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Biomedical subjects

D I Wilson

Publications and source records attributed to D I Wilson.

At least 19 recordsLinked to original sources
PubMed2006

Effects of drying technique on extrusion-spheronisation granules and tablet properties.

Extrusion-spheronisation was used to generate smooth, highly spherical granules of a microcrystalline cellulose/propyl gallate/water paste. Freeze-drying retained the shape and size of the granules, whereas oven-drying produced roughened granules due to the uneven shrinkage of the wet powders. Compaction of one size fraction indicated that the granule strength differed noticeably, with the oven-dried samples producing tablets of lower voidage for a given applied compaction pressure. There was a reasonable correlation between tablet crushing strength and voidage. Major differences were observed in tablet dissolution, with the freeze-dried material exhibiting a two-regime behaviour and an initial dissolution rate constant an order of magnitude greater than the oven-dried form. Both the voidage and dissolution characteristics are postulated to be determined by the microstructure established during drying.

Antioxidants↗
PubMed2006

Liquid phase migration in the extrusion and squeezing of microcrystalline cellulose pastes.

Extensive movement of the liquid phase relative to the solids in solid-liquid pastes during extrusion forming is an undesirable process phenomenon. The impact of formulation and flow pattern on liquid phase migration (LPM) during extrusion of model pharmaceutical pastes (40-50 wt% microcrystalline cellulose/water) has been investigated by ram extrusion through square-entry and 45 degrees conical-entry dies, and by lubricated squeeze flow (extensional flow). Threshold velocities for LPM were observed in both configurations. Squeeze flow testing showed that dilation during extension can cause LPM, while ram extrusion featured both dilation effects and drainage due to compaction. The threshold velocities observed in the two configurations agreed when presented as characteristic shear rates. The threshold velocity increased with paste solids content.

Algorithms↗
PubMed2006

Human embryo and early fetus research.

Studies of human embryos and fetuses have highlighted developmental differences between humans and model organisms. In addition to describing the normal biology of our own species, a justification in itself, studies of early human development have aided identification of candidate disease genes mapped by positional cloning strategies, understanding pathophysiology, where human disorders are not faithfully reproduced by models in other species, and, more recently, potential therapies based on human embryonic stem and embryonic germ cells. In this article, we review these applications. We also discuss when and how to study human embryo and early fetuses and some of the regulations of this research.

Animals↗
PubMed2005

Chromosomal localization, genomic organization and evolution of the genes encoding human phosphatidylinositol transfer protein membrane-associated (PITPNM) 1, 2 and 3.

Eukaryotic proteins containing a phosphatidylinositol transfer (PITP) domain can be divided into two groups, one consisting of small soluble 35-kDa proteins and the other those that are membrane-associated and show sequence similarities to the Drosophila retinal degeneration B (rdgB) protein. The rdgB protein consists of four domains, an amino terminal PITP domain, a Ca2+-binding domain, a transmembrane domain and a carboxyl terminal domain that interacts with the protein tyrosine kinase PYK2. Three mammalian phosphatidylinositol transfer protein membrane-associated genes (PITPNM1, 2 and 3) with homology to Drosophila rdgB have previously been described and shown to be expressed in the mammalian retina. These findings and the demonstration that the rdgB gene plays a critical role in the invertebrate phototransduction pathway have led to the mammalian genes being considered as candidate genes for human eye diseases. In order to facilitate the analysis of these genes we have used radiation hybrid mapping and fluorescence in situ hybridization to localize the PITPNM2 and 3 genes to human chromosomes 12p24 and 17p13 respectively and hybrid mapping to confirm the localization of PITPNM1 to chromosome 11q13. We have also determined the genomic organization of both the soluble and membrane-associated Drosophila and human PITP domain-containing genes. Phylogenetic analysis indicates that the two groups arose by gene duplication that occurred very early in animal evolution.

Animals↗
PubMed2004

An NMR study of the freezing of emulsion-containing drops.

