Allelic loss on chromosomes 8p, 22q and 18q (DCC) in human prostate cancer

Previous studies have suggested the involvement of tumour-suppressor genes on chromosomes 8p, 22q and 18q (DCC) in prostate cancer. The aim of this study was to further characterize these regions. We investigated 20 polymorphic regions on the 3 chromosome arms in 43 cancers and 10 cases of benign prostatic hyperplasia (BPH). Allelic loss was observed in 72% of cancers on 8p, 16% on 22q and 24% at DCC. For BPH, loss was observed in 20% on 8p and in 12% at DCC. The low incidence of LOH on 22q implies that this locus has no significant role in prostate carcinogenesis. At DCC, although the overall incidence was low, tumours with LOH were mostly of high grade or had metastases, suggesting a role for this gene in prostate cancer progression. On chromosome 8p, 29% of cancers had deletions at the LPL locus on 8p22 and 60% had deletions within a region flanked by the markers D8S339 and ANKI on 8p11.1-p21.1. Within this region, 2 distinct areas of allelic loss were observed, at one or both ANKI and D8S255, and in the region defined by the markers D8S259-D8S505. For the regions 8p22 and ANKI-D8S255, tumours with metastases had a greater frequency of LOH compared to non-metastasizing tumours, suggesting the presence of putative metastasis-suppressor genes in these regions. © 1996 Wiley-Liss, Inc.     

Do People With Diabetes Wear Their Prescribed Footwear?

Ill-fitting shoes are a common cause of foot ulceration in people with diabetes mellitus and prescribed footwear is used to prevent and treat such lesions. However, footwear is only effective if worn and the shoes supplied have to be acceptable to the patient. A study of patients who were supplied with footwear at a diabetic foot clinic was conducted using face-to-face interviews and a structured questionnaire, to assess footwear usage and patient preference. Of the 50 subjects who participated, only 11 (22 %) regularly wore their prescribed footwear and 19 (38 %) subjects wore slippers indoors. Only 12 subjects (24 %) were aware of the cost of their shoes. Most subjects were happy with their footwear and the service which was provided, whereas 9 (18 %) disliked the style of their shoes and stated that they were not cosmetically acceptable. Thus, although expensive footwear is supplied to patients to prevent and treat foot ulcers, it may not be used as intended. If shoes are to be worn, a wider choice of footwear should be available to the wearer.     

Localization of a nicotinic acetylcholine receptor-like antigen in the thoracic nervous system of embryonic locusts,Schistocerca gregaria

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequent immunoblotting of neuronal membrane proteins derived from thoracic ganglia of adult Locusta and Schistocerca reveal that a polyclonal antiserum raised against the Locusta nicotinic acetylcholine receptor (nAChR), binds strongly to an identical polypeptide band corresponding to 65 kDa in both locust species. This polyclonal antiserum was used to analyze the distribution of antigenic sites within the developing thoracic central nervous system of Schistocerca embryos. Axonal outgrowths from the earliest differentiated neurons are first labeled between 30% and 35% development. By 40% to 45% development, labeled granules appear in the cytoplasm of neuronal cell bodies. When the developing neuropil is first enclosed at approximately 45% to 50% development, it appears uniformly labeled, but by 55% development, unlabeled areas appear that represent the sites of future tracts and commissures. By 75%, an adult pattern of neuropil immunogenicity is established in which synaptic regions are stained but tracts and commissures are not. This suggests that during the early development of the thoracic nervous system nAChR-like antigenic sites are evenly distrubuted, but later become concentrated in the developing synaptic areas. © 1995 Willy-Liss, Inc.     

Mood change following an acute delay of sleep

A phase advance of some circadian rhythms (e.g., body temperature and rapid eye movement [REM] sleep propensity) relative to the sleep-wake cycle is thought to be implicated in the pathophysiology and pathogenesis of some affective disorders. Since this phase disturbance can be induced in normal subjects by acutely delaying their sleep onset, it follows that the outcome of this experimental procedure should resemble the symptoms of depressive illness. This hypothesis was tested by imposing a 6-hour phase delay of sleep in 10 young male subjects. There were reliable changes in observers' ratings of mood and in some self-report measures. For the most part, the effect was modest, being largely confined to variations within normal limits. Two of the subjects, however, were noticeably depressed when interviewed after either the first or the second night of phase shift.     

An alginate-based encapsulation system for delivery of therapeutic cells to the CNS

Treatment options for neurodegenerative conditions such as Parkinson''s disease have included the delivery of cells which release dopamine or neurotrophic factors to the brain. Here, we report the development of a novel approach for protecting cells after implantation into the central nervous system (CNS), by developing dual-layer alginate beads that encapsulate therapeutic cells and release an immunomodulatory compound in a sustained manner. An optimal alginate formulation was selected with a view to providing a sustained physical barrier between engrafted cells and host tissue, enabling exchange of small molecules while blocking components of the host immune response. In addition, a potent immunosuppressant, FK506, was incorporated into the outer layer of alginate beads using electrosprayed poly-ε-caprolactone core–shell nanoparticles with prolonged release profiles. The stiffness, porosity, stability and ability of the alginate beads to support and protect encapsulated SH-SY5Y cells was demonstrated, and the release profile of FK506 and its effect on T-cell proliferation in vitro was characterized. Collectively, our results indicate this multi-layer encapsulation technology has the potential to be suitable for use in CNS cell delivery, to protect implanted cells from host immune responses whilst providing permeability to nutrients and released therapeutic molecules.

Novel composite cell encapsulation system: dual-layer, micro-scale beads maintain cell survival while releasing immunomodulatory FK506 in a sustained manner. This biotechnology platform could be applicable for treatment of CNS and other disorders.     

Mechanisms of endothelin 1-stimulated proliferation in colorectal cancer cell lines

BACKGROUND: The peptide endothelin (ET) 1 promotes proliferation in a number of epithelial cancers. The aim of this study was to identify the mechanism of ET-1-stimulated proliferation in colorectal cancer cells in vitro. METHODS: The effects of ET-1 on colorectal cancer cell lines HT29, LIM1215 and SW620 were studied. Cells were cultured with ET-1 plus antagonists/inhibitors to ET(A) or ET(B) receptors, G protein subtypes, phosphoinositide 3-kinase (PI3K) or protein kinase C (PKC). DNA replication and apoptosis were investigated by 5-bromo-2'-deoxyuridine incorporation and Annexin V staining. Transactivation of the epidermal growth factor (EGF) receptor was investigated by blockade of the receptor in the presence of ET-1, measurement of levels of phosphorylated EGF receptor in the presence of ET-1, and comparing the effects of ET-1 and EGF on cell proliferation. RESULTS: ET-1 significantly stimulated growth of all cell lines via ET(A) receptors. ET-1 stimulated DNA replication, not apoptosis. ET-1-stimulated growth was inhibited by antagonism of pertussis toxin-sensitive G proteins, PI3K and PKC. Inhibition of the EGF receptor reduced the effect of ET-1. ET-1 increased levels of phosphorylated EGF receptor via the ET(A) receptor. CONCLUSION: ET-1 increased DNA replication in colorectal cancer cells via the ET(A) receptor. This mitogenic action was mediated via pertussis toxin-sensitive G proteins, PI3K, PKC and transactivation of the EGF receptor.