Production of secretory component and pathogenesis of gastric cancer in Helicobacter pylori-infected stomach.

The purpose of this study was to examine the production of secretory component (SC) and immunoglobulin A (IgA) in the gastric mucosa with Helicobacter pylori infection and to investigate the influence of immunological reactions on various phases of infection (gastritis, intestinal metaplasia, gastric cancer). Production of SC and IgA was assessed by immunohistochemical staining in (1) endoscopic biopsy samples of H. pylori-eradicated cases (n = 25), and (2) surgically resected stomach tissues of H. pylori-positive gastric cancer cases, intestinal type (IGC, n = 25) and diffuse type (DGC, n = 25). Before eradication therapy, all samples showed positive staining of SC and IgA in epithelial cells, and IgA was also positive in plasma cells in the mucosal layer. H. pylori bacteria were positively stained for SC and IgA. After treatment, the degree of SC and IgA staining in epithelial cells was reduced with successful eradication; but with intestinal metaplasia, SC staining was positive regardless of the results of treatment. In nonmetaplastic mucosa, SC-positive cells were increased in the glandular neck zone to the surface mucosal layer; and the intensity of SC staining was increased in proportion to the degree of mucosal inflammation and IgA-positive cell aggregation. In intestinal metaplasia, SC was positive irrespective of the degree of inflammation. Most cancer foci also showed positive staining of SC, irrespective of histological type. Production of SC and IgA was thought to be a specific reaction against H. pylori infection, occurring from the early to the late stages and not limited to intestinal metaplasia. It was suggested that immunological reactions against H. pylori infection might generally be involved with the pathogenesis of intestinal metaplasia and both histological types of gastric cancer (IGC and DGC).

Association of Helicobacter pylori and diffuse type gastric cancer.

The major purpose of this study was to evaluate the association of Helicobacter pylori and diffuse type gastric cancer (DGC) clinicopathologically (study 1). The second aim was to investigate genetic differences of H. pylori in patients with DGC and intestinal type cancer (IGC) (study 2). The prevalence of H. pylori and the types of histopathological changes were evaluated in resected early gastric cancer (DGC; 25 patients, IGC; 25 patients). Genetic differences of H. pylori in DGC patients (n = 19) and IGC patients (n = 22) were analyzed by polymerase chain reaction (PCR) methods in terms of restriction fragment length polymorphism patterns of the ureB gene and cagA gene positive rates. All patients had evidence of H. pylori infection in the resected stomach, but the positive rate for H. pylori in the area surrounding cancer was 52% (in DGC; 56%, IGC; 48%). But in 40.0% of DGC cases (10/25), mucosal atrophy and intestinal metaplasia were rarely seen in the area surrounding cancer and the positive rate of H. pylori was 80.0% (8/10), in contrast, in 60.0% of IGC cases (15/25), atrophy and metaplasia were progressed and positive rate of H. pylori was 26.7% (4/15) in the area. UreB gene products from 89.5% of DGC cases (17/19) were unable to be digested by Spe I. 31.8% of products from IGC cases (7/22) were also unable to be digested by Spe I, but the positive rate of cagA gene in this group was higher than other groups. The high prevalence of H. pylori infection in DGC patients suggests that H. pylori plays a role in the pathogenesis of DGC, but in the stomach with DGC, it is considered atrophy and intestinal metaplasia are not so implicated in H. pylori, compared with IGC. A genetic specificity of H. pylori in DGC and IGC was indicated by the results, suggesting that H. pylori may play different roles in the pathogenesis of DGC and IGC.

Bacteria closely resembling Helicobacter pylori detected immunohistologically and genetically in resected gallbladder mucosa.

A microorganism with close immunohistological and genetic resemblance to Helicobacter pylori was found in the resected gallbladder mucosa of a 41-year-old woman. The woman was admitted to hospital complaining of fever and right hypochondrial pain. Cholecystectomy was carried out under the diagnosis of gallstones and cholecystitis. A microorganism resembling H. pylori (stained with H&E, Giemsa, and Wartin-Starry) was detected incidentally on pathological examination. The microorganism was also positive for immunohistochemical staining. An amplification reaction was seen on genetic examination by the polymerase chain reaction (PCR) method (urease beta-genes). Our findings suggest that H. pylori may be present in tissues other than gastric mucosa.

Gastric mucosal damage accompanying changes in mucin induced by histamine in rats.