Various nuclear magnetic resonance (NMR) techniques were used to monitor the freezing behaviour of suspended 2-mm-diameter drops. The drops were composed of hydrocarbon oils emulsified in either water or water/sucrose mixtures. As such they were good model systems for the study of spray freezing, sharing structural similarities with potential products such as ice cream. In particular, simple 1H NMR spectroscopy was used to monitor and individually quantify the freezing or solidification behaviour of the various constituent species of the drops. In addition, the effect of freezing on the emulsion droplet size distribution (and hence emulsion stability) was also measured based on NMR self-diffusion measurements. The effect of freeze/thaw cycling was also similarly studied. The nucleation temperature of the emulsion droplets was found to depend on the emulsion droplet size distribution: the smaller the droplets, the lower the nucleation temperature. Emulsion droplet sizing indicated that oil-in-sucrose-solution emulsions were more stable, showing minimal coalescence, whereas oil-in-water emulsions showed significant coalescence during freezing and freeze/thaw cycling.

Journal Article↗
PubMed2004

The production of homogeneous extrudates of microcrystalline cellulose pastes.

The homogeneity of water-based microcrystalline cellulose (MCC) paste extrudates was investigated during ram extrusion as a function of ram velocity. Variations in the water content of the extrudates were caused by liquid phase migration within the paste. The evolution in water content was measured by sectioning and drying the extrudate, and the subsequent homogeneity was quantified by the standard error in water content. The homogeneity of the extrudates was found to decrease as the ram velocity decreased. This result was also inferred from the rate of increase of the extrusion pressure. The extrudate homogeneity was significantly improved by compensating for water migration in the barrel during the compaction stage. This was achieved using a non-uniform initial paste billet, created by packing the barrel with layers of paste of different water contents. This technique also produced a smaller variation in extrusion pressure over the ram displacement range, and a reduction in water loss from the upstream paste compact into the extrudate and/or through the apparatus tooling.

Cellulose↗
PubMed2004

Beta cell differentiation during early human pancreas development.

Understanding gene expression profiles during early human pancreas development is limited by comparison to studies in rodents. In this study, from the inception of pancreatic formation, embryonic pancreatic epithelial cells, approximately half of which were proliferative, expressed nuclear PDX1 and cytoplasmic CK19. Later, in the fetal pancreas, insulin was the most abundant hormone detected during the first trimester in largely non-proliferative cells. At sequential stages of early fetal development, as the number of insulin-positive cell clusters increased, the detection of CK19 in these cells diminished. PDX1 remained expressed in fetal beta cells. Vascular structures were present within the loose stroma surrounding pancreatic epithelial cells during embryogenesis. At 10 weeks post-conception (w.p.c.), all clusters containing more than ten insulin-positive cells had developed an intimate relationship with these vessels, compared with the remainder of the developing pancreas. At 12-13 w.p.c., human fetal islets, penetrated by vasculature, contained cells independently immunoreactive for insulin, glucagon, somatostatin and pancreatic polypeptide (PP), coincident with the expression of maturity markers prohormone convertase 1/3 (PC1/3), islet amyloid polypeptide, Chromogranin A and, more weakly, GLUT2. These data support the function of fetal beta cells as true endocrine cells by the end of the first trimester of human pregnancy.

Animals↗
PubMed2004

Design of reverse osmosis (RO) water treatment networks subject to fouling.

Identifying the optimal design for an RO membrane network is not straightforward when significant fouling occurs. The most robust optimal network design will feature the minimal capital and operating costs over the anticipated lifetime of the plant, and is therefore strongly dependent on the fouling behaviour and associated mitigation. This study considers the case where the likely fouling behaviour is known and investigates how to incorporate this knowledge into the design and operation of a network. The optimisation task is complicated by the highly non-linear nature of the problem owing to membrane behaviour, fouling behaviour, network interactions and operating parameter constraints (pressures and flows). In this work, fouling is modelled as an exponential decay in membrane permeability. Three optimisation approaches are used to evaluate candidate networks: (i) laborious comparison of pre-selected individual network designs; (ii) deterministic gradient search methods, and (iii) a simulated-annealing-based hybrid stochastic-deterministic method. All of the approaches consider various configurations of a two-stage network with a maximum of three membrane units in each stage, represented in a superstructure model. The results from the approaches are compared and the most effective method for network design is discussed.

Biofilms↗
PubMed2003

The reliability of digital images when used to assess burn wounds.

Sixty burn wounds were assessed in person. The same observer later assessed them using digital images of different sizes. The file sizes tested were 2.25, 5.5 and 9 MByte per image. There was good agreement between the diagnoses of burn depth made using the digital images and those made in person, with kappa scores of 0.53-0.60. There were no major differences between the three file sizes. The assessments made of the partial-thickness burns showed a lower rate of agreement between the in-person and the digital image assessments and for these burns the 2.25 MByte images were apparently as good or better than the larger images. There was little difference between the three file sizes in terms of observer confidence, usefulness of the location shot, or perceived image quality. There was no significant advantage in using larger file sizes to assess burn wounds.

