Search PubMed⌕ Search

Biomedical subjects

S Lightman

Publications and source records attributed to S Lightman.

At least 163 records · Page 9Linked to original sources

Permeability changes in blood-retinal barrier of galactosemic rats are prevented by aldose reductase inhibitors.

Permeability-surface-area products (PA) for sucrose at the blood-retinal barrier (BRB) were determined with quantitative in vivo techniques and compared in control rats, rats fed a 50% galactosemic diet, and rats fed a diet containing both galactose and the aldose reductase inhibitor sorbinil. The mean PA +/- SE for controls was 0.656 x 10(-5) +/- 0.13 ml.g-1.s-1 and increased by approximately 500% in galactose-fed animals to 3.13 x 10(-5) +/- 0.32 ml.g-1.s-1. Animals fed both galactose and sorbinil showed no significant difference from control animals (P greater than .05), with a PA of 0.91 x 10(-5) +/- 0.22 ml.g-1.s-1. No breach in the BRB to horseradish peroxidase was detected in any of the groups. These results demonstrate an increased permeability at the BRB to small molecules in galactosemic rats that is prevented by an aldose reductase inhibitor. This suggests that the retinal capillary basement membrane thickening seen in galactosemic rats is associated with an increased permeability of the BRB and that aldose reductase is implicated in its pathogenesis.

Aldehyde Reductase↗

Do L3T4+ T cells act as effector cells in protection against influenza virus infection.

This study aimed to analyse the roles of Lyt 2+ and L3T4+ memory T-cell subpopulations in murine influenza infection. Previous work has shown that Lyt 2+ cytotoxic T-cell (Tc) clones can adoptively transfer protection. We therefore wished to see whether L3T4+ (Th) cells could also act as protective effector cells. Donors for adoptive cell transfer were thymectomized mice, depleted in vivo of either Lyt 2+ or L3T4+ T cells with monoclonal antibodies (MAb) and then infected with influenza virus (A/X31). Primed spleen cells, after removal of the B cells, were transferred into irradiated hosts infected simultaneously or persistently with a heterologous influenza virus and the effect on lung virus replication determined. Depletion of L3T4+ T cells suppressed the formation of IgG antibodies after influenza virus infection, indicating significant depletion of T-helper function. Yet Lyt 2+ class I MHC-restricted Tc cells were effectively primed in these mice, albeit to half the normal level. Adoptive transfer of the Lyt 2+ memory T cells cleared virus in a persistent infection within 6 days. Spleen cells selected for L3T4+ T cells cleared virus within 21 days of transfer in a simultaneous infection and reduced viral titres in a persistent infection, but not as effectively as L3T4+-depleted spleen cells. Although no Lyt 2+ cells were detected by fluorescence staining in Lyt 2+-depleted spleens, we could detect low levels of class I MHC-restricted influenza-specific Tc memory cells in host spleens following influenza infection. Therefore, whether the early viral clearance is solely due to L3T4+ T cells is not clear. Lyt 2+ memory T cells appear more efficient in this respect than L3T4+ memory T cells.

Animals↗

Immunohistopathology of experimental uveitis induced by a non-ocular antigen.

Inflammation was induced in the eye by active and passive Arthus reactions using a non-ocular antigen and was examined by histologic and immunopathologic techniques. T cells were seen to infiltrate the eye when the inflammation occurred in the active Arthus reaction and were not seen after passive immunization. The findings were compared to those of experimental autoimmune uveoretinitis.

Animals↗

Lack of thirst, osmoreceptor dysfunction, early puberty and abnormally aggressive behaviour in two boys.

