Duodenal Epithelium Research Articles

Ageing and duodenal morphometry.

Small bowel morphometry was studied in 25 subjects under the age of 70 years and 22 over the age of 70. There was no evidence of malabsorption or malnutrition in either group. Two distal duodenal endoscopic biopsy specimens were examined morphometrically. There were no significant correlations between age and areas of duodenal surface epithelium, crypts and lamina propria, heights of villi and surface epithelium, depth of crypts, crypt to villus ratio, number of intraepithelial lymphocytes, duodenal architecture, enterocytes, brush border and Brunner glands. Contrary to previous reports there was no evidence for a significant effect of age on proximal small bowel morphometry.

Effects of nonsteroidal anti-inflammatory drugs and misoprostol on gastroduodenal epithelial proliferation in arthritis

In this study, quantitation of the epithelial proliferation status of gastric glands and duodenal crypts was performed using endoscopic biopsy specimens from patients with rheumatological conditions requiring long-term anti-inflammatory and analgesic therapy, testing the hypothesis that long-term administration of nonsteroidal anti-inflammatory drugs (NSAIDs) may lead to enhanced epithelial cell proliferation in the stomach and duodenum. After a 1-week washout period from NSAID administration, specimens were taken from endoscopically normal gastric antrum and duodenum, and microdissection was used to quantitate mitoses in these sites. Endoscopy and biopsy were then repeated after 2 weeks of NSAID administration, during which patients received in addition either the prostaglandin E1 analogue misoprostol (10 patients) or a placebo (10 patients). Mitotic counts in gastric glands increased similarly and significantly in the two groups from (mean ± SEM) 4.45 ± 0.57 to 7.69 ± 1.08 (P < 0.001) in the NSAID + placebo-treated group and from 4.31 ± 0.53 to 7.68 ± 1.08 (P = 0.006) in the NSAID + misoprostol-treated group. Similar changes took place in the duodenal crypts, from 5.44 ± 0.68 to 8.60 ± 1.28 (P = 0.013) in the NSAID + placebo-treated group and from 4.68 ± 0.56 to 6.35 ± 0.63 (P = 0.011) in the NSAID + misoprostoltreated group. NSAIDs increased the proportion of glands and crypts with bifid or more complex architectural forms. In a small group of patients, misoprostol alone did not alter mitotic rate in glands or crypts over 4 weeks. Thus, NSAIDs increase the rate of proliferation in endoscopically normal gastric and duodenal epithelium of patients with arthritis. This may form one of the mechanisms underlying gastric and duodenal adaptation to NSAIDs.

Sudden infant death syndrome victims show local immunoglobulin M response in tracheal wall and immunoglobulin A response in duodenal mucosa.

Twenty-two sudden infant death syndrome (SIDS) cases and 22 controls were examined immunohistochemically with regard to IgA, IgM, and IgG plasma cells in tracheal wall and duodenal mucosa. Furthermore, the presence of secretory component in tracheal surface and gland epithelium as well as in duodenal crypt and villus epithelium were evaluated. The examined specimens were obtained at autopsies. The control groups consisted of 11 infants who died of noninfectious causes and 11 who died of infections. In the tracheal wall, the SIDS group had higher IgM cell numbers than the control group that died of noninfectious causes (p less than 0.01), whereas the SIDS victims had lower IgA and IgM cell numbers than the infectious control group (p less than 0.01). In the duodenal mucosa, the SIDS group had significantly higher IgA cell numbers than the noninfectious control group (p less than 0.02) but lower IgA cell numbers than the infection group (p less than 0.01). Secretory component was present in the epithelium from all SIDS cases and controls, both in the tracheal wall glands and in the duodenal crypt mucosa. These findings indicate that the mucosal immune system is stimulated in SIDS.

