Gastric mucous neck cell and intestinal goblet cell phenotypes in gastric adenocarcinoma

AIM: To investigate the phenotype of cells comprising diffuse and intestinal-type gastric cancers using monoclonal antibodies to two antigens. One antigen (designated D10) is characteristic of gastric mucous neck cells, cardiac glands, pyloric glands, and Brunner's glands. The second antigen (designated 17NM) is specific to the mucous vacuole of intestinal goblet cells. METHODS: Thirty two gastrectomy specimens with adenocarcinoma were studied. Serial paraffin sections were stained immunohistochemically for D10 and 17NM and histochemically for acid and neutral mucins. The cancers were classified histologically as of either diffuse or intestinal type according to Lauren. RESULTS: Of 15 diffuse-type gastric carcinomas, 11 showed the majority of cancer cells staining for D10 while four were typical signet ring cell cancers staining predominantly for 17NM; five tumours displayed both phenotypes with the two phenotypes segregated in different areas of the tumours. In contrast, of 16 intestinal-type cancers, six expressed 17NM, three D10, five neither antigen, and two expressed both antigens. One indeterminate-type cancer expressed both antigens. The staining of individual cells for D10 and 17NM was mutually exclusive in both diffuse and intestinal types. In contrast to the diffuse cancers, intestinal-type cancers typically expressed either antigen only in occasional small groups of cells and individual cells. CONCLUSIONS: In disease, the gastric stem cell can assume the capacity of the duodenal stem cell for divergent differentiation into either intestinal goblet cells (for example, as in intestinal metaplasia) or Brunner's gland cells (for example, as in pyloric gland/Brunner's gland metaplasia). With neoplastic transformation, this potential for divergent differentiation is maintained and gives rise to diffuse-type cancers that display either the D10 phenotype, the 17NM phenotype, or the clonal expression of both phenotypes. In the more cell cohesive (intestinal-type) tumours, differentiation for antigen expression is poorly developed and more frequently directed towards the intestinal goblet cell phenotype.     

Effect of Helicobacter pylori eradication on intestinal metaplasia and gastric epithelium proliferation

Gastric epithelial turnover increase in Helicobacter pylori infection has been demonstrated by interventional and non interventional methods for proliferating cell detection. We have observed a progressive hyperproliferation with the progression of Helicobacter pylori-induced mucosal lesions until the development of intestinal metaplasia. A similar result has been reported in other studies in the succession from normal mucosa to gastric carcinoma even if interventional techniques show less conspicuous differences in comparison to non interventional ones, which give an overestimated picture of proliferation. Later studies show that Helicobacter pylori-related hyperproliferation reverses after eradication. We have observed that this reversibility does not occur in areas of intestinal metaplasia, where the oncoprotein ras p21, involved in early gastric carcinogenesis, is expressed. This finding agrees with that demonstrating that hyperproliferation in intestinal metaplasia or gastric cancer is not affected by Helicobacter pylori. Other oncogenetic changes in intestinal metaplasia (i.e., p53 mutation) may further explain the persistently modified proliferative pattern of the epithelium. Recent studies suggest a lack of reversibility of intestinal metaplasia after Helicobacter pylori eradication, but this problem remains controversial. Our experience suggests that the persistence of the bacterium may increase the extent of this lesion. In conclusion the development of intestinal metaplasia is associated with an impaired regulation of gastric epithelial proliferation. Nevertheless, from the biological point of view, the progression towards carcinoma requires further DNA changes. Moreover, many questions need to be answered in order to establish clear guidelines for the clinical management.     

Intestinal metaplasia with adherent Helicobacter pylori: a hybrid epithelium with both gastric and intestinal features

Helicobacter pylori seem to avoid areas of intestinal metaplasia in the gastric mucosa, but attachment of these bacteria to epithelium with the appearance of incomplete intestinal metaplasia has been documented. To characterize the nature of the epithelium to which H pylori was attached, we carried out an immunohistochemical study using monoclonal antibodies against gastric surface mucous cell mucins (M1), blood group-related carbohydrates antigens (Le(a), sialyl Le(a), Le(b), type 1H, and type 2H) and sialyl Tn antigen. The results of this study suggest that these areas of H pylori attachment represent a hybrid epithelium whose cells share characteristics of both gastric surface mucous cells and intestinal metaplastic cells. Whether all areas of incomplete intestinal metaplasia represent an intermediate stage between the normal gastric epithelium and the fully developed complete type of metaplasia remains to be determined.     

