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Biomedical subjects

C A Rubio

Publications and source records attributed to C A Rubio.

At least 127 records · Page 7Linked to original sources

Method to quantitate intestinal metaplasia of stomach by image analysis.

With the aid of an image quantifier, the distribution of histochemically labelled (alcian blue, pH 2.5) mucin-producing goblet cells was recorded from a gastrectomy specimen with a peptic ulcer to determine the degree of metaplasia. Of 254 measurements made, 130 were in the antrum and 124 in the fundic area. The areas occupied by cells positive for alcian blue were 7.5 (SD 9.89)% in the antral region, and 1.8 (1.84)% and 0.92 (1.15)% in the two zones representing the fundic area. The difference between the positive mucosal areas in the antrum was significantly higher (p less than 0.001) than in the fundic area. The positively stained area found along the lesser curvature was 7.76 (12.0)% while along the greater curvature, it was 2.17 (3.02)% (p less than 0.001). This method will be useful for future studies of the extent and topographical distribution of intestinal metaplasia among populations with disparate incidences of gastric carcinoma because it permits comparison of different areas of intestinal metaplasia in mucous gastric zones.

Gastric Fundus↗

DNA profiles in mitotic cells from gastric adenomas.

Quantitative DNA measurements were done in mitotic figures from 17 gastric adenomas having slight (3 cases), moderate (8 cases), or severe dysplasia (3 cases) or foci of invasive adenocarcinoma (3 cases). Values higher than for normal diploid control cells (2c) or their estimated tetraploid values (4c) were found to increase gradually from slight dysplasia to invasive adenocarcinoma through moderate and severe dysplasia. While none of the adenomas having slight or moderate dysplasia demonstrated aneuploid mitoses (ie, values higher than 5c), 1% of the mitoses in severe dysplasia and 27% of those with invasive adenocarcinoma had values higher than 5c. The present results thus suggest that aneuploid mitotic figures may help to recognize those gastric adenomas having invasive growth.

Adenocarcinoma↗

Quantitation of fibrosis in liver biopsies.

After 15 years of subjectively estimating the degree of fibrosis in liver biopsies stained with Sirius red F3BA, the amounts of Sirius red-stained fibrotic areas were quantitated with the help of a Cortex IQ 130 image quantifier. The percentage of Sirius red-stained areas was lowest in normal livers, increasing significantly in fatty livers, with stepwise higher values in chronic persistent hepatitis, toxic damage, chronic active hepatitis, fatty livers with obvious fibrosis, biliary cirrhosis and portal cirrhosis. Cases of portal cirrhosis had tenfold higher values than did normal livers. The results indicate that Sirius red is a reliable histochemical stain that can be used to quantitatively demonstrate the various degrees of fibrosis in liver biopsies.

Biopsy↗

A method for the quantitation of intestinal metaplasia of the stomach by morphometry.

A novel method to quantitate the extent of intestinal metaplasia in gastrectomy specimens is presented. Morphometric measurements of histochemically labeled mucin-producing goblet cells were done in three selected gastrectomies (one having a peptic ulcer, one with adenocarcinoma of the intestinal type, and one with adenocarcinoma of the diffuse type). The sectioning of the gastrectomy specimens was standardized. The results indicated that the intestinal metaplasia was significantly higher in the specimen with adenocarcinoma of the intestinal type (as compared to the other two specimens), both along the lesser and greater curvatures as well as in the fundic area. These quantitative results confirm nonquantitative reports based on subjective visual impressions. This quantitative histochemical method for measuring the actual length as well as the topographical distribution of intestinal metaplasia in resected stomachs will be used in future studies of intestinal metaplasia with the aim of disclosing possible differences among populations with disparate incidences of gastric carcinoma.

Adenocarcinoma↗

DNA profiles in dysplasia and carcinoma of the human esophagus.

