William K. Gourley

Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype

BACKGROUND & AIMS Studies have shown that gastric T cells are increased during Helicobacter pylori infection. The purpose of this study was to characterize the human gastric T-cell responses in the presence or absence of H. pylori. METHODS T-cell surface antigens were examined by immunohistochemistry or after isolation for evaluation of surface antigens and cytoplasmic cytokines using flow cytometry. RESULTS CD4+ and CD8+ T cells were increased in situ during infection with H. pylori. Freshly isolated gastric T cells expressed cytoplasmic interferon gamma (IFN-gamma) and interleukin (IL)-2 after a brief stimulation. Simultaneous four-color flow cytometry demonstrated that both CD8+ and CD4+ T cells expressed IFN-gamma. Because stimulation through CD30 favors the induction of IL-5 and Th2 cells, gastric and colonic T cells were examined for CD30 expression. Consistent with the notion that Th2 cells are found in the intestine, CD30 was evident throughout the lamina propria of the colon but was virtually absent in the stomach. Furthermore, freshly isolated gastric T cells produced little IL-4 and virtually no IL-5 or tumor necrosis factor beta. CONCLUSIONS These observations show that gastric T cells resemble the Th1 type, which may explain their failure to induce immunity to H. pylori and their ability to contribute to the pathogenesis of gastric disease.

Endoscopically removed malignant colorectal polyps: Clinicopathologic correlations

BACKGROUND/AIMS Treatment options for patients with endoscopically removed malignant colorectal polyps are polypectomy alone vs. polypectomy followed by surgery. The aim of this study was to define histopathologic parameters that can be used for clinically relevant treatment decisions. METHODS Five pathologists evaluated 140 polyps for the presence or absence of unfavorable histology. Unfavorable histology was tumor at or near (< or = 1.0 mm) the margin and/or grade III and/or lymphatic and/or venous invasion. Adverse outcome was recurrent and/or local cancer and/or lymph node metastasis. RESULTS Adverse outcome was 19.7% (14 of 71), 8.6% (2 of 23), and 0% (0 of 46) when unfavorable histology was present, indefinite (lack of agreement), and absent, respectively (P < 0.0005, present vs. absent). Four patients with cancer > 1.0 mm from the margin had an adverse outcome (2 with lymphatic invasion and 2 indefinite for lymphatic invasion). Four patients with negative resections later developed distant metastases. Eight patients (6.3%) died of disease, and 2 of 69 without unfavorable histology (both indefinite for lymphatic invasion) had an adverse outcome. Interobserver strength of agreement was substantial to almost perfect for margin, grade, and venous invasion and fair to substantial for lymphatic invasion. CONCLUSIONS This system is usable clinically. Patients with unfavorable histology are probably best managed by resection postpolypectomy, whereas in the absence of unfavorable histology, they probably can be treated by polypectomy only.

Expression of B7-1 and B7-2 costimulatory molecules by human gastric epithelial cells: potential role in CD4+ T cell activation during Helicobacter pylori infection.

Human gastric mucosal epithelial cells display class II MHC, the expression of which is increased during Helicobacter pylori infection. These observations suggest that the gastric epithelium may participate as antigen-presenting cells (APC) during local immune responses. The increase in class II MHC expression occurs in parallel with an elevation in gastric CD4+ T cell numbers within and adjacent to the epithelium. Since the expression of either B7-1 (CD80) or B7-2 (CD86) on APC is required for the activation of T cells, it was important to establish human gastric epithelial cells expressed those surface ligands. The expression of B7-1 and B7-2 was detected on human gastric epithelial cell lines and freshly isolated epithelial cells from gastric biopsies with specific antibodies. B7-2 expression was higher than B7-1 at both protein and transcript levels and was increased after crosslinking class II MHC molecules on IFNgamma-treated epithelial cells and in cells pretreated with the combination of IFNgamma and H. pylori. Similarly, B7-2 expression was higher on gastric epithelial cells from H. pylori-infected tissues compared with those from uninfected specimens. To determine the function of these molecules on gastric epithelial cells, antibodies to B7-1 and B7-2 were shown to reduce the ability of the cells to stimulate alloreactive CD4+ T cells. These observations are the first to demonstrate that B7-1 and B7-2 are expressed on mucosal epithelial cells in situ. Thus, the expression of B7-1 and B7-2 by epithelial cells may allow them to act as APC in regulating local responses such as those that occur during infection with H. pylori.

Giardiasis: Clinical Spectrum and Functional-Structural Abnormalities of the Small Intestinal Mucosa

We studied 17 adult and 11 pediatric patients with giardiasis in order to examine the clinical spectrum and the functional-structural changes of the small intestinal mucosa. The most common clinical manifestations were diarrhea, weight loss, abdominal cramps, and, in children, failure to thrive. Giardiasis was frequently associated with hypogammaglobulinemia (HGG) and intestinal nodular lymphoid hyperplasia (47% and 41% of adults, respectively). Malabsorption of D-xylose and vitamin B12 occurred in 55% and 60% of patients, respectively, steatorrhea in 64%, and hypocarotinemia and low serum folate in 36%. No or only slight mucosal abnormalities were present in pretreatment jejunal biopsies of 75% of those adults on whom biopsies were performed, whereas 25% (all with HGG) had marked inflammation and changes of the villus-crypt architecture. Marked structural changes were seen in 43% of subjects with HGG. Estimates of brush border enzymes showed a significant reduction in lactase, sucrose, and leucyl-naphthylamidase specific activity in about 80% of patients assayed, whereas maltase, isomaltase, and alkaline phosphatase were not affected. Five patients were studied prospectively and absorption tests and jejunal mucosal biopsies were repeated after treatment with metronidazole or quinacrine. Resolution of symptoms with restoration of the morphologic and functional abnormalities of the small intestinal mucosa occurred after treatment in all but 1 patient. These observations indicate that Giardia cause brush border damage, which, is usually reversible with eradication of the parasite. Other factors, alone or in combination with Giardia, may be responsible for the cell damage beyond brush border injury found in some patients.