Adhesion of Salmonella typhimurium var. copenhagen in the intestines of pigeons

The attachment of Salmonella typhimurium var. copenhagen to the intestinal epithelium of pigeons was studied. After experimental infection, the intestines of both young and adult pigeons were examined in vivo and in vitro. Investigations were carried out by electron and immunofluorescence microscopy. Attachment of the Salmonella strain to duodenal epithelium was established. Following repeated washing after inoculation, bacterial cells could be seen by SEM and TEM in association with the surface structure of the tissue. The adhesive properties of fimbriae, which are also involved in haemagglutination, could be demonstrated.

Role ofHelicobacter pylori in gastritis and duodenitis in man

Although Helicobacter pylori is now accepted as the major aetiological factor in chronic gastritis in man, many of the factors which determine its pathogenicity are unknown. The organism has adapted to survive in the low-pH environment of the stomach, partly through its ability to buffer hydrogen ion by the hydrolysis of urea and by the presence of lectins on its surface, which bind to gastric mucosa and epithelial cells. After attachment, harmful toxins and enzymes have access to the gastric cells and cellular damage and an immune response ensues. In patients with duodenal ulceration, Helicobacter pylori-related gastritis predominantly affects the gastric antrum and has a high prevalence. Excessive gastrin production has been suggested as a potential aetiological factor linking infection with duodenal ulcer development. Perhaps more important is the association between gastric metaplasia of the duodenal epithelium, which is correlated with acid load and is more extreme in H. pylori positive patients with duodenitis. Organisms may subsequently spread from the gastric antrum into areas of gastric metaplasia in the duodenal bulb, leading to areas of chronic duodenitis and ultimately frank ulceration. It should not be overlooked, however, that other factors such as genetic predisposition, blood group, stress, drugs and smoking all have a role to play in the outcome, given the comparatively small number of patients in the general population infected with H. pylori who develop ulcer disease.

The de novo and salvage pathways for the synthesis of pyrimidine residues of RNA predominate in different locations within the mouse duodenal epithelium.

RNA synthesis was examined by radioautography in mouse duodenal epithelium using 3H-uridine as a tracer of the salvage pathway and 3H-orotic acid as a tracer of the de novo pathway. The incorporation of the two precursors was estimated by counting silver grains in light-microscopic and electron-microscopic radioautographs at successive levels of crypt and villus. With both precursors, silver grains were found over all epithelial nuclei, but in numbers varying by location. Thus, after 3H-uridine injection, the number of grains was high over nucleolus and nucleoplasm in the base of the crypt, declined gradually in the middle and top of the crypt, and was low along the villus. After 3H-orotic acid, the number of grains was fairly low throughout, but peaked over the nucleoplasm in lower villus cells. The 3H-uridine reaction over nucleolus and nucleoplasm in crypt cells was interpreted as synthesis by the salvage pathway of ribosomal RNA and heterogeneous RNA, respectively, whereas the 3H-orotic acid reaction over the nucleoplasm of some villus cells indicated that these cells synthesized heterogeneous RNA by the de novo pathway.

Rumenectomy-induced proliferation in duodenal villous epithelium is mechanistically related to the disappearance of statin, a non-proliferation-specific nuclear protein.

We undertook this study to determine the effect of rumenectomy (a known cause of duodenal crypt cell hyperplasia) on the epithelial growth kinetics of the crypt-villus axis in rat duodenum. Ten rats were randomly assigned to control (gastrotomy) and experimental (rumenectomy) groups. After 14 days rats were sacrificed and representative sections were stained with the monoclonal antibody to statin, a non-proliferation-specific protein, by the immunoperoxidase procedure. In the control group, the mean percentages of statin-positive cells in the proximal duodenum, distal duodenum, proximal jejunum, and distal jejunum were 79 +/- 8.5, 79.5 +/- 5.7, 85 +/- 1.4, and 83.5 +/- 0.7, respectively. In the rumenectomy group, statin-positive nuclei were found in the region of the villous apices only, and the corresponding values for the above four areas were 26.2 +/- 4.9, 24.5 +/- 3.5, 31.7 +/- 4.5, and 80.5 +/- 2.1. Except for distal jejunum, the differences in statin expression in the control and experimental groups were significant (p less than 0.001). Rumenectomy leads to the disappearance of statin from the villous column cells of the duodenum and proximal small bowel. The lack of expression of statin in the rumenectomy group documents the potential usefulness of this measure in future studies in neoplasia were understanding of the proliferative status is of crucial importance.

