Derek B. Gordon

Studies of Intestinal Lymphoid Tissue: IX. Dose-Dependent, Gluten-Induced Lymphoid Infiltration of Coeliac Jejunal Epithelium

Jejunal biopsy specimens from coeliac patients who had received small, oral doses (100-1500 mg) of a peptic-tryptic gluten digest were analysed by morphometric methods. An increase in the total number of surface epithelial lymphocytes, maximal at 12 h after challenge, was dose-dependent, the mean percentage rise at this time being 53% (p less than 0.005), 44% (p = 0.01), and 25% (p greater than 0.05) with 1500, 1000, and 500 mg of gluten digest, respectively. This effect was not accompanied by any increased mitotic activity or blast transformation among the infiltrating lymphocytes, nor was there any demonstrable alteration in mucosal structure-that is, reduction in surface or increase in crypt epithelial volumes. The results of this controlled morphometric analysis indicate that oral gluten challenge causes an increase in the lymphocyte population of surface epithelium in coeliac disease but that this effect does not necessarily result in mucosal damage.

Studies of intestinal lymphoid tissue. XII. Epithelial lymphocyte and mucosal responses to rectal gluten challenge in celiac sprue

The immunopathologic, structural, and functional changes within rectal mucosa of known celiac sprue subjects were quantitated during local challenge with a peptic-tryptic digest of gluten. In the celiac sprue patients challenged with 2 g of digest, major effects occurred in lamina propria, submucosa, and local microvasculature. The lamina propria swelling was biphasic, starting 1-2 h after challenge with widespread extravascular deposition of fibrinogen, indicative of increased microvascular permeability, receding by 24 h postchallenge. A rapid fall in mast cells together with granule discharge suggested their involvement in this response. The late-phase swelling (48-72 h) was preceded by a rapid influx of neutrophils and basophils, the latter showing evidence of degranulation beyond 72 h. Reestablishment of vessel lumina, a rise in mast cells, and loss of neutrophils indicated tapering of the inflammatory cellular cascade by 96 h. Lymphocytes, first seen to enter the lamina by 2 h postchallenge, increased progressively, thereby resulting in substantial infiltration between 36 and 96 h. A marked rise in epithelial lymphocytes, maximal at 6-8 h, waned by 24 h. Volumes of surface and crypt epithelium remained constant throughout. In another challenge series with 4 g of gluten digest, electrical potential difference across rectal mucosa decreased significantly 12 h postchallenge, but the associated decreases in net sodium and chloride absorptive fluxes were insignificant. It is concluded that rectal mucosa is sensitized to gluten in celiac sprue disease and thus offers a promising and convenient in vivo substrate for investigative and diagnostic purposes.

Microbore liquid chromatography–electrospray mass spectrometry of selected synthetic pyrethroid insecticides

The pyrethroid insecticides kadethrin, α-cypermethrin, flucythrinate and SSI-116 have been studied by positive-ion electrospray mass spectrometry (+ESMS) in the presence of ammonium acetate and formic acid. Ammoniated molecule base peak ions [M + NH4]+ were observed for all the insecticides studied at low electrospray source sampling cone voltages. The effect of increasing the cone voltage (40–120 V) and its influence on the extent of fragmentation experienced by each insecticide were studied. A number of these key fragment ions found in +ESMS spectra of α-cypermethrin have been examined by MS–MS under low-energy collisional activation (CA) conditions. On-line microbore reversed-phase liquid chromatographic separations were performed on mixed pyrethroid standards. The eluates were analysed by +ESMS to establish the lower limits of detection using full-scan and selective-ion recording (SIR) modes. Limits of detection (signal-to-noise ratio better than 3:1) for each component of the pyrethroid mixture, injected on column, were in the range 120–300 pg (0.30–0.77 pmol) using full-scan mode and 12–60 pg (0.03–0.15 pmol) by SIR.

Monte Carlo simulations of quadrupole collision cells

Abstract This paper outlines a method for modelling the transmission of ions through a quadrupole collision cell. The resulting output obtained by using the computer programs is discussed and comments are made relating to instrument design.