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Context: Early studies suggested that gastric acidity declines as people age. However, sequelae of achlorhydria are uncommon in older people, making this conventional wisdom unlikely.Objective: To ascertain the prevalence of basal gastric acidity and atrophic gastritis (indicated by serum pepsinogen ratio) in older adults.Design: Cross-sectional study in a volunteer sample.Setting: Retirement communities in suburbs of Kansas City, Mo.Subjects: A total of 248 white male and female volunteers aged 65 years or older living independently.Main Outcome Measures: Presence of basal unstimulated gastric acid was evaluated noninvasively by having subjects swallow quininium resin. Gastric acid with a pH lower than 3.5 releases quinine, which is then absorbed and excreted into urine. Atrophic gastritis was defined as a ratio of serum pepsinogen I/pepsinogen II of less than 2.9.Results: Basal unstimulated gastric content was acidic (pH <3.5) in 208 (84%) of 248 elderly subjects. On retesting 66 subjects (35 normals and 31 hyposecretors), 28 (80%) of 35 had pH less than 3.5 both times, and 22 (71%) of 31 had pH of 3.5 or higher twice; in the remaining 16 subjects, low vs high gastric pH changed between tests. Weighted population prevalence estimates in this sample were 67% for consistent acid secretion, 22% for intermittent secretion, and 11% for consistent gastric pH higher than 3.5. Whereas 14 (67%) of 21 consistent hyposecretors had serum pepsinogen ratios of less than 2.9, indicating atrophic gastritis, only 2 (5%) of 44 consistent or intermittent secretors of acid had ratios in this range (P<.001).Conclusions: In contrast to what is commonly stated, nearly 90% of elderly people in this study were able to acidify gastric contents, even in the basal, unstimulated state. Of those who were consistent hyposecretors of acid, most had serum markers of atrophic gastritis. [ABSTRACT FROM AUTHOR]

Background and Aims: The risk of gastric cancer (GCA) is increased in atrophic gastritis. A low serum pepsinogen group I (SPGI) level is a good serologic indicator of atrophic gastritis of the gastric corpus and fundus, and can be used for diagnosis of subjects with atrophic gastritis and of increased risk for GCA. The present study was undertaken to investigate whether SPGI assay and a diagnostic gastroscopy could enable the diagnosis of GCA at an early stage., Material and Methods: The study was carried out as part of the Alpha-Tocopherol, Beta-Carotene Cancer prevention study (ATBC study) in Finland, in which 22,436 male smokers aged 50-69 years were screened by SPGI. Low SPGI levels (< 25 microg/l) were found in 2196 (9.8%) men. Upper GI endoscopy (gastroscopy) was performed in 1344 men (61%) and 78% of these had moderate or severe atrophic corpus gastritis in endoscopic biopsies. A control series of 136 men from the ATBC study cohort with abdominal symptoms, but with SPGI > or = 50 microg/l were similarly endoscopied, and 2.2% of these had corpus atrophy., Results: Neoplastic alterations were found in 63 (4.7%; 95% CI: 3.6%-5.8%) of the 1344 endoscopied men with low SPGI levels. Of these, 42 were definite dysplasias of low grade, 7 dysplasias of high grade, 11 invasive carcinomas, of which 7 were 'early' cancers, and 3 carcinoid tumors. In the control series, 1 man (0.7%) of the 136 men had a definite low-grade dysplasia. Thus, 18 (1.3%; 95% CI 0.7%-2.0%) cases with 'severe' neoplastic lesions (4 advanced cancers, 7 early cancers and 7 dysplasias of high grade) were found in the low SPGI group, but there were none in the control group. All four patients with advanced cancer died from the malignancy within 5 years (mean survival time 2.5 years), whereas surgical treatment in all those with early cancer or high-grade dysplasia was curative. One of the seven patients with early cancer and two of the seven with high-grade dysplasia died within 5 years, but none died from the gastric cancer. Thus, curative treatment was given to 14 of 18 men in whom a malignant lesion was found in gastroscopy. This is about 15% of all gastric cancer cases (92 cases) which were diagnosed within 5 years after SPGI screening in the 22,436 men. Among the gastric cancer cases of the main ATBC study, the 5-year survival rate was 33% (85% of the non-survivors died from gastric cancer)., Conclusions: We conclude that assay of SPGI followed by endoscopy is an approach which can enable the early diagnosis of gastric cancer at a curable stage.

