Immunocytochemical study of retinal diode laser photocoagulation in the rat.

AIM: To determine the nature of the cellular infiltrate, alterations in cell adhesion molecules, and MHC II antigen expression in the rat retina following diode laser retinal photocoagulation. METHOD: 20 normal Lister rats underwent diode laser photocoagulation of the retina. Frozen sections from eyes enucleated at 0, 1, 5, 13, and 33 days post laser were examined for T cells (R7.3), CD4 T cells (W3/25), activated CD4 T cells (OX-40), CD8 T cells (OX-8), B cells (OX-33), and macrophages (OX-42), MHC II antigen (OX-6), and E-Selectin-1, VCAM-1, and ICAM-1. RESULTS: Retinal diode laser photocoagulation stimulated a wound healing response in the outer retina and choroid. The cellular infiltrate included macrophages and activated CD4 T cells at 13 and 33 days post laser. Glial cells in the inner plexiform and inner nuclear layers expressed MHC II antigen at 24 hours only. ICAM-1 antigen was induced in RPE cells and in Muller cells in the inner retina at all time intervals post laser and intense staining for ICAM-1 was present around intraretinal migrated cells at 13 and 33 days post laser. VCAM-1 antigen expression was induced in the choroidal vascular endothelium and RPE at 13 and 33 days after laser as was E-Selectin-1 antigen expression which was also evident focally at the external limiting membrane in association with migrated cells adjacent to the burn. CONCLUSIONS: These results suggest that alterations in cell adhesion molecules may regulate the migration and activation of retinal pigment epithelium, macrophages and CD4 T cells at the outer blood-retinal barrier and choroid following diode laser photocoagulation of the normal Lister rat retina.     

Studies on the properties of some peripheral MAO inhibitors

1. Studies were carried out on three monoamine oxidase (MAO) inhibitors, two of which, debrisoquine and para- hydroxyphenelzine, are purported to be peripheral inhibitors and one, phenelzine, is a peripherally acting inhibitor, which has been included for comparitive purposes. 2. All three showed varying degrees of specificity towards MAO type A. 3. The action of debrisoquine was very rapid as was that of para- hydroxyphenelzine. 4. The inhibition caused by debrisoquine was competitive and reversible, while that caused by both phenelzine and para- hydroxyphenelzine was irreversible. 5. The inhibition caused by debrisoquine appeared to be unaffected by the pH of the medium.     

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.     

Problems with a ‘target’ approach to access in primary care: a qualitative study

We report an analysis of the qualitative phase of a study of patients' and carers' views of primary care services, focusing on their experiences of access to face-to-face general practitioner (GP) consultations during the period when new access policies were being implemented. Practices interpreted the new policy in various ways; restricted interpretations, including restriction of access to telephone booking, could cause distress to patients. Patients and carers welcomed flexible interpretations of the policy that offered choice, such as a choice of GP, or of booking in advance.     

Interactions between colour and luminance contrast in the perception of motion

It has been demonstrated widely that at isoluminance moving chromatic stimuli are seen to be stationary or moving more slowly than their luminance counterparts. We have examined the effect on perceived velocity of adding luminance contrast to an isoluminant chromatic stimulus. We show that moving luminance contrast 'captures' colour so that a combined colour and luminance stimulus is seen moving as a unified percept. However, in the presence of colour contrast, significantly higher levels of luminance contrast are required to achieve a veridical velocity than for monochromatic stimuli with only luminance contrast. We show that this interactive effect between colour and luminance contrast cannot be fully explained by a threshold masking of luminance by colour contrast. The effect suggests that a breakdown in the veridical perception of velocity should be expected for colours with a wide range of associated luminance contrasts and not just for those at the point of isoluminance.     

Correlations between nerve function and tissue oxygenation in diabetic patients: further clues to the aetiology of diabetic neuropathy?

