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Biomedical subjects

J Lees

Publications and source records attributed to J Lees.

At least 37 records · Page 2Linked to original sources
PubMed1991

Leukotrienes in brain: natural occurrence and induced changes.

Peptidoleukotrienes (SP-LTs) (both total product and individual LTC4 and LTE4 and LTB4 were measured by radioimmunoassay in cerebrospinal fluid (CSF) collected from the third ventricle of conscious cats. Total SP-LT was expressed as LTE4 after treating samples with crude gamma-glutamyltranspeptidase. Prostaglandin (PG) E2 and thromboxane (TX) B2, the stable metabolite of TXA2, were also assayed in part of the experiments. Under basal conditions, SP-LT and LTC4 were consistently measurable (respectively, 327 +/- 14 and 244 +/- 41 pg/ml), while native LTE4 was below the threshold of the assay (60-280 pg/ml) in most cases. LTB4 was barely detectable (30 +/- 2 pg/ml) or not detectable at all. PGE2 was normally less abundant than TXB2 (31 +/- 4 vs 281 +/- 47 pg/ml). Intracerebroventricular (i.c.v.) administration of arachidonic acid (40 microgram) caused a 4-fold increase in SP-LT levels which was relatively small and transient compared to PGE2 (76-fold) and TXB2 (23-fold), while there was no change in either native LTE4 or LTB4. A similar response was obtained with platelet-activating factor (PAF, 1 microgram i.c.v.), though SP-LT elevation (4-fold) was more persistent. A further rise in SP-LT (9-fold) was noted when PAF administration was preceded by indomethacin (500 microgram i.c.v.), whereas PAF effect was reversed by pretreatment with either the PAF antagonist, BN52021 (1 microgram i.c.v.), or the 5-lipoxygenase inhibitors, U-60,257 (75 micrograms i.c.v.) and L-651,392 (10 mg/kg p.o.). PAF was also effective in causing a 3-fold rise in LTC4. Unlike PAF, pyrogens (endotoxin i.c.v. or i.v.; interleukin-1 i.v.) at doses above threshold for fever had no effect on LT levels in CSF, both in the absence and presence of indomethacin pretreatment. We conclude that SP-LTs are a normal constituent of CSF, LTC4, being the major species. The response to PAF accords with a pathogenetic role of the compounds in inflammatory processes and the reactive changes to injury. No evidence was obtained for the involvement of SP-LTs in the central mechanism of fever.

Administration, Oral↗
PubMed1988

Occurrence of interleukin-1 in cerebrospinal fluid of the conscious cat.

Interleukin-1 (IL-1) is synthesized and released in response to various pathogens, including bacterial endotoxin, and is assigned an intermediary function in the genesis of fever. Its site of action in the central nervous system (CNS), however, is uncertain because the polypeptide is seemingly unable to cross the blood-brain barrier. Since several cell types, including astroglial, microglial, and vascular cells, can generate IL-1 upon appropriate stimulation, we examined whether IL-1 is formed in the CNS and may therefore serve as a messenger for systemic noxae. Experiments were conducted in the conscious cat and IL-1 was assayed in cerebrospinal fluid (CSF) from the third ventricle using a highly sensitive murine helper T cell line, D10.G4.1. In general, IL-1 levels were barely detectable in the absence of fever and did not increase at any stage of the sustained fever following intravenous injection of endotoxin (bolus) or crude monocyte supernate containing IL-1 (bolus plus infusion). In contrast, intracerebroventricular injection of a pyrogenic dose of endotoxin led to the appearance of IL-1 in the CSF. IL-1 levels reached maximal elevation during the uprise phase of the fever and declined thereafter. By the same route, natural or recombinant human IL-1 had no effect on CSF-IL-1 levels, though both preparations were as effective as endotoxin in eliciting fever. These findings confirm earlier data with radiolabelled pyrogens and indicate that the blood-brain barrier is impermeable to IL-1. We conclude that blood-borne IL-1 is likely to act at a discrete site outside the blood-brain barrier, possibly the organum vasculosum laminae terminalis. Centrally formed IL-1 may instead act diffusely in promoting fever and fever-related events (e.g. sleep).

Animals↗
PubMed1988

A psychological follow-up study of adult patients discharged from a British burn unit.

An investigation of the psychological sequelae of two samples of burns patients is presented. Both samples are a nearly complete consecutive series of adult patients treated at a British Regional Burns Unit. Sixteen patients were interviewed at their first discharge from the ward and 6 months later. A further 15 patients were assessed 2 years after their first discharge. Systematic assessment included psychological questionnaires giving estimates of the severity of psychological disturbance. Thirty-one per cent of adults at discharge, 38 per cent at 6 months and 40 per cent at 2 years were sufficiently disturbed to require specialist referral. The type of help received and preferred by patients is also discussed and conclusions drawn about how burns unit staff can improve the adjustment of burns-injured adults.

Adaptation, Psychological↗
PubMed1988

Further evidence implicating prostaglandin E2 in the genesis of pyrogen fever.

