Seroprevalence of Helicobacter pylori infection in patients with lymphoma.

To determine the Helicobacter pylori (HP) seroprevalence in patients with non-Hodgkin's lymphoma (NHL) and other hematological conditions. Sera were collected from 444 patients with NHL, Hodgkin's disease (HD), lymphoproliferative disorders (LPD), myeloproliferative disorders (MPD), and other hematological conditions. HP seropositivity was determined by ELISA and the results were compared among diagnostic groups HP seropositivity was observed in 168/444 (38%) of the total population. Higher seropositivity rates were associated with increasing age (p=0.001), and country of birth outside the USA and Canada (p=0.0001). Among the diagnostic groups, patients with NHL demonstrated the highest frequency (43%) and those with HD, the lowest frequency (20%; p=.026) of HP seropositivity. The differences among diagnostic groups remained statistically significant after controlling for country of birth (p<0.05), but not after controlling for patient age at diagnosis. The HP seroprevalence of G1 NHL was 55% compared to 40% for non-G1 NHL (p=NS). The highest rate of HP seropositivity (67%) occurred in gastric MALT lymphoma patients, although this did not reach statistical significance compared to the non MALT group (50%) due to small sample size. In conclusion, the rate of HP seropositivity in patients with MALT lymphoma in the USA appears to be lower than in Europe. Helicobacter pylori does not appear to be an important factor in other types of NHL of the G1 tract or elsewhere. Studies of HP prevalence should be controlled for country of birth as well as for age.

A rat model to study the role of STn antigen in colon cancer.

Expression of the mucin-associated sialyl-Tn (STn) antigen has been associated with a decreased survival in patients with colorectal, gastric, and ovarian cancer. To better understand the role of STn antigen in tumor biology, we developed STn(+) (called LP) and STn(-) (called LN) clonal cell lines from a parental metastatic rat colon carcinoma cell line (LMCR). Both derivative cell lines exhibited identical proliferation rates in vitro. LP cells strongly expressed STn antigen both in vitro and in vivo, and were poorly tumorigenic when given to syngeneic rats. LN cells did not express STn antigen in vitro, but as in vivo tumors these cells rapidly acquired STn expression, readily formed tumors, and were highly lethal. When rats were given an otherwise lethal inoculum of i.p. LN cells, pre-immunization with synthetic STn antigen conjugated to keyhole limpet hemocyanin (STn-KLH) resulted in a 60% survival rate. When LN cells were injected subcutaneously in the presence of STn-KLH-sensitized lymphocytes, tumor growth was decreased. Distribution of STn antigen in normal organs of host rats is quite similar to that of humans. This model mimics human disease and should facilitate studies of mucin-associated antigens in tumor biology and the development of immunotherapeutic agents based on mucin-related antigens.

The gastric mucosal barrier.

Most gastroduodenal ulcer disease results from a weakness in the normal gastric mucous barrier against the penetration of acid secreted by the stomach. Based on meticulous and insightful research, the distinguished physiologist Franklin Hollander hypothesized that the stomach is protected against its own acid secretion by a dynamic two-component mucus-mucosal barrier. Hollander and his co-workers defined the physical and chemical characteristics of the mucus components of this barrier, as well as the defense provided by the surface epithelial cell layer, which he viewed as the second line of defense (the second component). Barrier investigators at Mount Sinai demonstrated the effects of impairment of barrier function with resultant increased back-diffusion of acid, and they defined the consequences of this acid penetration into the gastric epithelium. The contribution of these workers included important observations on the natural impermeability of the gastric corpus and fundus as well as the normally increased permeability of the antrum. They also presented evidence on the role of bile in duodenogastric reflux in gastric ulcer disease and the presence of impaired barrier function in patients with gastric ulcer and pernicious anemia. Further studies included demonstration that stress and carcinogens could disrupt the gastric mucosal barrier. Disruption of the barrier, in turn, was shown to allow carcinogenesis to occur by permitting the absorption of certain carcinogens which otherwise are warded off by the barrier. The Hollander two-component gastric mucosal barrier hypothesis has, in recent years, been increasingly validated by experimental data coming from other laboratories.

Intestinalization of gastric signet ring cell carcinomas with progression.

