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Background and Aim: Gastric cancer is a major health burden in the Asia-Pacific region but consensus on prevention strategies has been lacking. We aimed to critically evaluate strategies for preventing gastric cancer., Methods: A multidisciplinary group developed consensus statements using a Delphi approach. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded., Results: Helicobacter pylori infection is a necessary but not sufficient causal factor for non-cardia gastric adenocarcinoma. A high intake of salt is strongly associated with gastric cancer. Fresh fruits and vegetables are protective but the use of vitamins and other dietary supplements does not prevent gastric cancer. Host-bacterial interaction in H. pylori infection results in different patterns of gastritis and differences in gastric acid secretion which determine disease outcome. A positive family history of gastric cancer is an important risk factor. Low serum pepsinogens reflect gastric atrophy and may be useful as a marker to identify populations at high risk for gastric cancer. H. pylori screening and treatment is a recommended gastric cancer risk reduction strategy in high-risk populations. H. pylori screening and treatment is most effective before atrophic gastritis has developed. It does not exclude the existing practice of gastric cancer surveillance in high-risk populations. In populations at low risk for gastric cancer, H. pylori screening is not recommended. First-line treatment of H. pylori infection should be in accordance with national treatment guidelines., Conclusion: A strategy of H. pylori screening and eradication in high-risk populations will probably reduce gastric cancer incidence, and based on current evidence is recommended by consensus.

Background: A biologically plausible link between gastro-oesophageal reflux (GOR), aspiration, and lung allograft dysfunction has been suggested, but there is no systematic evidence indicating the presence of gastric contents in the lung. We have tested the hypothesis that pepsin, as a marker of aspiration, is detectable in bronchoalveolar lavage (BAL) fluid of allograft recipients who had not reported symptoms of GOR., Methods: Standardised 3 x 60 ml surveillance BAL fluid samples from 13 chronologically sequential stable lung allograft recipients without chronic rejection (10 patients treated with a prophylactic proton pump inhibitor) were studied. Lavage supernatants were assayed by an ELISA based on a monospecific goat antibody for pepsin/pepsinogen. Pepsin levels were compared with those from four normal volunteer controls., Results: Pepsin levels were measurable in all allograft recipients, in keeping with gastric aspiration (median 109 ng/ml (range 35-1375)). In the control group the pepsin levels were below the limit of detection. Treatment with a proton pump inhibitor was not correlated with pepsin levels. There was no correlation between BAL fluid neutrophils and pepsin levels., Conclusion: These data demonstrate lung epithelial lining fluid concentrations of pepsin in lung allograft recipients which are much higher than blood reference levels, with no detectable pepsin in controls. This provides direct evidence of gastric aspiration, which is potentially injurious to the allograft.

Electrotitration curves (ETC) of a marker protein mixture, pH 2.5-5.65, and human pepsinogens were performed in an agarose gel, containing 2% acid carrier ampholytes, forming a pH range of 2.5-5. Although the establishment of the pH gradient by isoelectric focusing was not quite complete and linear, both biochemically and immunochemically different types of pepsinogen C (PGC) and pepsinogen A (PGA) zymogens as well as the acid isoelectric points (pI) marker proteins were separated with good resolution. Three main fractions of PGA (Pg3, Pg4, and Pg5) were detected. To obtain an exact determination of the pepsinogen pIs, a simple and very fast 10 s pressure blot technique was applied. Human pepsinogens were separated alone or mixed with pI marker proteins in the pH range 2.4-5.65. No effect of the markers was observed on the pepsinogen migration. To visualize the different protein samples in the gel and on nitrocellulose membrane, we have used colloidal gold (AuroDye) staining, proteolytic activity, and immunostaining with monoclonal antibodies anti PGA and PGC. The described method shows an ability to separate proteins at acidic conditions with a resolution comparable to isoelectric focusing with immobilized pH gradients, but much faster, easier, and cheaper. In addition, the technique allows us to determine precise and exact pI values, and is suitable for studies of the pepsinogen polymorphism and its role in gastric diseases.

The human gastric mucosa contains two main groups of aspartic proteinases, pepsin (EC 3.4.23.1) and gastricsin (EC 3.4.23.3), which differ by their structural, kinetic and immunological characteristics. The ratios between human aspartic proteases are important from the diagnostic point of view. Rabbit polyclonal antisera against human pepsinogen A and pepsinogen C (progastricsin) were obtained and tested for clinical purposes. Immunoblotting procedure seems to be a simple and sufficiently sensitive method for qualitative determination of pepsinogens in human gastric mucosa.

The ontogeny of pepsinogen C-producing cells in rat fundic glands was studied by means of light and electron microscopy using an antiserum raised against a synthetic peptide based on rat pepsinogen C. To confirm the immunocytochemistry results, the expression of rat pepsinogen C messenger RNA (mRNA) in the fundic gland was also examined by in situ hybridization using a digoxigenin-labeled RNA probe. In adult rats, pepsinogen C was produced by chief cells, mucous neck cells, and intermediate mucopeptic cells. Pepsinogen C-producing cells appeared in embryos as early as 18.5 days' gestation. The development of these cells could be classified into four stages: (1) 18.5 days' gestation to 0.5 days after birth; (2) 0.5 days to 2 weeks after birth; (3) 3-4 weeks after birth; (4) 4-8 weeks after birth. In embryos and young animals, pepsinogen C-producing cells were mucopeptic cells. By 4 weeks after birth, mucous neck cells could be distinguished morphologically. The maturation stages of the chief cells could be traced by electron microscopy along the longitudinal axis of the rat fundic gland by double-staining with anti-pepsinogen C antibody and periodic acid-thiocarbohydrazide-silver proteinate. Positive reactions for pepsinogen C and pepsinogen C mRNA expression were detected in mucous neck cells. Therefore, we conclude that mucous neck cells are precursor cells of chief cells. Mucous neck cells, intermediate cells, and chief cells are in the same differentiating cell lineage.

The effects of dietary urea supplementation and of a 10-week trickle infection regime, simulating chronic exposure to Haemonchus contortus, on the zymogenic population of the abomasa of Hampshire Down lambs was examined. At necropsy a variety of parameters including plasma pepsinogen concentration, the wet weights of abomasal fundic mucosal pieces and the amounts of pepsinogen contained in them, were assessed. Tissue pepsinogen concentration was measured as the total, acid-stable proteolytic activity present in mucosal homogenates, as well as immunohistochemically. The immunohistochemical findings were quantified using computer-aided image analysis. Elevation of plasma pepsinogen concentrations in infected animals was of borderline significance (P = 0.06). The fundic mucosae of infected animals were heavier (P < 0.02) than those of control animals, but there was no overall change in the pepsinogen content of tissues. Immunohistochemistry revealed that infected animals had increased numbers of zymogenic cells, due to mucous cell hyperplasia and the adaptation of cells to produce both mucins and pepsinogen. The pepsinogen content of chief cells, the major source of pepsinogen in uninfected animals, was reduced in infected lambs. Image analysis confirmed that at a mid-point of the mucosa of infected animals there was increased pepsinogen-specific immunoreactivity that corresponded with areas of mucosal hyperplasia. Mucous cell hyperplasia might therefore allow the maintenance of pepsinogen secretion in infected animals even if chief cell output is reduced.