Background: Vitamin E and beta-carotene are considered to decrease the risk of gastric cancer both in humans and in laboratory animals. We studied the effect of dietary supplementation with alpha-tocopherol and beta-carotene on the end-of-trial prevalence of premalignant and malignant lesions of the stomach in older men with atrophic gastritis., Methods: The study was carried out within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC study) in Finland, in which 29,133 male smokers aged 50-69 years were randomly assigned to receive daily 50 mg alpha-tocopherol, 20 mg beta-carotene, both of these agents, or placebo, for 5-8 years. Serum pepsinogen was determined at base line and after 3 years' supplementation to find men with atrophic gastritis. A low serum pepsinogen I level, indicating atrophic gastritis of the corpus area of the stomach, was found in 2132 men. These men were invited to have upper gastrointestinal endoscopy (gastroscopy), which was performed on 1344 subjects after a median supplementation time of 5.1 years., Results: Neoplastic alterations were found in 63 of the men (4.7%): 42 with definite dysplasias of low grade (moderate dysplasia), 7 with definite dysplasias of high grade (severe dysplasia), 11 with carcinomas (of which 7 were 'early' cancers), and 3 with carcinoid tumors. Neither alpha-tocopherol (relative risk, 0.98; 95% confidence interval, 0.57-1.69) nor beta-carotene (relative risk, 1.13; 95% confidence interval, 0.65-1.95) supplementation had any association with end-of-trial prevalence of gastric neoplasias after adjustment for other possible risk factors. The effect was not modified by base-line serum level or dietary intake of vitamins, prevalence of Helicobacter pylori infection, or other covariates., Conclusions: We thus conclude that supplementation with alpha-tocopherol or beta-carotene for 5 years has no major impact on the occurrence of neoplastic changes of the stomach in older male smokers with atrophic gastritis.

Helicobacter pylori infection is a major cause of gastritis and may be a key risk factor for stomach cancer, but its role in the process of gastric carcinogenesis is not well understood. Herein, we examine H. pylori prevalence in relation to demographic and lifestyle factors and to severity of precancerous lesions in an area of China with one of the highest rates of stomach cancer in the world. H. pylori serum IgG antibody positivity was assayed among 2646 adults, ages 35-64, participating in a population-based gastroscopic screening survey in the high-risk area. The prevalence of positivity was evaluated according to gastric histology, environmental and lifestyle variables determined by interviews during the screening, and level of serum pepsinogens. The odds of advanced precancerous lesions (intestinal metaplasia and dysplasia) of the stomach among those with antibody positivity were estimated by logistic regression. Seventy-two % of the population was H. pylori antibody-positive, with nonsignificant variation by sex, age, income, education, family size, and cigarette smoking habits. H. pylori positivity was higher among those who ate sour pancakes, a fermented indigenous staple that is a risk factor for gastric dysplasia and stomach cancer in this population. The prevalence of H. pylori varied most notably, however, with gastric pathology. The percent of H. pylori positivity increased from 55 to 60 to 87% among those with superficial (nonatrophic) gastritis, mild chronic atrophic gastritis, and severe chronic atrophic gastritis, respectively, before falling to 78% among those with intestinal metaplasia or dysplasia. H. pylori antibody positivity also was strongly correlated with serum pepsinogen concentrations, particularly pepsinogen II, but knowledge of H. pylori status did not markedly improve serological identification of advanced precancerous lesions above that provided by pepsinogen ratios alone. The findings suggest that H. pylori infection contributes to the process of gastric carcinogenesis, particularly during the early stages, in this high-risk area.

Background and Methods: To investigate the acquisition rate of Helicobacter pylori infection among Finnish adults, we obtained, in 1991, serum samples from 181 subjects who were shown to have histologically normal, noninfected gastric mucosa in 1974-76., Results: During the 15-year follow-up period 12 (6.6%) of the 181 subjects developed H. pylori antibodies (IgG), the overall annual acquisition rate being 0.44%. The acquisition rate correlated somewhat with age. Antibodies developed in 1(4.5%) of the 22 subjects less than 40 years old (in 1991) and in 4 (31%) of 13 subjects who were 70 years old or older. If it is assumed that H. pylori acquisition is a continuous and stable event through the whole life span, and the rate is similar in all birth cohorts, the observed annual acquisition rate of 0.44% or an increase of this rate with age does not explain the current prevalence of chronic gastritis in Finland. Extrapolations of the known and estimated prevalence rates of chronic gastritis in 1974/76 and 1991 indicated rather that the H. pylori acquisition is a birth-cohort-dependent phenomenon and that most of the acquisitions occurred in childhood in every cohort (generation). After being high in childhood (less than 20 years old), the acquisition rate exponentially slowed down with age in all cohorts., Conclusions: Among adults the acquisition rate of H. pylori infection is low, and the main period of acquisition is childhood. The relationship between the acquisition rate and age is inverse and exponential.

