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Biomedical subjects

M Boulton

Publications and source records attributed to M Boulton.

At least 19 recordsLinked to original sources
PubMed1995

Oxygen modulates production of bFGF and TGF-beta by retinal cells in vitro.

Vasoproliferative retinopathies result from retinal capillary non-perfusion and consequent inner retinal hypoxia. However, it is not known whether oxygen mediates vasoproliferation directly (at the nuclear level) or indirectly by regulating the production of growth factors. We have investigated the effect of oxygen on the production of basic fibroblast growth factor and transforming-growth-factor-beta by a variety of retinal cell types in culture. Confluent cultures were maintained for 48 hr under varying oxygen tensions ranging from 135 to 18 mmHg. A reduction in basic fibroblast growth factor levels was observed in the cell lysates and extracellular matrix from retinal microvascular endothelial cell, retinal microvascular pericyte and retinal pigment epithelial cell cultures when the oxygen tension of the medium was reduced from 135 to 18 mmHg. Levels of basic fibroblast growth factor in conditioned media from microvascular endothelial and retinal pigment epithelial cell cultures also decreased when the oxygen tension of the medium was reduced from 135 to 18 mmHg. Total transforming-growth-factor-beta (and specifically isoforms 1 and 2) in the conditioned media from all three cell types was similarly modulated by oxygen i.e. it decreased as the oxygen tension of the medium was reduced from 135 to 18 mmHg. In contrast, the steady state messenger RNA levels for both basic fibroblast growth factor and transforming-growth-factor-beta 1 genes in RPE cells increased significantly when the oxygen tension of the medium was reduced from 135 to 18 mmHg. These results support the putative role of oxygen in influencing the balance of growth factors during the development of preretinal new vessels.

Blotting, Northern↗
PubMed1994

Regular partners and risky behaviour: why do gay men have unprotected intercourse?

Studies in both the UK and the USA continue to show that gay and bisexual men put themselves at risk of exposure to HIV through unprotected intercourse, most often with regular partners. As part of a larger study of homosexually active men, 310 men who had had unprotected anal intercourse with a man in the previous year were asked to describe the last occasion on which this had happened. The majority of men had had unprotected intercourse with a regular partner and did not perceived it as risky, although most did not know the HIV status of their partner. Regular and non-regular partners were perceived differently. Men were more likely to be emotionally involved in regular partners and to perceive unprotected penetrative sex with a regular partner as not risky. Future health education initiatives must take into account men's emotional involvement in regular partners and their perception of unprotected intercourse with such partners as not risky.

Adolescent↗
PubMed1994

Regional variation and age-related changes of lysosomal enzymes in the human retinal pigment epithelium.

In this study the activities of two lysosomal enzymes in retinal pigment epithelial (RPE) cells isolated from three regions of the human fundus were examined: the macula, the nasal midzone, and the periphery. The results obtained showed that the activities of acid phosphatase and cathepsin D were significantly higher in the RPE cells derived from the macular region when compared with those in the periphery. The values for the midzone appeared to be intermediate between the other two regions. Furthermore, the overall activity of both enzymes increased as a function of age.

Acid Phosphatase↗
PubMed1994

Production of IGF-I and IGF binding proteins by retinal cells in vitro.

Insulin-like growth factor I (IGF-I) and its associated binding proteins (IGFBPs) have been identified in retinal tissues but their precise cellular origin remains unclear. The aim of this study was to examine the ability of three retinal cell types (microvascular endothelial cells, pericytes, and pigment epithelial cells) and a non-retinal cell type (Tenon's fibroblasts) to produce IGF-I and cell specific IGFBPs in vitro. Using a radioimmunoassay we demonstrated that all four cell types produce IGF-I and that this production continued over a 72 hour period. In addition, western ligand blotting revealed that each cell type produced at least one IGFBP and that each cell type produced a different IGFBP profile. Endothelial cells produced a 24 kDa band only, pericytes produced both a 24 kDa and a 34 kDa band, retinal pigment epithelial cells produced a 38-41 kDa band, while fibroblasts produced both a 24 kDa and a 30 kDa band. Laser scanning densitometry demonstrated that in the majority of experiments the IGFBPs accumulated in the culture medium over a 72 hour period. Neither IGF-I nor IGFBPs were observed in cell lysates indicating de novo synthesis and secretion in vitro. These results suggest an autocrine/paracrine function for IGF-I and its associated binding proteins which may play a significant role in both retinal physiology and disease.