Burns↗
PubMed2002

Novel SOX9 expression during human pancreas development correlates to abnormalities in Campomelic dysplasia.

Haploinsufficiency of SOX9, which encodes a homeodomain transcription factor, results in Campomelic dysplasia. Classical features of this disorder (e.g. skeletal dysplasia and 46,XY sex reversal) are in concordance with SOX9 expression profiles during human embryonic development. We report the robust expression of SOX9 throughout the pancreas during human embryogenesis, at levels of detection equivalent to the developing skeleton and testis. In the early foetal period, SOX9 expression declines and, in particular, is not apparent within the pancreatic islets. In keeping with this profile, examination of three cases with Campomelic dysplasia revealed abnormal pancreatic morphology. Epithelial cells were less densely packed within the mesenchymal stroma and islets less clearly formed with variable expression of hormone and beta cell markers. Taken together, these data indicate a novel potential role for SOX9 in pancreas development during human embryogenesis and early foetal life.

Bone Diseases, Developmental↗
PubMed2002

Steroidogenic enzyme expression within the adrenal cortex during early human gestation.

Aberrant adrenocortical function during the first trimester of human fetal development underlies the severe virilization of congenital adrenal hyperplasia due to cytochrome P450 21-hydroxylase (CYP21) deficiency. Although valuable information of human adrenocortical development after 12 weeks gestation is available, less is known earlier in pregnancy. In our studies, the adrenal cortex was first detected in human embryos by hematoxylin and eosin staining at 33 days post-conception (dpc) with distinction between the definitive and fetal zones possible at 52 dpc. Vascular development was apparent within the adrenal gland at 41 dpc. CYP11A and CYP17 were expressed centrally within the fetal zone at 50 dpc and all later time points during the first trimester. Weaker CYP11A immunoreactivity also was visible in the outer region of the adrenal cortex consistent with definitive zone expression. In this location, immunoreactivity was observed for 3beta-hydroxysteroid dehydrogenase and the proliferation marker, Ki67. These data raise the possibility of de novo cortisol biosynthesis during the first trimester of human development and are relevant to the pathophysiology of 46,XX virilization in CYP21 deficiency.

3-Hydroxysteroid Dehydrogenases↗
PubMed2001

A gene trap integration provides an early in situ marker for hepatic specification of the foregut endoderm.

We report the characterization of a gene trap integration that provides an in situ marker for one of the earliest events in liver development. Expression of the reporter gene is observed at the nine-somite stage in the hepatic field of the foregut endoderm. At 10.5 days post-coitus expression is observed exclusively and at high levels in the majority of cells in the developing liver bud. As development proceeds the proportion of expressing cells decreases with expression in adult liver being restricted to a few sporadic cells. This therefore provides the earliest, most specific in situ marker of the hepatic lineage reported to date and will be useful in the further characterization of the inductive events involved in hepatic specification. Molecular characterization of the gene trap insertion suggests that the expression pattern is the result of alternative promoter use in the ankyrin repeat-containing gene, gtar.

Amino Acid Sequence↗
PubMed2001

Differences between human and mouse alpha-fetoprotein expression during early development.

Alpha-fetoprotein (AFP) is the major serum protein during development. AFP is one of the earliest proteins to be synthesised by the embryonic liver. The synthesis of AFP decreases dramatically after birth and only trace amounts are expressed in the adult liver. The tissue distribution of AFP in early human embryogenesis has not been defined. We have studied the expression pattern of AFP mRNA in human and mouse embryos by in situ hybridisation. In humans, AFP is expressed in the hepatic diverticulum at 26 d postovulation as it differentiates from the foregut endoderm (i.e. in the most primitive hepatocytes). It is also expressed in the endoderm of the gastrointestinal tract and in the yolk sac at this age. AFP is subsequently expressed in the mesonephros and transiently in the developing pancreas. In the mouse, no expression of AFP was observed in the mesonephros but other sites of expression were similar. Thus AFP has a distinct temporospatial expression pattern during the embryonic period and this differs between human and mouse species. It is interesting that AFP is expressed by tumours such as primitive gastrointestinal, renal cell and pancreatic tumours as well as those of hepatocyte origin. This distribution reflects the sites of AFP expression during development.

Animals↗