Background: To date, it is unclear whether Helicobacter pylori infection is associated with disturbances of gastric emptying or acid secretion in patients with functional dyspepsia (FD). Our aim was to investigate whether, in the long run, cure of H. pylori infection significantly influences gastric emptying of solids, acid secretion, and gastrin and pepsinogen I (PGI) release in patients with FD., Methods: Thirty-eight consecutive H. pylori-positive patients with FD, whose complaints were scored for severity and frequency on the basis of a validated symptom questionnaire, were initially enrolled in the study. They were randomized to receive an eradicating regimen consisting of omeprazole plus clarithromycin and tinidazole for 1 week or full-dose ranitidine for 3 weeks. In 33 patients (18 H. pylori-cured and 15 with persistent infection) basal and pentagastrin-stimulated acid secretion, fasting and meal-induced gastrin concentrations, fasting serum PGI levels, and gastric emptying of solids were determined before and 6 months after therapy., Results: In the 18 H. pylori-cured patients meal-induced gastrin and fasting PGI levels were significantly reduced after 6 months as compared with pretreatment values (peak serum gastrin, 76.0 +/- 23.4 versus 111.9+/-37.4 pg/ml; PGI, 57.1+/-23.4 versus 72.9+/-29.1 ng/ml), whereas they remained virtually unchanged in the 15 patients with persistent infection. In contrast, both basal and stimulated acid secretion and gastric emptying time of solids remained unmodified over time in both groups of patients., Conclusions: We confirm that also in patients with functional dyspepsia H. pylori eradication in the long run significantly reduces gastrin and PGI release as a result of improvement in the underlying antral gastritis, but this is not accompanied by modifications of gastric emptying of solids or acid secretion.

We previously reported the induction with N-methyl-N-nitrosourea (MNU) of mouse glandular stomach carcinomas showing a gastric phenotype but variation in histologic appearance, as with human gastric carcinomas. In the present study, we established two cell lines, designated MGT-40 and MGT-93, from MNU-induced mouse glandular stomach carcinomas. These cell lines are keratin-positive and grow as epithelial monolayers in culture, requiring transforming growth factor alpha, epidermal growth factor or insulin/transferrin for optimal growth in addition to 10% fetal bovine serum. Retention of the differentiated phenotype for gastric surface mucous cells has been confirmed by cathepsin E immunohistochemistry and reverse transcriptase-polymerase chain reaction for mouse spasmolytic polypeptide. Neither transplantability in nude mice nor colony formation on soft agar was observed, except in one subline. Chromosome analysis revealed aneuploidy with modal chromosome numbers ranging from 58 to 78 and no specific structural abnormalities. This is the first report of cell lines derived from mouse glandular stomach carcinomas. They should prove useful for studies of the mechanisms of regulation of growth and differentiation.

Adenoma malignum of the uterine cervix (mucinous type of minimal deviation adenocarcinoma, mucinous MDA), is a unique neoplasm that is difficult to diagnose owing to the deceptively benign appearance of the tumour cells. The present study was undertaken to explore the phenotypic expression of this tumour compared with those of non-neoplastic cervical tissues and of cervical carcinomas of various types. Ten cases of mucinous MDA, 50 cases with non-neoplastic cervical tissues, 13 of cervical adenocarcinoma including the mucinous (endocervical or intestinal type) and endometrioid types, and 2 of mucoepidermoid carcinoma were examined by various histochemical staining methods, including those for gastric mucins, pepsinogen, lysozyme, chromogranin A and carcinoembryonic antigen. The results revealed that mucinous MDA characteristically exhibited gastric phenotypes. The presence of gastric metaplasia was also demonstrated in 9 cases of mucinous MDA and in 5 of the other cases examined. The 7 endocervical-type adenocarcinomas also included 4 that expressed gastric phenotypes, and 2 of the 3 intestinal-type adenocarcinomas showed the same properties focally. These results indicate the presence of a group of lesions expressing gastric phenotypes in the uterine cervix and suggest a close relationship between these lesions. Cervical adenocarcinomas expressing gastric phenotypes are probably derived from MDA.

Morphological and functional heterogeneity of parietal cells has been thought to be due to different maturation positions within the gastric gland. Morphodynamic studies have shown that 2% of parietal cells in mice derive from a pre-neck (chief) cell precursor. Intrinsic factor (IF) and pepsinogen, markers of rat chief cells, were used to determine if these proteins identified a subset of parietal cells that might reflect origin from the pre-neck cell lineage. The zymogenic region of the rat stomach and gradient-isolated fractions enriched in parietal and chief cells were fixed in 10% buffered Formalin or in Bouin's solution. Immunostaining was performed using indirect immunoperoxidase histochemistry and double-labeled immunofluorescence with antibodies raised against human IF, pepsinogen II, and H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase). In intact tissue, parietal (H(+)-K(+)-ATPase-positive) cells were found starting at the upper edge of the isthmus, but parietal cells positive for IF and pepsinogen were only found from just below the isthmus and neck region to the base of the gastric gland. Three to four percent of isolated parietal cells were positive for these ectopic markers. This subset of cells was also positive for H(+)-K(+)-ATPase. Thus products of rat chief cells are expressed in a subset of parietal cells. The percentage of positive cells is similar to that predicted to be derived from the pre-neck (chief) precursor lineage in the mouse. The distribution of these cells to the lower neck and base of the gland suggests that the expression of chief cell products is consistent with either predetermination by lineage or parietal cell maturation or with both processes.

