PubMed HealthSearch

Biomedical subjects

J Dawson

Publications and source records attributed to J Dawson.

At least 19 recordsLinked to original sources

Measurement of glucuronidation by isolated rat liver cells using [14C]fructose.

We have developed a simple and sensitive method for the study of the relative rates of glucuronidation of compounds, in isolated liver cells, based on the incorporation of 14C from fructose into glucuronide conjugates. Liver cells from fasted rats are used to minimize any reduction of the specific activity by glycogenolysis. Although rates of glucuronidation are lower in isolated liver cells from fasted rats than in those from fed rats, because of a reduction in the concentration of UDP-glucuronic acid, it is possible to compare the rates of glucuronidation of different compounds. Radiolabelled glucuronides are separated from [14C]fructose and [14C]glucose, produced by the liver cells, by normal-phase HPLC on a polar amino-cyano column. The specific activity of the glucuronide was found to be approximately 50% of that of the [14C]fructose. Absolute amounts of glucuronide can be determined by measuring the specific activity of the [14C]glucose, also produced by liver cells from fructose, which reflects that of the glucose-6-phosphate and hence the UDP-glucuronic acid used for glucuronidation, although for the measurement of relative rates this would not be necessary. We have used this method to examine the kinetics of the glucuronidation of N-acetyl-p-aminophenol (acetaminophen), 4-nitrophenol and 1-naphthol in isolated rat liver cells. The method should be applicable to the study of the rates of glucuronidation of a range of aglycones and, unlike other methods, does not require glucuronide standards or radiolabelled aglycone.

Acetaminophen

The monoclonal antibody MEL-14 can block lymphocyte migration into a site of chronic inflammation.

The effect of MEL-14, a monoclonal antibody which binds to the lymphocyte homing receptor (MEL-14 Ag) on lymphocytes for peripheral lymph node (PLN) high endothelial venules (HEV), was investigated on lymphocyte migration into a delayed-type hypersensitivity (DTH)-like lesion produced by sensitization and challenge to Bordetella pertussis vaccine (BPV). Pretreatment of lymphocytes with saturating concentrations of MEL-14 caused a highly significant inhibition of lymphocyte migration into the chronically inflamed site and PLN. This finding suggests that lymphocyte migration into the BPV-induced site of chronic inflammation may be regulated by the same mechanism as lymphocyte migration into the PLN. It further indicates that the ligand for the MEL-14 Ag adhesion molecule, recognized by lymphocyte which home to the PLN, may also be expressed on HEV-like vessels at sites of BPV-induced chronic inflammation.

Animals

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

Lymphocyte migration in the mouse. I. Time course of cell accumulation and the effect of antigen sensitisation and challenge in a murine model of chronic inflammation.

The effect of time and of antigen sensitisation and challenge on lymphocyte migration into a site of chronic inflammation has been examined in the mouse. Enhanced lymphocyte migration occurred at sites of chronic inflammation after sensitisation and challenge to Bordetella pertussis vaccine (BPV). Biphasic migration was observed with time (5 min to 24 h), the initial very rapid but transient localisation at the inflamed site being followed by a second slower more sustained influx of cells. Increased localisation was also obtained with time in the lymphoid tissues and was accompanied by a parallel decrease in the number of cells present in the blood. The relative importance of antigen sensitisation and challenge for lymphocyte migration to a site of chronic inflammation has also been assessed. Lymphocyte migration into the inflamed site was partially dependent on the immunological status of the injected lymphocytes, but the presence or absence of antigen at the site of inflammation was the major factor which determined the degree of migration to the site.

Animals

Lymphocyte migration in the mouse. II. Differential B and T-lymphocyte migration into a site of chronic inflammation.

Different patterns of B and T-lymphocyte migration were observed in normal mice and in animals with a site of chronic inflammation. The early migration of lymphocytes into a site of chronic inflammation, induced by sensitisation and challenge to Bordetella pertussis vaccine (BPV), comprised mainly B-cells. Subsequently, a greater influx of T-cells occurred as the inflammation progressed. The lymphocyte population in the inflammatory exudate was composed of equal numbers of B and T-cells throughout the 30 day time course. Preferential migration of B-cells to Peyer's patches (PP) and T-cells to peripheral lymph nodes (PLN) occurred in both normal mice and animals with a site of chronic inflammation. In contrast, B-cells migrated preferentially to the spleen in normal mice while in mice with chronic inflammation a greater migration of T-cell was observed. These findings indicate the presence of homing receptors for PP on B-cells and of PLN homing receptors on T-cells, with their distribution unaffected during the development of the inflammatory response. In contrast, the inflammatory process did alter the type of cell migrating into the spleen which may reflect an increase in antigen presentation in the mice challenged with BPV.

Animals

Ossification of the posterior longitudinal ligament in the thoracic spine causing intermittent paraplegia in an Englishman: case report.

Compression of the spinal cord due to ossification of the posterior longitudinal ligament (OPLL) often leads to quadriplegia or paraplegia in Japanese patients. This disease is uncommon in other races. We report the case of a middle-aged Englishman who presented with complaints of intermittent paraparesis due to OPLL at the T5-T6 level in his thoracic spine.

Humans

Quantitative studies of sulphate conjugation by isolated rat liver cells using [35S]sulphate.

