Publications by authors named "Duncan I"

The Long Evans shaker (les) rat is a myelin basic protein (MBP) mutant that exhibits severe central nervous system (CNS) dysmyelination. We used a combination of immunohistochemistry, immunoblot and Northern blot analyses to determine the effect of MBP deficits on the expression of other CNS myelin genes in this mutant. Immunohistochemistry revealed a marked reduction in all major myelin proteins and differences in their intracellular distribution.

View Article and Find Full Text PDF

During the last few years, the therapeutic use of stem and progenitor cells as a substitute for malfunctioning endogenous cell populations has received considerable attention. Unlike their current use in animal models, the introduction of therapeutic cells in patients will require techniques that can monitor their tissue biodistribution noninvasively. Among the different imaging modalities, magnetic resonance (MR) imaging offers both near-cellular (i.

View Article and Find Full Text PDF

Abciximab is one of a new class of platelet aggregation inhibitors that has to date been used mainly in the management of acute coronary ischaemic syndromes or during cardiac intervention for the prevention and treatment of acute vessel occlusion during and after angioplasty or stent placement. More recently, it has begun to play a similar role in neurointerventional work. Its administration during acute stent or vessel occlusions has usually been via systemic intravenous infusion.

View Article and Find Full Text PDF

The cuticle of the adult abdomen of Drosophila is produced by nests of imaginal histoblasts, which proliferate and migrate during metamorphosis to replace the polyploid larval epidermal cells. In this report, we present a detailed description of the expression of four key patterning genes, engrailed (en), hedgehog (hh), patched (ptc), and optomotor-blind (omb), in abdominal histoblasts during the first 42 h after pupariation, a period in which the adult pattern is established. In addition, we describe the expression of the homeotic genes Ultrabithorax, abdominal-A, and Abdominal-B, which specify the fates of adult abdominal segments.

View Article and Find Full Text PDF

We have explored the use of minocycline, a tetracycline with antiinflammatory properties, to treat chronic relapsing-remitting experimental allergic encephalomyelitis, an animal model of multiple sclerosis. Therapeutic treatment with minocycline dramatically suppresses ongoing disease activity and limits disease progression. Disease suppression is associated with immune deviation in the periphery and with suppression of the inflammatory cascade in the central nervous system.

View Article and Find Full Text PDF

Tensin is a focal adhesion molecule that binds to actin filaments and participates in signaling pathways. In this study, we have characterized a previously undocumented tensin family member, tensin2/KIAA 1075. Human tensin2 cDNA encodes a 1,285-aa sequence that shares extensive homology with tensin1 at its amino- and carboxyl-terminal ends, which include the actin-binding domain, the Src homology 2 (SH2) domain, and the phosphotyrosine binding (PTB) domain.

View Article and Find Full Text PDF

Magnetic resonance (MR) tracking of magnetically labeled stem and progenitor cells is an emerging technology, leading to an urgent need for magnetic probes that can make cells highly magnetic during their normal expansion in culture. We have developed magnetodendrimers as a versatile class of magnetic tags that can efficiently label mammalian cells, including human neural stem cells (NSCs) and mesenchymal stem cells (MSCs), through a nonspecific membrane adsorption process with subsequent intracellular (non-nuclear) localization in endosomes. The superparamagnetic iron oxide nanocomposites have been optimized to exhibit superior magnetic properties and to induce sufficient MR cell contrast at incubated doses as low as 1 microg iron/ml culture medium.

View Article and Find Full Text PDF

The remarkable developmental potential and replicative capacity of human embryonic stem (ES) cells promise an almost unlimited supply of specific cell types for transplantation therapies. Here we describe the in vitro differentiation, enrichment, and transplantation of neural precursor cells from human ES cells. Upon aggregation to embryoid bodies, differentiating ES cells formed large numbers of neural tube-like structures in the presence of fibroblast growth factor 2 (FGF-2).

View Article and Find Full Text PDF

The multidrug resistant protein MDR-1 has been associated with the resistance to a wide range of anti-cancer drugs. Taxol is a substrate for this transporter system and is used in the treatment of a wide range of human malignancies including lung, breast and ovarian cancer. We have generated a series of ovarian cell lines resistant to this compound, all of which overexpress MDR-1 through gene amplification.

