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Increase in expression of the homeobox gene, GBX1, in retinol-induced epidermal mucous metaplasia.

Using a degenerate RT-PCR-based screening method, we isolated the homeobox gene, Gbx1, from the shank skin of 13-day-old chick embryos. By in situ hybridization analysis we showed that the Gbx1 was expressed in the epidermis of the skin and the mucous epithelium of the intestine, and that among many homeobox genes isolated, expression of the Gbx1 strongly increased in the epidermis when the skin was cultured with 20 microM retinol, which induces epidermal mucous metaplasia. The Gbx1 expression in the epidermis was increased by interaction with the retinol-pretreated dermal fibroblasts, resulting in mucous metaplasia. These results suggest that the Gbx1 regulates the differentiation and transdifferentiation of the epithelium and controls the morphology of the epithelium. We isolated the chick Gbx1 cDNA clones. The amino acid sequences in homeodomain and its downstream encoded by human and chick Gbx1 cDNA were almost the same, but those upstream of the homeodomain were rather different.

Amino Acid Sequence↗

Helicobacter pylori virulence genes and host IL-1RN and IL-1beta genes interplay in favouring the development of peptic ulcer and intestinal metaplasia.

Helicobacter pylori infection outcome might depend on genotypic polymorphisms of both the bacterium and the host. We ascertained: (1) the functionality of H. pylori oipA gene; (2) the polymorphism of the hostinterleukin (IL-1beta) gene (-31 C/T) and of the IL-1RN gene (intron 2 VNTR); (3) the association between the above genes and the histological and pathological outcome of H. pylori infection. One hundred and sixty-five H. pylori positive and 137 H. pylori negative subjects (23 gastric adenocarcinoma, 58 peptic ulcer, 221 gastritis) were studied. oipA was sequenced, IL-1beta was RFLP analysed. Antral and body mucosal biopsies were histologically evaluated. Functional oipA genes were correlated with cagA gene; both genes were significantly associated with gastritis activity, peptic ulcer and gastric adenocarcinoma. In these patients heterozygousIL-1RN 1/2 and IL-1beta C/T genotypes were more frequent than in gastritis patients. Intestinal metaplasia was associated with cagA, functional oipA and IL-1RN 2 allele. In conclusion, peptic ulcer and the preneoplastic intestinal metaplasia are associated with H. pylori virulence genes and with IL-1RN 2 host allele. An interplay between bacterial virulence factors and cytokines genotypes, is probably the main route causing H. pylori infection to lead to benign mild disease, benign severe disease or preneoplastic lesions.

Adenocarcinoma↗

Florid endocervical glandular hyperplasia with intestinal and pyloric gland metaplasia: worrisome benign mimic of "adenoma malignum".

We describe three cases of florid endocervical glandular hyperplasia with intestinal and pyloric gland metaplasia, which can be a benign mimic of adenoma malignum. In two cases, adenoma malignum was seriously considered preoperatively because of watery vaginal discharge and the results of imaging studies. The three cases shared common histopathological features, i.e., (i) proliferating endocervical glands surrounded by clusters of smaller glands, resembling the pyloric glands of the stomach; (ii) occasional intestinal metaplasia; (iii) bland nuclear features; and (iv) predominantly PAS-positive neutral mucin in the glandular epithelium. In two cases, glands were densely and irregularly arranged in some areas. Immunohistochemistry disclosed that the intracytoplasmic mucin of the metaplastic epithelium was positive for M-GGMC-1 (HIK1083), which reacts with mucin of pyloric glands. Monoclonal CEA was negative in all cases. This pseudoneoplastic benign condition should be recognized by both gynecologists and pathologists, although it might be difficult to establish a definite diagnosis preoperatively even with deep cone biopsy.

Adenoma↗

Studies on Langerhans cells in the tracheal squamous metaplasia of vitamin A deficient rats.

LCs in the tracheal squamous metaplasia of vitamin A deficient rats were studied. The first appearance of LCs with Birbeck granules (BGs) was in the stage of stratification. The number of LCs increased along with the development of metaplasia, but decreased in number in the later stage, where basal cells also differentiate into flattened epithelium. In the area where only basal cells differentiated into flatter epithelium, without a cornified layer, LCs with BGs could also be found. These findings suggest that LCs which originate in bone marrow mature in squamous epithelium. The distribution and morphology of LCs are dependent on the state of keratinocytes, but not the presence of a cornified layer.

