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ABSTRACT: We recently identified a distinctive type of multilayered epithelium in two patients with Barrett's esophagus, which shows morphological characteristics of both squamous and columnar epithelium. This study was performed to prospectively evaluate the prevalence of multilayered epithelium in patients with Barrett's esophagus.
Mucosal biopsies were obtained from the squamocolumnar junction (Z-line) of 58 patients with endoscopic evidence of esophageal columnar epithelium and from the gastroesophageal junction in 21 patients without endoscopic evidence of esophageal columnar epithelium. Specimens were evaluated for the presence of multilayered epithelium and goblet cells.
Twenty-four of 58 (41%) of the patients with endoscopic evidence of esophageal columnar epithelium had multilayered epithelium compared with only one of 21 patients (5%) in the control group (p = 0.005). Of the 58 patients in the study group, 43 had goblet cell metaplasia and 15 did not (p < 0.001). Only patients with goblet cell metaplasia had multilayered epithelium. Shorter lengths of columnar epithelium were noted in the 24 patients with goblet cells and multilayered epithelium compared with the 19 patients with goblet cells and no multilayered epithelium (p < 0.05).
Multilayered epithelium is strongly associated with goblet cell metaplasia in patients with endoscopic evidence of esophageal columnar epithelium. These data support the hypothesis that multilayered epithelium may represent a transitional stage in the development of Barrett's esophagus.
The American Journal of Gastroenterology 12/2001; 96(12):3268-73. · 7.28 Impact Factor
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ABSTRACT: The factors that influence the decision to do an adequate evaluation for a positive test for fecal occult blood in a middle-aged or elderly patient are largely unknown. Our study was undertaken to determine whether factors such as the number of positive Hemoccult II card windows, age, gender, family history of colon cancer, the patient's concern that he or she might have colon cancer, or history of rectal bleeding influence the evaluation performed.
A mass screening program for colon cancer was performed using unrehydrated Hemoccult II cards in the Boston area.
Among the 23,593 Hemoccult II cards returned to Beth Israel Deaconess Medical Center, cards from 1,112 patients (4.7%) were found to be positive for one or more of the six possible card windows. Ninety percent, or 940 patients, over 40 yr of age had follow-up information available. As the number of positive windows increased from one to four, there was a significant trend (p < 0.001) for the adequacy of the evaluation to increase. Family history (p = 0.044) and a patient's worry that he or she might have colon cancer (p = 0.003) significantly improved a patient's chance for an adequate evaluation.
Hemoccult testing is not followed by an adequate evaluation in a significant proportion of patients. Our study points out for the first time that the number of positive Hemoccult windows significantly influences the decision-making.
The American Journal of Gastroenterology 01/2001; 96(1):196-203. · 7.28 Impact Factor
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ABSTRACT: The cell of origin for Barrett's epithelium is unknown. A multilayered epithelium within Barrett's epithelium has been noted recently. To investigate the hypothesis that this multilayered epithelium may be a transitional stage between squamous and Barrett's epithelium, cytokeratin immunocytochemistry was used to examine normal squamous, Barrett's, and multilayered epithelium.
Seventeen endoscopic biopsy specimens taken from the squamo-Barrett's junction of 8 patients with Barrett's epithelium and 3 biopsy specimens from the gastroesophageal junction of 3 patients without Barrett's epithelium were investigated. Antibodies to cytokeratins 4 and 13 were used as markers for squamous differentiation, and antibodies to cytokeratins 8 and 19 were used as markers for glandular differentiation. Coded samples were evaluated by immunocytochemistry.
In patients with Barrett's epithelium and control patients, staining with columnar markers was confined to either the Barrett's or the gastric columnar epithelium. Staining with squamous markers was confined to the adjacent squamous epithelium. In contrast, focal areas of multilayered epithelium amidst Barrett's epithelium stained with cytokeratin antibodies for both squamous and columnar epithelium.
A focal multilayered epithelium within Barrett's epithelium that expresses concurrently both squamous and glandular cytokeratin markers is described. These findings suggest a multipotential cell as the cell of origin of Barrett's epithelium.
