Jerry S. Trier

The Histologic Spectrum of Barrett's Esophagus

To define the histology of the columnarlined esophagus, we obtained esophageal biopsies from various levels with manometric control from 11 patients. There were three types of columnar epithelia above the lower esophageal sphincter: atrophic gastric-fundic-type epithelium with parietal and chief cells; junctional-type epithelium with cardiac mucous glands; and distinctive specialized columnar epithelium with a villiform surface, mucous glands and intestinal-type goblet cells. When present, specialized columnar epithelium was always the most proximal, and gastric fundic epithelium the most distal epithelium. Junctional epithelium was interposed between gastric fundic and specialized columnar or squamous epithelium. Four patients had unequivocal esophagitis in squamous epithelium, but its presence and severity did not correlate with inflammation in or length or type of distal columnar epithelium. Histoligic study of the columnar-lined esophagus demonstrated a spectrum of epithelial patterns. This heterogeneity helps to explain prior discrepant reports.

Early Vascular Injury and Increased Vascular Permeability in Gastric Mucosal Injury Caused by Ethanol in the Rat

The hypothesis that vascular injury contributes to the development of hemorrhagic erosions after intragastric administration of ethanol has been examined in the rat using vascular tracers. Extravasation of intravenously injected Evans blue into the gastric wall and into gastric contents was used as an indicator of vascular permeability. India ink and monastral blue, which label damaged blood vessels, were used to demonstrate vascular injury morphologically. Intragastric instillation of 75% and 100% ethanol induced increased vascular permeability within 1-3 min and resulted in monastral blue labeling of vessels in 13% and 17%, respectively, of the glandular mucosa within 1 min. After 1 h of 100% ethanol exposure, the areal density of monastral blue-stained blood vessels did not increase compared with that seen at 1 min, but the areal density of grossly visible hemorrhagic lesions increased strikingly and approximated that of vessel staining. The hemorrhagic erosions consistently occurred in regions of glandular mucosa where vessels were stained with monastral blue. Pretreatment with prostaglandin F2 beta or cysteamine reduced ethanol-induced Evans blue extravasation and monastral blue staining of mucosal blood vessels but did not reduce histologic evidence of gastric surface cell damage in the glandular mucosa. As increased vascular permeability and morphologically detectable vascular lesions consistently preceded the development of grossly visible hemorrhagic erosions in the glandular mucosa, we suggest that vascular injury is an early pathogenetic factor in the development of ethanol-induced gastric hemorrhagic erosions. The data also indicate that the degree of vascular damage, unlike the injury to surface epithelial cells, is reduced by pretreatment with prostaglandin F2 beta or the sulfhydryl cysteamine.

Clinical Immunity in Acute Gastroenteritis Caused by Norwalk Agent

To examine immunity in viral gastroenteritis, we challenged and then rechallenged 12 volunteers with Norwalk agent and evaluated symptoms, jejunal biopsies and serum antibody. With the first challenge, gastroenteritis developed in six volunteers but not in the others. When rechallenged 27 to 42 months later, the six who became ill initially again had gastroenteritis with jejunal lesions; in the six previously immune volunteers illness or jejunal lesions did not develop. Four of five ill volunteers had increases in serum antibody to Norwalk agent after both challenges. Serum antibody did not increase in three immune volunteers after either challenge. Four volunteers who had twice become ill underwent a third challenge four to eight weeks after their second illness. In one gastroenteritis developed; in three, it did not. These findings indicate two forms of immunity for viral gastroenteritis, one of short and the other of long duration. Factors other than serum antibody appear important in immunity to Norwalk gastroenteritis.

