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Biomedical subjects

A Garner

Publications and source records attributed to A Garner.

At least 127 records · Page 7Linked to original sources

Studies on the localization and properties of rat duodenal HCO3--ATPase with special relation to alkaline phosphatase.

Brush-border membrane fractions were isolated from rat duodenum. Purity and integrity of the fraction was confirmed by electron microscopy, enzymic analysis and demonstration of Na+-dependent glucose uptake. The membranes were enriched 15-fold in alkaline phosphatase and alpha-glucosidase and 6-fold in HCO3--ATPase activities. Assays of latent activity indicated that these enzymes were predominantly localised to the external aspect of the microvillus membrane. The enzymes were solubilised and subjected to analysis by gel filtration, ion exchange and phenylboronate chromatography. No separation of alkaline phosphatase and HCO3--ATPase was obtained and it is suggested that they reflect the same enzyme activity. The apparent activation by HCO3- was investigated, and was found to be due to shifts in the pH dependency of the activity due to changes in ionic strength.

Adenosine Triphosphatases↗

Hereditary sensory neuropathy with neurotrophic keratitis. Description of an autosomal recessive disorder with a selective reduction of small myelinated nerve fibres and a discussion of the classification of the hereditary sensory neuropathies.

A Kashmiri family with 3 members affected by a congenital sensory and autonomic neuropathy and corneal opacification is described. The 3 affected cases were offspring of consanguinous marriages in two generations; autosomal recessive inheritance is therefore probable. Pain and temperature sensation was lost in the limbs with a resulting mutilating acropathy. Sudomotor function was also impaired. Motor function, tendon reflexes, kinaesthetic sensation and sensory nerve action potentials were normal. Sural nerve biopsy showed a selectively reduced small myelinated nerve fibre population. Corneal histology revealed neurotrophic keratitis. The classification of the hereditary sensory and autonomic neuropathies is discussed. This family represents a previously unrecognized variant.

Adult↗

Retinoblastoma: report of a case with minimal retinal involvement but massive anterior segment spread.

The case is described of a unilateral retinoblastoma in a 7-year-old girl which was initially misdiagnosed because of massive anterior segment involvement in the apparent absence of a retinal lesion. Only on histopathological examination of the enucleated eye was the presence of retinal tumour established, this being confined to two minute foci at the extreme periphery.

Anterior Eye Segment↗

Congenital hereditary corneal oedema of Maumenee: its clinical features, management, and pathology.

The clinical and histological features of congenital hereditary corneal oedema in 23 patients are presented. The series includes cases of both recessive and dominant inheritance. Although the condition is present at birth or in early childhood, visual development appears to be little impaired, if at all. Penetrating keratoplasty carries a relatively good surgical prognosis and can produce a substantial visual gain even when carried out late in life.

Adolescent↗

Characterisation of ocular melanoma with cutaneous melanoma antibodies.

It can be difficult to distinguish between various forms of pale intraocular tumour, and in particular between an amelanotic malignant melanoma, a choroidal haemangioma, and a solitary metastasis. If a monoclonal antibody specific for melanoma could be identified, it might be radiolabelled to provide a scanning technique which could distinguish between an ocular melanoma and a similar lesion. This pilot, in vitro study was undertaken to determine if monoclonal antibody against cutaneous melanoma recognises any antigenic similarity in ocular melanomas. Three cutaneous melanoma MoAbs 225.28S, 376.96S, and 763-24T and a non-specific MoAb HMFG2 were studied. Cell impressions were obtained from fresh ocular malignant melanomas. Standard staining techniques with immunofluorescence were used. MoAb 225.28S, 376.96S, and 763.24T were positive in melanomas with a dominant epithelioid cell type and in those with a dominant spindle cell type. It is concluded that MoAb 225.28S, 376.96S, and 763.24T may be suitable for imaging ocular melanomas after labelling with 123I, 111In, or 99mTc.

Antibodies, Monoclonal↗

Gastroduodenal mucosal defence mechanisms and the action of non-steroidal anti-inflammatory agents.

This review summarises gastroduodenal protective mechanisms, the actions of non-steroidal anti-inflammatory (NSAI) agents on mucus and HCO3 secretions, and the basis of gastric mucosal injury induced by acetylsalicylic and salicylic acids (ASA and SA). Resistance to autodigestion by acid and pepsin present in gastric juice is multifactorial involving pre-epithelial (mucus-bicarbonate barrier) and post-epithelial (blood flow, acid-base balance) factors in addition to properties of the surface cell layer per se. The latter includes mucosal re-epithelialisation, a property which appears particularly important with respect to recovery from acute injury. A range of NSAI agents (ASA, fenclofenac, ibuprofen and indomethacin) inhibit gastric HCO3 transport in isolated mucosal preparations. Inhibition of duodenal HCO3 transport has been demonstrated in response to indomethacin in vitro and in vivo. These effects on secretion can be antagonised by exogenous prostaglandins of the E series. The layer of secreted mucus gel overlying the epithelial surface is not affected by NSAI drugs in the short term. However a number of these agents have been shown to inhibit glycoprotein biosynthesis by the epithelial cells. Thus loss of this protective coat could be anticipated during chronic drug exposure since erosion of adherent mucus by luminal shear and proteolysis would not be compensated by continued secretion. Detailed analysis of the gastric mucosal injury induced by salicylates both in vitro and in vivo reveals that much of the damage previously attributed to ASA is in fact due to the metabolic product SA. In this respect it is concluded that mucosal injury caused by ASA is due to a combination of two factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Oxygen-induced retinopathy in newborn kittens. A model for ischemic vasoproliferative retinopathy.

