Small intestinal plasma cells in coeliac disease

Using a modified immunoperoxidase technique to achieve optimum staining and reproducible counts of plasma cells in paraffin embedded tissue, IgA, IgM, IgE, and IgG plasma cells were studied in small bowel biopsies from 20 controls, 23 untreated coeliac patients, 19 treated coeliac patients, and seven patients with Crohn's disease not involving duodenum or jejunum. In controls the ratio of the mean counts for IgA, IgM, IgE, and IgG plasma cells was 2.5:1:1:1 respectively. In patients with untreated coeliac disease, counts of all types of plasma cell were significantly increased approximately two-fold compared with controls although for IgG cells there was considerable overlap. The ratio of the mean plasma cell counts in the untreated coeliac patients was 3.5:1.5:2:1. Counts fell significantly after treatment with a gluten-free diet. There was no significant difference between counts in the controls and the Crohn's disease patients. The changes found in coeliac disease may simply be a non-specific response to mucosal damage. The increases in IgA and IgM plasma cells, however, suggest that the deposits of extracellular IgA and IgM observed in coeliac mucosa are locally produced, and the increase in IgE plasma cells raises the possibility that reaginic type hypersensitivity may be involved in coeliac disease.     

Mucosal humoral immune response toHelicobacter pylori in patients with duodenitis

The humoral immune response to Helicobacter pylori infection in the duodenum has been investigated by short-term in vitro culture, ELISA, and immunoblotting techniques. H. pylori IgA secretion by duodenal bulb biopsies was significantly increased (P less than 0.001) in patients with duodenitis. The IgA response to H. pylori in patients with duodenitis was restricted to the first part of the duodenum; second part duodenal biopsies secreting significantly (P less than 0.001) less IgA during culture in vitro. H. pylori IgG antibody secretion by cultured biopsies was also significantly increased (P less than 0.01) in patients with duodenitis and those with gastric H. pylori infection but without duodenitis. Immunoblotting of duodenal bulb culture supernatants showed positive recognition by the mucosal IgA response of H. pylori antigens in the region of 120, 90, 61, and 31-26 kDa in patients with duodenitis. Serologically, such patients showed little evidence of IgA H. pylori antibodies by immunoblotting. These results demonstrate that the inflammatory response in the duodenal mucosa of patients with duodenitis represents a specific highly localized humoral response to H. pylori.     

Quantitative histological study of mucosal inflammatory cell densities in endoscopic duodenal biopsy specimens from dyspeptic patients using computer linked image analysis.

Inflammatory cell counting in endoscopic biopsy sections was carried out on duodenal mucosal samples from defined sites in patients with duodenal ulcer, duodenitis but no ulcer, non-ulcer dyspepsia, and asymptomatic controls using computer linked image analysis. The variables measured included polymorphonuclear and mononuclear cells per mm of superficial epithelium and per mm2 lamina propria. Duodenal ulcer crater margin and mucosal biopsy specimens from endoscopically inflamed mucosa in the group with duodenitis but no ulcer showed significantly higher inflammatory cell counts than endoscopically normal non-ulcer dyspepsia and control mucosa. Biopsy specimens from non-ulcer dyspepsia patients showed significantly higher lamina propria polymorphs than control group mucosa. Endoscopically normal duodenal ulcer and duodenitis but no ulcer mucosa also showed significantly higher acute and chronic inflammatory cell counts than controls. The prevalence of Helicobacter pylori in duodenal biopsy specimens was low (0-22%) and unrelated to local inflammatory response. Despite histological appearances, duodenal biopsy specimens from non-ulcer dyspepsia patients showed significantly higher inflammatory cell infiltration than control specimens, suggesting that at least some represent part of a spectrum of subclinical peptic disease.     