Cell Proliferation and Migration in the Stomach, Duodenum, and Rectum of Man: Radioautographic Studies

Summary Many data are available concerning cell proliferation and migration in the gut of animals. Little work has been done on man. In this study 2 ambulatory patients with incurable nongastrointestinal cancer were selected because of their excellent general health. Each was given 10 mc. of tritiated thymidine intravenously. Gastric, duodenal, and rectal suction biopsy specimens were obtained at 1 hour and at frequent intervals up to 14 days after injection. Within 1 hour many labeled cells were evident in the gastric pits and gland isthmuses and in the duodenal and rectal crypts. Parietal and chief cells were not labeled, but occasionally radioautographic reactions were seen over mucous neck cells deep in the gland. Rarely, duodenal goblet cells were labeled within the first hour; labeling of rectal goblet cells was not certain until later. Migration from gastric pits to surface usually took 4 to 6 days although cells from a few pits reached the surface in 36 hours. Duodenal cells migrated from the crypt mitotic zones up the villi to be extruded from the tips in 5 to 6 days. Rectal epithelial cells reached the surface in about 5 to 6 days. A few well labeled cells persisted in the mitotic regions of all 3 organs at 14 days. In these subjects the duodenal and rectal epithelial migration time was 5 to 6 days which is 2 to 3 times that reported in rodents. That of the human gastric fundal epithelium varied greatly between pits but was also probably longer than that reported in rodents. The labeling of goblet cells within 1 hour suggests that all goblet cells do not differentiate from undifferentiated columnar cells but that they may reproduce themselves. From this study it is apparent that animal data on gastrointestinal epithelial proliferation cannot be applied unreservedly to man.

Diagnosis of celiac sprue

Accurate diagnosis of patients with celiac sprue is, at times, challenging but always important: challenging because of the enormously varied spectrum of clinical manifestations encompassed by the disease, important because treatment with gluten withdrawal is dramatically effective. Moreover, recent data obtained by using sensitive screening methods indicate that the true prevalence of celiac sprue is substantially higher in many populations than previously thought (0.5% in 11‐15-yearold Italians, 1 0.35% in Swedish children, 2 and, in a preliminary report, 0.4% in healthy U.S. blood donors. 3

The mucosal lesion of the proximal small intestine in acute infectious nonbacterial gastroenteritis.

Abstract The pathogenesis of acute infectious nonbacterial gastroenteritis, a common illness, is uncertain. Indeed, the morphology of the mucosa of the small intestine in this disease has not been described. Fifteen volunteers with normal base-line intestinal biopsies ingested orally stool filtrate containing Norwalk agent. Twelve acquired clinical gastroenteritis and abnormal intestinal histology with mucosal inflammation, absorptive cell abnormalities, villous shortening, crypt hypertrophy and increased epithelial-cell mitoses. Abnormal mucosal histologic findings persisted for at least four days after clinical symptoms cleared. Biopsies six to eight weeks after illness were normal. In one of three asymptomatic volunteers a typical mucosal lesion developed; biopsies in the other two remained normal. These findings indicate that a characteristic intestinal lesion accompanies acute infectious nonbacterial gastroenteritis, is demonstrable a few hours before clinical illness, can occur in asymptomatic infec...

Early microcirculatory stasis in acute gastric mucosal injury in the rat and prevention by 16,16-dimethyl prostaglandin E2 or sodium thiosulfate

We used in vivo microscopy and laser-Doppler velocimetry to examine the effects on the gastric mucosal microcirculation and in gastric mucosal blood flow of agents that induce acute gastric mucosal damage. In vivo microscopic observation of superficial mucosal capillaries revealed vascular stasis within a mean of 54, 81, or 61 s after 100% ethanol, 0.6 N HCl, or 0.2 N NaOH, with the subsequent development of hemorrhagic mucosal lesions. Mucosal blood flow estimated by laser-Doppler velocimetry decreased by 30% at 5 min after luminal application of 100% ethanol, and decreased further to about 40% of basal levels by 15 min. The decreased mucosal blood flow 15 min after application of 50% ethanol correlated with the extent of hemorrhagic mucosal lesions. Examination of the submucosal vessels that supply and drain the mucosa showed moderate dilation of small arterioles 1, 3, and 6 min after exposure to 100% ethanol but there were no consistent changes in venules. Mild vasoconstriction of small- and medium-sized venules could be detected 6, 10, and 15 min after NaOH but not after exposure to HCl. Pretreatment with 16,16-dimethyl prostaglandin E2 or sodium thiosulfate before exposure of the mucosa to ethanol prevented capillary stasis, maintained mucosal blood flow, and prevented the development of hemorrhagic gastric mucosal lesions. Topical mucosal application of 16,16-dimethyl prostaglandin E2 decreased, whereas topical exposure to sodium thiosulfate increased gastric mucosal blood flow, indicating that change in blood flow per se is an unlikely mediator of protection.