Effects of nitrous acid exposure on human mucous membranes

Nitrous acid (HONO) is formed both indirectly from the reaction of nitrogen dioxide (NO2) with water on indoor surfaces, and directly during combustion. This gaseous pollutant may be a previously unrecognized causal factor in assessments of nitrogen oxide exposure effects. The present study is the first attempt to evaluate exposure effects of HONO on the human airways and the mucous membranes of the eyes and nose. Fifteen healthy adult nonsmokers were exposed for 3.5 h in a double-blind, balanced protocol to clean air, 77, and 395 ppb HONO. Each exposure was preceded by a 1-h baseline measurement period, and exposures were separated by 1 wk. There was a 10-min exercise period during exposure. Effects measurements included assessment of bronchial reactivity, measurement of specific airway conductance, spirometry, acoustic rhinometry, nasal lavage, tear-fluid cytology, a CO2 eye-provocation test, evaluation of eye redness, and subjective sensations. Effects of HONO exposure on the eyes were found as exposure-related changes in tear-fluid cytology. In particular, the number of squamous cells increased by 20, 67, and 80% following exposure to clean air, 77, and 395 ppb HONO, respectively (p = 0.004). Possible indications of exposure effects on sensitivity to CO2 eye provocation and on specific airway conductance were also measured. For specific airway conductance there was an approximate 10% decrease in conductance following exercise in association with HONO exposure, compared with a 2% decrease with clean air (p = 0.038).     

An evaluation of the efficacy of Pimafucin in candidiasis of the skin and mucous membranes

Results were studied of use of different dosage forms of pimafucin in candidiases in children. It was found out that the above medicinal agent is an effective anticandidiasis drug that can easily be tolerated by children. A beneficial clinical effect was noted in treatment of candidiasis complications in those children suffering from atopic dermatitis. The above drug can, we believe, come into widespread use in pediatric dermatovenereology.     

Atypical cilia in the oviductal epithelium of healthy dogs

Specimens of the uterine tube (ampulla) were obtained from seven healthy, ovario-hysterectomized dogs. Ultrastructurally, a total of 35,000 cilia were examined. Compound cilia ranged from 0.0 to 0.4%; both intracytoplasmic and swollen cilia ranged from 0.1% to 0.4%. The microtubular pattern was studied in 3,500 cross-sectioned cilia and an abnormal pattern was found in 2-5%. Similarly to the other animal species, abnormalities involving the peripheral microtubules were the prevailing defect. An electron-dense plug into the lumen was seen in 1-3% of the basal bodies; occasionally an abnormal spatial configuration of them was also observed. The incidence of abnormal cilia hence is lower than found in the tracheae.     

Inflammatory diseases of the mucous membranes. Part 2. Immunopathologic ulcerative and desquamative diseases

Bullous and desquamative diseases of the oral mucosa are not common, with the exception of ulcerative lichen planus. All produce mild to severe mucosal pain and some can be life-threatening. Recent studies have helped elucidate the pathogenesis of immunopathologic diseases, although the precise etiology for most of them remains unknown. Minor and major aphthae, lichen planus, pemphigoid, pemphigus and erythema multiforme are discussed.     

Intercalated (basal) epitheliocytes and the regeneration of cholangiocytic epithelium in the liver

To clarify the function of human atrial natriuretic peptide (hANP) in the cerebrospinal fluid (CSF), we examined hANP levels in the CSF of patients with various neurological diseases. The subjects were 16 controls without neurological disease and 45 patients with neurological disease. The 45 patients with neurological disease were divided into a group of 15 patients with intracranial hypertension (IH) and a group of 30 patients with normal pressure (NP). hANP in both CSF (1-hANP) and serum (s-hANP) was measured by RIA. Patients with IH were followed up. We analyzed correlations between 1-hANP and other parameters of CSF. Increase in concentration of 1-hANP was positively correlated with intracranial pressure (ICP; r = 0.72; p < 0.01), but not with other CSF parameters or with s-hANP. The concentration of 1-hANP appeared to be increased especially over a threshold value of ICP. In a followup study of patients with IH, changes in 1-hANP paralleled changes in ICP in every case (r = 0.79; p < 0.01). Our findings strongly suggest that 1-hANP plays an important role in the regulation of ICP in humans.     

Mechanical properties of intercellular contacts of small intestinal epithelium

It has been shown that when long-acting forces are applied, the intercellular contacts in the small intestine epithelium are destroyed at the values of these forces lower than the adhesion ones obtained at the application of short-term loads. Starting with some threshold value of the load viscose-elastic properties of intercellular contacts are shown up. Thus the threshold varies essentially for different cells of the population: 4 variations are observed. A removal of bivalent cations from the tissue significantly decreases the threshold value of the forces and decreases the viscosity while the excessive concentrations of bivalent cations increase the threshold value of forces, the membrane viscosity and contact components.     