Medical treatment for Helicobacter pylori (Hp) infection is now recommended in several types of gastroduodenal disease, and its success is usually monitored by hystology. The end-points of our work were to identify the most suitable serum index of Hp eradication among pepsinogen A (PGA), pepsinogen C (PGC), PGA/PGC ratio, gastrin, and IgG anti-Hp (IGG). We studied a total of 289 Hp positive (Giemsa staining) patients, who were treated with 40 mg/day omeprazole (140 cases) or with 480 mg/day bismuth subsalicylate (149 cases) for 4 weeks. All the patients also received 1 g/day metronidazole + 2 g/day amoxycillin for the first 2 weeks of treatment. Two months after the end of therapy, the patient underwent a second endoscopy and Hp histological assessment: the infection was eradicated in 192 and still present in the remaining 97 subjects. Gastrin, PGA, PGC, and IGG were measured before and after therapy. All indices significantly decreased after therapy in eradicated patients, while PGA and gastrin significantly decreased after therapy in both eradicated and noneradicated patients, although in the latter group the variations were less pronounced. We calculated the per cent decrease of the studied indices. PGC, with a decrease of more than 25%, was found to be the most accurate biochemical index. Variation in PGC levels before and after treatment were correlated with corresponding variations in Hp bacterial load. In conclusion, between the different biochemical parameters evaluated, PGC showed the highest clinical efficiency.

We have investigated the effect of therapy for Helicobacter pylori gastritis on serum concentrations of pepsinogen I and II in 43 patients. In the 22 patients in whom therapy resulted in dramatic decrease in gastritis scores and in clearance of the bacteria, there was a highly significant (P = 0.0001) fall in mean serum pepsinogen II from 13.3 +/- 0.8 to 7.9 +/- 0.7 micrograms/liter, and a less pronounced fall in pepsinogen I from 89.0 +/- 5.9 to 78.5 +/- 0.4 micrograms/liter (P = 0.01). These changes resulted in a significant (P = 0.01) increase in the pepsinogen I/II ratio. In contrast, nonsignificant declines of 3.5% and 11.6% were observed in mean pepsinogen I and II levels in the 21 patients whose gastritis failed to resolve histologically and whose infection did not clear. These findings suggest that serum pepsinogen levels, especially pepsinogen II, are a new tool that may be found to be clinically useful in evaluation of treatment outcome in patients with H. pylori-associated gastritis.

The objective of this project was to determine the association of Helicobacter pylori infection and serum pepsinogen levels on subsequent risk for gastric adenocarcinoma. This nested case-control study was set in a large health maintenance organization. One hundred thirty-six cases of gastric adenocarcinoma and 136 matched controls without adenocarcinoma from a large cohort that had contributed serum in the 1960's were studied. The presence of IgG against H. pylori had previously been determined by enzyme-linked immunosorbent assay. Serum levels of pepsinogens I and II were ascertained by radioimmunoassay. In a sample of subjects, the presence of antiparietal cell antibodies was determined by immunofluorescent antibody assay (Nichols Laboratory). There were 98 cases of adenocarcinoma of the antrum, body, or fundus (distal cancers) and 30 of the cardia or gastroesophageal junction (proximal cancers). By univariate analysis, H. pylori infection [odds ratio (OR), 3.6; P < 0.001] and serum pepsinogen I < 50 ng/ml (OR = 2.9; P = 0.003) were both associated with development of distal cancer. In multivariate analysis, there was interaction between the two variables; H. pylori in the absence of low pepsinogen I was independently associated with cancer (OR, 2.4; P = 0.04) but low pepsinogen I in the absence of H. pylori infection was not associated with cancer (OR, 0.8; P > 0.5). In combination, however, H. pylori infection and a low pepsinogen I were associated with a marked increase in the risk of developing distal malignancy (OR, 10.0; P = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Aims: To investigate the association between histologically confirmed gastritis, carriage of Helicobacter pylori and pepsinogen (PG) I and PG II concentrations., Methods: Prospective study of 81 dyspeptic patients undergoing upper gastrointestinal endoscopy was made. The extent of gastric mucosal inflammation and the presence of H pylori was determined, and serology to evaluate PG I and II concentrations and IgG titres to H pylori was carried out., Results: The presence of H pylori was strongly correlated with high IgG antibody titres to H pylori and gastritis. Patients who were H pylori positive had significantly higher PG I and PG II concentrations and a significantly lower PG I:PG II ratio than patients who were negative for H pylori. In 13 patients with duodenal ulcer and H pylori positive gastritis serum PG I concentrations were significantly higher than in H pylori positive patients without duodenal ulcer. Significant correlations were found between the age of patients and serum PG II, the PG I:PG II ratio, IgG antibodies to H pylori, the severity of body gastritis and H pylori infection, and between the degree of gastritis in the body of the stomach and the PG II concentration., Conclusions: Serum PG I and II concentrations, together with a fall in the PG I:PG II ratio, could be used as predictors of H pylori infection as well as serum IgG antibody response to H pylori.