Fourteen kittens were reared in 80% oxygen for 65-72 hr, after which they were returned to room air. At that time, funduscopic examination of all the kittens showed complete obliteration of the retinal vasculature and even optic disc vessels. In the following 18-21 days, florid preretinal new vessels were found growing into the vitreous from the revascularized retina and from the optic disc itself. Subsequent histologic examinations confirmed the above clinical findings and reinforced the authors to suggest this animal model as a future research tool for ischemic vasoproliferative retinopathy, rather than a model for retinopathy of prematurity (ROP). The similarities and dissimilarities between this animal model and the human ischemic retinal disease are discussed.

Animals↗

A double-blind comparative study of alprazolam and dothiepin hydrochloride in the treatment of anxiety associated with depression.

One hundred patients with mixed symptoms of anxiety and depression were enrolled into a prospective, multi-centre, randomized, double-blind study comparing the response to, and the side-effects of, alprazolam and dothiepin hydrochloride over 4 weeks of treatment. Mean daily doses were 2.33 mg alprazolam and 115 mg dothiepin. Data on 96 patients were evaluated for tolerance, and data for 85 patients were analyzed for therapeutic response. In each case, the groups were similar in numbers, mean ages and sex ratios. Both groups experienced satisfactory responses to therapy, with highly statistically significant changes (p less than 0.001) in the means of all efficacy measures within each group. No statistical difference was demonstrated in favour of either treatment group. Both dothiepin and alprazolam exhibited a similar profile of mild minor side-effects, but more patients suffered moderate to severe reactions to dothiepin, leading to a greater drop-out rate in the dothiepin-treated group. It is concluded that, as both treatments produced equally satisfactory responses in this study, alprazolam should be considered for the treatment of anxiety associated with depression in patients for whom tricyclic antidepressant drugs are either contra-indicated or poorly tolerated.

Adolescent↗

Free-radical-mediated fragmentation of monoamine oxidase in the mitochondrial membrane. Roles for lipid radicals.

A flux of hydroxyl radicals generated by gamma-irradiation can fragment monoamine oxidase in the membrane of submitochondrial particles. This fragmentation can be inhibited by mannitol and in addition is more extensive in monoamine oxidase preparations that have been depleted of lipid. This latter observation is consistent with the higher yields of fragmentation induced by hydroxyl radicals in soluble proteins in the absence of added lipids. In the absence of oxygen, gamma-irradiation of submitochondrial particles leads to cross-linking reactions. A flux of hydroperoxyl radicals also causes fragmentation, whereas one of superoxide is virtually inactive in this respect. The irradiation of submitochondrial particles leads in addition to the accumulation of products of lipid peroxidation. When these irradiated preparations are exposed to ferrous or cupric salts a further fragmentation of monoamine oxidase ensues, especially at acid pH. These transition-metal-catalysed reactions do not occur with irradiated preparations depleted of lipid, and the post-irradiation protein modifications are concomitant with further lipid peroxidation. The data indicate roles for lipid radicals in both fragmentation and cross-linking reactions of proteins in biological membranes. These reactions may have an important bearing on control of protein activity and of protein turnover in membranes.

Animals↗

Histochemistry of elastic and related fibres in the human eye in health and disease.

Although the presence of mature elastic fibres in the sclera, trabecular meshwork and Bruch's membrane of the human eye has been recognized for many years, it is only latterly that the existence of the elastic-related fibres oxytalan and elaunin has been appreciated. The microfibrillar component of elastic, oxytalan, which is present in several ocular structures in infancy, can either mature to fully-developed elastic tissue or, as in the cornea, disappear in subsequent years. Deposition of elastic fibres, particularly the incomplete forms, can occur in the post-developmental period in a variety of disease states but the stimulus and functional significance in most situations is obscure. The evidence suggests, however, that the capacity to form elastic-related tissue is not confined to any one cell type.

Contractile Proteins↗

Effects of 2-mercaptopropionyl glycine on radiation-induced lipid peroxidation in liposomes and in rat liver microsomal suspensions.

gamma-Irradiation of rat liver microsomal suspensions resulted in the accumulation of both malondialdehyde (MDA) and lipid hydroperoxides. The presence of 2-mercaptopropionylglycine (MPG) during the irradiation period decreased the formation of MDA and lipid hydroperoxides in a dose (MPG)-dependent manner. This may be attributed to the ability of MPG to scavenge the free radicals produced by irradiation. Post-irradiation incubation of microsomes further enhanced the production of both MDA and lipid hydroperoxides; when high concentrations of MPG were present during the incubations the production of MDA and lipid hydroperoxides was substantially decreased. This antioxidant role of MPG was demonstrated for both pre-irradiated microsomes and liposomes and is thought to be due to the conversion of the hydroperoxy to hydroxy fatty acids within the lipid bilayer, as well as the scavenging action on initiating free radicals.