The influence of chemoprophylaxis with an ivermectin sustained-release bolus in the first grazing season on the resistance of cattle to gastrointestinal nematodes during the following grazing season was investigated. In 1993 and 1994 dairy replacement calves were either given one bolus at the start of their first grazing season or left untreated. The two groups were grazed separately on a pasture that was divided into two similar sized paddocks. Faecal egg counts, serum pepsinogen and antibody levels were measured to evaluate host-parasite contact. Pasture infection levels were estimated by pasture larval counts and worm counts in tracer calves. After winter housing the animals were monitored during their second grazing season on a pasture that was also divided into two similar sized paddocks. Acquired resistance to gastrointestinal nematodes was evaluated by faecal egg counts and weight gains. Again, pasture infection levels were determined and pepsinogen and antibody levels were measured. During the first grazing seasons gastrointestinal nematode infections were controlled very effectively by the bolus, as shown by the greater weight gains, the negligible faecal egg counts and the low serum pepsinogen and antibody levels in the treated calves. In contrast, all parameters showed extensive parasite-host contact in the untreated animals. The efficient prophylaxis in the treated groups resulted in low levels of larval contamination on the paddocks grazed by the treated animals, compared to moderate infection levels at the end of both first grazing seasons on the paddocks grazed by the untreated animals. During the second grazing seasons (1994 and 1995) the faecal egg output was low in all groups. Although in the previously treated animals faecal egg counts were consistently higher, the differences were minimal, resulting in comparable levels of larval contamination on both paddocks. Serum pepsinogen and antibody levels were not significantly different between the groups and indicated a similar level of larval uptake on both paddocks. No negative effect of the previous chemoprophylaxis on the clinical condition and the weight gain of the second season grazing animals was observed.

CdxA, a chicken homeobox-containing gene related to caudal in Drosophila, has been implicated in the regionalization of endoderm. It is reported here that, in the development of the chicken embryo, CdxA expression appears in the endoderm at day 1.5 of development as bilateral bands on either side of the splanchnopleure which later contribute to intestinal epithelium. The CdxA-expressing area extends medially and caudally as formation of the gut tube progresses. It is also shown that the rostral limit of CdxA expression demarcates the boundary between stomach and duodenum after day 3 of development. CdxA is not expressed in digestive tract appendages which open into the intestine, such as pancreas, liver and allantois. Early restriction of CdxA expression in intestinal lineage suggests that the intestinal specification involving CdxA expression commences before the gut tube is formed. The expression of CdxA in epithelial-mesenchymal tissue recombinants suggests that mesenchymal influence regulating CdxA expression plays an important role in confirming the boundary between the stomach and intestine. Chronological change in the spatial distribution of CdxA transcripts and the results of tissue recombination experiments, together with precise fate maps of early endoderm and splanchnic mesoderm, lead to a model of mechanisms by which intestinal specification is brought about.

We developed mouse monoclonal antibodies (Abs) against pepsinogen C with highly purified antigen isolated from gastric mucosa. The Abs were used to construct a two-site sandwich-type assay for pepsinogen C with time-resolved fluorometry as a detection technique. The assay has a detection limit of 0.1 microgram/L and is precise (within-run and day-to-day CVs < 11%). We used this assay to measure pepsinogen C in seminal plasma, breast cyst fluid, amniotic fluid, male and female serum, serum from patients with prostate cancer, urine, breast tumor cytosolic extracts, breast milk, and cerebrospinal fluid. Highest pepsinogen C concentrations were in seminal plasma, followed by breast cyst fluid and amniotic fluid. We found no correlation between prostate-specific antigen concentrations and concentrations of pepsinogen C in serum of prostate cancer patients, and concluded that this marker is not useful for either diagnosing or monitoring prostatic carcinoma. The availability of a highly sensitive, reliable, and convenient method for quantifying pepsinogen C will allow investigations into the possible diagnostic value of this analyte in various clinical conditions, including benign breast diseases, breast cancer, fertility, and pregnancy.

In this work, we reported a method for the purification of pepsinogens from human gastric mucosa with high pressure gel filtration chromatography (HPLC) and medium pressure anion exchange chromatography (MPLC). First, the two fractions of Pg1 and mixture of PGI and PGII were separated from pepsinogens with HPLC on a Bio-Sil SEC-125 column within 50min. Then the mixture of fractions of PGI and PGII was further separated with MPLC on a Bio-Scale Q2 column within 30min.

Background/aims: Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by exocrine gland impairment. Up to now there have been no reports dealing with gastric mucosa involvement in this autoimmune condition, which is frequently associated with Sjögren's syndrome. The aim of this study was to investigate the morphologic, biochemical and immunological features of the gastric mucosa in PBC., Methods: A cross-sectional study with matching was performed. Thirty-three PBC patients (30 F, 3 M, mean age 58 years; 17 with stage II-III, and 16 with stage IV disease) and 33 sex- and age-matched dyspeptic controls were included. Six biopsy specimens from the fundus (2), body (2) and antrum (2) were taken from all patients and controls. A serological assessment was performed for each subject, i.e. pepsinogen A (PGA), pepsinogen C (PGC), gastrin (G), and antibodies against Helicobacter pylori (anti-Hp IgG)., Results: Endoscopic gastritis was found in 22 PBC patients (66.6%). There was no difference between PBC patients and controls regarding the percentage of subjects with mild, moderate, severe or atrophic gastritis (AG). There was no difference in gastric mucosal involvement between PBC subjects with or without secondary Sjögren's syndrome. A discrepancy was observed in the data obtained with respect to Helicobacter pylori (H. pylori) infection. H. pylori colonization was significantly more frequent in controls than in PBC patients (79% vs 49%, p < 0.002), but anti-Hp IgG were detected in the same percentage in the two groups (90% vs 83% respectively). There was no difference between the two groups in the PGA, PGC, PGA/PGC ratio, or gastrin. Eight PBC patients had esophageal varices., Conclusions: PBC patients are not characterized by chronic atrophic gastritis. Even though they present chronic gastritis with the same prevalence as dyspeptic controls, and show signs of previous H. pylori infection as frequently as dyspeptic patients, they are actually much less frequently infected. The reasons for this observation are unclear.

A combination of reversed-phase high-performance liquid chromatography (RP-HPLC) and capillary zone electrophoresis (CZE) was used for characterization of alpha-chymotryptic digests of human pepsinogen A, human pepsinogen C (both isolated from stomach mucosa of patients suffering from gastric cancer), swine pepsinogen and their dephosphorylated forms. Combining RP-HPLC and CZE for peptide mapping allowed to detect phosphorylations in molecules of the above mentioned gastric zymogens. We have found one phosphate group in the molecule of human pepsinogen A and two phosphate groups in the molecule of human pepsinogen C. The investigated sample was obtained from stomach mucosa of a patient suffering from gastric cancer. An increased number of phosphate groups in molecules of human pepsinogen seems to be associated with gastric cancer. The developed method represent a suitable tool for studying relationships between specific phosphorylations of proteins and cancerogenesis or potentially could serve for early diagnosis of gastric cancer.