Idiopathic neonatal iron-storage disease

A 21-day-old infant presented with anemia, conjugated hyperbilirubinemia, hypoproteinemia, and a severe coagulopathy. The hospital course was marked by progressive hepatic failure, encephalopathy, and renal insufficiency. The infant died on day 15 of hospitalization. Postmortem examination showed diffuse hepatic fibrosis and marked siderosis of the liver, pancreas, kidney, adrenal glands, and the duodenal epithelium, with sparing of the reticuloendothelial system. These findings were characteristic of idiopathic neonatal iron-storage disease. Previously reported cases are summarized and discussed. An increased awareness and understanding of this rapidly fatal disorder will be important for genetic counseling and possibly in defining an aberrant mechanism in the handling of iron.

Different types of peroxisomes in human duodenal epithelium.

Peroxisomes are ubiquitous organelles containing enzyme sequences for beta oxidation of fatty acids, synthesis of bile acids, and ether phospholipids. In the inherited peroxisomal diseases one or more enzymes are deficient in hepatic, renal, and fibroblast peroxisomes. We have examined peroxisomes by light and electron microscopy in 29 duodenal biopsy specimens (21 with normal mucosa) after staining for catalase activity, a marker enzyme. Peroxisomes were most numerous in the apices of the nucleus and at the villus base. Two types were distinguished: rounded to oval forms with a median lesser diameter of 0.23-0.31 microns, and tubular, vermiform organelles 0.1 microns thick and up to 3 microns long. Both types coexist in most patients. Tilting of sections and examination of semithin sections at 120 kV did not show connections between individual organelles. By morphometry, volume density was at least 0.45-0.62% of cellular volume, compared to 1.05% in human liver. In contrast, in four out of five individuals surface density of the peroxisomal membrane was 1.4-2.3 times higher than in control livers; this is expected to favour the exchange of metabolites. We suggest that intestinal peroxisomes contribute substantially to the breakdown of very long chain fatty acids.

Helicobacter‐associated duodenitis and gastric metaplasia in duodenal ulcer patients

Biopsy specimens were taken from the duodenal bulb and the distal duodenum in 45 duodenal ulcer patients before and after treatment with histamine-2 antagonists, prostaglandin analogues or antacids. After four weeks of treatment, the ulcer had healed in 31 patients. The treatment did not lead to a reduced frequency of helicobacter-associated duodenitis or gastric metaplasia of the duodenal epithelium. We found gastric metaplasia in 52.3% of all biopsy specimens from the duodenal bulb, chronic active duodenitis in 71.9% and helicobacter-like structures in 15.9%. The helicobacter organisms were found only in areas of gastric metaplasia, and an accompanying chronic active duodenitis was found in 94.1%. In the distal duodenum, we observed chronic active duodenitis in 15.0% of the specimens. Here the inflammation was not associated with gastric metaplasia or helicobacter-like structures. These observations support the hypothesis that Helicobacter pylori colonizes the duodenal mucosa only in areas of gastric metaplasia, and that such colonization may lead to an active duodenitis.

Serotonin-containing epithelial cells in rat duodenum. II. Quantitative study of the effect of 5HTP administration

The effect of 5-hydroxytryptophan (5HTP) administration on serotonin (5HT)-containing epithelial cells in rat duodenum was investigated quantitatively using three-dimensional morphometry to determine cell density and HPLC to measure 5HT and 5HTP concentrations. The results are interpreted in terms of the amine precursor uptake and decarboxylation (APUD) capacity of the cells. After administration of 5HTP, no significant change was observed in the density of 5HT-fluorescent epithelial cells in the duodenal region examined. Moreover, no evidence could be obtained that the concentration of 5HT in duodenal villi was increased after 5HTP administration, despite a highly significant increase in serum 5HTP and 5HT levels. These results indicate that no cells in the duodenal epithelium have the ability to decarboxylate exogenously administered 5HTP and convert it to 5HT under physiological conditions.