Two aspartic proteinases, pepsinogen II (PgII) and cathepsin E (CathE), were identified immunocytochemically in lung epithelia. In normal lung, type II pneumocytes were characterized by PgII immunoreactivity of variable intensity, while bronchiolar Clara cells reacted with CathE antibodies. With the exception of small groups of nonciliated bronchial cells overlying lymphoid follicles, no other CathE-immunoreactive cell was found in the lung. Immunoblots of crude protein extracts of lung tissue using PgII and CathE antibodies showed reactivity with single molecular species co-migrating with analogous bands obtained from gastric mucosa (molecular weight, 40,500 for PgII and 42,000 to 44,000 for CathE). In 75 cases of non-neoplastic lung disease, a highly significant correlation was found between the severity of histopathologic lesions and expression of both PgII (P < 0.001) and CathE (P < 0.001). Epithelial hyperplasia contributed more than inflammation and fibrosis to this relationship. Proteinase overexpression was not specific to any particular disease and was found in both focal and diffuse lesions. Segregation of PgII and CathE in different cells was lost in hyperplastic epithelium, where coexpression of both proteinases by the same cell was frequently observed. The location of both proteinases in distal airways and their enhanced expression in the proliferative, hyperplastic phase of several non-neoplastic pneumopathies suggest their possible involvement in the process of parenchymal remodeling that occurs in fibrosing lung diseases.

A specific rabbit anti-human serum was used selectively to localize the aspartic proteinase cathepsin E to follicle associated epithelium (FAE) of human and rat intestine, including jejunum, ileum, appendix, colon and rectum, as well as of human palatine, pharyngeal and lingual tonsils. Coexpression of class II histocompatibility antigen HLA-DR antigen has been observed in some of the cathepsin E-positive epithelial cells. In addition, cathepsin E has been detected in a few mononuclear cells of intestinal lymphoid structures and tonsils resembling interdigitating reticulum cells of lymph nodes. Another aspartic proteinase, cathepsin D, has been found to be poorly represented in FAE and intensely expressed by macrophages. Electron immunocytochemistry localized cathepsin E to endosomal vesicles and endoplasmic reticulum of M cells in rat and human ileum as well as of M-like cells in human palatine tonsil. The results suggest a possible role of endosomal cathepsin E in the processing of macromolecules and microorganisms transported by M cells and related epithelial cells to mucosal associated lymphoid tissue (MALT).

Ranitidine bismuth citrate was compared with an equipotent dose of ranitidine, to determine whether the former, by an anti-Helicobacter pylori activity, would counteract the rise of gastrin resulting from ranitidine's gastric acid antisecretory activity. Twenty four men with duodenal ulcers were studied before and on the 8th day of dosing with either ranitidine bismuth citrate 800 mg twice daily or ranitidine 300 mg twice daily (double blind, randomised, parallel groups). Fasting and postprandial plasma gastrin and plasma pepsinogen I and II concentrations were measured, and a 13C-urea breath test was performed before and on the 8th day of dosing. The 13C-urea breath tests were positive in 21 patients before dosing and remained positive in nine of nine of the ranitidine dosed patients, whereas only two of 12 patients treated with ranitidine bismuth citrate remained positive. The expected rise in meal stimulated plasma gastrin with ranitidine was seen in the 12 patients who received ranitidine but, despite suppression of H pylori urease activity in 10 of 12 patients taking ranitidine bismuth citrate, there was no attenuation of the meal stimulated gastrin rise. There was no significant difference in the mean derived (4 hour) plasma pepsinogen I and II concentrations after dosing with ranitidine or ranitidine bismuth citrate.