We have developed a simple, rapid and sensitive method for the study of sulphate conjugation in isolated liver cells based on the incorporation of 35S from [35S]sulphate. Excess [35S]sulphate is removed by a barium precipitation procedure, leaving [35S]sulphate conjugates in solution. We have used this method to examine the kinetics of sulphation of N-acetyl-p-aminophenol (acetaminophen), 4-nitrophenol and 1-naphthol in isolated rat liver cells. The efficiency of recovery of the sulphate conjugates was greater than 86%. The method is applicable to the quantitative study of sulphate conjugation of any substrate which forms a sulphate conjugate that is soluble in the presence of barium, without the need for standards or radiolabelled sulphate acceptors.

Acetaminophen

Risk of strangulation in groin hernias.

Although the elective repair of groin hernias is advised to prevent strangulation, the likelihood of this complication occurring is unknown. To quantify this risk, the cumulative probability of strangulation in relation to the length of history has been calculated for inguinal and femoral hernias presenting to this hospital between 1987 and 1989. Of 476 hernias (439 inguinal, 37 femoral), there were 34 strangulations (22 inguinal, 12 femoral). After 3 months the cumulative probability of strangulation for inguinal hernias was 2.8 per cent, rising to 4.5 per cent after 2 years. For femoral hernias the cumulative probability of strangulation was 22 per cent at 3 months and 45 per cent at 21 months. The rate at which the cumulative probability of strangulation increased was in both cases greatest in the first 3 months, suggesting that patients with a short history of herniation should be referred urgently to hospital and given priority on the waiting list.

Adolescent

IL-1 alpha inhibits lymphocyte migration into a site of chronic inflammation.

The effects of murine recombinant IL-1 alpha (muIL-1 alpha) on lymphocyte migration in the mouse have been investigated. Continuous infusion of muIL-1 alpha had marked effects on patterns of lymphocyte migration into a site of chronic inflammation, inflammatory exudate and spleen; the numbers of lymphocytes migrating to the inflamed tissue and spleen were reduced in a dose-dependent manner. The number of lymphocytes in the blood of muIL-1 alpha-treated animals was increased in a dose-related manner. The decrease in numbers of lymphocytes present in the chronically inflamed site may either be due to a direct inhibitory action of muIL-1 alpha or reflect an increased rate of cell migration through the inflamed tissues accompanied by a more rapid return to the circulation. These findings suggest that IL-1 alpha may act not only as an inflammatory cytokine, but also as a modulator with anti-inflammatory activity during chronic inflammation.

Animals

The HIV test and sexual behaviour in a sample of homosexually active men.

This paper aims to assess the effects of voluntary anti-HIV testing on homosexual sexual behaviour. A sample of 502 men were recruited from four different areas of England. The criterion for inclusion was 'any man who had had sex with another man in the previous 5 years'. Men were interviewed about their recent sexual behaviour, histories of sexually transmitted diseases, experience of HIV tests and attitudes to the test. Men with a history of sexually transmitted diseases were more likely to have had the test. Thirty-one percent of men reported passive anal sex in the last month and 19% had had unprotected passive anal sex. These behaviours were most often reported by those testing HIV antibody positive and least by those never tested. The findings suggest that homosexually active men who volunteer for an anti-HIV test are broadly similar to those who do not. The absence of any clear effects of the test alone on sexual behaviour suggests that the quality of counselling in this area needs urgent attention.

AIDS Serodiagnosis

A comparative study of the cellular, exudative and histological responses to carrageenan, dextran and zymosan in the mouse.

A murine 6-day air-pouch model of inflammation has been developed and used to compare the patterns of acute and chronic inflammatory response to three irritants, carrageenan, dextran and zymosan, each injected into the cavity of the pre-formed pouch. The inflammation was assessed by measurement of exudate volume and numbers of infiltrating leucocytes over a 30-day time course. Histological changes in the inflamed air-pouch lining tissue were also investigated. The inflammatory response to carrageenan was acute with moderate exudate formation and cell numbers. Dextran produced a mild inflammatory reaction with low cell infiltration into exudate. In contrast, the inflammatory response to zymosan was greater in terms of cell migration, but smaller in terms of exudate volume and occurred later in the time course. Histological changes in the inflamed air-pouch tissue were also markedly different in response to the three irritants. Carrageenan induced a rapid, mainly polymorphonuclear leucocyte (PMN) infiltrate into the tissue and deposition of fibrin on the luminal surface. The response to dextran was characterized by a rapid resolution of the inflammatory response, with fewer leucocytes present in the lining and no fibrin deposition. In contrast, zymosan caused a marked but slower leucocyte influx, with greater numbers of monocytes, and clearance of the zymosan particles from the air-pouch lining by macrophages. This study indicates that by using different irritants to produce inflammation, it may be possible to dissect the roles played by various cells and inflammatory mediators during acute and chronic inflammation.

Animals

Gay men, social support and HIV disease: a study of social integration in the gay community.

As part of a large study of the effects of HIV and AIDS on gay male sexual behaviour, we investigated the extent to which gay men in the UK have access to social support and informal care at times of illness. The study sample (n = 502) demonstrated high levels of willingness to disclose sexuality to others, sociability and social integration. Over 90% reported that they had access to people whom they could turn for practical help at times of temporary incapacity. Between 42% and 46% have known a person, or persons, with HIV symptomatic disease, AIDS or someone who has died of AIDS, although men recruited in larger towns and cities were more likely to know people at every stage of HIV infection and AIDS than those from smaller towns. Twenty-five per cent had provided practical help and support to at least one person with AIDS; men in this situation were more likely to have had a close friend, lover or former lover who had died of AIDS. It is argued that it is not possible to expect the gay community to provide fully for the non-medical care of its members and, whilst some needs can be fulfilled on an informal care basis, the demands of long-term serious illness are such that adequate support services should be available in the community.

Adolescent