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Biomedical subjects

D McLeod

Publications and source records attributed to D McLeod.

At least 127 records · Page 7Linked to original sources
PubMed1994

Identification of alternatively spliced variants of type II procollagen in vitreous.

Adult and foetal bovine vitreous were analyzed for the presence of unprocessed and partially processed forms of type II procollagen. Type II procollagen can exist in two alternatively spliced forms: a short form which lacks a large part of the N-propeptide due to the splicing out of exon 2 and a long form in which exon 2 is expressed and which has a full-sized N-propeptide. Both splice variants were demonstrated and analyses of type II pN-collagen demonstrated that the long form predominated, the ratio of the long form to the short form being 5:1 in foetal vitreous and 1.5:1 in adult vitreous. In foetal vitreous 35% of the type II collagen extracted was in the pN form, but there was very little unprocessed type II procollagen or type II pC-collagen. In contrast, adult vitreous extracts contained relatively less type II pN-collagen, but contained larger amounts of type II pC-collagen and unprocessed type II procollagen.

Alternative Splicing↗
PubMed1994

Extraction and characterization of the tissue forms of collagen types II and IX from bovine vitreous.

We report for the first time that, after centrifugation of adult bovine vitreous, the hyaluronan-rich supernatant contains collagens which can be isolated in their intact forms by precipitation with 4.5 M NaCl. This precipitate constituted approx. 4% of the total vitreous collagen and comprised collagen types IX and II (in the approximate ratio of 4:1) with negligible amounts of type-V/XI collagen. Type-II collagen was present partly in a pro-alpha 1(II) form, suggesting that there is active synthesis of type-II collagen into the matrix of adult bovine vitreous. Type-IX collagen was purified (2-2.5 mg/l of vitreous) and its glycosaminoglycan chain composition was analysed. Bovine vitreous type-IX collagen always possessed a glycosaminoglycan chain of comparatively low M(r) that was predominantly 4-sulphated, with chondroitin 6-sulphate representing a more minor component. By contrast, chick vitreous has been shown to contain type-IX collagen which always possesses a high-M(r) chondroitin sulphate chain that is predominantly 6-sulphated. The functional significance of these different glycosaminoglycan chain lengths and sulphation patterns is discussed.

Animals↗
PubMed1994

Localisation of alpha(2,3) and alpha(2,6) linked terminal sialic acid groups in human trabecular meshwork.

Sialic acid specific lectins were used to localise isomers of sialyl glycosides in human trabecular meshwork (TM) at the ultrastructural level. A lectin immunogold method demonstrated that sialic groups were concentrated on the endothelial surface of Schlemm's canal (SC) and in the adjacent juxta-canalicular tissue (JCT). One sialyl glycoside, alpha(2,6) linked N-acetyl neuraminic acid, was present mainly on the luminal aspect of the SC endothelium and in the cytoplasm of the JCT cells. Another, alpha(2,3) linked N-acetyl neuraminic acid, was localised predominantly to the extracellular fibrillar material of the JCT. The existence of a topographical segregation of these two sialyl glycosides within the TM supports the view that highly charged anionic molecules may be of significance in regulating aqueous outflow.

Adult↗
PubMed1994

Production of IGF-I and IGF binding proteins by retinal cells in vitro.

Insulin-like growth factor I (IGF-I) and its associated binding proteins (IGFBPs) have been identified in retinal tissues but their precise cellular origin remains unclear. The aim of this study was to examine the ability of three retinal cell types (microvascular endothelial cells, pericytes, and pigment epithelial cells) and a non-retinal cell type (Tenon's fibroblasts) to produce IGF-I and cell specific IGFBPs in vitro. Using a radioimmunoassay we demonstrated that all four cell types produce IGF-I and that this production continued over a 72 hour period. In addition, western ligand blotting revealed that each cell type produced at least one IGFBP and that each cell type produced a different IGFBP profile. Endothelial cells produced a 24 kDa band only, pericytes produced both a 24 kDa and a 34 kDa band, retinal pigment epithelial cells produced a 38-41 kDa band, while fibroblasts produced both a 24 kDa and a 30 kDa band. Laser scanning densitometry demonstrated that in the majority of experiments the IGFBPs accumulated in the culture medium over a 72 hour period. Neither IGF-I nor IGFBPs were observed in cell lysates indicating de novo synthesis and secretion in vitro. These results suggest an autocrine/paracrine function for IGF-I and its associated binding proteins which may play a significant role in both retinal physiology and disease.

Blotting, Western↗
PubMed1994

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.

Diabetic Retinopathy↗
PubMed1994

Oxygen regulation of TGF-beta 1 mRNA in human hepatoma (Hep G2) cells.

Solid tumours comprise populations of cells whose behaviour is thought to be influenced by growth factors and the local oxygen environment. We investigated the effect of oxygen on steady state levels of transforming growth factor-beta 1 mRNA in cultured human hepatoma cells. Northern blot analysis demonstrated that hypoxia mediated an early and sustained induction of TGF-beta 1 mRNA above that seen at higher oxygen tensions. The data suggests that modulation of TGF-beta 1 expression by the local oxygen environment may be important in tumour development and progression.

Blotting, Northern↗
PubMed1993

Taxol in advanced, hormone-refractory carcinoma of the prostate. A phase II trial of the Eastern Cooperative Oncology Group.