Proteolytic degradation (processing) of antigen by antigen-presenting cells is a major regulatory step in the activation of a T lymphocyte immune response. However, the enzymes responsible for antigen processing remain largely undefined. In this study we show that cathepsin E, and not the ubiquitous lysosomal cathepsin D, is the major aspartic proteinase in a murine antigen-presenting cell line, A20. This enzyme is localized to a non-lysosomal compartment of the endosomal system in these cells. Functional studies using a highly specific inhibitor of cathepsin E show that this enzyme is essential for the processing of ovalbumin by this cell line. Thus, cathepsin E, whose function was hitherto unknown, may play a major role in antigen processing.

Twenty-four-hour plasma pepsinogen I and II concentrations were determined in 8 healthy subjects with antibody to Helicobacter pylori, before and after treatment with tripotassium dicitrato bismuthate, amoxycillin and metronidazole, Therapy was successful in the 5 subjects with active H. pylori infection. In these subjects, median integrated 24-h plasma pepsinogen I and II concentrations significantly decreased from 2288 and 357 micrograms.h/L before treatment, respectively, to 1811 and 171 micrograms.h/L at 4-6 weeks after treatment, and 1643 and 150 micrograms.h/L at 20-24 weeks. By contrast, in the 3 subjects without evidence of active H. pylori infection, pre-treatment plasma pepsinogen I and II concentrations were similar to values found in the H. pylori-infected subjects after successful therapy, and they did not change significantly in response to therapy. H. pylori infection is associated with reversible hyperpepsinogenaemia.

In 100 mucinous tumors of the ovary (37 benign, 24 borderline, and 39 malignant), the authors determined by histochemical and immunohistochemical techniques the frequencies and patterns of expression of a total of nine markers of gastric, intestinal, and pancreatobiliary duct epithelial cells. M1, a mucin antigen, and cathepsin E (CaE), an aspartic proteinase, two markers of normal gastric superficial/foveolar epithelial cells, were expressed in 95 and 92 tumors, respectively. Periodic acid-concanavalin A-reactive mucin or pepsinogen (PG) II, markers of gastric mucus neck and pyloric gland cells, were found in 79 tumors. All of these tumors also expressed M1 or CaE. DU-PAN-2 and the N-terminal epitope of gastrin-releasing peptide, markers of normal pancreatobiliary duct cells, were found in 70 and 49 tumors, respectively, and CAR-5 and M3SI, markers of intestinal mucin, were expressed in 51 and 30 tumors, respectively. All tumors expressed at least two of the nine markers studied; none expressed PG I, a marker of gastric chief cells. The mucopeptic cell marker, PG II, was significantly more common in benign and borderline than in malignant tumors (P less than 0.005), whereas CAR-5 and M3SI, markers of intestinal mucin, were expressed significantly more often in malignant than in benign and borderline tumors (P less than 0.001). By electron microscopic examination, many tumor cells had fine structural features characteristic of gastric superficial/foveolar and pyloric gland cells, intestinal columnar or goblet cells, and endocervical cells. The results indicate that gastroenteropancreatic cell differentiation--and, in particular, gastric type differentiation--is a prominent feature of ovarian mucinous tumors.

Vitamin and mineral assays were performed on blood in 20 gastric bypass patients preoperatively and 6 and 12 months postoperatively. Values were compared with serial food records in nine patients. Postoperatively, all patients were prescribed a supplement containing the recommended dietary allowances (RDA) for vitamins and minerals. Weight, calorie and protein intake, and total serum protein decreased over the study interval (p less than 0.01). Dietary intakes of vitamins B1, B2, B6, folate, iron and zinc fell (p less than 0.01), but total intake (i.e., diet + supplement) did not decrease with the exception of iron. Blood indicators of these nutrients were normal preoperatively and did not decline. However, plasma vitamin B12 levels decreased from 385 pg/ml preoperatively to 234 pg/ml at 1 year (p = 0.0064), despite an increase in total vitamin B12 intake from 2.6 to 11.7 micrograms/day (p = 0.1173). Five patients (27.8%) had abnormally low plasma vitamin B12 levels at 1 year postoperatively; four were taking at least the RDA for vitamin B12 as supplements. Although oral supplementation containing the RDA for micronutrients can prevent abnormal blood indicators of most vitamins and minerals, it is insufficient to maintain normal plasma B12 levels in about 30% of gastric bypass patients.