Gastroenterology 03/1997; 112(3):760-5. · 11.68 Impact Factor
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ABSTRACT: Barrett's esophagus is a metaplastic condition in which the normal stratified squamous epithelium of the distal esophagus is replaced by columnar epithelium. Our group has previously characterized a unique surface cell (the "distinctive cell") at the junction of squamous and Barrett's epithelium. This cell is notable for the simultaneous presence on its surface of both squamous and columnar cell features. The aims of our present study were, first, to evaluate prospectively the frequency with which Barrett's patients have the distinctive cell at the squamo-Barrett's junction; second, to further elucidate the characteristics of the distinctive cell; and third, to perform a combined morphological study of the squamo-Barrett's junction using scanning electron microscopy followed by transmission and light microscopy. We divided study patients into two groups: Group I consisted of Barrett's patients and group II of non-Barrett's control patients. Of eight group I Barrett's patients with junctional biopsies, three were noted to have the distinctive cell (37.5%). In contrast, this cell was not observed in any of the group II control patients. Biopsies in control patients as well as Barrett's patients without the distinctive cell revealed abrupt squamogastric or squamo-Barrett's junctions by scanning electron microscopy and light microscopy. In contrast, biopsies from the Barrett's patients with the distinctive cell revealed junctions that were not abrupt and had the distinctive cells overlying normal squamous epithelium. By scanning electron microscopy, the distinctive cells were flattened, polygonal cells with surface microvilli (a columnar cell feature) and were demarcated from one another by shallow depressions, or by intercellular ridges (a squamous cell feature). By transmission electron microscopy, the distinctive cells were cuboidal in shape with abundant apical microvilli and secretory vesicles. We have confirmed that distinctive cells are present in some Barrett's patients. This cell is a morphologic hybrid, sharing features of both squamous and columnar cells, and may be analogous to hybrid cells identified in other locations that undergo metaplasia (eg, the human cervix). Its origin may be the result of transformation of multipotential basal cells of squamous epithelial origin. We hypothesize that the distinctive cells may represent an intermediate stage in the development of Barrett's epithelium.
Digestive Diseases and Sciences 07/1996; 41(6):1088-98. · 2.12 Impact Factor
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ABSTRACT: In Barrett's esophagus, metaplastic columnar epithelium replaces the normal squamous epithelium. The importance of this lesion lies in the increased incidence of adenocarcinoma of the esophagus occurring in patients with Barrett's esophagus. We characterized the surface epithelial cells of Barrett's esophagus using quantitative scanning electron microscopy. Three distinct surface cell types, in addition to the globlet cell, were recognized in Barrett's epithelium: the gastric-like cell and the intestinal-like cell, both of which were similar to normal gastric and small intestinal surface cells, respectively, by quantitative scanning electron microscopy, and the variant cell which had a range of surface features. In four biopsy specimens from the squamo-Barrett's junction in three patients, we found the distinctive cell that had features intermediate between those of squamous and columnar epithelium. On the distinctive cell's surface there are two disparate structures not normally present on the same cell in the gastrointestinal tract: microvilli (a scanning electron microscopy feature of glandular epithelium) and intercellular ridges (a scanning electron microscopy feature of squamous epithelium). The surface characteristics of this cell were almost identical to those of cells found in the transformation zone of the uterine cervix, an area in which squamous epithelium physiologically replaces columnar epithelium. Scanning electron microscopy of Barrett's esophagus has increased our understanding of this precancerous lesion by showing striking cellular heterogeneity. It has also identified the distinctive cell which may represent an intermediate step in the development of Barrett's epithelium during which the surface characteristics of two different cell types, columnar and squamous, coexist in the same cell.
Microscopy Research and Technique 07/1995; 31(3):248-56. · 1.79 Impact Factor
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ABSTRACT: Metaplastic columnar epithelium replaces the normal squamous epithelium in Barrett's esophagus. We characterized the surface epithelial cells of the junction between squamous and Barrett's epithelium using scanning electron microscopy and light microscopy. In four biopsy specimens from the squamous-Barrett's junction in three patients, we found a distinctive cell type having features intermediate between those of squamous and columnar epithelium. Its distinguishing characteristic is the presence on its surface of two disparate structures not normally present on the same cell in the gastrointestinal tract: microvilli (a scanning electron microscopy feature of glandular epithelium) and intercellular ridges (a scanning electron microscopy feature of squamous mucosa). The surface characteristics of this newly recognized cell were strikingly similar to those of cells found in the transformation zone of the uterine cervix, an area in which squamous epithelium physiologically replaces columnar epithelium. We also examined 28 biopsies of the gastroesophageal junction area from 14 patients with and without a history of heartburn but with no evidence of Barrett's esophagus. None of these biopsies showed the distinctive cell. We hypothesize that this distinctive cell represents an intermediate step in either the development or the healing of Barrett's epithelium, during which surface characteristics of two different cell types, columnar and squamous, coexist on the same cell.
