Gastrointestinal involvement in L-tryptophan (L-Trp) associated eosinophilia-myalgia syndrome (EMS).

We report a 45-year-old female who had symptomatic gastrointestinal involvement, eosinophils in the cellular infiltrate, and who proved to have L-tryptophan-associated eosinophilia-myalgia syndrome. This case illustrates that gastrointestinal disease can be a major, seemingly primary clinical presentation in this syndrome, and that a drug history, specifically L-tryptophan, needs to be included in the differential diagnosis of "eosinophilic gastroenteritis."

The alpha 1-antitrypsin gene is expressed in a human intestinal epithelial cell line.

alpha 1-Antitrypsin (alpha 1-AT) is considered a typical plasma protein and a prototype of the serine proteinase inhibitor (serpin) family. It is synthesized in hepatocytes and, to a lesser extent, in macrophages. In this study we show that the alpha 1-AT gene is also expressed in human intestine and in a human colonic epithelial tumor cell line, Caco2. A single 1.6-kilobase alpha 1-AT-specific mRNA is present in jejunum and in Caco2 cells. It is identical in apparent size to that present in human hepatoma HepG2 cells but slightly smaller than that present in human macrophages, cells in which an alternative upstream transcriptional start site is used. Synthesis and secretion of alpha 1-AT in Caco2 cells is similar to that in HepG2 cells. It is synthesized as an approximately 52-kDa precursor polypeptide, converted to its mature, fully glycosylated 55-kDa form intracellularly, and the native protein is secreted with a half-time of 37 min. Functionally active alpha 1-AT is secreted into the basolateral and apical (luminal) fluid in pulse-chase labeling experiments of Caco2 cells cultured in polarized orientation on collagen-coated nitrocellulose membranes. Expression of alpha 1-AT in Caco2 enterocytes is not affected by soluble factors that regulate expression of alpha 1-AT in macrophages and hepatocytes. However, expression of alpha 1-AT increases markedly in Caco2 cells as they differentiate into enteric villous-type cells.

Essential fatty acid deficiency reduces the inflammatory cell invasion in rabbit hydronephrosis resulting in suppression of the exaggerated eicosanoid production.

The rabbit hydronephrotic kidney (HNK) is a model of renal inflammation characterized by a marked increase in arachidonic acid metabolism which is temporally associated with an inflammatory cell influx into the injured tissue. The HNK exhibits an exaggerated elaboration of eicosanoids ex vivo in response to inflammatory agonists (bradykinin and the chemotactic peptide, n-formyl-methionyl-leucyl-phenylalanine). Essential fatty acid (EFA) deficiency [i.e., deprivation of (n-6) fatty acids] attenuated markedly the ex vivo elaboration of eicosanoids and prevented the enhancement of the microsomal cyclooxygenase and thromboxane synthase activity associated with 3 days of ureter occlusion. In contrast, postobstructive release prevented the ex vivo elaboration of eicosanoids by the HNK. When the HNK was assessed morphologically by electron microscopy, both EFA deficiency and postobstructive release markedly reduced the population of interstitial macrophages normally seen in the HNK. Apparently, EFA deficiency blocked the influx of macrophages whereas postobstructive release resulted in the efflux of macrophages from the HNK. Because EFA deficiency has been shown to inhibit the synthesis of leukotriene B4, a potential chemotaxin, it was hypothesized that EFA deficiency might prevent the influx of macrophages due to an inhibition of leukotriene B4 synthesis. Indeed, EFA deficiency suppressed the synthesis of this eicosanoid in blood whereas prostaglandin E2 and thromboxane A2 production were unaffected. In summary, this study demonstrates that EFA deficiency prevents the influx of macrophages into the HNK and prevents the enhanced arachidonate metabolism which normally occurs after ureter obstruction. A potential role for leukotriene B4 as a chemotactic agent in this model of renal inflammation also is suggested.

The gastrin-producing cells in tissue cultures of the rat pyloric antrum.

Tissue culture methods were used to study the gastrin-producing cells isolated from the pyloric antral mucosa of rats. Cultures were maintained for up to 7 days. Gastrin cells were identified by means of immunofluorescent and unlabeled antibody-enzyme techniques. The tissue culture medium was monitored for basal gastrin secretion. In addition, stimulation of gastrin release was achieved by the use of dibutyryl cyclic-AMP and theophylline. This is the first report of the successful application of tissue culture methods to the functional study of antral gastrin cells. The procedure has proven to be useful in assessing the mechanisms of gastrin secretion.

Myospherulosis. An electron-microscopic study of a human case.

An electronmicroscopic study of a human case of myospherulosis, which involved the nose and maxillary sinus, is reported. Large parent bodies limited by a thick electron-dense wall, enclosing variable numbers of spherules, were seen in cystic tissue spaces or adjacent connective tissue. Free spherules and shrunken degenerative forms were present as well. Similarity of these bodies to sporangium-like structures is suggested. The etiology of the disease remains unsettled.

The induction of human myospherulosis in experimental animals.

Tissue lesions similar to those in human myospherulosis were reproduced in experimental animals and studied by light and electron microscopy. The lesions were produced by the use of petrolatum-based antibiotic ointments. These ointments, which are marketed as nonsterile products, are similar to those used for hemostatic packing in otolaryngologic surgery. To date, use of these ointments has been reported to precede the finding of human paranasal sinus myospherulosis. The exact nature of the structures of myospherulosis remains unknown. The experimental evidence strongly suggests that they can be iatrogenically produced by the use of these nonsterile ointments.