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.     

The effects of patterned calorie-restricted diets on mammary tumor incidence and plasma endothelin levels in DMBA-treated rats

Chronic caloric restriction has been shown to inhibit mammary tumor promotion in the 7,12-dimethyl-benz[a]anthracene (DMBA) rat mammary tumor model. The objectives of this study were to determine (i) the effects of chronic caloric cycling (yo-yo dieting) on mammary tumor promotion by high fat diets and (ii) the effect of three dietary regimens +/- superimposed mammary tumor burden on plasma endothelin-1,2 (ET) levels. Female Sprague-Dawley rats were treated with DMBA (5 mg/rat) and divided into three dietary groups: ad libitum (AL) (containing 15% corn oil); 40% calorie restricted (CR) (containing 20% corn oil so consumption of fat was equivalent between AL and CR); a calorie cycled (CC) group fed alternatively AL and CR diets each 48 h period. After 10 weeks, tumor incidences were: AL, 63%; CR, 27%; CC, 57% (AL versus CR, P < 0.05; CC versus CR, P < 0.05; AL versus CC, NSD). ET levels (pg/ml plasma) were: AL, 16.0 +/- 6.54; CR, 32.31 +/- 0.34; CC, 23.44 +/- 5.04 (AL versus CR, P < 0.01; CC versus CR, P < 0.01; AL versus CC, P < 0.05). Plasma ET levels were independent of tumor incidence and tumor burden, but plasma ET levels were significantly increased in rats with a prior history of calorie restriction. As expected, maintained caloric restriction reduced mammary tumor incidence but intermittent caloric restriction (caloric cycling or yo-yo dieting) was without similar benefit.     

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.     

Reduced growth factor requirements and accelerated cell-cycle kinetics in adult human melanocytes transformed with SV40 large T antigen

Melanomas develop with high frequency in transgenic mice in which oncogenic sequences of the SV40 DNA tumor virus have been specifically targeted to melanocytes. To investigate the role of SV40 in melanomagenesis, cultured human melanocytes were transformed with a retroviral shuttle vector encoding the SV40 large T antigen and examined for changes in cell-cycle kinetics and growth-factor dependence. Colonies expressing the viral oncogene were morphologically indistinguishable from their non-T-antigen-transformed counterparts. Also like normal melanocytes, the infected cells remained anchorage dependent and non-tumorigenic in nude mice. However, T-antigen-positive cultures exhibited significantly accelerated population doubling times, increased saturation densities with highly confluent monolayers and a three- to fourfold extended life span. Most interestingly, cell-cycle analysis revealed a measurable shift from quiescent to cycling cells in T-antigen-expressing cultures and an acquired ability to progress more rapidly through G1. Moreover, T-antigen-positive melanocytes proliferated in the absence of PMA and required markedly reduced levels of exogenous bFGF. These studies indicate that the viral oncogen of simian virus 40 provides melanocytes with distinct growth advantages that may render these cells unusually susceptible to additional environmental challenges necessary for full expression of the malignant phenotype.     

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)