Blotting, Western↗
PubMed1994

Retinal and preretinal localisation of epidermal growth factor, transforming growth factor alpha, and their receptor in proliferative diabetic retinopathy.

A number of growth factors have been implicated in the development and perpetuation of preretinal fibrovascular membranes in patients with proliferative diabetic retinopathy (PDR). The aim of this study was to determine the potential role of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and their receptor (EGF-R) in PDR development. Immunostaining for EGF, TGF-alpha, and EGF-R was compared between normal retina, PDR retina, and PDR preretinal membranes. Weak staining for EGF and EGF-R was observed throughout the neural retina from non-diabetic eyes while weak to moderate staining for TGF-alpha was observed in the ganglion cell layer and the inner and outer nuclear layers. In contrast, intense staining for EGF and TGF-alpha and moderate staining for EGF-R were observed throughout the PDR retina. Immunoreactivity for EGF, TGF-alpha, and EGF-R was seen in the majority of the 11 excised membranes studied and, though variable, was generally greater than that observed in normal retinas. These results suggest an autocrine/paracrine role for EGF, TGF-alpha, and EGF-R in PDR.

Diabetic Retinopathy↗
PubMed1994

Oxygen regulation of TGF-beta 1 mRNA in human hepatoma (Hep G2) cells.

Solid tumours comprise populations of cells whose behaviour is thought to be influenced by growth factors and the local oxygen environment. We investigated the effect of oxygen on steady state levels of transforming growth factor-beta 1 mRNA in cultured human hepatoma cells. Northern blot analysis demonstrated that hypoxia mediated an early and sustained induction of TGF-beta 1 mRNA above that seen at higher oxygen tensions. The data suggests that modulation of TGF-beta 1 expression by the local oxygen environment may be important in tumour development and progression.

Blotting, Northern↗
PubMed1994

Membrane-bound carbonic anhydrase in human retinal pigment epithelium.

PURPOSE: Inhibition of carbonic anhydrase (CA) by acetazolamide causes a decrease in the standing potential of the retinal pigment epithelium (RPE) and an increase in the rate of subretinal fluid absorption, and it may improve cystoid macular edema. These effects are thought to be mediated by the RPE. Given the solubility coefficient of acetazolamide, the drug is most likely to act by direct inhibition of membrane-bound CA (CA IV). To identify a substrate for acetazolamide in the RPE, the distribution of CA activity and the isoform of CA in the RPE membrane were investigated. METHODS: Carbonic anhydrase activity was determined by Hansson's technique in fresh human eyes from donors of both sexes and different ages. The presence of the membrane-bound isoform CA IV was investigated immunohistochemically at the light and electron microscopic level, as well as by Western blotting in fresh RPE, and in adult and fetal RPE cultures. RESULTS: Hansson's histochemical method demonstrated CA activity on the apical and basolateral cell membrane of the RPE. Using the gamma-globulin fraction of a polyclonal antibody against pure CA IV, immunocytochemistry showed labeling for CA IV on the apical RPE membrane or morphologically polarized human adult and fetal RPE cultures. Gel electrophoresis and Western blotting demonstrated a major immunoreactive band at 55 kDa in homogenates, which was consistently reduced to approximately 35 kDa by incorporation of 0.1% Triton X-100 detergent. CONCLUSIONS: These results suggest that the clinical effects of carbonic anhydrase inhibitors on RPE function may be mediated via membrane-bound carbonic anhydrase activity in RPE and that CA IV is responsible for activity on the apical surface.