The nuclear DNA content was microspectrophotometrically measured in 16 resected esophagi having dysplasia, carcinoma in situ and/or early invasive squamous carcinoma. First, the epithelial thickness in (1) normal squamous esophageal epithelium and (2) dysplasia-carcinoma in situ areas was divided into three equal compartments (i.e., basal-parabasal, intermediate and superficial) in five cases. In the normal epithelium, while some of the nuclei in basal-parabasal normal squamous cells had elevated DNA values (corresponding to the natural DNA replication in these cells), intermediate and superficial (nonreplicating) normal squamous cells showed a more definite clustering about the 2c value. In the nonnormal epithelium, the percentage of cells with DNA levels exceeding the normal tetraploid value was highest for the intermediate zone. Therefore, in all 16 cases, normal intermediate cells were measured as internal controls, against which the DNA levels of cells in the intermediate compartment in the areas of dysplasia and/or carcinoma in situ were compared. In areas of dysplasia, two different DNA patterns were observed: one clustering around the normal diploid region and the other with aneuploid values. While the former corresponded to some of the lesions considered by conventional histologic examination to be slight and moderate dysplasias, the aneuploid pattern corresponded to the remaining slight and moderate dysplasias as well as to the severe dysplasias. The possibility that "diploid dysplasias" are reactive (i.e., nonneoplastic) lesions due to chronic inflammation or are "dormant" nonprogressive dysplasias, while aneuploid dysplasias are more aggressive lesions, seems to be substantiated by the fact that all areas with carcinoma in situ or with microinvasive squamous carcinoma had aneuploid nuclei.

Carcinoma, Squamous Cell↗

[DNA analysis of early esophageal cancer and epithelium adjacent to the cancer].

DNA distribution of 4 early esophageal cancers and their epithelial adjacent to cancer was analysed using photocytometry technique. In the tissues around the cancer, DNA content of the normal squamous epithelium always showed diploid (2 c) or proliferating diploid (less than 5 c). DNA content of 3 cases of the dysplastic cells in three specimens was predominantly proliferating diploid, comprising 68%, 38.2% and 59.4% but the aneuploid (greater than 5 c), 8%, 2.9% and 21.8%, respectively. In 4 cases of carcinoma in situ, the aneuploid increased to 86.7%, 68.7%, 17.2% and 28.6%, markedly higher than the dysplastic cells. In 3 cases of early esophageal cancer, the aneuploid accounted for 58.8%, 51.1% and 13.6%, similar to carcinoma in situ. The results indicate that in the dysplastic cells, there is a relative high ratio of the aneuploid cells except the increased proliferating diploid. This phenomenon could explain the unstability for dysplasia and might be the earliest manifestation of malignant change of the epithelial cells.

Aneuploidy↗

Classification of vacuolated cells in the gastric mucosa.

Five different types of vacuolated cells occurring in the gastric mucosa were described. In haematoxylin-eosin stained preparations, one type was characterized by supranuclear clear vacuoles, the other by supranuclear dark vacuoles, another by usually supranuclear vacuoles and cilia, a fourth type by subnuclear clear vacuoles centered by a lymphocyte, and the fifth type by subnuclear empty vacuoles. In the latter three types, a battery of mucous stains were negative. The significance of some of these vacuolated cell types remains to be elucidated.

Adenocarcinoma↗

A model for the study of metastases from colonic tumors by autotransplantation.

Thirty male Sprague-Dawley rats received weekly injections of dimethylhydrazine for three months. They were subsequently laparotomized and tumors were palpated in 21 rats. The colonic tumor was removed and a fraction was autotransplanted into the wall of the transverse colon and a second fraction into the subcapsular space of the left kidney. The results demonstrated successful autotransplantation of colonic tumors in 13 of 21 rats (i.e., 62 percent). In 11 of the 21 rats (52 percent) the tumor grew in the left kidney. Of the various experimental methods proposed for the study of tumor metastases, the one described herein appears to be the first in which primary and secondary tumors were studied in the same individual, since dimethylhydrazine-treated rats usually develop more than one colonic tumor per individual. The model may be useful to monitor the effect of various drugs known to affect tumor growth, not only at the primary site, but also at the site of metastasis.

Adenocarcinoma↗

Intestinal metaplasia of the stomach in Swedish and Japanese patients without ulcers or carcinoma.