Helicobacter pylori is rarely found in gastric biopsy specimens from individuals with atrophic gastritis of the body mucosa. To determine if subjects with atrophic body gastritis have evidence of previous infection with H. pylori, immunoglobulin G antibody to H. pylori was measured by enzyme-linked immunosorbent assay in sera of 399 Finnish subjects. In 124 subjects, multiple biopsy specimens from body and antrum had been evaluated for the presence of H. pylori by Giemsa staining. Antibody correlated well with H. pylori staining except in the subgroup with atrophic body gastritis, in whom the prevalence of seropositivity (86%) was significantly greater than the prevalence of positive staining (33%) (P less than 0.001). Twenty-five subjects had positive antibody and negative staining. This group had a significantly higher prevalence of atrophic body gastritis (80%), lower maximal acid output, lower serum pepsinogen I levels, and higher serum gastrin concentrations than did seropositive subjects with H. pylori. These data suggest that most patients with atrophic body gastritis, despite having a low incidence of current overt infection, have been infected with H. pylori at some point in their lives.

Serum pepsinogen I (S-PGI) and serum gastrin (S-gastrin) were examined in the screening of three types of atrophic gastritis with inherent high risk of gastric cancer: in 102 cases with severe atrophic corpus gastritis (SACG), in 5 cases with severe atrophic antrum gastritis (SAAG), and in 15 cases with severe atrophic pangastritis (SAPG) (atrophy both in corpus and in antrum) found among 916 subjects from three family series (265 from gastric cancer families, 425 from randomly selected control families and 226 from pernicious anaemia families). There is no way to screen directly atrophic gastritis restricted to the antral mucosa. In pangastritis atrophy of antral glands causes a failure of the hypergastrinemic reaction of achlorhydria. The combination of S-PGI less than 25 micrograms/l + S-gastrin less than 200 pmol/l detected 80.0% of our cases with SAPG, and only 17 subjects of 794 (2.1%) were false positives i.e. who had not advanced atrophic gastritis. The risk of gastric cancer may be significantly higher in SAPG than in SACG. The estimated prevalence of SAPG was 3% in random-family members over 60 years. The combination of S-PGI and S-gastrin is recommended when the cost/benefit ratio in the screening program of gastric cancer is considered and people from a general population are selected for endoscopic studies.

Serum alpha 1-antitrypsin (A1AT) allo- and phenotypes (including M1, M2 and M3 alleles) were studied in 99 patients with gastric ulcer (GU) and 56 patients with duodenal ulcer (DU) using agarose isoelectric focusing. The results were compared with the A1AT data of a random population sample of similar genetic background (1422 persons). An increase in M2 allotype and M1M2 phenotype as well as a decrease in Z allotype of A1AT was seen in GU in comparison to DU and the random population. There were no particular clinical features which would distinguish patients with M2 allotype from the remainder of the GU group. However, a trend toward elevated serum pepsinogen I and II levels in patients with M2 allotype was seen. When the pepsinogen levels were compared in the GU patient groups with and without M2 allotype, matched between themselves by the state of the gastric mucosa, a statistically significant difference was revealed between pepsinogen II levels in these two groups. No associations were found between DU and any of the A1AT phenotypes.

The possibilities to screen atrophic corpus gastritis with serum pepsinogen I (S-PGI) and serum gastrin (S-gastrin) concentrations have been studied in 774 subjects: 71 index subjects selected from a general population at random, 353 of their first-degree relatives, 276 first-degree relatives of patients with gastric cancer, 53 patients with pernicious anaemia, and 21 of their relatives. Discrimination function analysis was calculated from members of random and gastric carcinoma families. S-PGI less than 30 ng/ml had a high sensitivity for severe diffuse atrophic corpus gastritis (SDAG) alone (89.5%) and SDAG + severe patchy atrophic corpus gastritis (SPAG) (89.1%). Respective figures for specificity were 91.5% and 94.8%. The discriminatory power of S-PGI less than 30 ng/ml and S-PGI less than 25 ng/ml was of the same order. The sensitivity of low S-PGI decreased sharply in detection of slighter forms of atrophic corpus gastritis. The sensitivity of S-gastrin greater than 100 pmol/l to discriminate SDAG was 57.9% and SDAG+SPAG 58.7%. Respective figures for specificity were 90.2% and 92.2%. Diffuse and patchy atrophic changes behaved similarly regarding S-PGI and S-gastrin mean concentrations. Accordingly, the biopsy specimen with the severest atrophic changes indicates the degree of atrophy, which associates closely with the changes in S-PGI and S-gastrin. In conclusion, severe atrophic (diffuse or patchy) corpus gastritis may be screened from a general population with high sensitivity and specificity by low S-PGI less than 30 ng/ml, whereas an increased level of S-gastrin is too insensitive for this.