Recent developments in mucin histochemistry and immunohistochemistry have made reliable determination of the gastric and intestinal phenotypes of gastric carcinoma cells possible. Phenotypic expression changes from gastric epithelial cell type to intestinal epithelial cell type with the growth of gastric tumours in experimental animals. We studied cell differentiation in gastric signet ring cell carcinomas with progression in 203 surgically obtained specimens. The results showed that the proportion of gastric phenotype carcinomas, in which over 90% of the tissue consists of gastric epithelial cell type cells, decreases with the depth of invasion. The proportion of mixed phenotype carcinomas (between 10% and 90% of the tissue made up of gastric and/or intestinal epithelial cell type cells) increases. The intestinal phenotype (over 90% intestinal epithelial cell type carcinoma cells) was found in four carcinomas (about 2%) involving the serosa. No clear relationship was evident between phenotypic expression of carcinoma cells and the degree of intestinal metaplasia of the surrounding mucosa. Progression of gastric signet ring cell carcinomas is associated with a phenotypic shift from gastric to intestinal type expression.

Sialosyl-Tn antigen as a marker of gastric cancer progression: an international study.

Sialosyl-Tn, a mucin-associated carbohydrate antigen, is not expressed by normal mucus-producing cells of the stomach but becomes expressed in metaplastic, pre-malignant and malignant gastric tissues. Reports vary as to the frequency of STn expression and its prognostic role in gastric cancer. To determine whether these differences might be due to inter-country variations in gastric cancer biology, we immunohistochemically analyzed 340 gastric cancers from 2 countries at high-risk (high incidence) for gastric cancer (Japan and Chile), one with intermediate risk (Brazil) and one with low-risk (USA). Expression of STn was correlated with clinico-pathological features of the tumors and with cancer-related survival. Regardless of country, the frequency of STn-positive tumors was lower in non-invasive ("early") than in advanced gastric cancer. Consequently, high-risk countries where early gastric cancer is more common demonstrated a lower overall frequency of STn-positive tumors. In all 4 countries, STn expression directly correlated with depth of invasion, stage, and lymph node involvement. In addition, STn expression correlated with a poor prognosis in all 4 countries, but the effect of STn on survival was not independent of tumor stage. Our findings indicate the need to consider the inherent gastric cancer risk and prevalence of early gastric cancer in the study population when reporting frequency of STn expression in gastric cancer. Regardless of country, however, STn expression is a marker of gastric cancer progression suggesting that cancer-associated mucins play a role in the malignant behavior of this tumor.

Mucin-associated sialosyl-Tn antigen expression in gastric cancer correlates with an adverse outcome.

The expression of sialosyl-Tn (STn) antigen was evaluated by immunohistochemistry in primary gastric cancers. Twenty-one of 31 (68%) gastric cancers expressed STn, regardless of tumour location, stage or histological type. Eighty-one per cent of patients with STn-positive tumours died of their disease or had recurrent cancer, compared with 20% of patients with STn-negative tumours (P < 0.002). STn may be a useful prognostic marker in patients with gastric cancer.

Expression of sialosyl-Tn in intestinal type cancer cells of human gastric cancers.

A sample of 219 primary stomach cancers, 143 advanced cancers and 76 early cancers were examined for mucin histochemical staining (the paradoxical concanavalin A method, the galactose oxidase-Schiff [GOS] reaction, and the sialidase-GOS reaction) and immunohistochemical reactivity (pepsinogen [Pg] I, Pg II, SH-9 and TKH-2). Gastric cancer cells were clearly classified according to mucin histochemistry into a gastric type, including mucus neck cell, pyloric gland cell and surface mucus cell types, and an intestinal type, including goblet-cell, and intestinal absorptive cell types. TKH-2 monoclonal antibody, which recognizes the mucin-associated sialosyl-Tn antigen, reacted with the mucin of goblet cells in both the normal small intestine and in the intestinal metaplasia of the stomach. Sixty-five of 106 (61%) differentiated adenocarcinomas and 76 of 113 (67%) undifferentiated adenocarcinomas had over 10% of their cancer cells positive for TKH-2. The TKH-2-positive cancers were primarily classified as a goblet-cell type by mucin-histochemical staining and the other immunohistochemical staining methods. Therefore, it is concluded that sialosyl-Tn is an excellent marker of small intestinal mucins and is indicative of a small intestinal type of differentiation in two-thirds of gastric cancers.

Amyloidosis and inflammatory bowel disease. A 50-year experience with 25 patients.