Amino Acids, Sulfur↗

Malignant melanoma of the eyelid and conjunctiva.

Four patients with malignant melanoma of the eyelid skin and 14 patients with conjunctival malignant melanoma are presented. Surgery was recommended for eyelid lesions and local excision followed by cryotherapy for conjunctival lesions. One patient with an eyelid skin malignant melanoma died and two patients with extensive malignant melanoma of the conjunctiva died. Nodular lesions involving the lid margin have the worst prognosis of eyelid skin malignant melanomas, and the greater the extent of conjunctival involvement the worse the prognosis for conjunctival malignant melanomas. The complications of cryotherapy are minor, but the follow-up period in this series is too short to comment on survival times.

Adult↗

Effect of oxygen tension on the quantities of procollagenase-activating angiogenic factor present in the developing kitten retina.

Maintenance of newborn kittens in an oxygen rich atmosphere followed by a recovery period in a normal atmosphere mimicked the effects of the human disease retrolental fibroplasia. The retinas of such kittens contained significantly raised levels of low molecular weight angiogenic material (as measured by procollagenase activation) when compared with those of a control group of kittens.

Angiogenesis Inducing Agents↗

Future opportunities for drug therapy in peptic ulcer disease.

Attempts to develop antisecretory agents showing a significant increase in potency and duration of action over currently available H2 antagonists have had to contend with the problem of gastric tumour induction during long-term toxicity testing in rats, and their clinical future is currently uncertain. A number of potential pharmacological approaches to ulcer therapy, unrelated to inhibition of acid secretion, can be identified upon which to base the search for new antiulcer drugs. Whether such agents are a commercially attractive proposition is debatable, given the disappointing early clinical experience with prostaglandins in acute healing studies together with the established efficacy and safety of cimetidine and ranitidine. Indeed it is difficult to foresee any agent challenging the dominance of H2 blockers during this century. By analogy with beta adrenoceptor antagonists, it is likely that new developments will take the form of some additions to the H2 range, improved formulations, additional indications, and possibly combination therapies with other drugs. Future research must address the different aetiologies of gastric and duodenal ulcer and other acid-peptic conditions as well as attempting to cure the disease rather than simply heal the ulcer. Advances in fields traditionally unrelated to peptic ulcer research such as growth regulation, vascular disorders, and inflammation may well provide the most profitable basis for longer-term drug research. Finally, animal toxicity studies with second generation antisecretory agents have inadvertently focused attention on gastric cancer, a disease where the need for new drugs is unquestionable.

Animals↗

Endogenous E-type prostaglandins in regulation of basal alkaline secretion by amphibian duodenum in vitro.

Segments of proximal duodenum from Rana catesbeiana, stripped of external muscle and mounted as a tube in a glass chamber, alkalinized the luminal-side bathing solution at a rate of 1.70 +/- 0.16 microEq/cm . h (n = 18, gross surface area approximately 1.5 cm2/cm). A single change of the serosal-side bathing solution for fresh solution reduced the rate of titratable alkaline secretion, which achieved a new steady state after 45 min amounting to 66% +/- 2% of the initial rate; transmucosal potential difference (lumen negative) fell from 10.6 +/- 1.2 to 8.8 +/- 1.1 mV. Concentrations of E-type prostaglandins in the serosal-side solution measured by radioimmunoassay were 8.5 nM (3 ng/ml) before, 0.17 nM 5 min after, and 1.7 nM 90 min after the solution change (n = 8). Reapplication of the original bathing solution 90 min after the initial change reestablished original secretory rate and potential difference. The increases in alkaline secretion and potential difference were comparable in magnitude and profile to those induced by serosal administration of 10 nM prostaglandin E2. Addition of the metabolic inhibitor 2,4-dinitrophenol (100 microM, serosal side) reduced basal alkaline secretion to 30% +/- 7% of the initial rate and abolished the potential difference (n = 8). These data demonstrate that endogenous prostaglandin E production by an isolated preparation of amphibian duodenum accounts for a proportion of alkaline secretion that is equivalent to 50% of metabolism-dependent basal secretion.

2,4-Dinitrophenol↗

Cerebral and retinal vascular changes in systemic lupus erythematosus.

A 16-year-old white boy with acute systemic lupus erythematosus (SLE) who presented with chorea and florid retinopathy died in renal failure three months after diagnosis. Pathological studies revealed two types of lesion in both the cerebral and ocular vessels. Some meningeal and choroidal vessels showed a typical vasculitis with fibrinoid necrosis, whereas other meningeal and retinal vessels were occluded by amorphous hyaline material in the absence of vasculitis.

Adolescent↗