance and heparin. However, the use of these agents did not remove the requirement for an exogenous matrix. Fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, nerve growth factor, and thrombin did not increase proliferation.

Animals↗
PubMed1985

The role of alpha 1-antitrypsin deficiency in the pathogenesis of immune disorders.

The association between alpha 1-antitrypsin (alpha 1-AT) deficiency and a number of immune mediated diseases including rheumatoid arthritis, anterior uveitis, systemic lupus erythematosus, and asthma suggests that alpha 1-AT may be important not only as an anti-inflammatory protein but also as an immune regulator. That the relationship between decreased amounts of this inhibitor and these diseases is causal is suggested by both some of its physical properties and evidence indicating it is able to modulate immune function. alpha 1-Antitrypsin has a high plasma concentration, very broad range of inhibitory activity and is an acute phase reactant. Among other things, it is able to modulate lymphocyte proliferation and cytotoxicity, and monocyte and neutrophil function. Additionally, some of these changes are demonstrable in vivo in patients with severe alpha 1-antitrypsin deficiency. This paper reviews the important physicochemical characteristics of this protein, the association of its presence in decreased amounts with immune disorders, and finally the important mechanism that may underlie this disease association.

Connective Tissue Diseases↗
PubMed1985

Retinal vasculitis associated with HLA DR4. Brief definitive report.

Inflammation of retinal blood vessels may be associated with a variety of systemic immune diseases. Despite the fact that a number of immunological abnormalities have been reported in patients with retinal vasculitis (RV), previous studies have failed to demonstrate an immunogenetic predisposition to this disease. HLA A, B, and DR locus typing of 25 patients (14 females) with well-characterized RV revealed an increased incidence of HLA DR4 (corrected p value = 0.04, relative risk = 3.5). The HLA DR4 antigen was increased in patients with both central and peripheral RV as well as in patients with idiopathic disease (14 patients) and in those with Behcet's syndrome (8 patients). The results of this study indicate that immune response genes may be involved in the pathogenesis of RV.

Adolescent↗
PubMed1985

Decreased chemiluminescent associated phagocytic response of peripheral blood mononuclear cells to Chlamydia trachomatis in patients with HLA-B27+ anterior uveitis.

The chemiluminescent (CL) associated phagocytic response of peripheral blood monocytes to two serovars of Chlamydia trachomatis, Shigella flexneri and zymosan was assessed in a group of 26 patients with anterior uveitis (AU). HLA-B27+ patients with AU, when compared to HLA-B27- patients with AU and appropriate controls, had a significantly decreased CL response to C. trachomatis but no difference between groups in the response to S. flexneri and zymosan. The decreased chemiluminescent (phagocytic) response of mononuclear phagocytes to Chlamydiae may indicate an important abnormality in the pathogenesis of HLA-B27+ AU.

Adolescent↗
PubMed1985

Scleritis and the spectrum of external inflammatory eye disease.

Scleritis, episcleritis and Mooren's ulcer form a poorly understood spectrum of inflammatory syndromes involving the ocular surface. Their pathogenesis is thought to be a vasculitis and may be related to immune complex deposition, as these syndromes are often associated with systemic diseases which are assumed to be vasculitic in aetiology. Scleritis and Mooren's ulcer are amongst the most severe external inflammatory diseases, often causing extensive damage to the sclera and cornea. They require aggressive investigation and management, often including systemic anti-inflammatory therapy. Systemic immunosuppression may be necessary to control severe disease.

Anti-Inflammatory Agents↗
PubMed1985

Alpha 1 antitrypsin serum levels and phenotypes in patients with retinal vasculitis.

alpha 1 antitrypsin is an important immunoregulatory protein, the serum level of which is genetically determined. Deficient phenotypes of this ubiquitous protease inhibitor are associated with a variety of inflammatory diseases including anterior uveitis. In order to investigate the role of this protease inhibitor in the pathogenesis of retinal vasculitis (RV) 25 patients were investigated. Diseases associated with RV included Behcet's syndrome (8), SLE (2), and sarcoidosis (1). Deficient phenotypes of alpha 1 antitrypsin were not associated with RV. However, the serum alpha 1 antitrypsin level was significantly increased in patients with active RV and paralleled disease activity in patients studied prospectively.