View Article and Find Full Text PDF

Background: DISC-hGMCSF is a gH-deleted HSV-2 based vector expressing human GM-CSF that is being developed for cancer immunotherapy. To support first clinical use, a range of preclinical safety studies were performed using DISC-hGMCSF in addition to DISC-murine-GMCSF and the backbone vector, TA-HSV.

Methods: The toxicity of the DISC vectors was assessed by repeated dose, neurovirulence and neuroinvasiveness studies in mice, and by safety studies in rabbits, guinea pigs and athymic nude mice.

View Article and Find Full Text PDF

We have isolated and characterized a unique glial-restricted precursor cell (GRP) from the embryonic spinal cord. Clonal analysis demonstrated that these cells are able to generate oligodendrocytes and two distinct type of astrocytes (type 1 and type 2) when exposed to appropriate signals in vitro. We now show that many aspects of these cells are retained in vivo.

View Article and Find Full Text PDF

During oligodendrocyte development, signals relevant to process formation must be transduced into appropriate changes in cytoskeletal organization. We have explored how microtubules and microfilaments interact during the outgrowth and branching of oligodendrocyte processes in culture. We observed that microfilaments are enriched in the peripheral region beneath the plasma membrane and constitute the major cytoskeletal element at the leading edge of the process, which is also enriched in the B-isoform of the non-muscle myosin II heavy chain.

View Article and Find Full Text PDF

The relationship between microglial activation and dysmyelination/demyelination was analyzed in a long-lived myelin mutant, the Long Evans shaker (les) rat, which exhibits early dysmyelination and a later loss of abnormal myelin sheaths. A microglial reaction characterized by progressive morphological transformation and increasing cell density was localized exclusively to white matter during postnatal 2-4 weeks, suggesting a microglial response to dysmyelination and oligodendroglial pathology. A further microglial reaction as marked by microglial expression of MHC II and a concomitant expression in the brain and spinal cord of mRNA for interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) began around 4 weeks when the remaining myelin was lost.

View Article and Find Full Text PDF

To understand how the differentiation of stem cells to oligodendroglial progenitors is regulated, we established cultures of neural stem cells from neonatal rat striatum in the presence of epidermal growth factor (EGF) as free-floating neurospheres that were then exposed to an increasing amount of B104 cell-conditioned medium (B104CM). The resultant cells proliferated in response to B104CM but no longer to EGF. In vitro analysis and transplantation studies indicated that these cells were committed to the oligodendroglial lineage, and they were thus referred to as oligospheres.

View Article and Find Full Text PDF

The apparent diffusion tensor (ADT) was measured in excised and fixed spinal cords from myelin-deficient (md) rats and age-matched controls. These data were used to obtain the principal diffusivities of the ADT, and also the scalar invariant parameters _D (averaged principal diffusivity) and A(sigma) (anisotropy index) for four white matter and two gray matter regions. The results for white matter regions showed that the principal diffusivities were significantly higher for md animals, and while the _D was increased in tissue from md animals, the A(sigma) was found to be decreased.

View Article and Find Full Text PDF

The taiep rat is a myelin mutant in which initial hypomyelination is followed by progressive demyelination of the CNS. An in vitro study suggests that accumulation of microtubules within oligodendrocytes is the cause of the taiep myelin defects (Song et al., 1999).

View Article and Find Full Text PDF

Cervical scrapes from 116 British women referred with cervical cancer were tested for the presence of high oncogenic risk human papillomavirus (HPV) genotypes (HPV(hr)). Ninety-four per cent of the scrapes had one or more of these virus types and 66% were HPV16-positive. HPV18 was more frequent in adenocarcinoma.

View Article and Find Full Text PDF

Sexually dimorphic abdominal pigmentation and segment morphology evolved recently in the melanogaster species group of the fruitfly Drosophila. Here we show that these traits are controlled by the bric à brac [corrected] (bab) gene, which integrates regulatory inputs from the homeotic and sex-determination pathways. bab expression is modulated segment- and sex-specifically in sexually dimorphic species, but is uniform in sexually monomorphic species.

View Article and Find Full Text PDF