The mean pepsinogen I (PG I) level in a Finnish family sample was different in males and females and the difference was statistically significant. After exclusion of subjects with gastritis there remained 67 females and 68 males with morphologically completely normal antral and corpus mucosa. In females there was a significant increase of PG I with advancing age, the regression coefficient being 0.37 and statistically significant (p less than 0.01). In males no such increase was found, and individual cases revealed an almost random distribution with age. A similar increase with age has been noted in gastric acid output in females but not in males. Assuming that there is a linear relationship between PG I levels and the total chief cell mass, the PG I level would be determined by three main variables: thickness of the glandular layer, density of chief cells, and area occupied by chief cells. Of these variables the thickness and chief cell density showed neither in females nor in males any statistically significant increase with age, leaving the area as the variable which would account for the increase of PG I.

The behaviour of acid secretion, serum pepsinogen I and II (PG I and PG II) and morphology of the gastric mucosa were analyzed in 59 duodenal ulcer probands (DU probands), their 199 first-degree relatives and 228 control subjects. DU probands had as a rule antral gastritis with normal or slightly altered corpus mucosa, and higher mean peak acid output (PAO), PG I and II levels than their relatives and controls. Sibs of DU probands differed from their controls mainly with regard to morphology which showed features characteristic of DU probands, i.e. antral gastritis with normal or slightly altered corpus mucosa. Moreover, high PAO levels were found highly significantly more often in sibs of DU probands (13%) than in controls (6%). Likewise, the prevalence of endoscopic signs of active or past duodenal ulcer were present in sibs highly significantly more often than in controls and they accumulated in the subgroup of sibs with high PAO or PG I levels. It seems probable that the occurrence of high PAO and PG I levels in sibs of DU probands can be considered as signs of increased liability to duodenal ulcer. PAO and PG I were as expected significantly higher in male than in female probands, relatives and controls. Exclusion of cases of corpus gastritis decreased the levels but the sex difference persisted. PAO, PG I and II revealed a significant increase of the levels in middle age followed in older age in case of PAO and PG I by a significant decrease. The decrease was abolished when the cases of corpus gastritis were excluded suggesting an effect of gastritis. However, the earlier increase of the levels remained virtually unaffected although there was a uniform decrease of the mean values. This suggests the participation of factors unrelated to gastritis. The nature of the factors remains unknown, but literature data and data derived from our recent study suggest involvement of anatomical factors such as an increase in the size of acid and PG I secreting area.

It has been found by immunohistochemical staining that antigens normally found in gastric and/or intestinal epithelial cells are expressed in most differentiated duct cell carcinomas of the pancreas. Among 88 such tumors, 93% and 92%, respectively, expressed M1 and cathepsin E, markers of gastric surface-foveolar epithelial cells, 51% expressed pepsinogen II, a marker of gastroduodenal mucopeptic cells, 48% expressed CAR-5, a marker of colorectal epithelial cells, and 35% expressed M3SI, a marker of small intestinal goblet cells. Most of the tumors also expressed normal pancreatic duct antigens; 97% expressed DU-PAN-2, and 59% expressed N-terminus gastrin-releasing peptide. In agreement with these findings, electron microscopy revealed malignant cells with fine structural features of gastric foveolar cells, gastric mucopeptic cells, intestinal goblet cells, intestinal columnar cells, pancreatic duct epithelial cells, and cells with features of more than one cell type. Normal pancreatic duct epithelium did not express any marker of gastrointestinal epithelial cells, whereas such benign lesions as mucinous cell hypertrophy and papillary hyperplasia commonly expressed gut-type antigens but rarely expressed pancreatic duct cell markers. By contrast, lesions characterized by atypical papillary hyperplasia commonly expressed both gastric and pancreatic duct cell markers. Metaplastic pyloric-type glands expressed pepsinogen II and, except for their expression of cathepsin E, were indistinguishable from normal pyloric glands. In marked contrast, the immunohistochemical and ultrastructural features of 14 ductuloacinar cell tumors were those of cells lining terminal ductules, centroacinar cells, and/or acinar cells; none expressed any gut-type antigen. The results indicate that gastrointestinal differentiation is common in both benign and malignant lesions of pancreatic duct epithelium and suggest that duct cell carcinomas are histogenetically related to gastric- and intestinal-type metaplastic changes of epithelial cells lining the main and interlobular ducts of the pancreas.