Adolescent↗
PubMed1994

Awareness of sexual partners' HIV status as an influence upon high-risk sexual behaviour among gay men.

OBJECTIVE: To evaluate the extent to which 'high-risk' sexual behaviour is influenced by awareness of partners' HIV status among gay men. DESIGN: Structured interviews and collection of saliva samples for anonymous linked testing for HIV-1 antibodies. SETTING: Genitourinary medicine clinics and the gay community. SUBJECTS: Men (n = 677) who reported sexual contact with another man in the last 5 years. RESULTS: The majority of respondents (63%) had had an HIV-antibody test. Analysis of data showed that in 15% of the respondents' 1380 partnerships, HIV status was known by both parties. However, the majority of partnerships involved only safe sex. Only 26% of the partnerships in which unprotected penetrative anal sex had occurred involved mutual knowledge of HIV status and was most likely to occur with regular rather than non-regular/causal partners. Logistic regression revealed that this latter association could not be explained in terms of mutual HIV status knowledge. CONCLUSIONS: Despite widespread HIV testing, the majority of gay men engaging in high-risk sex are unaware of their partner's HIV status.

Adolescent↗
PubMed1994

Perceptions of general practice among homosexual men.

BACKGROUND: Primary care has an important role to play in the prevention and management of the human immunodeficiency virus (HIV). It has been suggested that homosexual men experience a variety of problems in relation to primary care. AIM: As part of a larger study, it was decided to examine the extent to which a sample of homosexually active men experienced difficulties in general practice and whether they consulted their general practitioner for problems related to HIV or the acquired immune deficiency syndrome (AIDS). METHOD: Homosexual men were recruited for interview in 1991-92 from a variety of sources including genitourinary clinics and homosexual organizations. RESULTS: Of 623 men registered with a general practitioner 44% had not informed their general practitioner of their sexual orientation and 44% of the 77 men who were HIV antibody positive, as confirmed by the study, had not informed their general practitioner of this fact. Men who viewed their practice as unsympathetic towards homosexual men were less likely to have informed their general practitioner of their sexual orientation or HIV status. The majority of men (87%) nevertheless viewed primary care as an appropriate source of HIV/AIDS advice. CONCLUSION: There is considerable scope for improvement in the acceptability of general practice to homosexual men.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Lipofuscin is a photoinducible free radical generator.

Despite the association between high concentrations of the age pigment lipofuscin and various age-related pathologies, there is contention as to whether or not the intracellular accumulation of such granules has an adverse effect on cell function. In this paper, we present evidence to indicate that lipofuscin is a photoinducible free radical generator. White light irradiation of lipofuscin granules resulted in the production of superoxide anions, their rate of production increasing with increased light intensity. This effect appeared to be maximal in the blue light region of the spectrum. We speculate that lipofuscin could be detrimental to bodily functions through free radical generation initiated either by light or interaction with endogenous free radicals.

Cytochrome c Group↗
PubMed1993

Glycan localization within the human interphotoreceptor matrix and photoreceptor inner and outer segments.

Glycoconjugates are likely to be of fundamental importance in the complex interactions between photoreceptors and the retinal pigment epithelium, but few have been characterized, especially in human tissue. As a preliminary step towards determining their biological functions in health and disease, a lectin-based histochemical study of the glycan expression of human outer retina was performed on glutaraldehyde-fixed, semi-thin, resin-embedded sections. The interphotoreceptor matrix and photoreceptor plasma-lemmata expressed complex bisected and non-bisected biantennary and/or triantennary N-glycans. In addition, both the rod and cone outer segments bound strongly Galanthus nivalis agglutinin (which binds terminal Man alpha 1, 3Man-) and the rod outer segments bound selectively the isolectin II of Bandeiraea simplicifolia (which binds terminal GlcNAc-). The cilia of the rods and cones were labelled selectively with Glycine max agglutinin after sialidase pretreatment. Four putative glycan outer sequences were identified within the interphotoreceptor matrix: (i) sialylated glycans with subterminal GalNAc alpha 1,3GalNAc-sequences; (ii) a sialylated type with subterminal N-acetyl-lactosamine residues; (iii) Gal beta 1,3GalNAc alpha 1- residues which were substituted with sialic acid except in the cone matrix sheath; (iv) GalNAc alpha 1,6Gal beta 1- residues which were substituted in part with sialic acid. The sialic acid expression throughout was predominantly of the 2,3-linked form with lesser amounts of 2,6-linkage, and rod-associated structures (including the surrounding interphotoreceptor matrix) were labelled more strongly with the sialic acid-binding lectins than cone-associated structures (including the cone matrix sheath).