Conscious cats were used to study the effects of endotoxin and interleukin 1 (IL 1) on levels of prostaglandin (PG) E2 and thromboxane (TX) B2 (the stable TXA2 byproduct) in cerebrospinal fluid (CSF) from the third ventricle. Pyrogens were given intravenously or intraventricularly and prostanoids were measured by radioimmunoassay. PGE2 was normally less abundant than TXB2 (mean, 37 vs. 528 pg/ml), and its level increased severalfold during the sustained fever following intravenous endotoxin (bolus) or IL 1 (bolus plus infusion). PGE2 elevation preceded the fever and was maintained thereafter. Likewise, intraventricular pyrogens promoted PGE2 formation, and their effect was also manifest during the latent period of the fever. The PGE2 metabolite, 13,14-dihydro-15-keto-PGE2, was not measurable in CSF from either afebrile or febrile animals. Basal content of PGE2, on the other hand, was higher in animals pretreated with probenecid (30 mg/kg ip or iv; 50 or 100 micrograms ivt), confirming the importance of transport processes in removing prostanoids from brain. Unlike PGE2, TXB2 levels did not change during the fever to intravenous endotoxin. TXB2 rose instead in response to intraventricular endotoxin, although the elevation did not extend beyond fever uprise. Furthermore, a TXA2 analog (ONO-11113;2 or 4 micrograms ivt) had inconsistent effects on body temperature, while a TXA2 antagonist (ONO-11120;2 micrograms ivt) did not interfere with endotoxin fever. These findings strongly support a causative role for PGE2 in the onset and progression of pyrogen fever. No evidence of a similar role was obtained for TXA2.

Animals↗
PubMed1985

Evidence for a role of prostaglandin I2 and thromboxane A2 in the ductus venosus of the lamb.

The prostaglandin (PG) endoperoxide, PGH2, and the thromboxane (TX) A2 analog, 9,11-epithio-11,12-methano-TXA2, were tested in vitro on the ductus venosus sphincter from fetal (premature and mature) and neonatal (1-day-old) lambs. PGH2 relaxed the indomethacin-contracted fetal ductus in a dose-dependent manner and its action was reduced after treatment with 15-hydroperoxyarachidonic acid. In contrast, reduced glutathione did not affect the PGH2 relaxation in the indomethacin-treated ductus, nor did it modify the response of the untreated ductus to constrictor stimuli. Unlike PGH2, the stable 9 alpha,11 alpha-epoxymethano-PGH2 analog contracted the vessel. Similarly, the TXA2 analog was a contractile agent, its action exceeding that of the PGH2 analog in potency and efficacy. The TXA2 analog was active on preparations from both premature (minimum 117 days gestation) and mature lambs, but a maximal effect was attained during the perinatal period. These results confirm the existence of a PG-mediated relaxing mechanism in the ductus venosus and suggest that the active compound is PGI2. This mechanism is likely responsible for keeping the ductus patent in the fetus. TXA2, formed within the liver parenchyma, is well suited for playing a role in postnatal closure of the vessel.

Animals↗
PubMed1981

The conversion of hepatitis B core antigen synthesized in E coli into e antigen.

The antigen (HBeAg) of hepatitis B virus (HBV) is a polypeptide of 17-20,000 daltons closely associated with the core antigen (HBcAg) of Dane particles, from which it is released by a variety of disruptive procedures. HBeAg could be a unique component of HBV core particles or a derivative of HBcAg. To resolve this question immunodiffusion experiments were carried out with preparations of HBcAg synthesized in E coli carrying a recombinant plasmid from which the HBcAg, but no other HBV gene, was expressed. HBcAg was converted into HBeAg by proteolytic degradation under dissociating conditions, thus confirming at the molecular level that HBeAg is a component of HBcAg. This offers a new route to the detection of HBeAg and antibodies to the antigen.

Cloning, Molecular↗
PubMed1972

Simulated human skin scales.

Human skin scales which have been shed naturally bear a flora of microorganisms which is unknown until tested. To replace these scales in a study of the micro-environment of both the human body and of models a method has been devised of making synthetic scales which behave both physically and aerodynamically in a similar way to the natural material. The synthetic materials carry no natural flora and it is possible to include in them test markers of several kinds to assist in identification after dispersion.

Air Movements↗
PubMedDate not supplied

Long-term effects of acquired aphasias in childhood.

This paper presents the results of study into the long-term effects of acquired childhood aphasia (ACA). Two groups of children, a longitudinal group followed up for at least 2 years (12 children), and a cross-sectional group seen at least 2 years post-onset (12 children) were examined for the severity and pattern of residual language deficits (total 24 children). The results are presented. Overall, these show that more children in group 2 had moderate or severe language deficits at 2 years post-onset than in group 1, in which most children achieved language scores within the normal range by this stage of recovery. These findings are discussed in respect of the educational needs and continuing development of children with acquired aphasias, and the service they require.

Adolescent↗