A systematic analysis of the cellular components of intestinal metaplasia (i.e., goblet cells with or without brush border cells and Paneth cells) was performed in endoscopic gastric biopsies from 984 patients without gastric ulcer or carcinoma; 359 Swedish and 625 Japanese patients. The Japanese patients, matched for age and sex, had twice as much intestinal metaplasia as the Swedes. The frequency of goblet cells and columnar cells with brush (absorptive) border increased with increasing age in both ethnic groups. Complete intestinal metaplasia (i.e. the presence of at least two or all three cellular components) was twice as frequent in the Japanese. This may reflect differences in the environment (including food habits) of the gastric mucosa in the two populations. Structural mucosal changes (i.e. pseudo-villus formations) were found more than twice as often in the Japanese. Since pseudo-villus changes occurred as often as goblet cells and brush border cells in both groups, it is suggested that the above-mentioned mucosal structural change should be considered for inclusion among the histological criteria of intestinal metaplasia of the stomach. Incomplete intestinal metaplasia (i.e. the occurrence of goblet cells without the other cellular components) occurred in similar proportions in the two populations. The present findings support the theory that incomplete intestinal metaplasia may be a para- rather than a preneoplastic phenomenon.

Adult↗

Nuclear DNA changes during pathogenesis of squamous carcinoma of the cervix in 3,4-benzopyrene-treated mice.

The pathogenesis of squamous carcinoma of the uterine cervix was studied by means of morphologic and cytochemical techniques in mice treated with 3,4-benzopyrene. The results indicate that carcinogen-induced transformation of normal cervical epithelium into squamous carcinoma occurs through a sequence of cellular alterations, demonstrated by progressively increasing cellular atypia and a progressively increasing and scattered DNA content.

Animals↗

Further studies on the therapeutic effect of indomethacin on esophageal tumors.

The effect of treatment with the nonsteroid anti-inflammatory drug indomethacin, was investigated in 250 3-month-old C57Bl female mice following induction of esophageal tumors with diethylnitrosamine (DEN). Already 3 months after DEN treatment, many esophageal tumors were committed to occur: despite discontinued DEN treatment, the number of tumors had increased significantly at 6 or 9 months of observation. Following 3 and 4 months of DEN administration, the development of many already committed esophageal tumors was significantly abrogated by treating the mice with indomethacin.

Animals↗

Monitoring the histogenesis of colonic tumors in the Sprague-Dawley rat.

A total of 306 male Sprague-Dawley rats, injected with dimethylhydrazine (DMH), dose 21 mg/kg body weight s.c., were investigated. Of the 109 rats receiving the dose once only, seven colonic adenocarcinomas developed; all seven (100%) were seen to originate in discrete lymphoid patches. Of the 97 rats treated with one dose/week for 3 months, only 6% of the 50 adenocarcinomas developed in discrete lymphoid patches, while 46% were seen to originate in a pre-existing adenoma. Of the remaining 100 rats, receiving one dose/week for 6 months, only 3.5% of the 57 adenocarcinomas arose from discrete lymphoid patches; 43.9% arose from a pre-existing adenoma. Thus, the histogenesis of adenocarcinomas at our laboratory appears to be dose-dependent. Experiments are therefore being designed to monitor in detail the events of these two histogenetically different adenocarcinomas in the colonic mucosa in our animal model.

1,2-Dimethylhydrazine↗

The intramucosal cysts of the stomach. VII: A pathway of gastric carcinogenesis?

Gastric specimens from 259 patients (69 Swedish and 190 Japanese) were examined for the presence of intramucosal cysts. The number of cysts for each centimeter of mucosa analyzed (cystic index) was calculated. The material included 153 patients with peptic gastric ulcer, 41 with elevated dysplasias, and 65 with early gastric cancer. The results demonstrated that in the Japanese material, the normal-looking gastric mucosa adjacent to a variety of gastric lesions such as gastric peptic ulcer, focal elevated dysplasias, or incipient adenocarcinomas, had a significantly higher cyst index than the gastric mucosa adjacent to similar lesions in Swedish patients. At this point, it should be stressed that the Japanese have a high incidence of gastric cancer (82/100,000 males) while the Swedish have a relatively low incidence (28/100,000 males). The results presented herein appear to suggest that cystic formation in the gastric mucosa may herald an early neoplastic growth at the luminal aspect in some of the cysts.

