Serum IgA antibodies from patients with coeliac disease react strongly with human brain blood-vessel structures

BACKGROUND: Our objective was to determine the possible presence of IgA antibodies directed against human central nervous system (CNS) structures in sera from coeliac disease (CD) patients. METHODS: Serum samples were collected from 4 patients with active CD on a gluten-containing diet, 11 biopsy-proven CD patients on a gluten-free diet (GFD), and 52 non-coeliac gastrointestinal controls. In all patients IgA antigliadin antibody (AGA) titres were determined with enzyme-linked immunoassay (ELISA), and IgA antiendomysium antibodies (EMA) with indirect immunofluorescence on human umbilical cord. Cryostat sections of human brain occipital cortex were incubated with the patients' sera and subsequently labelled with anti-human IgA fluorescein conjugate. RESULTS: All sera from patients with active CD on a gluten-containing diet yielded positive results in both the IgG-AGA and EMA test and in indirect immunofluorescence on brain tissue, disclosing a strong fluorescence over blood-vessels structures. All sera from CD patients on a GFD and from non-coeliac gastrointestinal controls gave a negative result on both the EMA test and the immunofluorescence reaction on human brain. CONCLUSIONS: Sera from patients with active CD contain IgA antibodies that react with human brain vessel structures, giving intense fluorescence. These antibodies are not present in sera from coeliac patients on a GFD or non-coeliac controls. This finding might be involved in the abnormal nervous system manifestations frequently described in association with coeliac disease.     

X-ray digital subtraction angiography to magnetic resonance-digital subtraction angiography using three-dimensional TRICKS. Historical perspective and computer simulations: a review

Seventeen years after the introduction of x-ray digital subtraction angiography (DSA), gadolinium-enhanced magnetic resonance (MR) angiography techniques have become available for the performance of MR-DSA. For the purposes of this article, we will consider this to include two-dimensional and three-dimensional approaches using time-resolved and non-time-resolved applications. Magnetic resonance-DSA is one in a historical progression of techniques which have aimed to produce less invasive forms of angiography. After outlining some historical milestones, several current issues regarding current methods for MR-DSA are discussed.     

Neocortical ectopias in BXSB mice: effects upon reference and working memory systems

BXSB mice have an approximately 40-60% incidence of neocortical ectopias in layer I of the prefrontal/motor cortex. Prior studies have found major behavioral differences between those with ectopias and their non-ectopic littermates. Some of these findings indicate that the two groups differ with respect to spatial reference and working memory. The purpose of this study was to measure reference and working memory in the same animals to test the hypothesis that the ectopics would have better reference memory but less effective working memory. The Lashley III maze has cul-de-sacs which must be eliminated, and T-choices where the animal has to decide whether to go left or right. Ectopic and non-ectopic mice were equally able to learn the maze and did not differ on cul-entry or T-choice errors. Then the maze was inverted and the animals were retested. Turning the maze upside down did not change the relative status of the blind alleys. Therefore, the reference memory knowledge from the prior week's training could be used to avoid entering the culs. However, inverting the maze caused a left-right mirror image reversal of the T-choices. Therefore, prior reference memory information would interfere with learning the new path through the maze, whereas working memory would enable the mouse to eliminate T-choice errors. Ectopic mice made less cul-entry errors and more T-choice errors than their non-ectopic littermates, as predicted.     

Chronic exposure of cultured bovine endothelial cells to oxidized LDL abolishes prostacyclin release

We investigated the effect of chronic exposure (3 days) with low-density lipoprotein (LDL) and oxidized (Ox)-LDL on the unstimulated and stimulated formation of prostacyclin (6-keto-prostaglandin [PG]F1 alpha) and total inositol phosphates (IPs) by cultured bovine aortic endothelial cells. Neither basal nor bradykinin-stimulated (1 to 10 nmol/L) formation of 6-keto-PGF1 alpha was affected by LDL, except at the highest concentration of bradykinin tested (100 nmol/L). In the presence of the antioxidants N-acetyl-L-cysteine (NAC, 10 mumol/L) or vitamin E (100 mumol/L), basal and bradykinin-stimulated formation of 6-keto-PGF1 alpha was potentiated by 20 micrograms protein/mL of LDL. Ox-LDL decreased unstimulated formation of the eicosanoid from 3.1 +/- 0.2 pg/micrograms protein in control cells to 1.6 +/- 0.1 and 0.5 +/- 0.1 pg/microgram protein after 3-day incubation with 5 and 20 micrograms protein/mL of Ox-LDL, respectively (P < .05). As in the basal state, Ox-LDL decreased bradykinin-induced 6-keto-PGF1 alpha formation. NAC or vitamin E did not influence Ox-LDL-induced endothelial cell changes in eicosanoid production. IPs formation by endothelial cells increased to a similar extent in the presence of 20 micrograms protein/mL of either LDL or Ox-LDL. However, no change was apparent in the bradykinin (10 mumol/L)-induced increase in total IPs formation after incubation with the lipoproteins. The data indicate that chronic exposure to Ox-LDL abolishes the production of prostacyclin by cultured endothelial cells. The oxidatively modified lipoprotein seems to more specifically affect the prostacyclin pathway.(ABSTRACT TRUNCATED AT 250 WORDS)     

New lipid lowering drugs and new effects of old drugs

Old lipid acting drugs (fibrates, resins and niacin) continue to demonstrate morbidity and mortality benefits with variable efficacy and safety. Controlled trials have provided efficacy and safety data that support the use of statins as the first choice in the treatment and prevention of atherosclerosis. Knowledge of old and new mechanisms of action, optimal doses, pharmacokinetic behavior and drug interactions improve the safety and effectiveness of these hypolipidemic agents.     

Prostate cancer clinical trials of the Southwest Oncology Group

The changing clinical dynamics of prostate cancer have resulted in a broadening of the research focus of the Genitourinary (GU) Cancer Committee of the Southwest Oncology Group (SWOG). Beginning with an emphasis on hormone-refractory disease in its early years, SWOG prostate cancer trials now cover the entire spectrum of the disease: localized, locally advanced, metastatic and hormone-refractory disease. As the world's largest GU cancer research group, the GU committee of SWOG has pioneered studies in combined androgen therapy for metastatic disease, quality-of-life (QOL) assessments for patients with localized and advanced disease, adjuvant therapy models, and prostate cancer chemoprevention. The committee has also formed the GU Global Group, whose purpose is to convene the chairs of the GU committees of all the major national and international oncology cooperative groups. Meeting semiannually, this group discusses activities within their respective organizations, plans collaborative strategies and protocols, and establishes global strategy in prostate cancer clinical research. The future directions of national and international prostate cancer trials will build on this broad foundation of well-conceived, logically sequenced studies.