The present study was carried out to clarify the mechanism of histamine-induced gastric mucosal damage in rats. Following an injection of histamine (80 mg/kg), pH dropped within 30 min. and then recovered control value (pH = 4-5) 4 hr later. The decrease in mucosal mucin content and the appearance of haemorrhagic erosions followed the drop in pH. The recovery of mucosal mucin content preceded the healing of haemorrhagic erosions and pH recovery to the control level. Histamine also caused qualitative changes in corpus mucins. These qualitative changes induced by histamine were eliminated at 7 hr following the administration of histamine. It appears from the present results that increase in HCl and decrease in mucins induced by histamine bring about gastric damage.

Efficacy of famotidine in patients with acute gastric mucosal injury after continuous infusion of cisplatin plus vindesine.

The effect of famotidine (H2 blocker) on the gastroduodenal mucosal injury induced by chemotherapy in non-small-cell lung cancer patients was prospectively evaluated from the clinical and endoscopic findings obtained in a randomized double-blind study. The patients, who were administered cisplatin (25 mg/m2/day, continuous infusion, days 1-5) and vindesine (3 mg/m2, bolus, days 1 and 8), were randomized into two groups, those administered famotidine (40 mg/day, oral) and those administered the placebo. The patients were examined by gastroduodenoscopy within 7 days before and after chemotherapy. There were 27 patients in the famotidine group and 28 patients in the placebo group. The gastric mucosal score after chemotherapy was significantly lower in the famotidine group than in the placebo group (P < 0.01), and in the 42 patients without symptoms than in the 13 patients (placebo group: 8, famotidine group: 5) with upper gastrointestinal symptoms (P < 0.01). The pH of the gastric juice after the chemotherapy significantly decreased in the placebo group (P < 0.05), and was significantly lower in the placebo group than in the famotidine group (P = 0.01). The co-administration of famotidine was effective in the prevention and control of chemotherapy-induced gastric mucosal injury.

Changes in levels of mucosal glycoprotein on cysteamine-induced duodenal ulcers in rats.

Duodenal ulcers were induced in rats by cysteamine administration. Time-course changes in duodenal hexosamine, blood flow and intragastric pH were measured, as well as changes in the susceptibility of Brunner's glands to concanavalin A (Con A) staining. Hexosamine contents in the duodenum decreased significantly at 5 and 24 h. In the control group, Brunner's glands were stained brown using Con A staining. One day after cysteamine administration, the extent of Con A staining markedly decreased. At 3 and 7 days, gland susceptibility to staining was essentially the same as that of the control group.

Gastric mucus glycoprotein in different rat strains.

The extent of gastric damage induced by aspirin was found to differ according to rat strain. The occurrence of ulcers varied, from high to low, in the following strain order: Donryu, Sprague-Dawley (SD) and Wistar. The content of corpus mucus glycoprotein was essentially the same in all the strains: about 6 mg as hexose of dry tissue. Antral mucus glycoprotein content increased in the order Wistar, SD and Donryu: 7.1, 8.3 and 9.1 mg, respectively. Gastric mucus glycoprotein carbohydrate composition was essentially the same in all three strains. The relatively low proportions of N-acetylglucosamine, galactose and sialic acid from the antrum was a characteristic feature in contrast to mucus glycoprotein from the corpus which contained a high proportion of these sugars.

A possible regulatory role of Ca++-calmodulin system in cellular cholesterol ester hydrolysis in the steroidogenic response to ACTH in bovine adrenocortical cells.

In order to corroborate the regulatory role of Ca++-calmodulin system in the steroidogenic response to adrenocorticotropic hormone (ACTH), the effects of calmodulin inhibitors (chlorpromazine, trifluoperazine, and W-7) on cortisol production and cellular cholesterol ester hydrolysis induced by ACTH in bovine adrenocortical cells were examined. Three calmodulin inhibitors diminished not only the cholesterol ester hydrolysis and cortisol production induced by ACTH in the presence of Ca++, but also inhibited the Ca++-induced hydrolysis and cortisol production in the absence of ACTH. Neither cortisol production in crude mitochondrial fraction nor the ACTH-induced Ca++-influx was affected by chlorpromazine. These results indicate that Ca++f-calmodulin system plays a significant regulatory role in the supply of free cholesterol to the adrenal mitochondria in the steroidogenic response to ACTH.