Cell renewal in non-specific duodenitis, ulcer-related duodenitis and duodenal ulcer. Experiments in Mastomys (Praomys natalensis)

Cell renewal in the duodenal mucosa of Mastomys was studied by autoradiography 1 and 24 h after intraperitoneal injection of tritiated thymidine. Non-specific duodenitis and duodenal ulceration were produced with a continuous infusion of histamine. Mucosal renewal in the duodenum of 30 control Mastomys was compared with 30 which received histamine dihydrochloride for 5 days. No abnormality developed in the controls, but 11 of the experimental group developed non-specific duodenitis and 12 duodenal ulcers. The size of the proliferative zone was increased in the Mastomys sacrificed 1 h after injection of tritiated thymidine which received histamine, compared with controls (p = 0.004). The number of labelled nuclei (p = 0.0003) and the size of the columns of labelled nuclei (p = 0.001) were increased in the Mastomys receiving histamine and sacrificed 24 h after injection of tritiated thymidine, compared with controls. The number of labelled nuclei (p = 0.004) and the size of the columns of labelled nuclei (p = 0.01) were increased in the Mastomys with ulcers compared with the other Mastomys which had received histamine. Cimetidine prevented duodenitis and ulceration, normalising the pattern of cell renewal. There was correlation between the severity of non-specific and ulcer-related duodenitis as judged by Lance's system and the number of labelled nuclei (Spearman rank correlation coefficient 0.771, p less than 0.002). Cell renewal increased as duodenitis became more severe and duodenal ulcers were found in duodenal mucosa where cell renewal was fastest.     

Ultrastructural changes in non-specific duodenitis

AIM: To investigate the ultrastructural and morphological changes of non-specific duodenitis (NSD) in an attempt to grade them according to the extent of the lesions. METHODS: Biopsies were taken from the mucosa of duodenal bulb of 44 patients selected from the patients undergoing upper gastrointestinal endoscopy for epigastric discomforts. From each patient, two pinch biopsies on the same area were obtained from duodenal bulb. One was for scanning electron microscopy and the other was stained with hematoxylin-eosin, Warthin-Starry silver and both were then examined under light microscope. A total of 12 specimens (three from each degree of the normal and I-III of NSD diagnosed and graded by histology) selected from the 44 patients were dehydrated, critical point dried, coated with gold palladium and examined under a JEOL JSM-30 scanning electron microscope (SEM) at 20 kV. RESULTS: According to the ultrastructural morphologic changes, non-specific duodenitis was divided into normal (as control group), mild, moderate and severe degrees according to results of SEM. The normal villi of duodenal bulb were less than 0.2 mm. There were inflammation cells, occasionally red blood cells and macrophages on the mucosal epithelial surface. Erosion and desquamation of epithelium could be seen. Three cases (25%, 3/12) had gastric metaplasia and Helicobacter pylori(H pylori) infection could be found in 5 cases (41.67%, 5/12) in duodenal bulb mucosa. The most distinctive feature was the ulcer-like defect on the surface of epithelial cells. CONCLUSION: Non-specific duodenitis is a separate entity disease caused by different factors. SEM is of value as an aid in the diagnosis of mucosal diseases of duodenum.     

Altered Concentrations of Gastrin-Releasing Polypeptide and Somatostatin in Fundic and Duodenal Bulb Mucosa of Patients with Duodenal Ulcer Disease

The concentrations of gastrin-releasing polypeptide, somatostatin (SS), and gastrin in extracts of endoscopically obtained biopsies from the fundus, antrum, and duodenum of patients with uncomplicated bile stones (controls) or duodenal ulcer disease were measured with specific radioimmunoassays. The validity of the tissue sampling was confirmed by characteristic and significant differences between gastrin concentrations at the different biopsy sites. Gastrin-releasing polypeptide levels were at their highest in the fundic and duodenal bulb compared to the antrum in controls (p less than 0.01), whereas no differences in gastrin-releasing polypeptide content of the different parts of the stomach were found in duodenal ulcer patients. Compared to controls gastrin-releasing polypeptide in duodenal ulcer patients was reduced in fundic and duodenal bulb mucosa (p less than 0.01). SS levels were highest (p less than 0.05) in the first part of duodenum in controls. Compared to controls duodenal ulcer patients had lower SS concentrations present in fundic (p less than 0.01) and highest SS concentrations present in duodenal bulb mucosa (p less than 0.01). There was no correlation between acid secretion and mucosal gastrin-releasing polypeptide or SS concentrations in any part of the stomach and duodenum.     