Adenocarcinoma↗

Ciliated metaplasia in the gastric mucosa. Studies on Japanese patients.

A total of 137 consecutive gastrectomy specimens from Japanese patients having either chronic peptic ulcer, focal (elevated) dysplasia or intramucosal carcinoma were scrutinized under high-power examination (X 1000) for the presence of ciliated cells. In 48 specimens (35.0%) ciliated cells were found in non-neoplastic dilated pyloric glands. The highest percentage was found in cases with focal (elevated) dysplasia (42.6%) or intramucosal carcinomas of intestinal type (41.6%) and the lowest in cases with intramucosal carcinoma of the diffuse type (15.4%) or chronic peptic ulcer (16.0%). Ciliated cells in the gastric mucosa seem therefore to be a common phenomenon in Japanese subjects and appear to be a new indication that the gastric mucosa of Japanese patients may differ from the gastric mucosa of Europeans.

Adenocarcinoma↗

Minimal invasive carcinoma of the colon in rats.

The careful histologic examination of the macroscopically normal colon in rats treated 8 months previously with a single dose of the colonotropic carcinogen dimethylhydrazine (DMH) demonstrated atypical colonic glands in normally occurring lymphoid mucosal patches. The atypical glands were characterized by the absence of cytoplasmic mucus, hyperchromatic cell nuclei, cell stratification, and increased number of mitotic figures. In 61.7% of the experimental animals, atypical colonic glands were found beyond the boundary of the muscularis mucosae, but in none of the controls. Thus, microinvasive adenocarcinoma of the colon seems to be a common finding in rats treated with a single dose of DMH. These adenocarcinomas remain, however, undetected at macroscopic examination. Measurements performed in consecutive lymphoid aggregates demonstrated that 50% of rats receiving DMH had thicker lymphoid aggregates than control animals. In spite of this, no tumor was recorded at naked eye examination in these areas. The macroscopic examination appears to be an unreliable method of ruling out malignancy in experimental rats treated with a single dose of the above-mentioned carcinogen.

Adenocarcinoma↗

The lymphoepithelial phenomenon in the gastric mucosa.

Lymphocyte-like cells surrounded by a clear halo were found within the foveolar epithelium both in the fundus and the antrum in a gastrectomy specimen containing concomitantly a benign gastric ulcer. Electron microscopic studies demonstrated that these "in halo" cells had the ultrastructural characteristics of lymphocytes. "In halo" lymphocytes were found present in the subnuclear aspect of the foveolar cell cytoplasm, even in areas without inflammation in the lamina propria. The possible significance of the present finding is discussed.

Adult↗

Atypical mitoses in elevated dysplasias of the stomach.

The number and topographic localization of spontaneously occurring mitotic figures were studied in 22 elevated dysplasias of the stomach. The lesions were divided into 3 equally thick zones. Mitoses occurred in 5 of 7 slight dysplasias, in 7 of 8 moderate dysplasias, and in all 7 severe dysplasias. When present, mitoses were localized to the superficial zone in slight, moderate and severe dysplasias, in the middle zone in some moderate dysplasias, and in almost all severe dysplasias. In the deeper zone, mitoses were seen in one of the moderate dysplasias and in as much as 5 of the severe dysplasias. The number of mitoses were significantly higher in moderate and severe dysplasia, when compared to slight dysplasia. The percentage of atypical mitoses increased gradually from 27% in slight dysplasia to 41% in moderate, and 52% in severe dysplasias. In the adjacent, non-dysplastic gastric mucosa, a 1.5% of atypical mitoses was found. Significantly higher amounts of atypical mitoses were recorded in severe dysplasias, as compared to slight and moderate dysplasias. The results suggest that the various types of elevated dysplasias (slight, moderate and severe) of the stomach may be distinguished, not only by the characteristics of the atypical cells in interphase--as is the case today--but also by the topographic distribution of mitoses and by the difference in percentage of atypical mitoses occurring in these lesions. The possible significance of the mitosis as a biohistological marker of the behaviour of elevated dysplasias of the stomach is discussed.

Biopsy↗