Animals↗

Sebaceous gland metaplasia in cardiac-type mucosa of the oesophago-gastric junction.

The first case of sebaceous gland metaplasia arising in cardiac-type mucosa of the oesophago-gastric junction of 71-year-old man is reported. Within cardiac glands, small nests composed of clear cells closely resembling sebaceous glands of the skin were found. Immunohistochemically, the cell nests stained positively for a monoclonal antibody 115D8 against milk-fat globule membrane (MAM-6). These cells were sometimes covered by cylindrical cells positive for foveolar-type mucin of the stomach (MI), and basal marginal cells of these nests expressed high molecular weight cytokeratins (34BE12). This study documents a new type of metaplasia of the gastric mucosa.

Aged↗

Multiple imagings to diagnose the chondrosseous metaplasia within a lipoma near the knee.

A 61-year-old man with a slow-growing, painless mass in the area of the right knee underwent radiographic, computed tomographic (CT), arthrographic, arteriographic, and bone scintigraphic imaging studies. Scintigraphy showed an area of intense uptake in the anterolateral part of the knee; the uptake of the knee was much higher than that of the knee joints, but the area was not connected to the joint. Radiographic findings suggested an osteocartilaginous mass which was seen to contain low-density fatty tissue on the CT exam. Arthrography revealed that there was no connection of the mass to the knee joint. Arteriography showed a mildly vascularized tumor mass. Upon removal, the mass was well encapsulated, measuring 10 x 7 x 7 cm, and consisted of integrated nodules of bone, cartilage, and fat tissue. Microscopic examination confirmed lipoma with osteochondromatous metaplasia. The intense uptake in the lipoma near the bone or joint on the bone scan and multiple osteochondromatous nodules shown on CT may serve as characteristic features of the rare chondrosseous metaplasia within a lipoma.

Arthrography↗

Squamous metaplasia following necrosis of the adenohypophysis and of a chromophobe adenoma of the pituitary.

Two cases of pituitary necrosis was presented, one occurring post partum in an otherwise normal gland, the other in a large chromophobe adenoma. In both cases the necrotic tissue became surrounded by squamous epithelial nests that developed through metaplasia from glandular cells of the adenohypophysis and adenoma cells respectively. The squamous elements were seen 6 days after the clinical events leading to pituitary necrosis in the first case and 20 days after pituitary apoplexy (hemorrhagic necrosis of an adenoma) in the second case. In contradistinction to the commonly found squamous nests which are usually located in the pars tuberalis and presumably develop through a slower process, the changes in the present two cases indicate that squamous metaplasia can develop quite rapidly at the margins of a necrotic process of the pituitary, either deep in the gland as in case 1 or occupying the entire circumference of a necrotic tumor as in case 2.

Adenoma, Chromophobe↗

A novel subtyping of intestinal metaplasia of the stomach, with special reference to the histochemical characterizations of endocrine cells.

Intestinal metaplasia of the stomach was grouped into 3 subtypes (A, B and C) according to the degree of pyloric gland involution which was judged from patterns of paradoxical Concanavalin A staining after Katsuyama and Spicer. The appearance of endocrine cells was investigated with immunohistochemical and silver methods. Type A metaplasia with slightly to moderately atrophic pyloric glands corresponded to the incomplete type in the previous classification, while Type C showing complete disappearance of pyloric glands corresponded to the complete type. Type B with severely atrophic pyloric glands was an intermediate. This subtyping reflects the cell kinetics in the intestinalized mucosa well. Regarding the endocrine cells, their total number varied in the order Type A greater than Type B greater than Type C. The selective populations of the endocrine cells including glicentin-containing cells, Grimelius-positive argyrophil cells without argentaffinity and intestinal-type enterochromaffin cells frequently formed hyperplastic foci in the intestinalized areas, where the other gut-type and proper gastric-type endocrine cells were scarcely noted. Immunoreactivity of glucagon or bovine pancreatic polypeptide were occasionally identified in a subpopulation of the glicentin-containing cells.

Adult↗

Glicentin-containing cells in intestinal metaplasia, adenoma and carcinoma of the stomach.