BACKGROUND: Recent clinical trials have documented activity for combinations of chemotherapeutic agents that target the microtubular apparatus in patients with hormone-refractory prostate cancer. Taxol has a novel antimicrotubular mechanism, acting by stabilizing polymerized tubulin. METHODS: Twenty-three patients with hormone-refractory prostate cancer and bidimensionally measurable disease were treated with Taxol by 24-hour continuous infusion at 135-170 mg/M2 every 21 days for a maximum of 6 cycles. RESULTS: Eighty-five courses of Taxol were administered to 23 patients. One patient (4.3%) experienced a partial response lasting 9 months, and four other patients with radiographically stable disease had minor reductions in the serum prostate-specific antigen (PSA) of 16-24%. Eleven patients (47.8%) had stable disease, and progressive disease developed in 9 patients (39.1%) during therapy. Median survival was 9 months. Leukopenia was the dose-limiting toxicity with 13% of patients having Grade 3 and 61% having Grade 4 toxicity, and granulocytopenic fever developed in 26%. Three patients experienced sudden cardiovascular events while participating in the study, including one patient with a nonfatal, non-Q-wave myocardial infarction that occurred during a taxol infusion, and two patients who had sudden deaths 9 days and 30 days after receiving their last taxol dose, respectively. CONCLUSIONS: In the subset of patients with hormone-refractory prostate cancer and bidimensionally measurable disease, Taxol at this dosage has only minor activity.

Aged↗
PubMed1993

Effect of diabetes mellitus on the cardiovascular responses to induction of anaesthesia and tracheal intubation.

We have compared cardiovascular responses to induction of anaesthesia and to tracheal intubation after propofol 2.5 mg kg-1 and pancuronium 0.1 mg kg-1 in 10 diabetic and 10 matched, non-diabetic (control) ASA I patients. Anaesthesia was maintained with 0.8% enflurane and 50% nitrous oxide in oxygen, with assisted ventilation. The trachea was intubated 3 min after induction of anaesthesia. All 10 diabetic patients (but no controls) had abnormal autonomic function when tested on the day before surgery. There was no difference between the two groups in the pre-induction cardiovascular state. Mean arterial pressure and vascular resistance decreased after induction in each group (P < 0.05). Heart rate increased (P < 0.01) and cardiac index was sustained in the control group, but in the diabetic group heart rate did not change and cardiac index decreased (P < 0.01). There was an earlier decrease in stroke index in the diabetic group (2 min) compared with the controls (5 min). After tracheal intubation, heart rate and cardiac index in the control group and cardiac index in the diabetic group remained unchanged. However, there was a greater increase in heart rate, mean arterial pressure and vascular resistance in the diabetic group compared with the controls after tracheal intubation (P < 0.05). The exaggerated pressor response to tracheal intubation, in the diabetic patients, may reflect autonomic dysfunction.

Adult↗
PubMed1993

Glycan localization within the human interphotoreceptor matrix and photoreceptor inner and outer segments.

Glycoconjugates are likely to be of fundamental importance in the complex interactions between photoreceptors and the retinal pigment epithelium, but few have been characterized, especially in human tissue. As a preliminary step towards determining their biological functions in health and disease, a lectin-based histochemical study of the glycan expression of human outer retina was performed on glutaraldehyde-fixed, semi-thin, resin-embedded sections. The interphotoreceptor matrix and photoreceptor plasma-lemmata expressed complex bisected and non-bisected biantennary and/or triantennary N-glycans. In addition, both the rod and cone outer segments bound strongly Galanthus nivalis agglutinin (which binds terminal Man alpha 1, 3Man-) and the rod outer segments bound selectively the isolectin II of Bandeiraea simplicifolia (which binds terminal GlcNAc-). The cilia of the rods and cones were labelled selectively with Glycine max agglutinin after sialidase pretreatment. Four putative glycan outer sequences were identified within the interphotoreceptor matrix: (i) sialylated glycans with subterminal GalNAc alpha 1,3GalNAc-sequences; (ii) a sialylated type with subterminal N-acetyl-lactosamine residues; (iii) Gal beta 1,3GalNAc alpha 1- residues which were substituted with sialic acid except in the cone matrix sheath; (iv) GalNAc alpha 1,6Gal beta 1- residues which were substituted in part with sialic acid. The sialic acid expression throughout was predominantly of the 2,3-linked form with lesser amounts of 2,6-linkage, and rod-associated structures (including the surrounding interphotoreceptor matrix) were labelled more strongly with the sialic acid-binding lectins than cone-associated structures (including the cone matrix sheath).

Adolescent↗
PubMed1993

Removal of silicone oil following diabetic vitrectomy.

The outcome of the removal of silicone oil from previously vitrectomised diabetic eyes was studied in a series of 25 eyes in 24 patients. Originally the patients presented with complex retinal detachments associated with proliferative diabetic retinopathy and all had reattached retinas after the initial operation. During the silicone tamponade, a number of complications had occurred. Cataract had developed in 14 eyes, glaucoma in eight, and reproliferation of fibrous membranes in 12. After the removal of silicone the retina redetached in three eyes (in all cases associated with severe postoperative haemorrhage), hypotony occurred in five eyes (transiently in four) and the seven eyes remaining phakic developed a cataract. In spite of these problems the eventual visual acuities returned to the immediate post-vitrectomy levels in almost all the eyes.

Adolescent↗
PubMed1993

Suture needle drainage of subretinal fluid.

A simple technique is described for the transcleral drainage of subretinal fluid during retinal detachment repair. In a prospective study of 94 consecutive suture needle drainage procedures subretinal fluid was successfully drained in 91 cases. There were six 'significant' subretinal haemorrhages associated with the procedure, but none was subfoveal in location or directly compromised the surgical outcome. In no case was retinal incarceration or retinotomy observed.

Adolescent↗