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Biomedical subjects

M Loughnan

Publications and source records attributed to M Loughnan.

13 recordsLinked to original sources
PubMed2000

Management of alkali burns : an 11-year retrospective review.

OBJECTIVE: To review the spectrum of patients with alkali burns admitted over an 11-year period and to assess the clinical outcomes after the introduction of a standard alkali burn treatment protocol. DESIGN: Retrospective nonrandomized comparative study. PATIENTS AND INTERVENTIONS: A total of 121 patient records with alkali burns (n = 177 eyes) admitted to a tertiary hospital between 1987 and 1998 were reviewed. Eyes treated with a standard alkali burn treatment protocol, which included intensive topical steroids, ascorbate, citrate, and antibiotics, were compared with eyes treated by conservative management with antibiotics, and a short course of steroids. MAIN OUTCOME MEASURES: Time to corneal reepithelialization, final best-corrected visual acuity, and time to visual recovery, length of hospital stay, and complications were analyzed. RESULTS: The standard protocol tended to delay corneal reepithelialization by one day (P: = not significant) in eyes with grade 1 burns (n = 76) and by 2 days (P: = 0.04) in grade 2 burns (n = 52), with no difference in final visual outcome. There were 37 eyes with grade 3 burns. Those treated with the standard protocol showed a trend toward more rapid corneal reepithelialization. Twenty-seven of 29 (93%) eyes with grade 3 injuries achieved a final best-corrected visual acuity of 20/40 or better compared with 3 of 6 (50%) eyes not treated according to the standard protocol (P: = 0.02). Eyes with grade 4 burns (n = 12), whether treated with the standard protocol or not, required 10 to 12 weeks for corneal reepithelialization. There was no statistically significant difference in final visual acuity. CONCLUSIONS: On the basis of our findings, a number of recommendations can be made for the management of alkali injuries. Patients with a grade 1 or 2 injury do not require routine admission and do not benefit from the use of intensive treatment with ascorbate and citrate. A trend toward more rapid healing and a better final visual outcome were apparent in grade 3 burns, but our standard protocol made no difference in grade 4 burns.

Administration, Topical↗
PubMed1998

The 1.1 A resolution crystal structure of [Tyr15]EpI, a novel alpha-conotoxin from Conus episcopatus, solved by direct methods.

Conotoxins are valuable probes of receptors and ion channels because of their small size and highly selective activity. alpha-Conotoxin EpI, a 16-residue peptide from the mollusk-hunting Conus episcopatus, has the amino acid sequence GCCSDPRCNMNNPDY(SO3H)C-NH2 and appears to be an extremely potent and selective inhibitor of the alpha3beta2 and alpha3beta4 neuronal subtypes of the nicotinic acetylcholine receptor (nAChR). The desulfated form of EpI ([Tyr15]EpI) has a potency and selectivity for the nAChR receptor similar to those of EpI. Here we describe the crystal structure of [Tyr15]EpI solved at a resolution of 1.1 A using SnB. The asymmetric unit has a total of 284 non-hydrogen atoms, making this one of the largest structures solved de novo by direct methods. The [Tyr15]EpI structure brings to six the number of alpha-conotoxin structures that have been determined to date. Four of these, [Tyr15]EpI, PnIA, PnIB, and MII, have an alpha4/7 cysteine framework and are selective for the neuronal subtype of the nAChR. The structure of [Tyr15]EpI has the same backbone fold as the other alpha4/7-conotoxin structures, supporting the notion that this conotoxin cysteine framework and spacing give rise to a conserved fold. The surface charge distribution of [Tyr15]EpI is similar to that of PnIA and PnIB but is likely to be different from that of MII, suggesting that [Tyr15]EpI and MII may have different binding modes for the same receptor subtype.

Amino Acid Sequence↗
PubMed1998

alpha-conotoxin EpI, a novel sulfated peptide from Conus episcopatus that selectively targets neuronal nicotinic acetylcholine receptors.

We have isolated and characterized alpha-conotoxin EpI, a novel sulfated peptide from the venom of the molluscivorous snail, Conus episcopatus. The peptide was classified as an alpha-conotoxin based on sequence, disulfide connectivity, and pharmacological target. EpI has homology to sequences of previously described alpha-conotoxins, particularly PnIA, PnIB, and ImI. However, EpI differs from previously reported conotoxins in that it has a sulfotyrosine residue, identified by amino acid analysis and mass spectrometry. Native EpI was shown to coelute with synthetic EpI. The peptide sequence is consistent with most, but not all, recognized criteria for predicting tyrosine sulfation sites in proteins and peptides. The activities of synthetic EpI and its unsulfated analogue [Tyr15]EpI were similar. Both peptides caused competitive inhibition of nicotine action on bovine adrenal chromaffin cells (neuronal nicotinic ACh receptors) but had no effect on the rat phrenic nerve-diaphragm (muscle nicotinic ACh receptors). Both EpI and [Tyr15]EpI partly inhibited acetylcholine-evoked currents in isolated parasympathetic neurons of rat intracardiac ganglia. These results indicate that EpI and [Tyr15]EpI selectively inhibit alpha3beta2 and alpha3 beta4 nicotinic acetylcholine receptors.

Amino Acid Sequence↗
PubMed1998

Laser refractive surgery.

