Generation of oligodendroglial progenitors in acute inflammatory demyelinating lesions of the rat brain stem is associated with demyelination rather than inflammation

Remyelination is an extremely efficient process in the adult rodent central nervous system yet the source of new oligodendroglia that appear following primary demyelination is still subject to much debate. Using a reliable marker for oligodendroglial progenitor cells in vivo, the NG2 chondroitin sulphate proteoglycan, we have evaluated the response of endogenous NG2⁺ cells in the adult rat brain stem and cerebellum to inflammatory demyelinating lesions in an experimentally induced animal model of multiple sclerosis (MS), antibody augmented experimental allergic encephalomyelitis (ADEAE). We have manipulated T-cell mediated EAE in Lewis rats by injecting in addition, either anti-myelin/oligodendroglial glycoprotein (MOG) antibodies to induce inflammatory demyelination, or non-specific mouse immunoglobulins to induce an inflammatory response without demyelination. We have examined the relationship of NG2⁺ progenitor cells to microglia (OX-42⁺), astrocytes (GFAP⁺) and mature oligodendroglia (CNP⁺), in the normal and demyelinated CNS. In the normal CNS NG2-expressing cells are closely intermingled with other glia but represent a distinct cell population. A prominent inflammatory response, identified by the presence of large perivascular and periventricular accumulations of reactive OX42⁺ macrophages/microglia, occurred in animals with ADEAE at 7–9 days post injection (DPI), coinciding with severe clinical symptoms. In animals injected with anti-MOG antibodies inflammation was followed by the appearance of large areas of demyelination at 11–14 DPI, at which point the animals had recovered clinically. The response of NG2⁺ cells was different depending on whether the inflammation was accompanied by demyelination. In the presence of inflammation, NG2⁺ cells responded by an increase in immunoreactivity and an alteration in their morphology, exhibiting enlarged cell bodies and an increased number of intensely stained processes. In areas of demyelination NG2⁺ cells had fewer intensely stained processes reminiscent of progenitor cells seen during development. Quantitative analysis revealed a 3-fold increase in the number of NG2⁺ cells in demyelinated lesions at 11 DPI, whereas no change was observed in areas of inflammation in the absence of demyelination. Mitotic figures were only seen in NG2⁺ cells in areas of demyelination. NG2⁺ cell numbers appeared to return to control levels following remyelination. These results suggest that endogenous oligodendroglial progenitors divide and/or migrate, in response to signals triggered by demyelinating rather than inflammatory events, to generate a large progenitor population sufficient to promote the rapid and successful remyelination observed in this model.     

Inferring causality from relational data and designs: historical and contemporary lessons for research and clinical practice

My address to you today is born of frustration with the growing claims, evident in the research literature and in clinical reports that happen to cross my desk, of causation made on the basis of correlational data. I recall, as a sophomore in college, being taught early in my first experimental psychology course, "you cannot infer causality from correlation." This point was made adamant in my first face-to-face critique of an experimental psychology research paper by Dr. Robert T. Brown, who pointed out, in lowering my grade, that I had inferred organic causes to behavior patterns in gerbils based solely on correlational data. This caution was reiterated in my statistics courses until it must have been indelibly stamped upon my then still somewhat plastic brain.     

Serum cholesterol and impulsivity in personality disorders

Decreased serum cholesterol has been associated with impulsive aggressive behaviors. This study was designed to explore the relationship between serum cholesterol levels and measures of impulsive aggression in personality disordered patients. Forty-two personality disordered patients (14 borderline personality disorder, 28 other personality disorders) were included. Fasting serum cholesterol was measured by standard enzymatic assay. An ANOVA was performed with factors of gender and diagnosis, looking at two-way interactions between the factors and serum cholesterol. Patients with borderline personality disorder were found to have significantly lower serum cholesterol than non-borderline personality disorders. A significant interaction effect was also seen between gender and diagnosis with the male patients having lower cholesterol levels. This study suggests there may be a relationship between borderline personality disorder and low serum cholesterol.     

Evaluation of reports of periconceptual occupational exposure: maternal-assessed versus industrial hygienist-assessed exposure.

BACKGROUND: While the number of women entering the work force has grown, so has the importance of investigating occupational reproductive hazards. The objective of this study was to examine the concordance between maternal-assessed and industrial hygienist-assessed exposure to four classes of occupational agents - video display terminals, paints, solvents, and agricultural chemicals. METHODS: Case (n=87) and control (n=102) mothers who participated in a population-based study of orofacial clefts provided occupational histories and exposure (yes/no) to selected classes of agents for the one-year period prior to their child's delivery. Two industrial hygienists reviewed the occupational histories and assigned mothers an exposure status for each class of agent. Using industrial hygienist-assessed exposure as the "gold standard", sensitivity and specificity of maternal reports were calculated for each class of agent. Kappa statistics were calculated for the study population to account for chance agreement between the two exposure assessment methods. RESULTS: Sensitivity estimates for cases were the highest for video display terminals (77%) and lowest for agricultural chemicals (14%). Respective estimates for controls were 74% and 14%. Specificity estimates tended to be high for both groups. Kappa values ranged from 0.16-0.45. CONCLUSIONS: With regard to the classes of agents examined, these data suggest screening questions alone may not be the preferred method of obtaining occupational exposure histories, even when the time period of interest is fairly short and recent.     

Iris crystals in chronic uveitis.

AIMS: To analyse the unusual physical sign of iris crystals occurring in patients with uveitis. METHODS: Demographic details and clinical features were documented in 24 patients with chronic uveitis and iris crystals. Plasma immunoglobulin subclasses were measured, and a histopathological review of iridectomy specimens from 33 patients with chronic uveitis was also undertaken. RESULTS: The mean age of patients was 38 years, with a slight preponderance of females. 17 patients had Fuchs' heterochromic cyclitis although a number of other uveitis entities were represented. There was no correlation between severity of clinical signs and presence of iris crystals. Over a mean follow up period of 15 months no significant change in the number, size, or position of the crystals was seen except in four patients who underwent intraocular surgery. Only three patients had raised plasma IgG1. The review of the histology of iridectomy specimens failed to show evidence of Russell body formation in any patient. CONCLUSIONS: Iris crystals appear to be rare but may be underreported as they are small and can easily be missed. They are likely to be associated with disease processes in which there is active immunoglobulin production within the anterior chamber, such as Fuchs' heterochromic cyclitis.     

Book review

Basic Guide to Pesticides: Their Characteristics and Hazards

Shirley A. Briggs & Rachel Carson Council, 1993 Hemisphere Publishing Corporation (a member of the Taylor & Francis Group), Washington, Philadelphia and London 283 pp. ISBN 1 56032–253–5, £28.00     

D-aspartate binding to the glutamate uptake site in human brain tissue — effects of leucotomy

Summary Binding of [3 H]D-aspartate, as an indicator of glutamate uptake sites, was investigated in post-mortem human brain tissue by use of a centrifugation assay to separate free and bound ligand. Binding was displaceable, apparently saturable and to a single site, with mean K_D and Bmax values of 2.3 M and 40.3 nmol/g tissue in the frontal cortex. The method was applied to the study of tissue from frontal and temporal cortices and the caudate nucleus of five psychiatric patients who had undergone a frontal leucotomy. The effects of this neurosurgical procedure were to diminish by almost 50% the density of D-aspartate binding sites in the frontal cortex and caudate nucleus, while the temporal cortex was less affected. It is concluded that the method provides a potentially useful correlate of glutamatergic innervation in human brain tissue.