Summary Transcutaneous oxygen, laser Doppler flowmetry, peroneal nerve motor conduction velocity and skin temperature were assessed in both legs of 34 diabetic patients, who had a mean age of 41 (range 29–77) years, and diabetes duration of 21 (3–34) years. Transcutaneous oxygen significantly correlated with peroneal nerve motor conduction velocity (r=0.59 p<0.001) and laser Doppler flowmetry (r=0.7 p<0.001). Laser Doppler flowmetry correlated weakly with peroneal motor conduction velocity, (r=0.34 p<0.05). In each patient the leg with the higher transcutaneous oxygen (mean 70.2±9.3 (SD) mmHg) had a significantly higher peroneal motor conduction velocity (45.3±7.1 vs 41.5± 6.3 m/s, p<0.01), than the leg with the lower transcutaneous oxygen (61.0±11.9 mm Hg), though no difference in skin temperature was observed, 31.4±0.4 vs 31.1±0.5°C. We then assessed the potential for reversibility of conduction velocity deficits in ten non-diabetic patients, aged 59 (52–77) years, undergoing unilateral femoro-popliteal bypass, measuring transcutaneous oxygen, peroneal nerve motor conduction velocity and skin temperature pre- and 6 weeks post-surgery. In the control leg (unoperated) there was no significant change in transcutaneous oxygen (63.2±8.8 vs 63.0±4.6 mm Hg), peroneal nerve motor conduction velocity (45.1±7.8 vs 43.4±7.2 m/s) or skin temperature (30.8±1.3 vs 30.2±1.2°C) after surgery (all NS). In the operated leg, transcutaneous oxygen increased from 59.3±10.7 to 70.7±7.2 mm Hg (p<0.01), and peroneal nerve motor conduction velocity from 42.6±6.1 to 46.7±3.2 m/s (p<0.01), but skin temperature was unchanged 30.3±0.4 vs 30.4± 1.3°C (NS). These studies provide further evidence that peripheral nerve function is associated with tissue hypoxia and that improving tissue oxygenation can significantly improve nerve conduction over a short period of time.     

Isolation and characterization of subgenomic DNAs encapsidated in "single" T = 1 isometric particles of Maize streak virus

"Single" T = 1 isometric particles of Maize streak virus (MSV) have been isolated from infected maize leaves. Biochemical and genetic characterizations show that these particles contain subgenomic (sg) MSV DNA encapsidated by the MSV coat protein. The largest sg DNA is 1.56 kb, slightly larger than half genome size, although sg DNAs as small as 0.2 kb were also cloned. The sg DNAs are not infectious, and they do not appear to play a role in the pathogenicity of MSV. This is the first report of sg DNAs for MSV and, to our knowledge, the first time that encapsidated sg DNAs have been characterized at the sequence level for any geminivirus. These data will assist in our investigations into the role of genomic DNA in the formation of the unique geminate capsid architecture of the Geminiviridae.     

Intestinal hypersensitivity reactions in the rat. I. Uptake of intact protein, permeability to sugars and their correlation with mucosal mast-cell activation.

We have confirmed previous observations that intestinal anaphylaxis induced in rats previously sensitized to ovalbumin (OVA) is associated with an increased uptake of an unrelated 'bystander' protein, bovine serum albumin (BSA) fed 1 hr previously. In this study, this enhanced protein uptake was associated with an increased lactulose/rhamnose excretion ratio after administration of these sugars, although there was no correlation between the two measurements. One hour after antigen challenge the serum levels of rat mast-cell protease II (RMCPII), a specific marker for mucosal mast-cell secretion, were significantly higher than both the pre-challenge levels and those of sham-challenged controls (P less than 0.002). There was a significant positive correlation between the serum levels of RMCPII and the lactulose/rhamnose excretion ratios (P less than 0.05), but no such correlation existed between RMCPII and BSA levels in the challenged rats. In other studies the urinary lactulose/rhamnose ratios of rats with cetrimide-induced gut damage were found to be significantly increased, although BSA uptake into the serum remained unaltered. We conclude that there is no simple correlation between gut permeation of low-molecular weight sugars and and the uptake of macromolecular proteins.