M1, a mucin antigen, and cathepsin E, an aspartic proteinase, are both expressed in normal gastric superficial-foveolar epithelial cells. In this study, we determined by immunohistochemical staining the prevalence of these antigens in 316 gastric cancers representative of the main histologic types and stages of the disease. M1 was expressed in 201 cases (64%) and cathepsin E was expressed in 235 cases (75%) of the 313 cases investigated. Both antigens were expressed more commonly in diffuse and mixed cancers than in glandular tumors. M1 was found in 64 of 83 (77%) diffuse cancers and in 48 of 59 (81%) mixed cancers, but in only 74 of 146 (51%) glandular cancers. For cathepsin E, the prevalence was 93% in diffuse cancer, 81% in mixed cancer, and 71% in the 143 glandular cancers examined. Among 25 mucoid tumors, 15 (60%) expressed M1 but only eight (32%) expressed cathepsin E. Overall, 262 (84%) of the tumors expressed at least one of these antigens and of these, 173 (66%) expressed both antigens. No significant difference in the prevalence of M1 or cathepsin E was found between early and advanced cancer or between metastatic and nonmetastatic cancer. The two markers differed in their intracellular localization. In superficial-foveolar cells, M1 immunostaining was concentrated in secretory granules, Golgi complex, and luminal mucous, whereas cathepsin E was found in the endoplasmic reticulum. Moreover, cathepsin E, but not M1, was found in the enterocytes of duodenal villi and, occasionally, in mucopeptic cells. Parallel histochemical and ultrastructural investigations confirmed the occurrence in gastric cancer of foveolar-type cells, manifested by periodic acid-Schiff- and/or alcian blue-reactive mucous granules having a punctate substructure. We conclude that superficial-foveolar cell differentiation is common in gastric cancer and is a major component of this type of tumor. However, pure foveolar cell differentiation is rare. Rather, most gastric cancers consist of cells exhibiting features of foveolar, intestinal, and mucopeptic cell lines.

Sucralfate is a basic aluminum salt of a sulfated disaccharide. In this study, patients with gastric ulcer were given oral multiple doses of sucralfate prior to partial gastrectomy, and binding of the drug to the ulcer lesion and to nonulcerated mucosa was estimated by chemical determination of aluminum and sulfated disaccharide. The ulcerated mucosa was found to contain, on the average, 6-7 times more sucralfate per square centimeter than the control mucosa (P less than 0.01 and less than 0.05 for aluminum and sulfated disaccharide, respectively). The high affinity of sucralfate for ulcerated mucosa, particularly the sucrose sulfate moiety, supports previous data that the beneficial effect of sucralfate in ulcer disease is due in part to complex formation between sucrose sulfate and proteins at the ulcer site.

We have examined relationships among the aspartic proteinases in rat and human gastric mucosa by electrophoretic analysis in polyacrylamide gel and by immunoblotting and immunohistochemical staining using rabbit antisera to human pepsinogen I (PG I), pepsinogen II (PG II), and slow-moving proteinase. By electrophoretic analysis, the major proteolytic bands in mucosal extracts from each of three strains of rats had rates of anodal migration that were similar to the fastest migrating isozymogens of human PG I. However, immunoblots revealed that these bands and several minor proteolytic bands with slower rates of anodal migration reacted with antiserum to PG II. Two proteolytic bands in rat gastric mucosa that migrated concurrently with human slow-moving proteinase reacted with antihuman slow-moving proteinase reacted with antihuman slow-moving proteinase. None of the proteolytic bands in rat gastric mucosa reacted with anti-PG I. By immunohistochemical staining, anti-PG I failed to stain any cells in rat fundic gland or antral mucosa. By contrast, anti-PG II stained mucus neck and chief cells in fundic gland mucosa and pyloric gland cells in antral mucosa, and anti-slow-moving proteinase stained surface and foveolar epithelial cells throughout the stomach. The results indicate that the gastric mucosa of the rat does not contain PG I.

Among 7498 Japanese men who were examined from 1967 to 1970, 48 were subsequently diagnosed with stomach cancer and had premorbid stored sera available for serum pepsinogen I analysis. The median interval between serum collection and diagnosis of cancer was 44.5 months (range, 3 to 103 months). A low pepsinogen I level was found in 15 of the 48 patients with stomach cancer and in only six (6.3%) of 96 matched control subjects (p < 0.001). All 15 patients with low pepsinogen I levels belonged to the subgroup of 38 who had the intestinal-mixed-other histologic types of gastric cancer. This finding indicates that a low serum pepsinogen I level is a subclinical marker of increased risk for these histologic types of gastric cancer.