Butylated hydroxyanisole (BHA) does not cause forestomach hyperplasia by inhibiting the release of gastric mucus

High doses of BHA cause hyperplasia and subsequent neoplasia in the rodent forestomach and can inhibit gastric prostaglandin (PG) synthesis in vitro. This paper examines the hypothesis that BHA induced forestomach hyperplasia occurs in response to a reduction of gastric mucus, with consequent irritation of the forestomach. This could result from inhibition of the formation of the PG's which mediate the synthesis and release of protective mucus. Groups of 10 rats received 0 or 2% BHA in the diet for 1 or 3 weeks and a positive control group was fed a diet containing indomethacin (3.5 mg/kg), a potent inhibitor of PG synthesis. After 1 week BHA caused focal erosion and ulceration of the forestomach consistent with an irritant effect, but 2 weeks later the epithelium was healed, thickened and markedly hyperplastic. Histochemical staining for mucus showed that the development of forestomach hyperplasia was associated with increased amounts of gastric and duodenal mucus and increased numbers of serotonergic-cells in the gastric and duodenal epithelium. In contrast, indomethacin caused a marked reduction in both gastric and Brunner's gland mucus. Neither BHA nor indomethacin exerted an effect on one specific type of mucus (viz: neutral, acidic or mixed) in the stomach. These results do not support the hypothesis that forestomach hyperplasia arises from an inhibition of either the synthesis or release of gastric mucus. It is possible that the increased numbers of serotonergic-cells are related to the initial ulcerative, or subsequent hyperplastic response.

Life cycle and transmission of Schellackia cf. agamae, a parasite of the starred lizard Agama stellio

Patent infections with Schellackia cf. agamae were established in the starred lizard Agama stellio by feeding blood or liver or by injection of blood from A. stellio infected with sporozoite stages. Mosquitoes, Aedes aegypti and Culex molestus, and larval ticks of Hyalomma aegyptium were fed on sporozoite infected A. stellio and themselves gave rise to patent infections after ingestion by uninfected A. stellio. Merogony in the duodenal epithelium usually lasted to the 14th day post-infection (d.p.i.), while in some lizards it persisted until 18 d.p.i. Microgamonts, macrogamonts and zygotes occurred 11–14 d.p.i. Oocysts migrated into the lamina propria before sporulation. Sporulation had terminated by 18 d.p.i., when sporozoites first appeared in the liver and the blood. Small, young sporozoites invaded hepatocytes and liver macrophages, while a few occurred in the erythrocytes. Sporozoites which occurred from 25 d.p.i. were larger and had invaded erythrocytes and aggregated in melanin-containing liver macrophages. Parasitaemias of medium and high levels as well as hepatic sporozoites persisted in some experimentally infected lizards for 357–370 d.p.i. Lizards could not be reinfected while a parasitaemia was detectable in them. Reptiles other than A. stellio could not be infected with S. cf. agamae.

A physical approach to coeliac disease

The morphological changes used to confirm a diagnosis of coeliac disease (CD) are precisely those predicted if the surface energy of the interface between duodenal epithelium and the luminal contents were raised to levels comparable to those demonstrated by the hydrophobic nature of the stomach wall. This hypothesis pursues the concept that, in coeliac patients, the gastric mucosal barrier (GMB) is effectively extended from the stomach to coat the duodenum, thus closing the window of absorption in the GI tract. If studies are correct which indicate that the GMB is a physical reality provided by an adsorbed monolayer of surface-active phospholipid (surfactant) which renders surfaces hydrophobic, then it could also act as a barrier to the absorption of nutrients in the duodenum. Gluten, or its more active polypeptide fragment gliadin, exacerbates the situation in CD by acting as very effective carriers for the insoluble phospholipid which is deposited at the duodenal surface where they are digested by brush-border and pancreatic enzymes.

