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Biomedical subjects

D J Moran

Publications and source records attributed to D J Moran.

16 recordsLinked to original sources

Cataract, cost: curious questions.

An investigation of the pricing of implantable prosthetic devices in Australia reveals some alarming practices. A governmental mechanism exists to prop up the pricing of 7500 listed devices to levels that are unacceptably high by world standards. Private hospitals and doctors are able, legally, to profit by marking up the cost of these devices from the market price to this artificially inflated price. Even the open market prices of implantable prosthetic items, such as intra-ocular lenses, are high by international standards. In a time of budgetary constraint for health spending and rapidly increasing use of these devices, these issues urgently need to be addressed in Australia.

Australia↗

Maternal plasma progesterone levels fall after rectal administration of estriol.

Maternal plasma unconjugated estriol (E3), progesterone (P), and estradiol (E2) levels were measured at 30-min intervals for 6 h after the rectal administration of a 100-mg E3 or placebo suppository to 28 pregnant women at term. Mean plasma unconjugated E3 levels showed a sustained rise approximately 50% above baseline levels 2 h after rectal E3 administration (P < 0.003). There was a simultaneous sustained fall of approximately 20% in mean plasma P levels (P < 0.05); the fall in mean P levels was greatest in the women who delivered within 48 h of E3 suppository administration (P < 0.05). There was no change in mean plasma E2 levels. This study demonstrates that a significant rapid increase in maternal circulating E3 levels can be obtained by the rectal administration of E3, and that this increase in maternal E3 levels is associated with a decrease in circulating P levels.

Adult↗

Subcellular distribution of tyrosinase and tyrosinase-related protein-1: implications for melanosomal biogenesis.

Are tyrosinase, encoded at the albino locus, and tyrosinase-related protein-1 (TRP-1), encoded at the brown locus, similarly distributed in melanocytes? We determined the subcellular distribution of tyrosinase and TRP-1 using density fractionation of postnuclear supernatants from mouse melanoma cells of defined genotype followed by immunoblotting with specific antipeptide sera. In highly melanized cells, the majority of tyrosinase cosedimented on Percoll density gradients with visible melanin and with the peak of DOPA incorporation, confirming its presence predominantly in stage III-IV melanosomes. In contrast, the distribution of TRP-1 was limited to a less-dense melanosomal compartment, devoid of melanin. In amelanotic or minimally melanized cells, the majority of tyrosinase shifted into these lighter peaks. To explore a suspected relationship between lysosomes and melanosomes, we analyzed the distribution of lysosome-associated membrane protein-1 (LAMP-1). An overlap in the distribution of LAMP-1 and TRP-1 was demonstrated by immunomicroscopy and confirmed by immunoisolation. LAMP-1 was not present in the dense, melanin-rich melanosomal peak on gradient analysis. TRP-1 from melanoma cells homozygous for the brown mutation is not fully glycosylated, is more rapidly degraded, and is restricted in its distribution compared to its wild-type counterpart. In these mutant cells, all melanosomal compartments contain LAMP-1. Our results demonstrate that in wild-type cells the majority of tyrosinase eventually localizes to stage III-IV melanosomes. TRP-1 is limited to a less dense melanosomal compartment that is also LAMP-1 positive. The existence of this compartment suggests that it may represent a common step in the biogenesis of melanosomes and lysosomes.

Antigens, CD↗

Lysosome-associated membrane protein-1 (LAMP-1) is the melanocyte vesicular membrane glycoprotein band II.

Coated vesicles play a critical role in the process of melanogenesis. Antisera raised against a coated vesicle fraction from mouse melanoma cells recognize two major glycoprotein antigens, band I (47-55 kd) and band II (90-120 kd). We demonstrate that band II is lysosome-associated membrane protein 1 (LAMP-1) by the following criteria: 1) the molecular weight and abundance of LAMP-1 varies among tissues but is always identical to that of band II; 2) band II and LAMP-1 co-migrate in sucrose gradient sedimentation studies; 3) immunodepletion of cell extracts with antivesicle serum removes all LAMP-1; and 4) intact organelles immunoisolated with antivesicle serum contain band II and LAMP-1. Our results further confirm the long-suspected relationship between melanosomes and the lysosomal lineage of organelles.

Animals↗

Calcium in the developing Ambystoma neural axis shown by 3H and fluorescent chlortetracycline and atomic absorption spectrometry.

The calcium ion has been implicated in the mediation of the morphogenetic movements that occur during neural tube formation. The present study identifies high levels of calcium in the neuroepithelium of the neural plate, folds, and tube. These levels are substantially higher than those discerned elsewhere in the embryo. The calcium is localized in morphogenetically active regions by using the antibiotic chlortetracycline (CTC) which chelates calcium and is demonstrated in this investigation by both autoradiography and calcium-linked fluorescence. The specificity of CTC reaction for calcium in the developing neural axis is confirmed by EGTA competition. A comparison of the actual calcium levels in the developing neural axis (dorsal) with equivalently weighted ventral tissues was obtained by atomic absorption spectrometry (AAS). This method provides a total count of the calcium without any loss during tissue processing. For AAS, living tissues were precisely excised and immediately dessicated. Each tissue sample (dry weight 1.5 mg) was then solubilized for analysis. The spectrometric data reveal that the embryonic dorsal aspect forming the neural tube contains 57% more calcium than an equivalent weight of the ventral aspect.

Ambystoma↗

White noise and sleep induction.

We studied two groups of 20 neonates, between 2 and 7 days old, in a randomised trial. Sixteen (80%) fell asleep within five minutes in response to white noise compared with only five (25%) who fell asleep spontaneously in the control group. White noise may help mothers settle difficult babies.

Acoustic Stimulation↗

Cervical ligamentous instability in a canine in vivo model.