A study of the influence of gastric acid on the extension of regenerative epithelium of gastric ulcer

Nursing research is generally located within the paradigm of the social sciences, and therefore reflects the concerns and agenda of social research. In particular, nursing has become embroiled in the ongoing dispute between the advocates of qualitative and quantitative methodologies. However, it is argued in this paper that whereas the aim of social research is to develop knowledge, the aim of nursing research is primarily to advance practice. This paper offers an alternative model of nursing research which categorizes approaches to research not according to the methodology employed but on the extent to which the research process is likely to bring about change. These approaches are termed level 1, level 2 and level 3 research, where level 1 researchers are concerned with generating information for others to conceptualize and implement, while level 3 researchers see their aim as directly bringing about clinical change. Two approaches to level 3 research are suggested, and examples of projects at all three levels are examined. Finally, it is contended that only by adopting an appropriate model of research for a practice-based discipline can nursing address the real issues of relevance to nurses and patients in clinical settings.     

Ultrastructural and carbohydrate histochemical studies on the differentiation and renewal of mucous cells in the rat gastric fundus

Gastric surface mucous cells (SMC), mucous neck cells (MNC) and their undifferentiated and immature precursors were studied by light and electron microscopic histochemistry. The secretory granules of SMC were smaller, more electron dense and more reactive to PAS and its analogues than those of MNC. Alcian blue demonstrated that the mucus of SMC was acidic and that of MNC was neutral. The periodic acid-thiocarbohydrazide-silver proteinate method revealed the pressence of carbohydrates in the golgi apparatus, condensing vacuoles, secretory granules, apical vesicles and tubules and cell coat. Maturation of SMC during their migration towards the free surface was reflected by an increase in size and number of secretory granules, an increase of RER and microfilaments, and a decrease of microvilli and apical vesicles and tubules. The secretory granules of older SMC were less acidic and possessed a proteinaceous core. Most MNC were fully differentiated, but some immature MNC containing only a few granules were found. Furthermore, undifferentiated cells and intermediates between SMC and MNC were also observed. The presence of both transitional and intermediate forms indicates that both SMC, and MNC arise from the same population of undifferentiated cells. Incorporation of 3H-thymidine revealed that undifferentiated cells, use isthmic SMC, MNC and intermediate cells are proliferative. No proliferative activity was found in foveolar SMC, parietal, chief, fibrillovesicular or endocrine cells.     

Damage to and regeneration of the kidney epithelium following crushing of the soft tissues of the extremities

Dynamics of the cellular composition in the proximal thin, thick areas of the loop, distal portions and collective tubules of the kidney was studied in rabbits after crush of the soft tissues of the limb. Planimetric method was applied to determination of the area of the nuclear epithelium of the proximal, distal portions and the collective tubules. A relationship was revealed between the injury of the epithelium of the nephrons and the collective tubules and its restoration, and also an intensification of mitotic activity, elevation of the relative number of pathological mitoses, and increase of the mean size of the cell nuclei.     

Evaluation of frog gastric mucous secretion by 7T magnetic resonance imaging

This work describes a new method to evaluate the action of drugs on gastric mucus secretion by 7 T MRI. A polyethylene probe was inserted into the stomach of frogs, a water washing cycle was performed, air was inflated into the stomach, and the probe was removed. Drugs were administered topically by mixing them with the water used for stomach washing, and a series of images was collected. In untreated animals, a mucous layer emitting a high intensity signal covered the gastric mucosa. Atropine administration strongly reduced the mucous layer thickness. After pilocarpine administration, MRI images showed that the mucous layer was thicker than in controls. After metacholine administration, the thickness of the mucous layer was increased in comparison with both controls and pilocarpine-treated animals, in accord with the expected drug-induced increase of mucous secretion. Quantitative analysis of the mucous layer thickness on MRI images confirmed the above findings. In conclusion, these results indicate that MRI at 7 T is a sensitive in vivo screening test to evaluate the effect of drugs on gastric mucus secretion in absence of surgical manipulation, thereby enabling morphofunctional studies that cannot be performed by conventional methods.     

Effects of anticancer agents of the intestinal epithelium. A morphologic study

In order to make clear the pathophysiology of digestive symptoms which are caused with anticancer agents, three anticancer agents, i.e., mitomycin C, 5-FU and cytosine arabinoside were administered pre-operatively, and the ultrastructure of the intestinal epithelium, especially that of absorptive cells, were studied on the specimens collected intra-operatively. In view of the finding that severe degeneration occurred inside cytoplasms, chiefly their nuclei, it was surmised that the biosynthesis and supply of proteins such as digestive enzymes were not amply carried on; hence, the chemotherapy could give rise to severe digestion and absorption disorders. It appeared necessary to further study the dosage and dosage schedule of the anticancer agents, along with the necessity for taking ample care of patients presenting such disorders.