Treatment of intestinal ischemia with oxygenated intraluminal perfluorocarbons

Liquid perfluorocarbons are biologically inert compounds capable of dissolving up to 40 percent oxygen by volume. This remarkable and reversible oxygen solubility has encouraged investigations into therapeutic application in situations where tissue oxygen delivery is impaired. One such setting is intestinal ischemia. Identically prepared devascularized segments of rat intestine were treated with either intraluminal oxygenated perfluorocarbon (perfluorotributylamine) or physiologic saline solution. After timed sacrifice, blinded quantitative histologic evaluation for ischemic injury was performed. The perfluorotributylamine treatment groups had histologic scores indicative of less severe injury between 1 and 4 hours. These scores achieved statistical significance (p less than 0.05). We conclude that intraluminal oxygenated perfluorocarbons have a significant protective effect in this model of intestinal ischemia. This quantitative analysis is unique and is an important aspect of the preclinical evaluation of the perfluorocarbon preparations.

Photosensitization of experimental hepatocellular carcinoma with protoporphyrin synthesized from administered δ-aminolevulinic acid: studies with cultured cells and implanted tumors

BACKGROUND/AIMS Photodynamic therapy using porphyrins or related compounds and laser light is an investigational treatment for neoplasms. The aim of this study was to establish whether this might be applicable for hepatocellular carcinoma using protoporphyrin synthesized in the tissue from administered delta-aminolevulinic acid. METHODS We measured porphyrin accumulation in normal rat hepatocytes and Morris hepatoma cells in culture, and in subcutaneously implanted hepatomas and other tissues of the rat after administration of delta-aminolevulinic acid, and assessed cell and tissue damage after application of laser light. RESULTS Porphyrin accumulation after delta-aminolevulinic acid was added to the medium was greater and continued to increase for a longer period of time in hepatoma cells than in hepatocytes (1337+/-42 vs 513+/-31 fluorescence units/cell at 8 h, means+/-SE, p<0.001). After intraperitoneal injection of delta-aminolevulinic acid to rats with subcutaneously growing hepatomas, porphyrin content in tumor and liver was similar at 4 h but was higher in tumor at 6 h. Laser light caused necrosis of normal and malignant liver cells in culture and subcutaneous hepatomas in vivo. CONCLUSIONS We conclude from these in vitro and in vivo studies that porphyrin accumulation after administration of delta-aminolevulinic acid in this hepatoma is substantial and time dependent, and delivery of laser light locally can cause tumor photosensitization and necrosis.

Granular cell myoblastoma of the esophagus

Granular cell myoblastoma, a rare, but generally benign tumor, is being encountered with increasing frequency in the digestive tract. Seventy-two cases have been described in the esophagus; we report two additional cases. A follow-up, available in 13 patients (including ours), reveals a low likelihood of malignant transformation or recurrence after surgical removal. Guidelines for the management of these tumors are presented.

Comparison of biopsy and serological methods of diagnosis of Helicobacter pylori infection and the potential role of antibiotics

Objective:Endoscopic biopsy and serological methods were compared for their ability to detect Helicobacter pylori infection in patients undergoing upper gastrointestinal endoscopy at a state university hospital.Methods:Subjects were characterized on the basis of gastrointestinal symptoms, endoscopic findings, socioeconomic and demographic features, and the use of certain medications, tobacco, and alcohol. Current infection was detected in gastric antral specimens by rapid urease testing, histopathology, and bacterial culture. Serum levels of IgG to H. pylori were measured by ELISA.Results:Of 240 subjects, 115 (47.9%) were currently infected as determined by rapid urease testing, histopathology, and/or culture results, whereas 63.3% had elevated anti-H. pylori IgG levels (p < 0.001). This difference in the prevalence of current infection and seropositivity was preserved when the study population was analyzed according to age, race, gender, and other characteristics. Prior use of antibiotics was associated with a significant reduction in the frequency of H. pylori infection.Conclusions:Serological evidence of H. pylori infection was consistently greater than the prevalence of infection documented by biopsy methods in this study, suggesting suppression or recent clearance of infection. Further studies are needed to examine the factors that may affect the detection of H. pylori infection.

Allergic fungal sinusitis with cranial base erosion

Allergic fungal sinusitis (AFS) usually follows a slow, nonaggressive course. However, massive bone destruction can occur, with extension of the disease process outside of the confines of the sinuses.

Effects of Preparation-H on wound healing in the rectum of man

The wound-healing property of Preparation-H, a widely used over-the-counter hemorrhoidal product was investigated in a randomized, controlled, double-blind trial. Artificial ulcers were created in the rectum of 12 healthy male volunteers and the size of these ulcers followed until complete healing by visual examination on days 4, 8, 15, and 22. There were two groups of patients, one using placebo suppositories (placebo group) and another using Preparation-H (Preparation-H group). On day 8, biopsies were obtained from the edge of the ulcer in both groups to assess histological healing. On day 15, all the five subjects in the Preparation-H group had achieved complete healing of their rectal lesion, whereas only three of six subjects in the placebo group had done so. Although the difference in healing does not achieve statistical significance, it may be that with larger numbers of patients, Preparation-H could be shown to increase the rate of wound healing in artificially created rectal ulcers in man.