Prostaglandin E 2-induced hyperplasia of the rat antral epithelium is followed by a secondary inhibition of the mitotic activity

The aim of the study was to examine the mitotic activity in the antral and duodenal epithelium of Sprague-Dawley rats given trophic doses of E 2 prostaglandins during a prolonged period of time. Natural prostaglandin E 2 (dose range: 0.2–5.0 mg·k −1) and 15 (R) 15 methyl prostaglandin E 2 (dose range: 0.03–2.0 mg·kg −1) were administered for 11 days, and mitoses were arrested with vincristine for 4 h before estimation of the cumulative mitotic index. A dose-related hyperplasia of the antral glands was observed after treatment with prostaglandin E 2 and the synthetic analogue (p < 0.05). The proliferative zone was enlarged in rats treated with high doses of the analogue but natural prostaglandin E 2 did not effect the limits of the proliferative zone. A dose-related reduction of the mitotic index was observed in animals treated with prostaglandin E 2 despite the presence of hyperplastic changes. All doses of the analogue induced antral hyperplasia without affecting the mitotic index except in rats given the highest dose whod had a significantly lower mitotic index than controls (p < 0.05). Hyperplasia of both crypts and villi was observed in the duodenum of rats given high doses of E 2 prostaglandins (p < 0.05) whereas the mitotic index and the growth fraction were not affected by treatments. It is concluded that hyperplasia by prostaglandins is developed in absence of changes of the mitotic activity. The observed reduction of the mitotic index is interpreted as a secondary phenomenon, possibly mediated by a regulatory mechanism of cell proliferation which is triggered to reduce further epithelial growth. It is suggested that prostaglandin E 2 might influence such regulatory mechanisms.

Radioprotection of the Intestinal Crypts of Mice by Recombinant Human Interleukin-1α

Recombinant human interleukin-1 alpha (rHIL-1 alpha or IL-1) protected the intestinal crypt cells of mice against X-ray-induced damage. The survival of crypt cells measured in terms of their ability to form colonies of regenerating duodenal epithelium in situ was increased when IL-1 was given either before or after irradiation. The maximum degree of radioprotection was seen when the drug was given between 13 and 25 h before irradiation. The IL-1 dose producing maximum protection was about 6.3 micrograms/kg. This is the first report indicating that the cytokine IL-1 has a radioprotective effect in the intestine. The finding suggests that IL-1 may be of potential value in preventing radiation injury to the gut in the clinic.

Ultrastructural and functional abnormalities of intestinal and renal epithelium in the SHR

Intestinal calcium transport, renal tubular calcium reabsorption, and plasma 1.25 (OH)2 vitamin D3 (calcitriol) levels have all been reported to be diminished in the spontaneously hypertensive rat (SHR) compared with its genetic control the Wistar Kyoto rat (WKY). In the present study, absorptive duodenal and renal tubular epithelia of 12- to 14-week-old male SHR and WKY were examined by electron microscopy to determine whether such disturbances could be related to structural abnormalities. Patchy loss of microvilli in both duodenal and proximal tubular epithelia was observed in the SHR, whereas brush border membrane was entirely normal in the WKY. Irregular spaces were observed between the basal aspects of SHR intestinal epithelial cells and their basement membrane. In addition, the average height of duodenal and renal microvilli was reduced in the SHR. Two specific markers of the brush border membrane, alkaline phosphatase and villin, as well as the cytoplasmic vitamin-D dependent calcium-binding proteins, CaBP9K and CaBP28K were determined. Duodenal alkaline phosphatase activity was reduced in the SHR, compared with the WKY: 0.145 +/- 0.002 vs. 0.186 +/- 0.002 IE/min.microns 3 x 10(3) brush border, mean +/- SEM, N = 10 pairs, P less than 0.001. However, duodenal villin expression was not different from that of the WKY. Duodenal CaBP9K and renal CaBP28K content was diminished in the SHR: 21.0 +/- 0.80 vs. 29.9 +/- 2.19 micrograms/mg protein, N = 6 pairs, P less than 0.01 for duodenum, and 4.47 +/- 0.39 vs. 7.67 +/- 0.54 micrograms/mg protein, N = 6 pairs, P less than 0.001 for kidney. These data showing structural and functional abnormalities of intestinal and kidney cells in the SHR appear to reflect a disorder of transporting epithelia which may be either intrinsic or related to reduced circulating calcitriol.

