Central nervous system control of fluid balance: physiology and pathology.
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Animals↗
Biomedical subjects
S Lightman
Publications and source records attributed to S Lightman.
Cavernous sinus involvement in recurrent Nelson's syndrome.
Nelson's syndrome is rare and difficult to cure. The tumours in this condition may behave invasively and require multiple interventions. Two patients who had been followed up for nearly 20 years developed signs of cavernous sinus involvement, one with an empty sella. Long term follow-up for such patients is emphasized.
Adult↗
Sclerokeratitis after keratoplasty in atopy.
The authors report a series of five markedly atopic patients in whom a severe sclerokeratitis developed within 1 to 4 weeks of keratoplasty. The onset was acute with discomfort, photophobia, hyperemia, and mucus production. This resulted in early loosening of sutures and was associated with microbial keratitis in two cases and graft rejection in one. The inflammatory reaction was controlled with high-dose oral steroids and did not recur when the treatment was terminated. Serum IgE levels were elevated in all these patients (range, 421-8434 kU/l). Binding of this IgE onto the surface of mast cells in the conjunctiva with subsequent degranulation may be involved in the pathogenesis of the induced inflammation. Principal recommendations include the use of interrupted sutures and early immunosuppression with high-dose oral steroids at the onset of this condition together with the control of risk factors for microbial keratitis.
Adolescent↗
Immune mechanisms in choroido-retinal inflammation in man.
The immunohistopathological findings of enucleated eyes and immunological abnormalities in several clinical disorders which result in intraocular inflammation are presented. With current immunological techniques, it is possible to define the type and activation status of the cells infiltrating the tissues. In all eyes examined, the predominant cell type was of activated CD4+ T-cells suggesting that the mechanisms involved in the perpetuation of the inflammatory response are similar and it is the initiating events which are likely to determine the site of pathology. The effects of activated CD4+ T-cells and the lymphokines they secrete in the chronic inflammatory process in the ocular tissues are discussed.
Behcet Syndrome↗
Aldose reductase messenger RNA in the lens epithelium in vivo: effects of diabetes mellitus and galactosaemia.
1. Quantitative in situ hybridization histochemistry was used to examine the regulation of aldose reductase messenger RNA in the rat lens after the induction of diabetes mellitus or after feeding a 50% (w/w) galactose diet. 2. Although increased staining for aldose reductase in the lens epithelium has previously been observed by immunohistochemistry after 3 weeks of diabetes or after 7 days of galactose feeding, we have not been able to detect any increase in the amount of aldose reductase messenger RNA in these cells as compared with controls (113 +/- 7%, 105 +/- 9%, 100 +/- 7%, respectively) at these time points (P greater than 0.05). 3. After 15 days of galactose feeding, however, there was a significant increase of 140% (+/- 12%) in the amount of aldose reductase messenger RNA in the lens epithelial cells as compared with controls (P = less than 0.001). 4. These results demonstrate that increased availability of galactose, a high-affinity substrate for the enzyme, leads to increased aldose reductase messenger RNA, which suggests a role for aldose reductase in sugar metabolism in the lens.
Aldehyde Reductase↗
Permeability changes at blood-retinal barrier in diabetes and effect of aldose reductase inhibition.
Sensitive quantitative in vivo techniques were used to assess the permeability at the blood-retinal barrier (BRB) to [14C]sucrose in the anesthetized streptozocin-diabetic rat at various time points (3 wk, 6 mo, 13 mo) after induction of diabetes. The effects of concomitant administration of an aldose reductase inhibitor (ARI) on sorbitol levels in the retina and on BRB permeability were also measured. No increase in BRB permeability was found in rats diabetic for 3 wk or 6 mo, but after 13 mo of hyperglycemia there was an increase in permeability of 240%. No effect on permeability was seen in diabetic animals given the ARI despite the retinal sorbitol levels being decreased in the treated compared with the untreated diabetic group fed a normal diet. This study suggests that the accumulation of sorbitol within the cells of the BRB is not responsible for the breakdown of BRB permeability seen after 7-13 mo of hyperglycemia and that the enzyme aldose reductase is not involved in its pathogenesis.
Aldehyde Reductase↗
Treatment of scleritis with combined oral prednisone and indomethacin therapy.
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Administration, Oral↗
Vasopressin RNA in the neural lobe of the pituitary: dramatic accumulation in response to salt loading.