Adolescent↗
PubMed1985

A monoclonal antibody-based radioimmunoassay for the in vitro production of IgE by lymphocyte cultures.

Very sensitive radioimmunoassay systems have been described for the measurement of IgE produced in cultures of human peripheral blood mononuclear cells. However, differing results have been reported when cultures from non-atopic donors are stimulated with pokeweed mitogen, which may be due to cross-reactivity of anti-IgE antibodies with IgG. A monoclonal antibody specific for the Fc region of human IgE, and two polyclonal affinity-purified antibodies to IgE were tested for binding to 125I-labelled IgE myeloma proteins and polyclonal IgG in a sensitive double antibody precipitation assay. The monoclonal antibody and one of the polyclonal antibodies bound only IgE, whereas the other polyclonal antibody bound a significant proportion of labelled IgG. A solid phase radioimmunoassay was developed which combined the specificity of the monoclonal antibody with the sensitivity of the first polyclonal antibody as radioactive tracer. A second assay system was also tested using the cross-reacting antibody as tracer. Supernatants of pokeweed mitogen-stimulated peripheral blood mononuclear cell cultures from non-atopic donors were examined for IgE synthesis using both assays. The assay based on the monoclonal antibody did not detect IgE synthesis, whilst the second assay, based on the cross-reacting antibody indicated that spurious IgE had been produced in the same cultures. This study shows that protein-binding assays provide a simple means for checking the specificity of antibodies in solid phase radioimmunoassays, and confirms that pokeweed mitogen does not stimulate IgE production by cells from non-atopic donors when measured by a specific radioimmunoassay.

Antibodies, Monoclonal↗
PubMed1985

Episodic secretion of melatonin in pre- and postpubertal girls and boys.

The concentration of melatonin was determined in serum samples obtained at 15-min intervals during a 4-h period from seven normal girls, 9.5-16.5 yr of age, and eight normal boys, 9.0-16.8 yr of age. All samples were obtained between 0800 and 1300 h. An episodic pattern of melatonin secretion was found in all subjects. There was no significant (P greater than 0.1) difference between girls and boys as to number of episodes [3.1 +/- 0.4 (+/- SD) vs. 3.4 +/- 0.5 per 4 h), absolute melatonin increase (49.0 +/- 6.7 vs. 50.4 +/- 4.1 pg/ml), or apparent melatonin half-life (20.3 +/- 0.8 vs. 20.8 +/- 1.0 min). The mean absolute increase during secretory episodes correlated (r = 0.843; P less than 0.005) with the mean melatonin concentration per 4 h, and a significant (P less than 0.05) inverse correlation (r = -0.508) was found between the mean percent increment of the melatonin secretory episode and the mean apparent melatonin half-life. A significant correlation between melatonin secretion and previously reported (22) episodic LH secretion was not found. In girls and boys, the mean melatonin concentration increased with advancing puberty. The increase in melatonin concentration was due to an increase in the amplitude of secretory episodes. These data are consistent with an influence of gonadal function on melatonin secretion.

Adolescent↗
PubMed1985

Suppression of IgE synthesis in vitro by allogeneic T cells from atopic and non-atopic subjects.

The role of T cells in the regulation of IgE synthesis by human PBMC was studied. PBMC or separated and recombined populations of T and B cells from both normal and atopic donors were cultured for 10 days with and without cycloheximide. IgE and IgG synthesis were determined by specific RIA. IgE synthesis was detected in 0/30 non-atopic, 6/34 mildly atopic and 25/31 severely atopic subjects. Autologous T cells from 10/26 atopic donors, whose B cells synthesised IgE, significantly suppressed this IgE synthesis. The addition of allogeneic T cells from atopic or non-atopic subjects to atopic B cells resulted in greater suppression of IgE synthesis than the addition of autologous T cells. These data support the notion that atopic subjects have naturally occurring IgE isotype-specific suppressor T cells as well as suppressor T cells which can be activated during incubation with alloantigen.

Adult↗