Quantitation of immunoglobulin-containing cells in the jejunal lamina propria in tropical sprue.

Ten patients with tropical sprue (TS) and 10 with irritable bowel syndrome (IBS) as controls were studied to characterize the immunocytes in the jejunal mucosa. IgA cells numbered 516,155 +/- 48,715 cells/mm3 in TS and 729,308 +/- 146,011/mm3 in the IBS patients. IgG cell counts were 28,885 +/- 8,081/mm3 in TS and 10,615 +/- 4,100/mm3 in IBS; IgM counts were 170,729 +/- 25,015/mm3 in TS and 169,253 +/- 45,353/mm3 in IBS. A positive correlation was present between IgM-bearing plasma cells and corresponding serum immunoglobulins (r = +0.71; p less than 0.05). No correlation was evident between the different immunocytes (IgA, IgG, and IgM) and the duration of illness, serum albumin, and tests for absorption of fat, B-12, and D-xylose (p greater than 0.05). The gut immunocytes expressed in absolute numbers were higher in our controls and TS patients than reported in Western populations.     

十二指肠球部微小黏膜隆起的临床分析

目的探讨十二指肠球部直径≤0.5cm黏膜隆起性病变的内镜特征、病理及其与临床的关系。 方法回顾性分析解放军总医院海南分院消化科2012年8月至2018年3月期间25例十二指肠球部微小黏膜隆起性病变的内镜表现特点及病理。 结果25例患者内镜表现为单个或多个广基息肉状隆起,10例患者于十二指肠球部黏膜隆起行活检病理检查,其中,十二指肠球慢性炎3例,十二指肠球慢性炎伴腺体增生2例,十二指肠球胃黏膜异位5例。 结论十二指肠球部黏膜直径≤0.5 cm的广基息肉状隆起多为慢性炎症所致的良性增生性病变及胃黏膜异位。     

Low activities of disaccharidases associated with inflamed duodenal bulb mucosa

In order to establish whether an enzymatic method (a "functional" test) could be used instead of the histological picture as an indicator of damage to enterocytes of duodenal mucosa, biopsies were taken from 39 patients with upper gastrointestinal symptoms suggestive of peptic ulcer disease, but without active ulcers at endoscopy. Eleven patients with a normal appearance of the duodenal bulb mucosa and twenty-eight patients with various degrees of endoscopic inflammation ("bulbitis") were evaluated. The histological degree of duodenitis was assessed, and the activities of maltase, invertase, trehalase and lactase in the biopsy specimens were measured. Disaccharidase activities were inversely proportional to severity in both endoscopic and histological scoring of degree of inflammation. Low disaccharidase activities were also present in patients with endoscopic inflammation of the duodenal bulb, but without histological duodenitis. Focal and especially widespread gastric metaplasia was, in itself, significantly associated with low disaccharidase activities. The correlation between endoscopic and histologic scoring of inflammation of duodenal mucosa was not significant as assessed by kappa statistics. A previous history of peptic ulcer disease was significantly more common in patients with, than in those without, endoscopic inflammation of the duodenal bulb.     

Epithelial Cell Proliferation in Duodenal Ulcer

Epithelial cell proliferation in the duodenum was investigated in 50 patients by incubating mucosal biopsy samples with tritiated thymidine, followed by autoradiography. Fifteen patients had a normal duodenum, 15 duodenal ulcer undergoing elective surgery, 10 perforated duodenal ulcer, and 5 severe non-ulcer-associated duodenitis. The mean crypt cell labelling index in the duodenal bulb of controls was 8.8 ± 0.4% (mean ± SEM), at the edge of perforated ulcers 19.1 ± 2.0%, at the edge of elective ulcers 18.6 ± 1.4%, and in biopsy specimens from non-ulcer-associated duodenitis 14.0 ± 1.2%. The mean labelling index in the distal first part of duodenum of control patients was 9.1 ± 0.8 similar to the values found in histologically normal specimens distal to ulcer or duodenitis. The results indicate active epithelial cell proliferation in both duodenal ulcer and duodenitis. There was no evidence of impairment of epithelial cell proliferation in duodenal ulcer patients.     