Campylobacter (Helicobacter) pylori. Is peptic disease a bacterial infection?

Despite extensive investigation, the cause of peptic ulcer disease remains unknown. It is generally accepted that peptic ulcers result from an imbalance between aggressive factors and innate mucosal protective mechanisms. Much attention over the last 30 years has been directed at the role of acid in the generation of peptic ulceration. Suppression of acid production with the histamine 2 (H2)—receptor antagonists is a highly effective means of healing acute ulcers. Ulcer recurrence rates as high as 90% in the first year, however, are a testament to the fact that the underlying pathophysiological mechanisms of ulcerogenesis are unaltered. Although we can heal the ulcers, we cannot cure the disease. This fact has prompted intense ongoing investigation into the whole issue of ulcer pathogenesis, and investigators are paying increasing attention to factors that might weaken the defenses of the gastric and duodenal epithelium. In the last 7 years, attention has

Infected cells and immune cells in the gastrointestinal tract of AIDS patients. An immunohistochemical study of 127 cases

Human immunodeficiency virus (HIV) proteins were detected by immunohistochemistry in the duodenal and rectal mucosa of 30% of 127 AIDS patients studied. HIV-infected cells were present in the lamina propria in 95% of the positive biopsies. They were immune cells, either isolated lymphocytes and macrophages (1-4 per positive biopsy) or dendritic reticulum cells forming a network in the germinal centres of mucosal lymphoid follicles. HIV proteins were not found in the duodenal epithelium or in the superficial rectal epithelium. In two cases (5% of the positive biopsies), they were found in rectal glands: the HIV-infected cells could be either epithelial cells or immune cells. This study confirms that the gut can be a target organ for HIV and that HIV is mainly carried by gut immune cells. The phenotypic study of lymphoid populations and macrophages in the gut mucosa of AIDS patients showed an inverse CD4/CD8 ratio in the lamina propria, compared with normal controls. This was independent of the presence of HIV proteins and is probably responsible for the appearance of opportunistic infections in the mucosa. An increase in activated macrophages was also noted in the mucosa of AIDS patients.

Antigens similar to major histocompatibility complex B-G are expressed in the intestinal epithelium in the chicken

A monoclonal antibody directed against the erythrocytic B-G antigens of the major histocompatibility complex (MHC) of the chicken, an antiserum raised against purified erythrocytic B-G protein, and a cDNA probe from the B-G subregion were used to look for evidence of the expression of B-G genes in tissues other than blood. Evidence has been found in northern hybridizations, in immunoblots, and in immunolabeled cryosections for the presence of B-G-like antigens in the duodenal and caecal epithelia. Additional B-G-like molecules may be expressed in the liver as well. The B-G-like molecules in these tissues appear larger and somewhat more heterogeneous than the B-G antigens expressed on erythrocytes. Further characterization of these newly recognized B-G-like molecules may help to define a function for the enigmatic B-G antigens of the MHC. al. 1977; Miller et al. 1982, 1984; Salomonsen et al. 1987; Kline et al. 1988), and in the multiplicity of B-G restriction fragment patterns found in genomic DNA from different haplotypes (Goto et al. 1988; Miller et al. 1988; Chaussé et al. 1989). The B-G antigens have contributed, together with the B-F (class I) and B-L (class II) antigens, to the definition of over 27 B system haplotypes in experimental flocks (Briles et al. 1982). Yet the function of the B-G antigens remains entirely unknown. No mammalian counterparts have been identified, although the possibility remains that there may be similar antigens among the blood group systems of mammals. In an effort to define a function of the B-G antigens, a recently cloned B-G sequence (Miller et al. 1988; Goto et al. 1988) and antibodies to the B-G polypeptides (Miller et al. 1982, 1984) were used to examine other tissues for evidence of B-G expression.