Amyloidosis is a rare but serious complication of inflammatory bowel disease (IBD), especially Crohn's disease (CD). It occurred in 15 of our 1709 patients with CD (0.9%) (706 with ileocolitis, 310 with colitis, and 693 with enteritis), but in only 1 of our 1341 patients with ulcerative colitis (UC) (0.07%), admitted to The Mount Sinai Hospital between 1960 and 1985. Eleven of the patients with CD who had amyloidosis had ileocolitis, 2 colitis, and 2 ileitis; these figures represent a frequency within each group of 1.6%, 0.6%, and 0.3%, respectively. Amyloidosis was thus associated 4.4 times more often with CD of the colon than with pure small bowel disease. We have added to this group of 15 patients the 5 cases of CD that were originally reported by Werther et al in 1960, plus another 4 (2 with UC and 2 with CD) who have been seen since 1985, making a total of 25 patients in this series, 22 with CD and 3 with UC. There was a striking male preponderance, 16 of 22, among patients with CD, although 2 of the 3 patients with UC were female. Amyloid disease was diagnosed at a mean age of 40 years, 15 years (range, 1-42) after the onset of CD. Six major forms of amyloidosis occurred: nephropathy, enteropathy, cardiomyopathy, hepatosplenomegaly, thyroid mass, and generalized amyloidosis. Renal disease with proteinurea and/or renal insufficiency occurred in 18 of the 22 patients with CD and in all 3 with UC. Nephropathy was by far the most common lethal manifestation of IBD-associated amyloidosis in this series. Nephrotic syndrome developed in 15 patients with CD and was accompanied by renal failure, the major contributor to mortality, in 10 of the 13 patients who died. Amyloidosis may be associated with suppurative or other extraintestinal manifestations of IBD. Fifteen of the 22 patients with CD who had amyloidosis also had suppurative complications of their bowel disease, although the other 7 had no recognizable suppuration. Extraintestinal manifestations were also common in this series, occurring in 12 of 22 patients with CD and in 2 of the 3 patients with UC; 6 of the 18 patients with nephrotic syndrome also had arthritis. However, there is no evidence that patients with IBD with amyloidosis have extraintestinal manifestations more frequently than do IBD patients without amyloidosis. Earlier reports of amyloid associated with IBD came from autopsy series. In recent years, biopsy has allowed diagnosis to be made during life.(ABSTRACT TRUNCATED AT 400 WORDS)

Experimental models for gastric leiomyosarcoma. The effects of N-methyl-N'-nitro-N-nitrosoguanidine in combination with stress, aspirin, or sodium taurocholate.

A series of experiments was devised to determine possible modifying effects of stress, aspirin, and sodium taurocholate on the activity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the Buffalo rat stomach. MNNG is a well known, direct-reacting carcinogen, and has been a reliable agent for the experimental production of gastric adenocarcinoma. The authors were able to produce adenocarcinomas in rats, but found a great number of gastric leiomyosarcomas. These occurred only in the groups given MNNG in combination with stress, aspirin, or sodium taurocholate, and did not occur in experimental groups given either MNNG, stress, aspirin, or sodium taurocholate alone, and did not occur in the control group.

Effect of N-methyl-N'-nitro-N-nitrosoguanidine on the gastric mucosal barrier in rats.

The gastric mucosal barrier to hydrogen ion (H+) after the administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on the rat stomach was studied. Increased H+ back-diffusion was observed 3 hr after oral doses of 1 mg of MNNG over a 3-day period. MNNG in concentrations of 250 microgram/ml, 167 microgram/ml, 86 microgram/ml, and 50 microgram/ml in the presence of acid caused increased H+ back-diffusion across the gastric mucosa within 1 hr. Gastric mucosal barrier disruption by MNNG may play a pathogenic role in gastric carcinogenesis.

Acid absorption in the canine duodenum.

Alterations in composition of isosmotic acid solutions were studied in exteriorized segments of the proximal (Brunner's gland area) and distal canine duodenum, mounted in lucite chambers. Varying concentrations of HCl (40, 80, 120, 160 mEq/l) made isotonic by the addition of NaCl were instilled into the chamber, removed in 15 minutes and analyzed for volume, electrolytes, protein content and osmolality. Both proximal and distal duodenal mucosa modified the instilled solution with a loss of H+ and a gain in Na+ and K+, which occurred at similar rates independent of the acid concentration of the instilled solution. The rate of ionic movement was twice that for the antrum, and 30-100 times that of the fundus. Calculated H+ loss across the entire duodenal mucosa at these rates could account for 17.5% of the peak acid output from the canine stomach. The loss of H+ could not be accounted for on the basis of neutralization and probably represented transmucosal insorption. In addition to the neutralization of gastric acid by pancreatic juice and bile, duodenal mucosa thus plays an important role in the maintenance of intraluminal pH. Duodenal mucosal permeability to H+ may be related to the vulnerability of the duodenal mucosa to acid-peptic ulceration.