The peptides vasopressin (VP) and oxytocin are derived from preprohormone precursers encoded by highly homologous linked genes that are expressed in discrete groups of hypothalamic neurons. The mature hormones are released into the peripheral circulation from the neural (posterior) lobe of the pituitary and have also been implicated in the regulation of anterior lobe. We have used Northern blotting and in situ hybridization to RNA in tissue sections to describe the presence, anatomical localization, and regulation of VP and oxytocin RNAs in the pituitary gland itself. We were unable to detect VP transcripts in the anterior and intermediate lobes of the pituitary. Rather we found low levels of VP RNA in the neural lobe. Furthermore, the osmotic stimulation of a 2% (wt/vol) NaCl drinking diet resulted in a marked accumulation of VP RNA in the neural lobe. We suggest that VP, locally synthesized in pituicytes, may have paracrine effects on VP receptors in the neural lobe.
Animals↗
Neural function: metabolism and actions of inositol metabolites in mammalian brain.
In the nervous system, a variety of cell types respond to external stimuli through the inositol lipid signalling pathways. The stimulus-coupled sequence of intracellular events has been investigated in a homogeneous model system, the cloned mammalian neural cell line NG115-401L. The neural peptide bradykinin stimulates a rapid production of identified inositol phosphate isomers and an intracellular Ca2+ discharge followed by a persistent plasma membrane influx. The temporal sequence suggests that Ins(1,4,5)P3 or Ins(1,3,4,5)P4 or both may coordinate these events in a neuronal cell, as has been suggested in other cell types. Thapsigargin, an irritant and tumour-promoting plant product, produces calcium transients in the absence of inositol phosphate production, and may provide a new tool for investigating the interactions between inositol phosphates and changes in cellular calcium homeostasis. In the 401L line, high levels of radiolabelled InsP5 and InsP6 have been detected, which has led to the evaluation of their possible occurrence and actions in normal brain. Both InsP5 and InsP6 are produced from a radiolabelled myo-inositol precursor in intact mature brain in a region-specific manner. This suggests that both inositol polyphosphates may be end products of regionally regulated biosynthetic pathways. When microinjected into a nucleus of the brainstem, or iontophoretically applied to the dorsal horn of the spinal cord, both InsP5 and InsP6, but not Ins(1,3,4,5)P4 isomers, appear to be potent neural stimulants. These results suggest that the inositol lipid signalling pathways may generate both intracellular and extracellular signals in brain.
Animals↗
Central cardiovascular effects of calcitonin gene-related peptide: interaction with noradrenaline in the nucleus tractus solitarius of rats.
The haemodynamic responses to microinjections of rat or human calcitonin gene-related peptide (CGRP) into the nucleus tractus solitarius (NTS) of rats were studied. 40 fmol rCGRP did not significantly modify cardiovascular parameters, but 0.2 pmol decreased blood pressure and heart rate (HR), whereas 2 pmol produced a pressor response with no effect on HR. hCGRP elicited a transient fall in blood pressure when administered at the highest dose (2 pmol), but had no effects when given at 0.2 pmol. A possible functional relationship with catecholamines was also investigated. The hypotensive response to 20 nmol noradrenaline (NA) was significantly modified by simultaneous administration of a low dose (40 fmol, ineffective alone) of rCGRP. When rCGRP (40 fmol) was coinjected simultaneously with an ineffective dose (10 pmol) of NA, a hypotensive response was observed. Our results provide evidence that rCGRP may play a role in the control of cardiovascular homeostasis in the NTS, and suggest a functional interaction between this peptide and NA.
Animals↗
Immune mechanisms in autoimmune ocular disease.
Aberrant expression of Class II MHC antigens (Ia) by non-immune cells is considered to be an important mechanism in the pathogenesis of autoimmune disease processes including those affecting the eye. It is suggested that circulating autoreactive T-cells are directed to their target organ as a result of aberrant expression of Ia antigens by the vascular endothelium of that organ. This hypothesis was tested in this study using two different models of severe ocular inflammation, induced by either S-antigen or bovine serum albumin (BSA). The retinal vascular endothelium becomes Ia + in S-antigen induced inflammation but not in inflammation induced by BSA. The accumulation in the eye of a T-cell line, ThS, specific for an ocular antigen (S-antigen), was compared in the two types of ocular inflammation and compared to that of another T-cell line, ThP, specific for a non-ocular antigen (PPD). In S-antigen induced inflammation, there was much greater accumulation of ThS than ThP whereas in BSA induced inflammation, both T-cell lines accumulated to the same extent but more than in uninflamed eyes. These results suggest that when the retinal vascular endothelium expresses Ia antigens during an inflammatory process, autoreactive T-cells will be specifically retained in the eye as a result of this and perpetuate the autoimmune destructive process.
Animals↗
Cerebrospinal fluid neurohypophysial peptides in benign intracranial hypertension.