Digestive Diseases and Sciences 02/1993; 38(1):97-108. · 2.12 Impact Factor
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ABSTRACT: The surface epithelial cells of Barrett's esophagus were characterized using quantitative scanning electron microscopy and light microscopy with mucin histochemical stains. Fifty-one biopsy specimens of Barrett's esophagus from 15 patients and 31 control specimens of the stomach and intestines from 9 patients were examined. Three distinct surface cell types, in addition to the goblet cell, were recognized in Barrett's epithelium: the gastric-like cell in 31% of specimens, which was similar to the normal gastric surface cell by quantitative scanning electron microscopy; the intestinal-like cell in 41%, which was most similar to the normal small intestinal surface cell; and the variant cell in 80%, which had a range of surface features. By light microscopy, all specimens with variant and intestinal-like cells were classified as specialized columnar epithelium. The surface mucous cells in Barrett's epithelium displayed a variety of mucin staining patterns with acid nonsulfated (small intestinal-like) mucin present in 90% of specimens and acid sulfated (colonic-like) mucin in 43% of specimens. Quantitative scanning electron microscopy and mucin histochemical stains reveal a striking cellular heterogeneity not apparent by routine light microscopy.
Gastroenterology 07/1986; 90(6):1932-41. · 11.68 Impact Factor
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ABSTRACT: Monospecific antisera to purified hepatic fatty acid-binding protein (hFABP) and gut fatty acid-binding protein (gFABP) have been used to localize these two proteins in the small intestine of fed rats at the light microscopic level. Pieces of duodenum, jejunum, and ileum were removed from 4-, 10-, 20-, 22-, and 60-day-old Sprague-Dawley rats. Both cryostat and paraffin sections were studied for the presence of hFABP or gFABP by the avidin-biotin immunoperoxidase method. Slides were graded blind for the intensity of staining. Despite the structural and immunological differences between these two proteins, we showed no major differences between their staining patterns or their staining intensity throughout the intestine during postnatal development. The staining for both fatty acid-binding proteins was cytoplasmic. No brush border staining was found. Staining was more intense in the proximal rather than distal intestine, in the villus rather than crypt cells, and in the apex rather than the base of intestinal cells. Shifts in staining patterns, and staining intensity occurring during development may be related to variations in dietary fat intake, rates of cell proliferation, intestinal anatomy, and mechanisms for fat absorption.
The Journal of Lipid Research 06/1986; 27(5):549-57. · 5.56 Impact Factor
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ABSTRACT: This study was conducted to determine whether scanning electron microscopy of colonic mucosal biopsy specimens can help to detect dysplasia in patients with chronic ulcerative colitis. In the first phase of the study, using light microscopy as the standard for the diagnosis, the scanning electron microscopic appearance of specimens from patients with chronic ulcerative colitis and control patients was examined. Descriptive criteria were established to identify normal, atrophic, and dysplastic colonic mucosa. In the second phase, quantitative techniques were used to develop more objective criteria for the diagnosis of dysplasia in ulcerative colitis. Twenty-one coded colonic specimens from 11 patients were sequentially examined by scanning electron microscopy and by light microscopy. The three morphometric analyses performed on the surface epithelial cells were number of cells per unit area, number of microvilli per unit area, and percentage of microvilli with a normal width. The cell count and percentage of microvilli with a normal width were significantly reduced in the seven specimens with colonic dysplasia as compared with non-dysplastic tissues. Scanning electron microscopy may serve as an adjunct to light microscopy in the diagnosis of colonic dysplasia.
Gastroenterology 08/1985; 89(1):62-72. · 11.68 Impact Factor
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ABSTRACT: Our prior immunocytochemical studies using monospecific antibody to alkaline phosphatase, Bouin's fixation, and paraffin sections demonstrated a decreasing gradient of villus brush border staining from the proximal to the distal rat small intestine. In addition, we noted an unusual pattern of staining in the terminal centimeter of the adult rat ileum: the villus brush border staining was less intense than crypt brush border staining. To determine whether this pattern of staining was present throughout the entire ileum, we examined alkaline phosphatase staining in two separate jejunal sites and the entire lowest third of the intestine of adult Wistar rats. With Bouin's fixation and paraffin embedding, both conventional and germ-free rats showed the same unusual staining pattern throughout the entire ileum. This pattern suggested that bacterial proteases were not responsible for the diminished ileal brush border alkaline phosphatase. However, when acetone fixation and cryostat sections were used with the avidin-biotin-peroxidase complex system, the previously noted reversed gradient of staining between the ileal villus and crypt areas was no longer present. Rather, ileal crypt brush border staining was less than ileal villus brush border staining. With either methodology, jejunal villus brush border staining was significantly more intense than ileal brush border staining, whereas the deep crypt brush border staining was not significantly different between the two regions. The present study reinforces the need for a combination of methodologies in order to best and most accurately localize certain antigens with immunocytochemistry. It also confirms a decreasing proximal to distal gradient for villus brush border alkaline phosphatase despite similar deep crypt brush border staining throughout the small intestine.