We performed ultrastructural immunogold localization of osteopontin in the mucosa of human stomach. This adhesive glycoprotein was present in mucous and chief cells of the epithelial layer and in macrophages in the lamina propria. Parietal and endocrine cells of the epithelial layer and mast cells and plasma cells in the lamina propria did not contain osteopontin, serving as internal negative controls. Subcellular localizations of osteopontin included secretory granules and synthetic organelles in mucous and chief cells and phagolysosomes in macrophages. Extracellular concentrations of osteopontin were present in the glycocalyx and in an electron-lucent band between epithelial surface cells and the gastric lumen. Paracellular edema between the epithelium of the same cells was devoid of osteopontin. Immunogold localization of pepsinogen II was done to identify cells with mixed granule populations and contents of multicompartmental secretory granules. These studies revealed mucous cell granules and chief cell granules, each containing compartmentalized storage products, which included osteopontin and mucigen in mucous cells and osteopontin and pepsinogen II in chief cells. Cytochemical controls for the immunogold localizations were negative. The subcellular distribution of osteopontin in human gastric mucosa suggests possible roles for this glycoprotein in barrier function, host defense, and/or secretion.

There are five stages in the development of the cat's gastric glands: 1. During the stage of the indifferent epithelium from day 19 to day 24, the anlage of the stomach develops with all layers; 2. The stage of gland formation from day 24 to day 41 is the beginning of the gland buds. They develop in connection with endocrine cells on day 34 into primitive oxyntic and primitive mucous cells. The latter form the basis for all other cells, including the surface mucous cells; 3. During the stage of gland evagination from day 42 to 55, the anlagen are separated into primitive pits and tubules, while the cells continue to differentiate and the first intermediate cells are seen; 4. The stage of gland branching from day 56 to birth is characterized by the formation of additional glands at the bottom of the pits which change the ordinary anlagen into branched glands. During this stage, the cardiac glands are formed; 5. In the stage of gland maturation from birth to the 9th week, the peptic cells are formed and the glands start functioning. The oxyntic cells show carbonic-anhydrase activity and signs of acid secretion, and, between the weeks 4 and 8, the peptic cells contain pepsinogen, producing a negative reaction to PAS and a positive reaction to HID. Mucous cells and mucous neck cells produce PAS- and AB-positive mucin.

It has previously been assumed that, in contrast to porcine pepsinogen, the human pepsinogens are not phosphorylated. The present investigations show that phosphorylation does contribute to the electrophoretic heterogeneity of the human pepsinogens. A new chromatographic method for analysis of phosphoamino acid was developed. Quantitative determinations of phosphoserine were carried out after hydrolysis in 6 mol l-1 HCl (4 h, 110 degrees C). The recovery value of an authentic sample of phosphoserine, treated in parallel with the unknown samples, was used for calculations.

The human gastric mucosa contains five isozymogens of pepsinogen (pepsinogens PGA1-PGA5), two isozymogens of gastricsinogen (gastricsinogens PGC6-PGC7) and zymogens of cathepsins. Ratios between some individual pepsins or pepsinogens are very important from a diagnostic point of view. The ratio of pepsinogen 3 to pepsinogen 5 is significant marker of gastric cancer and gastric ulcer. High-performance ion-exchange chromatography is an easy and fast method for determination of ratios between individual proteolytic zymogens in human gastric mucosa and thus could serve for additional diagnosis of gastric diseases.

We have recently shown that antigastric autoantibodies occur in a considerable number of Helicobacter pylori (H. pylori) infected patients. Particularly, autoantibodies to canaliculi within parietal cells of human gastric body mucosa are strongly associated with H. pylori gastritis. In this study we analyzed the implications of this type of autoantibody for histological and for clinical parameters of the disease. 126 patients with upper abdominal complaints were included in our study. Several histological and clinical parameters were evaluated. Presence of anticanalicular autoantibodies is significantly correlated with a higher degree of gastritis in the body mucosa, with atrophic changes in the gastric mucosa, with elevated fasting gastrin levels and a decreased pepsinogen I/pepsinogen II ratio. These data indicate, that the host's autoimmune response to canaliculi of parietal cells is of relevance for the pathogenesis and outcome of H. pylori gastritis.

Faecal nematode egg counts were monitored in 184 Scottish Blackface lambs during natural exposure to a mixed, predominantly Ostertagia circumcincta infection and 12 lambs were selected which showed consistently zero (low count group; nine lambs) or consistently positive faecal egg counts (high count group; three lambs). These lambs were then treated with anthelmintic and challenged with 50,000 infective larvae of O. circumcincta and monitored thrice-weekly for 38 weeks; they were then re-challenged with another 50,000 infective larvae of O. circumcincta and monitored for a further 8 weeks. All sheep gave positive egg counts following deliberate infection. However, there was considerable variation among sheep in the size and timing of the peak in egg production. In particular, the pattern of mean values for faecal egg counts was different in the two groups. Egg counts were lower in the later periods of the extended infection in both groups of sheep. During the first half of the extended infection, egg counts were lower in sheep from the low count group, but during the second half of the infection the pattern was reversed and egg counts were lower in sheep from the high count group. There was a weak positive correlation between egg counts following anthelmintic treatment and 28 days exposure to natural infection and egg counts 28 days after a deliberate infection. Egg counts in the later stages of the deliberate infection were strongly but negatively correlated with egg counts following natural infection. The results of these studies show that differences in egg count following natural infection can be reproduced in experimental infections and that there is substantial variation in the pattern of egg production over time in different sheep. They also suggest that naturally resistant lambs are better able to delay worm development than naturally susceptible lambs.

The present study was undertaken to elucidate the relationship between the distribution of potentially proliferative tumor cells and the organoid differentiation of tumor cells in gastric carcinomas. One hundred four specimens of surgically removed human gastric carcinomas, including 68 and 36 specimens of early and advanced carcinomas, respectively, were studied by using a battery of histochemical techniques. Serial 3-microns thick paraffin sections were stained by galactose oxidase-cold thionine Schiff-paradoxical concanavalin A staining (GOCTS-PCS), or were immunostained for pepsinogen types I and II, lysozyme, and proliferating cell nuclear antigen (PCNA). In addition, to identify proliferative tumor cells parts of fresh carcinoma tissues were incubated in a solution containing bromodeoxyuridine (BrdU), embedded in paraffin, and immunostained for BrdU. The results indicated that in intramucosal carcinoma tissues showing organoid differentiation the proliferative tumor cells were located predominantly between the covering epithelial cell type tumor cells and the glandular mucous cell type tumor cells, and the disturbance in the distribution of proliferative cells coincided with the submucosal invasion.

