Repopulation of oligodendrocyte progenitor cell depleted tissue in a model of chronic demyelination

Some, but not all chronically demyelinated MS lesions are depleted of oligodendrocyte progenitor cells (OPCs) suggesting that OPCs are destroyed during the process of demyelination and some factor impedes OPC repopulation of the depleted tissue. The chronically demyelinated axons in MS lie in an astrocytic environment and it has been proposed that this might impede entry of OPCs into such regions. By depleting a short length of spinal cord of its OPCs using 40 Gy of X-irradiation in both normal rats and rats with progressive myelin loss accompanied by an astrocytosis (taiep rats), we investigated whether such changes affect the ability of OPCs to repopulate OPC-depleted tissue. In both taiep and normal rats, the rate of repopulation decreases with age, but no difference was detected in the rate at which OPCs repopulated normally myelinated and chronically demyelinated and astrocytosed tissue. This indicates that, if the astrocytic environment of the taiep CNS is comparable to that found in MS lesions, then the presence of chronically demyelinated axons and astrocytosis in chronic MS lesions does not represent a barrier to repopulation of the tissue by OPCs. However, similar to the situation in the normal adult rodent CNS, the rate of repopulation by endogenous OPCs in aged taiep rats is very slow, approximately 0.2 mm per week.     

Pattern motion is present in V1 of awake but not anaesthetized monkeys

We compared responses of neurons, recorded in striate cortex (area V1) of awake, fixating monkeys, to a single drifting grating with those to a 'plaid' pattern comprised of two superimposed drifting gratings separated in orientation by 90 degrees. Five out of 54 (9%) of V1 direction selective neurons responded to the direction of motion of the whole pattern [pattern motion (PM) selectivity]. Tuning curves for plaid stimuli were similar in both optimum direction and width of tuning to those for single gratings. Twenty nine out of 54 (54%) responded simply to the motion of individual orientated gratings within the pattern [component motion (CM) selectivity]. The remaining 37% (20/54) neurons were unclassified. In control experiments, 39 direction selective neurons were recorded in area V1 of anaesthetized monkey and cats. Unlike area V1 in behaving monkeys, none of these neurons exhibited PM selectivity to the drifting plaids. Twenty eight out of 39 (72%) of them responded to the direction of the component gratings and were classified as CM selectivity. Our results indicate that although most V1 neurons are CM selective, as described in anaesthetized animals, a subpopulation is clearly PM selective in behaving monkeys, reflecting integration of locally derived motion signals. Neurons in V1 therefore carry signals that may contribute to pattern motion processing and perception. This perceptual interpretation in V1 might depend much more critically on information integration mechanisms that only function properly in awake, perceiving animals.     

The remyelinating potential and in vitro differentiation of MOG-expressing oligodendrocyte precursors isolated from the adult rat CNS

There is a long-standing controversy as to whether oligodendrocytes may be capable of cell division and thus contribute to remyelination. We recently published evidence that a subpopulation of myelin oligodendrocyte glycoprotein (MOG)-expressing cells in the adult rat spinal cord co-expressed molecules previously considered to be restricted to oligodendrocyte progenitors [G. Li et al. (2002) Brain Pathol., 12, 463-471]. To further investigate the properties of MOG-expressing cells, anti-MOG-immunosorted cells were grown in culture and transplanted into acute demyelinating lesions. The immunosorting protocol yielded a cell preparation in which over 98% of the viable cells showed anti-MOG- and O1-immunoreactivity; 12-15% of the anti-MOG-immunosorted cells co-expressed platelet-derived growth factor alpha receptor (PDGFRalpha) or the A2B5-epitope. When cultured in serum-free medium containing EGF and FGF-2, 15-18% of the anti-MOG-immunosorted cells lost anti-MOG- and O1-immunoreactivity and underwent cell division. On removal of these growth factors, cells differentiated into oligodendrocytes, or astrocytes and Schwann cells when the differentiation medium contained BMPs. Transplantation of anti-MOG-immunosorted cells into areas of acute demyelination immediately after isolation resulted in the generation of remyelinating oligodendrocytes and Schwann cells. Our studies indicate that the adult rat CNS contains a significant number of oligodendrocyte precursors that express MOG and galactocerebroside, molecules previously considered restricted to mature oligodendrocytes. This may explain why myelin-bearing oligodendrocytes were considered capable of generating remyelinating cells. Our study also provides evidence that the adult oligodendrocyte progenitor can be considered as a source of the Schwann cells that remyelinate demyelinated CNS axons following concurrent destruction of oligodendrocytes and astrocytes.     