Gastroenterology 11/1984; 87(4):827-35. · 11.68 Impact Factor
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ABSTRACT: This study was performed to determine the characteristics of esophageal dysplasia by scanning electron microscopy. A total of 82 esophageal biopsy specimens were taken from 30 patients who were divided into three groups. Group 1 patients had no known esophageal disease. Group 2 patients had squamous cell cancer. Group 3 patients had esophagitis. Mucosal biopsy specimens that had been diagnosed by light microscopy as normal, esophagitis, or dysplastic mucosa were examined by scanning electron microscopy. A characteristic appearance for each type of mucosa was recognized by scanning electron microscopy. A quantitative analysis of the scanning electron microscopy feature of microridge density showed a statistically significant difference not only between normal and dysplastic mucosa, but also between esophagitis and dysplastic mucosa. The addition of scanning electron microscopy to light microscopy may prove helpful in the diagnosis of dysplasia as well as in the understanding of the biologic behavior of dysplastic cells and possibly their relationship to esophageal carcinoma.
Gastroenterology 02/1984; 86(1):39-50. · 11.68 Impact Factor
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ABSTRACT: Monospecific antibody to purified alkaline phosphatase hs been used to localize alkaline phosphatase in the rat small intestine at the light microscopic level. Pieces of duodenum, jejunum, and ileum were removed from 2-, 9-, 12-, 18-, 21-, 26-day-old and adult wistar rats. They were fixed in Bouin's fluid and examined for the presence of alkaline phosphatase by th immunoperoxidase method. Slides were graded blindly for the intensity of staining. The localization of alkaline phosphatase by the immunoperoxidase method extends previous histochemical observations in several ways. First, diffuse cytoplasmic staining is present particularly in the opical portion of the villus and crypt epithelium. Second, staining for alkaline phosphatase is present on the brush border and in the apical portion of the deep crypt cells throughout the duodenum, jejunum, and ileum at the various ages tested. Third, in the adult rat distal ileum there is more staining on the brush border of the deep crypt epithelial cells than on the villus absorptive cells. These observations are consistent with the presence of a non-brush border alkaline phosphatase in all intestinal cells and with fan enzymatically inactive form of alkaline phosphatase in the deep crypt epithelium.
Gastroenterology 01/1982; 82(1):39-45. · 11.68 Impact Factor
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ABSTRACT: In an vitro organ culture system, we studied the effects of pentagastrin on rabbit fundic mucosa and small intestinal protein synthesis. The incorporation of [14C]leucine into protein was measured after 24 hr of incubation at 37 degrees C in a 95% oxygen-5% CO2 atmosphere. Biopsies were taken from the stomach, duodenum, jejunum, and ileum of rabbits fasted for 64 hr. Pentagastrin (0.5 microgram/ml) significantly increased protein synthesis in stomach explants at the 24-hr period but did not significantly increase protein synthesis in the duodenum, jejunum, or ileum explants. The results of these in vitro experiments may indicate that pentagastrin is not trophic for rabbit small intestine or, in contrast to its direct effect on the fundic mucosa, pentagastrin acts indirectly in the previously noted in vivo stimulation of intestinal protein synthesis.
Digestive Diseases and Sciences 11/1980; 25(10):769-75. · 2.12 Impact Factor
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ABSTRACT: Ileum from rats 4, 9, 11, 12, and 15 days old can best be maintained for 24 hours in a system using Hanks' Balanced Salt Solution without fetal calf serum, at 25 degrees C and 21% O2. Suckling rat duodenum and jejunum were difficult to maintain well for 24 hours in this system or a variety of other systems that were tried. A temperature of 37 degrees C hastened deterioration of duodenum, jejunum or ileum. With ileum, 3H-thymidine and 14C-leucine were increasingly incorporated into DNA and protein over the 24-hour period. Light microscopy, as well as scanning and transmission electron microscopy, showed very good preservation of the ileum after 24 hours. The addition to the medium of hydrocortisone, 1 micron, and thyroxine, 0.01 micron, alone or in combination, did not change DNA or protein synthesis, or morphology, possibly because of the relatively short (24 hour) time period. Our organ culture system emphasizes the differences between suckling rat ileum and the rest of the intestine, and provides a new tool for evaluating, over a 24-hour period, the developing rat small intestine.
American Journal of Anatomy 08/1979; 155(3):375-89.