The aspartic protease progastricsin (EC 3.4.23.3) is found in all parts of the mammalian stomach and has also been found extragastrically. In humans and monkeys, seminal fluid usually contains high concentrations of progastricsin. Using immunohistochemistry and in situ hybridization, we determined in this investigation the origin of seminal progastricsin to be the epithelia of both the prostatic gland and the seminal vesicles. In addition, Northern (RNA) blotting showed the presence of a 1.8-kb transcript in both tissues. Seminal progastricsin clones from two human prostatic gland cDNA libraries were isolated and sequenced. The combined sequence manifested only six nucleotide differences from the published genomic and gastric cDNA sequence. One conservative base substitution was present in both libraries. N-Terminal amino acid sequencing of all 43 residues of the seminal proenzyme and the first 34 residues of the mature enzyme yielded sequences identical to those deduced from cDNAs derived from both gastric and prostatic origin. The results obtained indicate that gastric and seminal progastricsin are products of the same gene and that the observed molecular differences between the zymogen from the two sources are probably due to posttranslational modifications.

Aims: To investigate the immunohistochemical expression and the serum concentrations of pepsinogen I and II in different histological types of gastric cancer as compared with other gastric disorders., Methods: Formalin fixed, paraffin wax embedded tissue specimens of 38 gastric cancers obtained from surgical cases were used for the immunohistochemical studies performed with the avidin-biotin complex method using monoclonal antibodies against purified pepsinogen I and II. Pepsinogen concentrations from serum obtained from the above patients, from patients with various other gastric disorders, and from normal controls were measured with a rapid non-radioactive one step enzyme linked immunosorbent assay (ELISA)., Results: Eight of 38 (21%) and seven of 38 (18%) gastric carcinomas showed immunoreactivity to pepsinogen I and pepsinogen II, respectively, without any correlation to histological classification or differentiation. Decreased pepsinogen I concentrations and low pepsinogen I:II ratios were found specifically in cases of gastric carcinoma and polyp, in good accordance with the immunohistochemical results., Conclusions: Low serum pepsinogen I concentrations and a low pepsinogen I:II ratio are predictive of gastric neoplasia, correlating with low tissue immunoreactivity to monoclonal antibodies raised against pepsinogen I and II. For mass screening of gastric disease including carcinoma, ELISA using a one step immunoassay performed in the present study is a rapid and reliable non-radioactive method of detecting serum pepsinogen. In addition, immunohistochemical studies showed that pepsinogen production may be increased or diminished as a result of tumour histogenesis, depending on the area of origin and the processes of cell transformation and dedifferentiation.

The development of progastricsin-immunoreactive cells in the abomasal mucosa of cattle fetuses was studied by immunohistochemistry. Progastricsin-immunoreactive cells were detected first in the fundic and pyloric regions of 52 cm in crown-rump length (CRL) fetuses (about 180 days of gestation). The frequency of occurrence of progastricsin-immunoreactive cells and the intensity of their immunoreactivity increased with the progress of gestation, but most of these immunoreactivities were restricted to the basal portion of the fundic and pyloric glands. After birth, in the fundic mucosa, progastricsin immunoreactivities were found not only in the chief cells but also in the surface mucous cells of the gastric pits. In the cow, the immunoreactivity of the surface mucous cells was even stronger than that of the chief cells. In the pyloric mucosa, progastricsin immunoreactivities were found in the gastric pits and in the basal portion of the pyloric glands, but they were organized in small groups and showed a patchy distribution in the basal portions.

Purpose: Here we evaluate in breast cancer patients the prognostic value of pepsinogen C, a proteolytic enzyme involved in the digestion of proteins in the stomach that is also synthesized by a significant percentage of breast carcinomas., Patients and Methods: Pepsinogen C expression was examined by immunoperoxidase staining in a series of 243 breast cancer tissue sections, and results obtained were quantified using the HSCORE system, which considers both the intensity and the percentage of cells staining at each intensity. Evaluation of the prognostic value of pepsinogen C was performed retrospectively in corresponding patients by multivariate analysis that took into account conventional prognostic factors. The mean follow-up period was 48.5 months., Results: A total of 113 carcinomas (46.5%) stained positively for this proteinase, but there were clear differences among them with regard to the intensity and percentage of stained cells. Pepsinogen C values were significantly higher in well differentiated (grade I, 89.1) and moderately differentiated (grade II, 88.5) tumors than in poorly differentiated (grade III, 27.7) tumors (P < .001). Similarly, significant differences in pepsinogen C content were found between estrogen receptor (ER)-positive tumors and ER-negative tumors (85.9 v 41.2, respectively; P < .05). Moreover, results indicated that low pepsinogen C content predicted shorter relapse-free survival duration and overall survival duration (P < .0001). Separate Cox multivariate analysis for relapse-free survival and overall survival in subgroups of patients as defined by node status showed that pepsinogen C expression was the strongest factor to predict both relapse-free survival and overall survival in node-positive patients (P < .0001 for both) and node-negative patients (P < .005 and P < .01, respectively)., Conclusion: Pepsinogen C is a new prognostic factor for early recurrence and death in both node-positive and node-negative breast cancer. In addition, and in contrast to most studies that concern the prognostic significance of proteolytic enzymes in cancer, pepsinogen C production by breast cancer cells is associated with lesions of favorable evolution.

The stomach of the lesser mouse deer was studied at the light microscopic level using histological and immunohistochemical methods. The stomach was clearly differentiated into rumen, reticulum including reticular groove, a small transition zone and abomasum. The mucosal surface of the rumen, reticulum and transition zone was lined with a stratified squamous epithelium and that of the abomasum with a simple columnar type. The epithelial keratinization was weak in the rumen, floor of the reticular groove and transition zone, while it was strong in the reticulum, especially on the tip of the reticulum papillae. Large sinusoidal capillaries were often present in the ruminal papillae. In the ruminal mucosa, a thin layer of alpha-smooth muscle actin immunoreactive cells was demonstrated by immunohistochemistry. The muscularis mucosae of the reticulum was continuous and well-developed. The transition zone appeared as a nonglandular area having many low mucosal folds and two layers of tunica muscularis. The abomasal mucosa consisted of cardiac, proper gastric and pyloric glands. Cells immunoreactive for bovine pepsinogen and bovine prochymosin antisera were demonstrated in the abomasum. It is suggested that the characteristic features observed might be adaptations to a relatively rapid passage and rapid absorption of the fermentation products. There is some evidence that the transition zone is not a part of either the floor of the reticular groove or the abomasum, suggesting a possible reevaluation of the term used for the reticulo-abomasal orifice in the mouse deer.