Two unrelated boys (C.C. 13 years; J.W. 18 years) presenting with early puberty and episodes of aggressive behaviour were found to have hypernatraemia and hypodipsia. Plasma vasopressin (AVP) levels were inappropriately low in relation to plasma osmolality, but the patients did not have diabetes insipidus since 24 h urinary volumes were less than 1 litre and the maximal urinary osmolality was 1232 in C.C. and 950 in J.W. Plasma renin activity was elevated (greater than 2000 mg AI/1/h) although aldosterone concentrations were normal. Excretion of a water load (20 ml/kg) was delayed, but plasma renin and aldosterone fell with increased naturesis. An infusion of 0.85 mol/l saline produced a rise in AVP in C.C. but not in J.W. Insulin and hypotension resulted in the release of AVP in both boys suggesting a selective defect of osmoreceptor function. Hyperprolactinaemia and an exaggerated PRL response to TRH were also noted but no intracranial lesion was demonstrable on CT scan. These boys appear to have a hypothalamic syndrome with early puberty, hyperprolactinaemia, hypodipsia and osmoreceptor dysfunction which may be associated with aggressive behaviour.

Adolescent↗

Mechanism of polyuria and natriuresis in atrioventricular nodal tachycardia.

A woman with tachycardia associated with polyuria was investigated. Electrophysiological analysis showed that the tachycardia was an atrioventricular nodal re-entrant tachycardia. Programmed stimulation was then used to provoke and sustain the tachycardia for 40 minutes. Polyuria, with an appreciable increase in free water clearance, was observed. This was associated with reduction in plasma and urinary arginine vasopressin concentrations. Appreciable natriuresis also developed. These results support the hypothesis that the polyuria with increased free water clearance and the natriuresis occurring during sustained tachycardia in man are due to inhibition of secretion of vasopressin and the release of natriuretic factor.

Arginine Vasopressin↗

The application of a cytochemical bioassay to measure thyroid stimulating antibodies; a study of patients with euthyroid Graves' ophthalmopathy.

Using a cytochemical bioassay for thyroid stimulators, we have studied in detail the responses to IgG preparations from sera of 11 patients with euthyroid Graves' ophthalmopathy. This assay is based upon changes in naphthylamidase activity in response to the addition of thyroid stimulators. A wide range of dilutions of each IgG preparation was tested, and bell-shaped dose response curves were obtained where thyroid stimulating antibody (TSAb) was present. Such dose-response curves, giving a maximum response at one dilution (higher or lower concentrations giving a decreased or nil response) are characteristic of this assay. Results were expressed as a titer which is defined as the reciprocal of the dilution giving the maximum response for a given sample. Our routine strategy for titer determination for a given IgG preparation, including the use of "negative" and "positive" controls is described. Retesting of IgG's in separate bioassays showed that the titers were reproducible. Serum from one of the 11 patients was TSAb negative, i.e. did not provoke a response at any dilution tested in this ultrasensitive bioassay. The others were TSAb positive with a wide range of titers (1:10(2) to 1:10(8)). In addition one patient (initial titer 1:10(5)) was plasmapheresed, first in the absence of immunosuppression, when rebound resulted in a titer of 1:5 X 10(7), and secondly in combination with immunosuppression when the titer was reduced to less than 1:10(2). These large changes in titer for samples from one patient were consistent with the strikingly wide ranges of titers found for the 10 other patients.

Adult↗

Hypothalamic integration of dopaminergic and opiate pathways controlling vasopressin secretion.

Lesions of the circumventricular organs were produced by administration of monosodium-L-glutamate to neonatal rats. At 16 weeks of age these rats were given different stimuli to vasopressin release. In control rats, morphine (50 micrograms) injected into the third ventricle resulted in a rapid increase in plasma vasopressin concentrations at 10 min, followed by a reduction at 20 min. The circumventricular organ-lesioned rats, however, showed a pronounced fall in vasopressin secretion both at 10 and 20 min after 50 micrograms morphine. A similar abolition of the morphine-elicited rise in plasma vasopressin could also be achieved by the iv infusion of small doses of dopamine in normal rats. Hypoxic stimuli, which result in a marked rise in vasopressin in normal rats, failed to elicit any increase in circumventricular organ-lesioned animals. Vasopressin release after stimulation with 9% saline, however, was augmented in the lesioned animals. These results suggest that circumventricular organs have an important role in controlling neurohypophyseal secretion and that they differentially control different stimuli to vasopressin release via dopaminergic and opiate pathways.