Epithelial cell proliferation in duodenal ulcer

Epithelial cell proliferation in the duodenum was investigated in 50 patients by incubating mucosal biopsy samples with tritiated thymidine, followed by autoradiography. Fifteen patients had a normal duodenum, 15 duodenal ulcer undergoing elective surgery, 10 perforated duodenal ulcer, and 5 severe non-ulcer-associated duodenitis. The mean crypt cell labelling index in the duodenal bulb of controls was 8.8 +/- 0.4% (mean +/- SEM), at the edge of perforated ulcers 19.1 +/- 2.0%, at the edge of elective ulcers 18.6 +/- 1.4%, and in biopsy specimens from non-ulcer-associated duodenitis 14.0 +/- 1.2%. The mean labelling index in the distal first part of duodenum of control patients was 9.1 +/- 0.8 similar to the values found in histologically normal specimens distal to ulcer or duodenitis. The results indicate active epithelial cell proliferation in both duodenal ulcer and duodenitis. There was no evidence of impairment of epithelial cell proliferation in duodenal ulcer patients.     

Rectal mucosal plasma cells in inflammatory bowel disease.

To achieve optimum staining and reproducible counts of plasma cells in paraffin embedded tissue with the immunoperoxidase technique we have found it essential to obtain a plateau count by titration of antisera for each specimen. This modification was used to study IgA, IgM, IgE, and IgG plasma cells in rectal biopsies from 20 controls, 20 patients with ulcerative proctocolitis, 20 with Crohn's colitis, 20 with non-specific proctitis, 15 with bacterial colitis, and seven with Crohn's disease but no apparent large bowel involvement. Counts were correlated with the characteristic histological features of inflammatory bowel disease. In controls the ratio of the mean counts for IgA, IgM, IgE, and IgG plasma cells was 8:3:3:1. All types of plasma cells were very significantly increased in the patients with ulcerative proctocolitis, Crohn's colitis, and non-specific proctitis and counts correlated with the severity of inflammation. There was no significant difference between the counts in these three groups. All counts tended to be higher in bacterial colitis than in controls, the difference being significant for IgA and IgE. When matched for severity of inflammation there was no significant difference between the counts in bacterial colitis and inflammatory bowel disease. The counts in patients with Crohn's disease but no large bowel involvement were not significantly different from controls. These results suggest that changes in plasma cell counts in inflammatory bowel disease are a non-specific response to mucosal damage, possible by a luminal irritant, and do not differentiate the type of inflammatory bowel disease.     

Helicobacter pylori, smoking and gastroduodenitis.

There is epidemiological evidence of an association between cigarette smoking and gastritis. To find out whether the reason for this might be related to the presence of Helicobacter pylori, biopsies were taken from the gastric corpus and antrum and from the duodenal bulb in 106 consecutive patients referred for oesophagogastroduodenoscopy because of epigastric pain. Patients with ulcer disease or cancer were excluded. The biopsy specimens were cultured for H. pylori and examined histologically for the presence and grade of gastritis and duodenitis. Thirty-five percent of the patients were H. pylori-positive and 57% had histological gastritis; 37% were cigarette smokers and among these, H. pylori was found significantly less frequently than in non-smokers (18 and 45%, respectively; 2p = 0.0083). Among patients colonized with H. pylori, gastritis was found in 89% compared to 39% in non-colonized patients (2p less than 0.0001). In spite of this, 51% of the smokers and 60% of the non-smokers (2p = 0.85) had histological gastritic mucosa. No differences in the severity of the gastritis or the duodenitis in patients with histologically positive findings could be seen when comparing smokers to non-smokers and H. pylori-positive to H. pylori-negative patients.     