The cerebrospinal fluid (CSF) concentrations of arginine vasopressin (AVP) and oxytocin (OT) were investigated both in patients with benign intracranial hypertension and in age and sex matched controls. Twenty eight lumbar punctures were performed on 15 patients with benign intracranial hypertension as part of their routine investigation and therapy. All patients had raised intracranial pressure (27.4, SE 1.7 cm.CSF). CSF AVP levels were significantly elevated in benign intracranial hypertension (2.1, SE 0.3 pmol/l) compared with controls (0.7, SE 0.1 pmol/l, p less than 0.001) but CSF OT concentrations were similar in both groups. CSF osmolality and plasma AVP and osmolality were identical in patients and controls. There was no correlation between CSF AVP concentration and intracranial pressure. The selective elevation of AVP in CSF may be of importance in the pathogenesis of raised intracranial pressure in benign intracranial hypertension.
Adolescent↗
Immunodeficiency, immunity, and staphylococcal infection.
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Humans↗
Intraocular Ia expression in vivo induced in the absence of immune T cells.
The expression of Ia antigen on the ciliary body, retinal pigment epithelium, and retinal vascular endothelium was investigated using two models of ocular inflammation. Active systemic immunization with bovine serum albumin with subsequent ocular challenge resulted in increased Ia expression in the ciliary body and retinal pigment epithelium. This was compared with passive transfer of hyperimmune serum to bovine serum albumin followed by ocular challenge when Ia expression was found to occur only in the ciliary body. An intraocular T-cell infiltrate occurred only in the actively immunized animals and was not present after passive transfer, suggesting that the Ia induction in this latter situation occurred in the absence of T cells.
Animals↗
Retinal venous sheathing in optic neuritis. Its significance for the pathogenesis of multiple sclerosis.
A systematic study of the frequency of retinal vascular abnormalities and cells in the media has been made in 50 patients presenting with acute optic neuritis. Abnormalities were found in 14 (fluorescein leakage in 10, perivenous sheathing in 6, cells in the vitreous in 6 and in the anterior chamber in 4; in 2 the cells in the media were seen without vascular changes). After a mean follow up of 3.5 years multiple sclerosis (MS) had developed in 8/14 patients with vascular abnormalities and/or evidence of inflammation and in 5/32 without; the difference is significant (P less than 0.02). The occurrence of perivenular abnormalities in a region free of myelin and oligodendrocytes provides evidence that the vascular changes in MS can occur independently of contiguous demyelination, and may be the primary event in the formation of a new lesion.
Adolescent↗
Ocular and cerebral metastases in the VX2 rabbit tumor model: contrast-enhanced MR imaging.
Ocular and cerebral metastases developed after the inoculation of a VX2 tumor cell suspension into the internal carotid artery of 15 rabbits. The hematogenous spread of tumor cells resulted in ocular metastases in 13 of 15 animals (86.7%) and cerebral system metastases in 14 of 15 animals (93%). Magnetic resonance (MR) imaging with Gd-DTPA demonstrated early disruption of the blood-ocular barrier and blood-brain barrier 5-7 days after infusion of tumor cells. Quantitative assessment of contrast enhancement revealed a mean increase in signal intensity of 145% +/- 51% in the anterior chambers, 102% +/- 70% for choroidal metastases, and 51% +/- 29% for central nervous system (CNS) metastases. These results indicate that contrast-enhanced MR imaging can be used to demonstrate a loss of blood-ocular barrier integrity that is similar to the breakdown of the blood-brain barrier associated with metastatic tumors to the CNS and eye.
Animals↗
Assessment of the permeability of the blood-retinal barrier in hypertensive rats.
We assessed the permeability surface area products at the blood-retinal barrier and blood-brain barrier to sucrose (molecular weight, 340) and microperoxidase (molecular weight, 2000) following acute hypertension induced by metaraminol in Wistar-Kyoto rats (controls) and during chronic hypertension in spontaneously hypertensive rats. In acute hypertension, the permeability surface area product for sucrose was increased at the blood-retinal barrier and at the blood-brain barrier over control values (p less than 0.02), and the vessels became leaky to microperoxidase. In chronic hypertension, the permeability of the blood-retinal barrier to sucrose was increased over that in control animals (p less than 0.02), whereas the permeability of the blood-brain barrier was unaffected. Neither barrier leaked microperoxidase. These results indicate that the blood-brain barrier and the blood-retinal barrier are similarly affected in acute hypertension and that in chronic hypertension, the blood-brain barrier is unaffected whereas the blood-retinal barrier is rendered more permeable to small, but not large, solutes.
Acute Disease↗