Adrenalectomy caused a significant decrease in the mucosal level of pepsinogen in the adult rat stomach. This decrease was mainly due to a reduction in the level of the main component of rat pepsinogen isozymogens, namely, Pg1 and in the level of expression of Pg1 mRNA, with a maximal effect being evident 48 hours after operation. Immunohistochemical analysis revealed that the level of expression of Pg1 in the pepsinogen-producing cells was decreased throughout the stomach mucosa and this decrease was especially marked in the immature chief cells located in the glandular neck of the fundic mucosa. Adrenalectomy also increased the proliferation of mucosal cells and suppressed the expression of cathepsin E and class III mucin, markers of differentiated stomach mucosa. All these changes were reversed by hydrocortisone replacement and the extent of the recovery of the level of Pg1 mRNA was dependent on the dose of hydrocortisone, indicating the transcriptional control of the Pg1 gene by hydrocortisone. The observed results suggest that the continuous presence of glucocorticoids is necessary for active transcription of Pg1 gene in fully differentiated stomach mucosa and that glucocorticoids are important regulators of both the function and the morphology of stomach mucosal cells.

Saliva secreted by right and left parotid glands was collected using Leshley-Krasnogosky's capsules. Salivary secretion and aminolytic activity were found to be higher on the chewing side than on the contralateral. Bilateral differences in salivary gland secretion of alkaline and acid phosphatases and pepsinogen were less expressed. Salivary secretion in right-handed and left-handed subjects and in patients with hemiplegias after brain stroke was studied by citric acid stimulation. Bilateral asymmetry of enzymic secretion was revealed, particularly marked in the patients: not only the volume of salivary production and enzyme debit, but salivary enzymic activity on the side of motor paralysis were lower than on intact side. Bilateral functional asymmetry of secretion was more manifest for amylase than for other enzymes whose origin is largely influenced by recretion process.

Potential proteolytic activity of prochymosin (PCh) and pepsinogen (PG) as well as relative activity of the proteolytic fractions in the mucosal extracts of the whole stomach, pyloric region of the stomach and duodenum were investigated. The main activity in the lambs stomach after birth demonstrated PCh however a small amount of PGA activity was also present. The highest activity of PCh from the whole stomach was observed in day 2 and 3, PG activity from the whole and pyloric region of the stomach increased in the first day of life and later was not significant by changed. Mucosal extracts of the whole stomach contained 3 to 4 of pepsinogen fractions of the fast migration (Pg1, Pg2, Pg3 and Pg4) in which Pg3 was of the highest activity in the majority of lambs. Pyloric region revealed 3 fractions: Pg2, of a small and Pg3 and Pg4 of high and equal activity. In duodenum Pg3 and Pg4 were of equal activity. The beginning of Pg2, Pg3 and Pg4 relative activity changes were observed in lambs stomach in respect to increase of Pg2 and decrease of Pg3 activity. The group of 3-4 fractions of slow electrophoretic migration contained probably progastricsin of small--and prochymosin of the highest activity within this group and a small non-pepsinogen fraction.

The paper deals with a description of the biochemical properties of the isoforms of pepsinogen pepsin of gastric mucosa and blood serum in children suffering from duodenal ulcerative disease as well as in atrophic and subtrophic lesions of gastric mucosa. Atrophic gastritis was found to involve an inhibited biosynthesis of the Ist fraction of pepsinogen while ulcerative-erosive lesions of the gastro-duodenal area--an increased level of the 3rd isoform of pepsinogen.

Special immunohistochemical stains for the identification of gastroenteropancreatic antigens in two cases of primary retroperitoneal mucinous cystoadenocarcinomas (PRMC) show that these tumours have patterns similar to ovarian mucinous tumours. Markers of pyloric type gastric mucosa differentiation (M1, cathepsin E, concavavalin A, pepsinogen II) are mostly positive in benign and borderline areas with endocervical type differentiation, while immunoreactivity for intestinal cell markers (M3SI and CAR-5) and for DU-PAN-2 is present mainly in frankly malignant areas, regardless of differentiation type. DNA analysis shows a point mutation of K-ras oncogene at codon 12 (GGT to CGT) in one case. The immunohistochemical and genotypic similarity of PRMC and ovarian mucinous tumours may indicate similar mechanisms in their histogenesis.

Serum pepsinogen A (PGA) and total pepsin activity (PA) in gastric juice were investigated in 87 duodenal ulcer patients. The analysis of data shows a significant increase of PGA and PA in comparison with controls. The grouping of duodenal ulcer patients according to Helicobacter Pylori (HP) infection revealed in HP positive patients a significant increase of PGA, while PA does not change. This contrast may be due to various factors: in particular the two parameters are an expression of different cellular activities and the PA in gastric juice is expression of all pepsinogens. It can be concluded that the damaging action of HP on duodenal mucosa is due to a direct action and not related to alteration of pepsin activity in gastric juice. Moreover, serum PGA can be held as useful parameter of HP infection.

Parietal cells of gastric glands are specialized to produce acid. Tight junctions between the parietal cells and their neighbouring cells (usually chief cells and mucous cells, less commonly parietal cells) avoid acid back-diffusion. Alterations of these junctions are accompanied by a defective epithelial barrier function. The conditions leading to junction formation, e.g. during epithelial restitution and regeneration are entirely unknown. The present study has the purpose to establish an in vitro model which allows studying these junctions. Freshly isolated gastric epithelial cells of guinea pig, moderately enriched with parietal cells, were cocultured for 2 days. Highly specific staining techniques showed the following composition in the near-confluent monolayer: 45% parietal cells (succinic dehydrogenase-positive), 36% mucous cells (lectin-binding granules), 18% chief cells (pepsinogen-positive granules) and 1% subepithelial cells (vimentin-positive). Ultrastructural investigations of sections of these monolayers revealed a high tendency of parietal cells to form cell junctions with the following characteristics: 1) virtually all parietal cells formed junctions with their neighbouring cells; 2) only junctions, but no desmosomes, were observed among neighbouring parietal cells; 3) junctional complexes and desmosomes were regularly present between parietal cells and their neighbouring mucous and chief cells; 4) parietal cells were sometimes integrated into three-dimensional structures, resembling rudimentary gastric glands. In conclusion, parietal cells under standard coculture conditions, generate de novo the same types of cell junctions that are observed in the intact gastric epithelium. The results show that parietal cells in vitro spontaneously make junctions with parietal and non-parietal cells, resembling the junctions in the intact tissue.

Studies have been made on the isozymic composition of pepsinogen (polyacrylamide gel electrophoresis) and peptidase activity in gastric mucosa of the ground squirrel at various stages of hibernation. Eight pepsinogen isoforms were found in acid-producing zone of the mucosa, pyloric mucosa lacks first three of them, its peptidase activity being two times lower than in other parts of the stomach. During hibernation, no significant changes were found in fractional composition of pepsinogen, peptidase activity being decreased twofold only in the fundulus of the stomach, remaining practically constant in other parts of the latter. This finding indicates that the stomach is ready for the activity irrespectively of food uptake.