Glicentin-containing cells (Glic. cells) in intestinal metaplasia, adenoma and carcinoma of the stomach were examined using immuno-histochemical techniques. Glic. cells first occurred in the gastric mucosa of the transitional area between metaplastic and intact gastric glands. They frequently showed hyperplasia or micronoduli in the budding area of the deeper metaplastic glands, but in completely intestinalized mucosa these endocrine cells decreased remarkably. Gastric adenomas with mild dysplasia had a good number of glicentin-immunoreactive cells which were located in the deeper adenoma glands. Gastrin- and somatostatin-positive cells were also detected in the adenomas. The incidence of glicentin-positive tumor cells was significantly higher in well differentiated adenocarcinoma than in poorly differentiated adenocarcinoma. Among the seven cases of scirrhous argyrophil cell carcinoma, three showed glicentin- and glucagon-immunoreactivity in the same area of the tumor. These findings suggest that the selective increase of Glic. cells in intestinal metaplasia may be closely related to the development of gastric adenoma. Glicentin positive tumor cells in gastric carcinomas can be regarded to be an expression of intestinal or fetal markers.

Adenoma↗

Immune aspects of intestinal metaplasia of the stomach: an immunohistochemical study.

Immune characteristics of intestinal metaplasia of the stomach were analyzed by the immunoperoxidase technique in frozen and paraffin-embedded specimens. In fetal and minimally inflamed adult gastric mucosa, secretory component (SC) was absent from epithelial cells. Non-intestinalized gastric mucosa with evident inflammatory changes showed weak SC immunoreactivity at the generative cell zone. Enhanced immunoreactivity of SC with evidence of transepithelial transport of IgA and IgM, but not of IgG, was demonstrated in intestinalized glands of either the complete or incomplete type. The number of inflammatory cells and lymphoid follicles was decreased in intestinalized mucosa when compared with that in non-intestinalized gastritic mucosa; J chain-negative IgG plasma cells and T cells, both of which were fairly abundant in the latter mucosa, were remarkably decreased in the former mucosa, whereas the decrease of J chain-positive IgA or IgM plasma cells was slight or equivocal. In either mucosa, IgA was the most popular immunoglobulin class in plasma cells. IgD plasma cells were very rare. In the germinal centers of lymphoid follicles which were preferentially distributed in non-intestinalized gastritic mucosa, IgM or IgG germinocytes predominated over IgA germinocytes, and a few T cells and NK cells also were present. Intraepithelial lymphoid cells with a T-suppressor phenotype were detected in intestinalized glands. The possibility that intestinal metaplasia is an adaptation to long-standing chronic gastritis is discussed.

Adult↗

Squamous metaplasia of extrahepatic biliary system in an AIDS patient with cryptosporidia and cholangitis.

AIDS-related cholangiopathy is an increasingly recognized syndrome associated with significant morbidity and mortality. The mechanism of cholangiopathy is unknown but is assumed to be related to infectious pathogens such as CMV and cryptosporidia. The case of a Haitian with HIV and long-standing intestinal cryptosporidiosis who presented with cholangitis and protuberant intrabiliary filling defects is reported. Histopathological examination of biliary biopsies revealed previously unreported extensive squamous metaplasia of the bile duct epithelium, and the histogenesis of this condition is discussed. Chronic cryptosporidial infestation may be directly pathogenic resulting in squamous metaplasia that mimics biliary malignancy.

AIDS-Related Opportunistic Infections↗

Serum pepsinogen I and gastrin in relation to extent and location of intestinal metaplasia in the surgically resected stomach.

A study of 177 patients undergoing distal subtotal gastrectomy indicates that a preoperative serum pepsinogen I (PGI) level below 20 ng/ml predicts the presence of gastic carcinoma and the degree of intestinal metaplasia of the gastric antrum. The serum gastrin level was not predictive of carcinoma or of the degree of intestinal metaplasia. Of the 15 patients with a low serum PG level, 13 had carcinoma and 2 had atypical polyps. The PG I level in a stored serum sample from 4 of 30 patients fell from normal to abnormal over a period of 8-9 years. Each of these converters had invasive carcinoma of the stomach. This suggests that persons showing a fall in serum PG I to abnormal levels during serial analyses should be evaluated for the possibility of gastric carcinoma.