Cimetidine tablets or suspension for the prevention of gastrointestinal mucosal lesions caused by non-steroidal, anti-inflammatory drugs

We compared the protection offered by cimetidine 400 mg b.i.d. as tablets or suspension vs. placebo, in Naproxen-induced gastrointestinal damage in 17 healthy males. Upper endoscopy was performed before and after each drug period, with separate evaluation of duodenal mucosa distal to the duodenal bulb. 51Cr-EDTA absorption tests were done to assess distal mucosal integrity, and symptoms were registered. All regimens caused a significant increase in mucosal damage (p less than 0.01). Cimetidine tablets gave a significantly lower damage score than placebo for gastritis/duodenitis and hemorrhagic lesions in the stomach/duodenal bulb, and for the sum of scores in both scoring regions (p = 0.02). Cimetidine suspension was not significantly different from placebo for any of the endoscopic parameters. The 51Cr-EDTA absorption was significantly increased after all drug periods. However, there was no difference between the three drug combinations. Symptoms reported were mild and equal in the three groups. Cimetidine tablets offered protection against Naproxen-induced mucosal damage, primarily in the stomach and duodenal bulb, but lacked any effect on permeability changes. Cimetidine suspension was not significantly different from placebo in any respect.     

Systemic and local immune responses against Helicobacter pylori urease in patients with chronic gastritis: distinct IgA and IgG productive sites

BACKGROUND: Helicobacter pylori urease is a major target for immune responses among various bacterial components in H pylori infected patients. AIMS: To analyse the relation between systemic and local humoral immune responses to H pylori urease and grades of chronic gastritis. PATIENTS: Seventy five patients with chronic gastritis associated with H pylori infection were classified into three groups (grade I, superficial gastritis; II, atrophic gastritis, quiescent; or III, atrophic gastritis, active). METHODS: Anti-H pylori urease specific antibodies in the serum, gastric juice, and biopsy specimens were determined by ELISA or western blotting analysis. The sites for H pylori urease and its specific antibody producing B lymphocytes were confirmed by immunohistochemical analysis. RESULTS: In the sera of patients with grade I gastritis, weak IgG but relatively strong IgG responses to H pylori urease were observed; dominant strong IgG responses were detected in grade II gastritis. In grade III gastritis, significant IgG and IgA responses were obtained. A similar pattern of IgA and IgG responses was detected in gastric juice and tissue. H pylori urease specific, antibody producing B cells were not found in the gastric mucosa of patients with grade I gastritis despite the presence of such B cells in the duodenal bulb. Specific B cells were observed in the gastric mucosa of patients with grade II and III gastritis with atrophy. CONCLUSIONS: Purified H pylori urease, together with localisation of its specific antibody producing B cells, are useful for serological testing and histopathological analysis for determining the stage of chronic gastritis and studying the pathogenesis of H pylori infection.     

Mucosal cell proliferation in duodenal ulcer and duodenitis.

Mucosal cell proliferation in the first part of the duodenum was studied in 24 patients using a tissue culture technique in which endoscopic biopsies were subjected to autoradiography after exposure to tritiated thymidine. Eight patients had a normal duodenum, eight had duodenal ulcer, and eight had symptomatic chronic non-specific duodenitis. The mean crypt labelling index (LI) in normal duodenum was 8.8 0.4% (SEM). Increased labelling indices of 15.6 +/- 1.7% were found near the edge of duodenal ulcers and 17.8 1.8% in duodenitis. Treatment with cimetidine reduced both the severity of duodenitis and the mean crypt LI. The LI of histologically normal duodenal mucosa distal to ulcer of duodenitis was similar to that of the control subjects' mucosa. The increased mucosal cell proliferation seen in severe duodenitis, either alone or associated with duodenal ulceration, suggested that erosions and ulcers arose when the crypts passed into 'high output failure' and were unable to compensate for further epithelial cell loss. There was no evidence in out study for a generalised failure of mucosal cell proliferation in duodenal ulcer or duodenitis.     