The presence of Pepsinogen II (PG II), gastral mucin (2B5), CA 19-9, BW 494 and Cytokeratin 20 (CK 20) was investigated in 69 adenocarcinomas of the esophagogastric junction (15 carcinomas in Barrett's esophagus, 9 distal esophageal carcinomas, 31 carcinomas of the cardia and 14 subcardial carcinomas). Evidence of gastric differentiation (expression of Pepsinogen II and/or gastric mucin) was found in more than 50% of the Barrett's carcinomas and the carcinomas of the cardia, but only in 20% of the subcardial carcinomas. High rates of antigen expression were found for the "intestinal" markers CA 19-9 (between 55.5% and 100%) and BW 494 (between 42.9 and 86.7%). CK-20 expression was detected to a significantly higher degree in Barrett's carcinomas (73.3%) than in the other groups (between 29% and 44.4%). These data indicate that the distribution of adenocarcinomas with gastric and/or intestinal differentiation at the esophagogastric junction forms a continuum without clear-cut borders.

The levels of serum pepsinogen I (PG I) and pepsinogen II (PG II) were determined by IRMA (immunoradiometric assay) and the ratio of PG I/II calculated in 37 patients with type A gastritis and concomitant pernicious anemia (PA) and in 97 with chronic gastritis (type B gastritis) among Japanese. In several patients from each group, PG I and PG II in the gastric mucosa were stained by an enzyme antibody assay to compare the percentage of positively stained cells with levels of serum PG I and PG II. The levels of serum PG I and PG II in chronic gastritis decreased as the degree of atrophy increased. Serum PG I and PG II levels in PA were lower than those of patients with severe atrophy. Most of serum PG I levels in PA were less than 10 ng/ml. The PG I/II ratio also decreased as the severity of atrophy increased, distinctly showing that in PA, the ratio were quite low and most of them are less than 1.0. Gastric mucosal pepsinogen showed a tendency similar to that of serum levels and also refrected the degree of atrophy. Therefore, by measuring these parameters it should be easier to determine the extent of atrophy, and to establish a serological diagnosis of type A gastritis associated with PA.

The radioimmunological method was used to examine the content of blood plasma gastrin and pepsinogen in the blood plasma and bioptate of gastric mucosa in 22 patients with duodenal ulcer and 20 patients with chronic atrophic gastritis. Patients with atrophic antral gastritis show a reduction of the blood gastrin level while the pepsinogen level remained unchanged. In atrophic fundal gastritis the gastrin content rose while the pepsinogen level dropped. There was a clear increase of the pepsinogen level both in the blood plasma and bioptate of the gastric mucosa. The obtained data are of diagnostic significance in duodenal ulcer and chronic gastritis.

An aspartic proteinase present in cyst fluid from women with gross cystic breast disease was purified by a procedure involving affinity chromatography on pepstatin-agarose and size-exclusion high performance liquid chromatography. The amino-terminal sequence of the purified breast proteinase was identical to that corresponding to gastric pepsinogen C. Additional data on cleavage specificity, pH optimum, and immunological properties supported the close relationship between both molecules. Northern blot analysis and polymerase chain reaction amplification studies performed on RNAs obtained from normal and pathological breast tissues demonstrated that the protein is produced by mammary carcinomas and cysts, but not by the normal resting mammary gland. Immunohistochemical staining of paraffin-embedded tissue sections confirmed the existence of a subset of tumors that have the ability to synthesize and secrete this pepsin zymogen. On the basis of these results, we suggest that pepsinogen C expression by human mammary epithelium may be involved in the development of breast diseases, being also of potential interest as a biochemical marker of the hormonal imbalance underlying these pathologies.

The immunohistochemical expression of pepsinogen I (PI) and pepsinogen II (PII) was studied in 103 gallbladder carcinomas, 25 non tumoral gallbladder lesions and 23 gallbladder cancer metastases. PI was positive in 6% of carcinomas and only in 2% of non tumoral contiguous mucosa. PII was positive in 46% of carcinomas and 43% of controls. Metastases were negative for both enzymes. Pyloric gland metaplasia of non tumoral mucosa adjacent to the tumor expressed PII in 68.9% and PI in 3.4% of cases. The same lesion in non tumoral gallbladders was positive for PII in 66.6% of cases, and no case expressed PI. There was no relationship between PI expression and the histological degree of differentiation. Only tumors with serosal or subserosal involvement were positive for PI. PII had a higher expression in early or well differentiated tumors. Tumors with pyloric gland metaplasia in the contiguous non tumoral mucosa expressed PII more frequently. Our results, based on the expression of PI and PII, suggest a relationship between the presence of pyloric gland metaplasia and some types of gallbladder cancer.

Dog gastric lipase (DGL) secretion is stimulated in vivo by urecholine, pentagastrin, histamine, 16,16-dimethyl prostaglandin E2, and secretin. Under fasting conditions, DGL is irreversibly inactivated by gastric acid below pH 1.5; consequently, DGL output can be underestimated. This problem has been resolved by buffering the acid or by using an antisecretory drug such as omeprazole during stimulation. There is a clear parallelism between the secretion of DGL and of gastric mucus. This observation led to the present investigation of the cellular localization of DGL using immunofluorescence techniques. Results showed that DGL is cytolocalized in mucous pit cells of gastric glands. Pepsinogen is found in chief cells. To the authors' knowledge, this is the first description of an enzyme (gastric lipase) secreted by mucous-type gastric cells. In contrast to other species, gastric lipase of the dog is located in cardiac, fundic, and antral mucosae.

The present paper describes mucous cells in the forestomach glandular region which immunoreacted to antibovine pepsinogen serum in adult and young bactrian camels, Camelus bactrianus (female, 25 years old; female, 6 months old; from Hilar Inner Mongolia, People's Republic of China, in August 1988). These immunoreactive cells in forestomach glandular regions also reacted to Alcian blue (pH 1.0) and/or periodic acid-Schiff. Cross-reactivity of antibovine pepsinogen serum against extracts from the forestomach glandular region was analyzed by Western blotting, supporting that this serum could detect pepsin and/or pepsinogen in the bactrian camel. It was suggested that mucous cells in forestomach glandular regions produce pepsinogen molecules.