Adult↗

Gastric metaplasia in duodenal bulb and Campylobacter-like organisms in development of duodenal ulcer.

Multiple biopsies were taken from 50 patients with endoscopic appearance of duodenitis in order to study the relationship between gastric metaplasia in duodenum and the presence of Campylobacter-like organisms (CLOs) and the development of duodenal ulcer disease. Metaplasia was found in at least one biopsy specimen from 46 of the 50 patients; CLOs were seen in 25 of the 50 patients, only in metaplastic areas. In four cases a "transitional epithelium" with the presence of cells containing few apical mucoid granules and absorbent-type brush border as well as goblet cells was seen. In two cases, this epithelium was colonized by a small number of CLOs. Gastric heterotopia appears to be a rare condition.

Adult↗

The impact of squamous metaplasia in transitional cell carcinoma of the bladder.

The authors report a case of squamous cell carcinoma of the bladder induced by radiation therapy for transitional cell carcinoma, possibly from sites of squamous metaplasia, which were present at the time of initial diagnosis. Although data in the literature are not sufficient at the moment in terms of implication on prognosis, foci of squamous metaplasia during the initial diagnosis of transitional cell carcinoma must be carefully sought and their presence warrants caution in utilizing irradiation in the management of the disease.

Aged↗

Squamous cell metaplasia in the human lung: molecular characteristics of epithelial stratification.

Squamous cell metaplasia (SCM) is a frequent epithelial alteration of the human tracheobronchial mucosa. This review pays particular attention to the fact that SCM can mimic esophageal, and in some instances even skin-type differentiation, showing striking similarities not only in morphology but also in terms of gene expression. Therefore, characterization of this dynamic process lends insight into the process of stratification, squamous cell formation, and "keratinization" in a pathologically relevant in vivo situation in man. First, the concept of metaplasia is presented with certain historical viewpoints on histogenesis. Then, the morphological characteristics of normal bronchial epithelium are compared with the altered phenotype of cells in SCM. These changes are described as a disturbance of the finely tuned balance of differentiation and proliferation through the action of a variety of extrinsic and intrinsic factors. Molecular aspects of altered cell/cell and cell/extracellular matrix interactions in stratified compared with single-layered epithelia are discussed with reference to SCM in the lung. Intracellular organizational and compositional changes are then summarized with special emphasis on the differential distribution of the cytokeratin (CK) polypeptides. Finally, the still unresolved problems of the histogenetic relationships between normal bronchial mucosa, SCM, and pulmonary neoplasms are addressed. As these questions remain open, examples for detection of well defined "markers" are provided that may be employed as objective criteria for determining clinically important cellular differentiation features.

Cell Differentiation↗

Expression of HBs- and HBc-antigen in neoductular epithelium in chronic active hepatitis B. A further support for hepato-ductular metaplasia.

Biopsy specimens (n = 61) from patients with chronic active hepatitis B and progressive fibrosis (n = 61) were studied immunohistochemically to obtain information about the histogenesis of neoductules. All the biopsies contained clusters of oval-shaped cells often arranged in the form of neoductular aggregates. These expressed cytokeratins 7 and 19 which in the normal liver are found only in bile duct and ductular epithelium but not in hepatocytes. Using monoclonal and polyclonal antibodies both hepatocytes and these oval neoductular cells were found to express HBs- and HBc-antigen in 15% and 20% of the biopsies, respectively. Taking into consideration the strong hepatocytotropism of the hepatitis B virus, the expression of HBV-antigens in neoductular cells suggest their development from HBV-infected hepatocytes. Using proliferating cell nuclear antigen (PCNA) as a marker of cell proliferation positive staining was detected only in hepatocytes but not in neoductular cells. Taken together findings further support the concept of hepatoductular metaplasia in the histogenesis of so-called "proliferating" ductules. In general the data show that hepatitis B virus infection does not prevent hepatocytes from undergoing ductular metaplasia.

Bile Ducts, Intrahepatic↗

Trends in incidence and prevalence of specialized intestinal metaplasia, barrett's esophagus, and adenocarcinoma of the gastroesophageal junction.