Adolescent↗
PubMed1993

Risk behaviour, anti-HIV and anti-hepatitis B core prevalence in clinic and non-clinic samples of gay men in England, 1991-1992.

OBJECTIVE: To describe the sexual risk behaviour of and HIV and hepatitis B antibody prevalence in gay men in England. DESIGN: Cross-sectional. RESPONDENTS: Gay men recruited from community settings (bars, clubs, gay organizations) and genito-urinary clinics in London, Manchester, the Midlands and Bristol; men who participated in an earlier study. METHODS: Interview including demographic information, sexual behaviour, partner type and health service use. Subjects donated saliva, which was screened for antibodies to HIV-1 by immunoglobulin G (IgG) antibody capture enzyme-linked immunosorbent assay (GACELISA) and to hepatitis B core (HBc) antigen by IgG antibody capture radioimmunoassay (GACRIA). RESULTS: Ninety-four out of 580 (16.2%) men were HIV-antibody-positive; 6.2% of men aged < or = 25 years were positive versus 19.5% of men aged > or = 26 years. HIV-antibody prevalence was highest in London (21.1%), and twice that previously reported outside London (10.5%). Ninety-four out of 568 (16.5%) men were HBc-antibody-positive; 6.9% of men aged < or = 25 years were positive versus 19.7% of men aged > or = 26 years. Anti-HBc prevalence was highest in London (19.8 versus 12.7% outside London). Manual workers were more likely to be anti-HBc-positive, as were men who reported recent high-risk intercourse. Sexually transmitted diseases associated with frequent partner change (gonorrhoea, non-specific urethritis) were reported. CONCLUSION: The HIV epidemic in gay men in England continues, particularly outside London, where prevalence was double that of previous studies. We found relatively high rates of infection in young men whose main sexual experience has been in a time of unprecedented awareness of AIDS. Our data on hepatitis B suggests that further pro-active immunization programmes are urgently required. These findings add to concerns about provision of interventions targeting gay men.

Adult↗
PubMed1992

Predictors of high risk sexual behaviour in gay and bisexual men.

Evidence of high risk sex between gay men continues to be reported, as does a range of sexual behaviour. Three hundred and sixty-nine homosexually active men from different areas of England were each assessed twice at an an interval of 9 months in order to examine the extent to which a number of social-psychological factors predicted subsequent high risk sexual behaviour. Few of the variables were significantly related to unprotected receptive anal sex in the way that the Health Belief Model predicted, except for some perceptions of costs and benefits of safer sex. However, whether or not men were involved in a regular relationship with a partner was strongly associated with high risk behaviour. The implications of these results are that health education interventions should focus on alerting all men to the social context in which high risk sex is more likely to happen: the regular partnership.

Attitude to Health↗
PubMed1992

The sexual behaviour of bisexual men in relation to HIV transmission.

Relatively little is known about the behaviour of bisexual men which may help in assessing their role in HIV transmission. A sample of 60 behaviourally bisexual men were asked about their sexual behaviour with male and female partners and their perceptions of risk of HIV infection. Only a minority of men engaged in unprotected anal sex with their male partners while two thirds had unprotected vaginal sex with their female partners. This asymmetrical pattern of sexual behaviour reflects a differential perception of risk of HIV infection with male and female partners. A quarter of the men had unprotected penetrative sex with both male and female partners in the previous year. The pattern of risk behaviour varied amongst men living in gay, heterosexual or bisexual contexts.

Adult↗