Animals↗

Naloxone increases the nicotine-stimulated rise of vasopressin secretion in man.

Intravenous nicotine was administered to a group of six subjects during the concurrent intravenous infusion of either the opiate antagonist naloxone, or of saline. Nicotine stimulated vasopressin secretion in all subjects. Naloxone infusion increased both the plasma vasopressin response to nicotine and the resulting rise in urine osmolality.

Adult↗

Herpes zoster ophthalmicus: a medical review.

Patients with herpes zoster undergo extensive screening to detect underlying malignant disease which is compromising their immunity. In a retrospective survey of 1000 patients with herpes zoster ophthalmicus 12 patients had malignant disease which was known on presentation. No new cases were detected or discovered on follow-up. Three patients developed a disseminated rash, but none of these had an underlying malignant disease.

Adolescent↗

The responsibilities of intervention in isolated societies.

Development pressures are pushing industrial society into the remaining refuge areas of the world. As it spreads it destroys much of the biological and cultural variety that has evolved over millions of years. Not only is mammalian life diminishing, but also the genetic pool of plants and cultivars, as well as the culture-specific knowledge of their use. Even culture itself, the highest attribute of mankind, is being rapidly erased, often before any attempts are made to record it. The medical problems of remaining tribal groups are severe. Western medicine has developed to deal with western problems and is often poorly equipped to deal with the many-sided health hazards of tribal man. The effects of contact upon disease status are discussed with particular reference to North and South American Indian history. Infectious disease is only one of many causes of ill-health, and the problems of nutritional change and social disruption are also considered. The approach to health care in tribal communities is discussed and axioms for the initiation of health care programmes are proposed.

Acculturation↗

Hypopyon uveitis.

Hypopyon uveitis has inflammatory, infective, and neoplastic causes and a high association with systemic disease. Careful questioning of the patient and detailed examination of the eye for other signs is necessary to guide the differential diagnosis and relevant investigations. Because the underlying causes require very different types of investigation and, if missed, can have serious sequelae for the patient, a rational approach based on the understanding of the causes of hypopyon uveitis is imperative. In this review, hypopyon uveitis is considered in the context of the associated ocular and systemic diseases that cause it.

Anterior Chamber↗

Immunopathology of the noninfectious posterior and intermediate uveitides.

The posterior and intermediate uveitides share an underlying immune etiology; however, they can be clinically and immunopathologically distinguished. Although the initiating stimuli for posterior and intermediate uveities are not known, it is believed that an exogenous agent (such as a bacterium or a virus) or an endogenous molecule may induce disease. In either case, T-helper lymphocytes in conjunction with human leukocyte antigens are likely to be involved. This review examines the epidemiology, histology, immunopathology, and theories of pathogenesis of several posterior and intermediate uveitides, including sympathetic ophthalmia, Vogt-Koyanagi-Harada syndrome, Behçet's disease, sarcoidosis, intermediate uveitis, white dot syndromes, and birdshot retinochoroidopathy.

Cytokines↗

The eye in systemic infection.

Bacterial, fungal, viral, and parasitic pathogens all cause systemic infection and can spread to the eye. Dissemination of pathogens via the bloodstream can lead to direct involvement of the eye. Visual loss is common in bacterial or fungal endophthalmitis, and toxoplasmosis is a major cause of ocular morbidity and poor vision after congenital or acquired infection. Some infections cause intraocular damage by indirect mechanisms (eg, HIV-mediated immunosuppression), leading to opportunistic infections such as cytomegalovirus infection, periocular nerve involvement due to leprosy, and hypersensitivity reactions in tuberculosis. Eye symptoms might indicate the outcome of an underlying infection, such as development of retinal ischaemia in severe malaria, which is associated with a poor prognosis. Successful outcome for patients with ocular infection depends on close collaboration between clinicians identifying and treating underlying disease, specialist ophthalmic review, and ophthalmic interventional skills (when needed).

Eye Diseases↗