IgG3 and IgG4 cells are increased in active ulcerative colitis

Cells containing various subclasses of IgG and IgA were counted in the rectal and colonic mucosae from 14 pediatric patients with ulcerative colitis (UC) and in rectal biopsy specimens from 10 control subjects using monoclonal antibodies and the peroxidase-staining method. In both the patients and controls, the IgG1 cells predominated. The numbers of IgG1, IgG2, IgG3 and IgG4 cells were highest in the colonic specimens of patients with UC. The numbers of IgG3- and IgG4-containing cells were increased in the rectal mucosa of untreated UC patients compared to controls. In the rectal mucosa of patients with UC, the percentage of IgG2 cells was decreased compared to the controls (20 vs. 28%; p less than 0.05). In the great majority (37 out of 40) of specimens the number of IgA1 cells was higher than that of IgA2. The median number of IgA1 cells in the rectal specimens of untreated patients was slightly higher than that in the rectal specimens of the controls, for IgA2 the numbers were similar. Accentuation of colorectal IgG3 and IgG4 responses may be characteristic early changes in UC.     

Biochemical diagnosis of duodenitis

The activities of enteropeptidase, alanine aminopeptidase, sucrase, and leucine aminopeptidase were determined in mucosa biopsies taken from three defined places of the duodenum and in duodenal juice. We examined 23 adults with a histological proven normal mucosa and 10 patients suffering from duodenitis grade I. Using multivariate evaluation of all the four enzyme activities of the three mucosa sites, we could differentiate duodenitis from normal mucosa with an efficiency of 88%.     

Crohn's Disease in Endoscopic Biopsies of the Gastric Antrum and Duodenum

Forty-five patients with Crohn's disease in whom the upper gastrointestinal tract was normal by x-ray were examined by gastroduodenoscopy. Biopsies were analyzed histologically from the lower esophagus, body of the stomach, gastric antrum and duodenal bulb. Cell counts were made of 500 connective tissue cells of the duodenal mucosa. Histological examinations and cell counts of the duodenal mucosa were also performed on 50 healthy volunteers used as controls.
Histological lesions were found in 19 Crohn's disease cases; 11 (24%) were considered pathologically diagnostic and all these were found in the antrum or duodenum. In 11 the mucosa was endoscopically normal. Granulomas were present in three cases (7%), all from normal appearing mucosa. Microscopic alterations of the antrum and duodenum, similar to findings in the normal appearing rectal mucosa, support the concept that Crohn's disease involves the entire alimentary canal and that lesions are seen grossly only where the disease is most advanced.     

Intraluminal pH in the stomach, duodenum, and proximal jejunum in normal subjects and patients with exocrine pancreatic insufficiency

In situ pH was measured simultaneously with microelectrodes in the stomach, duodenal bulb, midduodenum, duodenojejunal junction, and proximal jejunum. Fourteen healthy subjects and 8 patients with exocrine pancreatic insufficiency were studied under fasting conditions and for 3 h after a standard liquid meal. The luminal pH gradient was steepest in the proximal 10 cm of the duodenum, where acidity was reduced from pH 2 to pH 5 in the fasting state and from pH 1.7 to pH 4.3 in the second and third postprandial hour. Acidity was further reduced in the distal duodenum to a pH between 5 and 6 at the duodenojejunal junction. The frequent wide and rapid pH fluctuations seen in the duodenal bulb were gradually reduced along the duodenum and became rare in the jejunum. In patients with pancreatic insufficiency, duodenal or jejunal acidity did not differ significantly from the controls, with the exception of the single 10-min period occurring 70-80 min after the meal when duodenal bulb pH was 2.1 as compared with 3.1 in the normal subjects (p less than 0.05). All patients, including 2 patients with a very high duodenal acidity, demonstrated a duodenal pH gradient as steep as that found in the normal subjects, indicating sources of bicarbonate other than the pancreas.