A canine in vivo model of midcervical ligamentous instability was developed by dividing the anterior longitudinal ligament, anulus fibrosus, and all posterior ligamentous structures including the ligamentum flavum. The natural history of healing in the model, the effect on its healing by an adjacent one-level arthrodesis, and the effect of a one-level arthrodesis on normal adjacent ligamentous structures were studied radiographically, mechanically, and histologically. The authors determined that healing takes place primarily by anterior scar formation in their instability model but not to a degree sufficient to recreate normal mechanical stability. After three months, healing in the model was not affected by an adjacent arthrodesis; however, acutely, instability apparently was increased as three animals became quadriplegic between the second and fourth postoperative days. Arthrodesis did not affect adjacent normal ligamentous structures, during this period. Incomplete healing in the authors' model supports those who advocate arthrodesis as the treatment of choice for destabilizing cervical ligamentous injury. The authors previously reported the case of a patient who sustained bilateral facet dislocations adjacent to an arthrodesed segment and questioned whether this resulted from a stress-concentrating effect. This study indicates that this could well have been the case acutely. Thus, inadvertent exclusion of an unstable segment from an arthrodesis has potentially catastrophic results. Finally, the authors also have previously questioned whether arthrodesis of a midcervical segment could lead to instability of adjacent normal segments. This project does not support such a concern, at least for the three postoperative months of study.

Animals↗

The effects of ethanol on embryonic actin: a possible role in teratogenesis.

When the neural crest is cultured in the long or short term presence of ethanol, monoclonal anti-actin reveals the development of a disorganized actin cytoskeleton. In the long term, many cells fail to differentiate morphologically, whereas in the short term already differentiated cells rapidly alter their shape and their cell-to-cell contacts.

Abnormalities, Drug-Induced↗

Effects of ethanol on the cytoskeleton of migrating and differentiating neural crest cells: possible role in teratogenesis.

Neural crest mesenchyme participates in the formation of craniofacial structures that are malformed in the fetal alcohol syndrome (FAS). We studied the effects of continuous ethanol treatment (0.05%, 0.10%, 0.15%, 0.20%) on developing neural crest cells in vitro. These cells migrate, but many fail to develop their usual arborized dendrites. Exposure of well differentiated dendritically arborized cells to ethanol only on day 6 for 2 hr and 20 min results in rapid cell retraction and alteration in cell-to-cell contacts. Longer treatment causes loss of substratum adhesion. Monoclonal antibodies against tubulin and actin reveal that these ethanol-induced morphological changes are related to disruption of microtubules and microfilaments. Thus ethanol may exert at least part of its teratogenic effect by interferring with the structure and function of the cytoskeleton.

Ambystoma↗

Pterygium and ultraviolet radiation: a positive correlation.

Pterygium has long been believed to be an environmental disease, Ultraviolet (UV) radiation playing a major role in its development. In examination of more than 100 000 Aborigines and non-Aborigines in rural Australia a strong positive correlation between climatic UV radiation and pterygium prevalence was found, providing further evidence of a causal relationship. In addition interesting differences were found in prevalence in the different racial groups and between the sexes. These differences may be explained by differences in lifestyle.

Adolescent↗

Ear disease in rural Australia.

Aboriginals in rural Australia have a higher over-all prevalence of otitis media and tympanic scarring than non-Aboriginals. Over-all, 11% of 60273 Aboriginals had otitis media and 29.1% had scarring in one or both ears, although the rates varied widely in different regions. Of 37713 non-Aboriginals, 1.1% had otitis media and 13.5% had scarring in one or both ears. Children less than 10 years of age had the highest prevalence of otitis media in both racial groups. A lower proportion of the otitis media was "glue ear" in Aboriginals than in non-Aboriginals. The pattern of prevalence of otitis media and scarring suggests that otitis media occurs more frequently and lasts longer in Aboriginals. Scarring rates suggest that otitis media is less frequent now than in the past in non-Aboriginals, but is more frequent in Aboriginals.

Adolescent↗

A scanning electron microscopic and x-ray microanalytic study of cell surface material during amphibian neurulation.

Treatment with lanthanum (La3+) after fixation in phosphate (PO4-3)-buffered glutaraldehyde results in the deposition of a cell surface material (CSM) primarily on the developing urodele amphibian neural axis. X-ray probe microanalysis indicates that calcium (CA2+) levels are considerably higher in the neural fold region. La3+ displaces Ca2+ from negatively-charged moieties on biological membranes. Once bound, La3+ likely interacts with residual phosphate(s) resulting in deposition of CSM. Elemental X-ray microanalysis shows CSM contains mostly lanthanum and phosphorus. The high level of regional La3+ binding is correlated with inherently greater Ca2+ levels in the developing neural axis.

Ambystoma↗

A scanning electron microscopic and flame spectrometry study on the role of Ca2+ in amphibian neurulation using papaverine inhibition and ionophore induction of morphogenetic movement.

SEM observations reveal that papaverine, which interferes with Ca2+ flux, inhibits neural fold formation causing a flattening of the cellular surface and a broadening of cellular junctions. Ionophore A23187 and EGTA both counter this effect promoting a rapid cellular constriction which results in the formation of neural ridges and folds as individual cells become uplifted and ruffled. Flame spectrometry data indicate that as Ambystoma maculatum or mexicanum embryos neurulate Ca2+ is released to the medium, a condition which is impeded by papaverine. Ionophore A23187 induces Ca2+ influx whereas EGTA induces an efflux. Since both agents affect similar morphological changes it is suggested that the availability of free Ca2+ is crucial in controlling the morphogenetic movements of neurulation. It is now apparent that neuro-axial development in the urodele is accompanied by a Ca+2 efflux, but the mechanism(s) responsible for the ion's release is unknown.

Ambystoma↗