Alagille syndrome: prenatal diagnosis and pregnancy outcome

The Alagille syndrome (AGS) is a multisystem autosomal dominant condition. In this case report, we describe a pregnant woman with this unusual disorder, in whom serial fetal sonography revealed severe pulmonary stenosis and progressively severe intrauterine growth retardation, suggesting that the fetus also had AGS, a diagnosis which was confirmed postnatally. In this report, the potential complications for pregnancy, labor and delivery when both mother and fetus are affected with AGS are described.     

Non-mosaic trisomy 20 presenting at 21 weeks' gestation as a thoraco-abdominal mass

Non-mosaic trisomy 20 is rare in fetuses surviving beyond the first trimester. We report a case of a fetus with non-mosaic trisomy 20 in amniotic fluid cultures obtained during the prenatal evaluation of an unusual thoraco-abdominal mass which was found at autopsy to be pulmonary sequestration. Gross inspection and autopsy of the fetus revealed multiple anomalies.     

D2 lymphadenectomy in the management of gastric cancer

Background Gastric carcinoma is a significant cause of death in Ireland. Surgery offers the best option of cure, but the five-year survival following resection remains dismal at 10–15%. Experience from Japan and from some Western units suggest that an extended (D2) lymphadenectomy in association with gastrectomy increases the prospect of cure, but concern about the morbidity and mortality of this operation and lack of evidence from randomised studies has limited its acceptance. Aims This study reports the experience of a specialist upper gastrointestinal unit with D2 gastrectomy in a four-year audit. Methods Sixty-two resections were performed for gastric cancer. Results Nineteen patients were deemed unsuitable for the D2 procedure and underwent a more limited lymphadenectomy (DO or D1). Forty-three patients underwent D2 resection, 12 with an oesophagogastrectomy, 22 with total gastrectomy and nine with a sub-total distal resection. Eight patients undergoing D2 resection had extended resections, five with splenectomy and three with a distal pancreatectomy. Post-operative complications occurred in 31% of patients. Thirty-day and 90-day mortality were zero. Median survival was 822 days in the D2 group (range 120–1,320). Conclusions These results show that a D2 gastrectomy can be performed with a low morbidity and mortality and a median survival of greater than two years.     

Psychophysical Evaluation of Cochlear Hair Cell Damage Due to the A3243G Mitochondrial DNA Mutation

Mitochondrial dysfunction is an important cause of human deafness, implicated in genetic deafness, toxin and noise damage. We assessed the mechanism of cochlear dysfunction in a population of 11 subjects with a specific mitochondrial disorder caused by the A3243G mitochondrial DNA mutation. Psychophysical tests were carried out to assess the inner and outer hair cell functions in vivo. Inner hair cell function was assessed using a measure of hearing threshold in the presence of "threshold-equalizing noise" which can indicate "dead regions" where the transduction mechanism fails. Outer hair cell function was assessed by using the notched-noise method to measure auditory filter width, dependent on active mechanisms in the outer hair cell. The results support the conclusion that this mitochondrial disorder causes both inner and outer hair cell dysfunctions. Evidence of inner hair cell dysfunction was found mainly in basal (high frequency) regions of the cochlea and occurred even in some subjects with only mild hearing loss. Evidence of outer hair cell dysfunction was found in some instances where pure tone threshold was at or close to normal. The common occurrence of dead regions in the basal cochlea has treatment implication for this form of deafness; such people may not be helped by amplification of high frequencies.     

SNOMED takes the next step

Healthcare terminologies SNOMED and the Read Codes have been around for a long time. Now, a new terminology combining the two promises to take the industry one step closer to realizing the vision of an electronic patient record. Here 's a sneak peek at SNOMED CT.