Most available information on the epidemiology of Barrettacute;s esophagus (BE) relates to patients with long segments (> 3 cm) of specialized intestinal metaplasia (SIM). Its prevalence is 3% in patients undergoing endoscopy for reflux symptoms and 1% in those undergoing endoscopy for any clinical indication. The latter prevalence is similar to the 1% found in autopsy series. A "silent majority" with BE remain unrecognized in the general population. BE is more common in men, and the prevalence rises with age. Recent endoscopic series document a rise in the diagnosis of endoscopically apparent short segments (< 3 cm) of BE (SSBE). The prevalence of SSBE in both unselected and reflux patients is 8% to 12%. Specialized intestinal metaplasia at the cardia, below a normal-appearing squamocolumnar junction, has been reported to vary from 6% to 25% in patients presenting for upper endoscopy. Unlike patients with long segment Barrett's esophagus (LSBE), the role of gastroesophageal reflux disease in the pathogenesis of SSBE and SIM of the cardia is controversial. Recent data suggest that the etiology of SIM of the cardia might be secondary to Helicobacter pylori infection, although the role of other environmental factors cannot be ruled out. The incidence of adenocarcinoma of the esophagus and esophagogastric juction (EGJ) has been increasing over the past 15 years in Western countries. Surgical series and population-based studies show that by 1994 adenocarcinomas of the esophagus accounted for half of all esophageal cancer among white men. LSBE and SSBE predispose to the development of adenocarcinoma of the esophagus and EGJ. The role of SIM of the cardia as a precursor lesion for EGJ adenocarcinoma is still unclear. The prevalences of dysplasia in LSBE and SSBE are around 6% and 8%, respectively. The incidence of adenocarcinoma in patients with LSBE is about 1 in 100 patient-years. Cancer risk for SSBE and SIM at the cardia is unknown. Smoking and obesity increase the risk for esophageal and EGJ adenocarcinomas.

Adenocarcinoma↗

Kinking, coiling, and tortuosity of extracranial internal carotid artery: is it the effect of a metaplasia?

INTRODUCTION: Morphological anomalies of the extracranial internal carotid artery (ICA) cause symptomatic cerebrovascular insufficiency in 4-16% of the cases. The aim of the present study is to evaluate macroscopic and microscopic features of a group of extracranial ICA anomalies, specifically kinking, coiling, and tortuosity, eventually affecting the surgical approach. MATERIALS AND METHODS: From January 2003 to December 2005, 10 out of 169 (6%) revascularized patients (pts) were operated upon because of an ICA anomaly. They were all but two symptomatics. Seven pts were treated by ICA transection and end-to-side reimplantation of the ICA at the level of the carotid bulb; three pts were treated by ICA resection and end-to-end anastomosis. In all the cases a segment of ICA was resected; in three cases one more segment was also obtained from a common carotid artery (CCA) and these specimens were histologically examined. Patients were followed-up through a 3-year period. RESULTS: No pts died and none suffered of neurologic events. Duplex scan and arteriographic postoperative control showed the correct surgical reconstruction. Matching preoperative clinical findings with presence or absence of significant atherosclerotic stenotic lesion, we found out a positive cerebral CT in one pt (20%) in both groups; fluent neurological deficit was preeminent in pts with pure ICA anomalies (40% vs. 0%) (P = 0.2); pts with pure ICA anomalies were significantly younger than 65 years old (80% vs. 0%) (P = 0.03) and males were more involved by pure ICA anomalies (60% vs. 40%) (P = 0.1). The histological examination of ICA specimens showed a reduction of elastic fibers and muscular cells with a compensative increase of connective fibers. CONCLUSIONS: At our knowledge this is the first study focused on ICA anomalies like kinking, coiling, and tortuosity, comparing histologic features of CCA and ICA specimens coming from the same affected carotid axis. Our results, although preliminary, show elastic and muscular tissue substituted by loose connective tissue, configuring a metaplasia of tunica media limited to the ICA. Our hypothesis is that extracranial ICA, being a segment of transition between an elastic vessel (CCA) and a muscular vessel (intracranial ICA), is particularly subject to metaplastic transformation, analogously to other transition zones in human body. Our purpose is now to confirm by ultrastructural and molecular biology techniques, in a wider series, the presence of this metaplasia, since this could condition also the revascularization techniques.

Age Factors↗