The histogenesis of human stomach cancer was assessed based on the determination of the differentiation of component cancer cells. Specimens of 229 surgically obtained primary gastric cancers were used. Histochemical staining of mucins [paradoxical concanavalin A, galactose oxidase-Schiff (GOS), and sialidase-GOS sequence] and immunohistochemical demonstration of pepsinogens (Pg) I and II allowed the differentiation of gastric elements including mucous neck cells, pyloric gland cells, and surface mucous cells as well as intestinal goblet and absorptive cell types. Of 122 papillary and tubular adenocarcinomas, the proportion consisting mainly of intestinal type cells increased with progression from 22.9% (early) to 41.9% (advanced). Similarly, intestinal features increased with progression from 8.3% (early) to 25.4% (advanced) in the 107 poorly differentiated adenocarcinomas, signet ring cell carcinomas, and mucinous adenocarcinomas studied. A phenotypic shift from gastric- to intestinal-type expression was thus observed with progression of each histologic type of gastric cancer. Furthermore, tumors consisting mainly of gastric-type cells were commonly found within intestinal metaplastic mucosa, suggesting that this latter is not a preneoplastic lesion for gastric cancers in humans.

In an earlier study, we found compound tubular glands distributed in the lamina propria mucosae of human and fowl esophagus. Subsequently, we discovered bottle-shaped glands in the Japanese lizard and gecko esophagus in the same lamina as that of the human and fowl. Moreover those glands produced equivalent pepsinogen granules. We provide below, a detailed description on the results. 1. Bottle-shaped glands were distributed in the lamina propria mucosae of the Japanese lizard and gecko esophagus. 2. A large number of those glands were distributed in the lower region of the esophagus, but did not exist in the upper and middle regions of the esophagus. 3. The esophageal mucous membrane of the gecko and Japanese lizard were covered with a simple columnar ciliated epithelium, and the same epithelium reacted strongly to PAS and AB (pH 2.5), moderately to AB (pH 0.5) or negatively. 4. PAS-AB (pH 2.5) stain presented a dark blue color or a deep red color or a deep red and dark blue mixed color in one section. 5. The above-mentioned glands contained pepsinogen granules. 6. Those glands do not possess parietal cells.

We demonstrated a large number of pepsinogen granules in the esophageal pseudostratified ciliated epithelium of the rock snake. 1. The snake esophagus is covered with a pseudostratified ciliated epithelium. 2. This epithelium develop mostly in the upper portion of the esophagus. 3. Long supranuclear portions of the same cells are strongly PAS-positive and contain pepsinogen granules. Those cells possess cilia. 4. The strongly PAS-positive cells and pepsinogen granules decrease or are lost in the middle and lower portions of the esophagus. 5. Glands are distributed in the lamina propria mucosae of the esophagus of the Japanese lizard and gecko. Those in humans and the bird are compound tubular glands and those of the Japanese lizard and gecko are bottle-shaped. The pepsinogen granules of these glands are secreted into the excretory ducts and then discharged into the esophageal lumen. 6. However, the same granules of the snake are contained in the supranuclear portion of the epithelium and are secreted directly into the esophageal lumen. 7. The mode of pepsinogen granule secretion of the esophagus is most simple in the snake.

Some researchers have already described the fowl proventriculus. However, we believed there was a need for detailed carbohydrate histochemical investigations on the same glands. Moreover, some researchers had erred about the lamina muscularis mucosae. The results of these investigations are as follows. 1. The proventricular glands consist of both superficial and profound gastric glands. 2. The superficial glands are distributed in the lamina propria mucosae while the profound glands exist in the tela submucosa. 3. The superficial glands are simple, branched tubular glands. The columnar glandular cells are arranged in a simple layer and react strongly to PAS, AB (pH 2.5 and 0.5). These appear to be dark purple when they are stained with PAS-AB (pH 2.5). Some other methods have also been tried. 4. Judging from the data 3), the superficial gastric glands contain neutral, weak and strong acids, sulfuric and acid mucopolysaccharides, sialomucin, and II and III neutral mucus type. 5. Glandular cells in the body and basal portions of the superficial gastric glands contain a large number of fine pepsinogen granules. 6. Judging from the data of 3)-5), we believe that the superficial gastric glands are undifferentiated gastric glands and that they are same kinds of glands that are found in mammals. 7. A large number of profound gastric glands fill the tela submucosa. They are compound tubular glands, and are composed of many glandular alveoli. Their columnar glandular cells are arranged in a simple layer. 8. These glandular cells react moderately to PAS, negatively to AB (pH 2.5 and 0.5) and PAS-AB (pH 2.5). Moreover, we observed some other reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

In a series of 100 prostatectomy specimens obtained for adenocarcinoma, 107 additional incidental microscopic (less than 0.05 cm3) carcinomas were identified. Their morphologic features including location, histologic grade, and associated premalignant changes were documented. In 51 cases there was strong evidence of transition between microcarcinoma and the premalignant lesion, duct-acinar dysplasia. Invasive cancer was usually related to dysplasia through a characteristic intermediate morphologic stage of transitive glands. These glands were smaller than prostatic ducts; they appeared to arise by budding from dysplastic duct walls and showed the same distinctive lining epithelium. They were distinguished from invasive glands by their pseudo-stratified epithelial lining and by consistent association with a sparse, discontinuous basal cell layer. Cytoplasmic differentiation at the point of junction of invasive cancer with transitive or dysplastic glands was studied by immunohistochemical staining for the differentiation markers prostate-specific antigen and pepsinogen II, and staining for mucin. Markedly reduced cytoplasmic differentiation was common in dysplastic and transitive glands. Invasion often coincided with an abrupt increase in cytoplasmic differentiation with expression of ectopic differentiation products. This sequence of biologic changes should be tested in other carcinomas where the exact point of invasion can be identified.

In rabbit stomach, gastric lipase activity level was found to increase from birth to 30 days old (weaning), and then decreased. In contrast, pepsin activity only appeared between 30 to 45 days old, and increased till to the adult level. It was observed that maturation of gastric glands in cardial mucosa was a downward elongation process from the mitotic cell pool. These mitotic cells were always found in the neck of the gastric glands, corresponding to the bottom of the gland at 6 days old and to the mid-zone of the gland in adult. Location of rabbit gastric lipase (RGL) cells in cardial glands varied with age and was found along the pit of the gastric glands at 6 days old. The extent of this cellular location decreased with age, whereas a second RGL cell zone appeared below the mitotic cell area at 18 and 30 days old. At 45 days old, the pepsinogen cells appeared in the bottom of the gland, and consequently the RGL cells were located in the mid-zone of the gastric glands, between mitotic cells (neck of the gland) and pepsinogen cells (lower part of the gland). Ultrastructural study of cardial gastric glands revealed different morphologies of the secretion granules in the cells along the gastric glands. In 6-day-old rabbits, secretory granules were found uniformly electron dense in the bottom of the glands and were RGL-labeled by the immunogold technique. In the medium part of the glands, granules appeared biphasic, with a clear and a dense part, and RGL labeling was confined to the electron-dense part.(ABSTRACT TRUNCATED AT 250 WORDS)