BACKGROUND: Refractive errors; myopia, hypermetropia and astigmatism, have traditionally been corrected by glasses and more recently contact lenses. For nearly 100 years surgical techniques to treat such disorders have also been developed. The latest of these are based upon the use of the excimer laser to ablate the corneal stroma either directly under the corneal epithelium (surface PRK) or under a flap of superficial stroma (LASIK). OBJECTIVE: To look at the development of laser refractive surgery and to put this in the context of appropriate and inappropriate indications for usage. DISCUSSION: While the development of such techniques has revolutionised the field of refractive surgery unrealistic expectations with regard to the outcome of such procedures may have been raised in recent advertising by some ophthalmologists and laser centres. The most important influence on the refractive outcome of such procedures is the pre-operative refraction. The best outcomes are seen with treating low degrees of myopia and/or astigmatism. Outcomes for treating high degrees of myopia or astigmatism are often disappointing. The treatment of hypermetropia remains experimental.

Humans↗
PubMed1997

Late recurrences and the necessity for long-term follow-up in corneal and conjunctival intraepithelial neoplasia.

PURPOSE: The purpose of the study was to elucidate the natural history of corneal-conjunctival intraepithelial neoplasia (CIN) and suggest treatment and follow-up guidelines. METHODS: The records of all histologically proven cases of CIN at the Royal Victorian Eye and Ear Hospital between 1979 and 1994 were reviewed. RESULTS: Seventy-nine eyes of 76 patients had a pathologic diagnosis of CIN and were observed for up to 15 years. The lesion recurred in 31 eyes (39%) overall. There was no statistical difference shown in the likelihood of recurrence based on histologic classification. Complete excision was attempted in each case. In 18 eyes, dysplastic cells were evident at the excision margin. Ten (56%) of these tumors recurred, compared to a 33% recurrence rate in completely excised lesions. The time to the first recurrence ranged from 33.0 days to 11.5 years between the first and second surgeries, with 11 lesions recurring after more than 4 years. Incompletely excised lesions reappeared more rapidly (average, 2.5 years) than did those with clear surgical margins (average, 3.8 years). Seven cases progressed to invasive squamous cell carcinoma and four cases led to blindness or removal of the eye. CONCLUSIONS: This study suggests that excision margin at the time of surgery is the most important factor in predicting recurrence. The slow growth of the recurrent lesions combined with the ever-present malignant potential leads the authors to suggest that all patients with a history of CIN warrant annual follow-up for the remainder of their lives.

Adult↗
PubMed1992

Dependence of hypotensive effect of neuropeptide-Y 18-36 fragment on intact vagus nerves.

Effects of neuropeptide Y (NPY 2.35-4.7 nmol) and the fragment NPY 18-36 (3.6-36 nmol) were studied in anaesthetized rats before and after vagotomy for actions on blood pressure (a postjunctional action) and on the change in pulse interval evoked by stimulation of the cut, peripheral vagus nerve (a prejunctional action). In intact rats NPY increased blood pressure. Low doses of NPY 18-36 (2.3-4.7 nmol) also increased blood pressure slightly but higher doses only transiently increased blood pressure and this was followed by a prolonged decrease in blood pressure. In vagotomised rats NPY increased blood pressure and attenuated cardiac vagal action. In higher doses the presynaptic effect of NPY 18-36 was more marked than its pressor action. NPY 18-36 (3.6-36 nmol) also increased blood pressure and attenuated cardiac vagal action. Thus, we conclude that the hypotensive action of NPY 18-36 depends on the intact vagus nerves: in the vagotomised rat NPY 18-36 has similar biological activity to NPY, but with reduced potency. To examine further the mechanism of hypotensive action of NPY 18-36 arterial rings from the central artery of the rabbit ear were also tested for direct actions of the peptides. This preparation is also suitable for testing any potentiation of contraction evoked by injection of noradrenaline. Neither NPY nor NPY 18-36 caused direct constrictor action in concentrations up to 10 microM. NPY 18-36 had no relaxing effect on constricted arterial rings.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Isolation, partial sequence and asynchronous appearance during lactation of lysozyme and alpha-lactalbumin in the milk of a marsupial, the common ringtail possum (Pseudocheirus peregrinus).

1. Lysozyme and alpha-lactalbumin from the milk of the common ringtail possum have been purified and partially sequenced. 2. The lysozyme had similar enzymic activity to the c-type lysozyme of the domestic hen and 43% homology over the N-terminal 49 residues. 3. alpha-Lactalbumin was present in the milk in two biologically active forms; the more acidic form had 66% sequence homology with the N-terminal 35 residues of red-necked wallaby, 54% with human and 43% with bovine alpha-lactalbumin. 4. SDS polyacrylamide-gel electrophoresis of milk samples showed that alpha-lactalbumin was present in the milk throughout lactation but that lysozyme first appeared only in mid-lactation. The implications of this functional adaptation are discussed.

Amino Acid Sequence↗
PubMedDate not supplied

A strategy for obtaining active mammalian enzyme from a fusion protein expressed in bacteria using phospholipase A2 as a model.

An active preparation of human phospholipase A2 (PLA2) was made after expression as an insoluble fusion protein in Escherichia coli. The new key elements required for PLA2 isolation were the maintenance of the fusion protein in solution after the initial solubilization and the use of a tryptophan cleavage procedure for regeneration of native PLA2 from the fusion protein. The fusion protein was composed of a beta-galactosidase leader peptide incorporating six consecutive threonine residues to aid in insoluble inclusion body formation, followed by a tryptophan adjacent to the N-terminus of PLA2. The fusion protein was purified from cell lysates, and the leader peptide was cleaved on the C-terminal side of the tryptophan residue with N-chlorosuccinimide. The released PLA2 was refolded and renatured to produce an enzyme with activity comparable to that of other phospholipases A2.

Amino Acid Sequence↗