Morphologic alterations induced by methotrexate in the mucosa of human proximal intestine. I. Serial observations by light microscopy.

Summary Samples of mucosa from the small intestine obtained from human subjects before, and at intervals after, intravenous administration of single doses of methotrexate ranging from 2 to 5 mg. per kilogram were studied with the light microscope. The small bowel villous pattern was normal in all biopsies and there was no quantitative reduction in epithelial length after drug. The number of mitoses in the crypts decreased within 3 hours, became negligible in 6 to 48 hours and subsequently returned to at least normal levels by 96 hours after methotrexate. There was an increase in the number of mitoses during the week following methotrexate-induced inhibition. During the period of mitotic reduction, many small, spherical, DNA-containing inclusion bodies appeared in the cytoplasm of the crypt cells. These intracytoplasmic bodies disappeared as the number of mitoses returned to normal. These changes do not seem to be specific for methotrexate but were observed by us after radiation and by others after a variety of noxious agents.

EPITHELIAL CELL RENEWAL IN CULTURED RECTAL BIOPSIES IN ULCERATIVE COLITIS

Epithelial cell proliferation and migration were studied in cultured mucosal biopsies of the rectum from 14 patients with ulcerative colitis (DC) and eight normal volunteers. More than twice as many epithelial cells in the proliferative zone of the rectal crypts were labeled in autoradiographs of DC biopsies cultured for 6 hr over thymidine-3H-containing medium than in normal biopsies. Moreover, after 18 hr of additional culture over isotope-free medium, many more labeled cells had migrated to the upper crypts and the absorptive surface in the DC biopsies than in the normal biopsies. Electron microscopy of the surface epithelium of uncultured and cultured biopsies showed that the cytological abnormalities seen in freshly fixed DC biopsies persisted after 24 hr of culture. These studies indicate that epithelial cell proliferation is increased and the migration is accelerated in the rectal mucosa in patients with UC.

Rat intestinal M cells contain acidic endosomal-lysosomal compartments and express class II major histocompatibility complex determinants

BACKGROUND It is generally believed that M cells do not modify the antigens they transport from the intestinal lumen to underlying immunocompetent cells because it has been reported that M cells contain few elements of the lysosomal system. METHODS We used specific cytochemical and immunocytochemical probes to examine whether M cells in jejunal Peyers patches of adult rats contain the requisite intracellular components to process and potentially present endocytosed antigens. RESULTS M cells contained acid phosphatase-enriched prelysosomelike and lysosomelike structures. A basic congener of dinitrophenol, which concentrates in acidic cell compartments, is localized following its instillation into Peyers patch-containing ligated jejunal loops to the endosomal-lysosomal system of M cells. Prelysosomelike and lysosomelike structures in ultrathin cryosections of M cells reacted with polyclonal antibody to a membrane glycoprotein (lgp120) enriched in prelysosomes and lysosomes. Using monoclonal antibody OX6 as a probe, M cells expressed the major histocompatibility complex (MHC) class II determinant, Ia, on the basolateral plasma membrane and in organelles with structural features of endosomes, prelysosomes, and lysosomes. Expression was enhanced by pretreatment with interferon gamma. CONCLUSIONS M cells possess acidic endosomal and acid phosphatase-containing prelysosomal and lysosomal compartments and express MHC class II determinants. Hence, M cells may have the capacity to process and present endocytosed antigens to adjacent intraepithelial T lymphocytes.