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C A Rubio

Publications and source records attributed to C A Rubio.

284 records · Page 16Linked to original sources

Apoptosis in flat neoplasias of the colorectal mucosa.

Intraepithelial and intramacrophageal inclusion granules (Leutchenberger bodies) were found in 83.9% of 174 flat neoplastic lesions of the colorectal mucosa. Flat adenomas with high grade dysplasia and flat adenocarcinomas originating in flat adenomas demonstrated a higher proportion of moderate to large (++/ ) numbers of granules than flat adenomas with low grade dysplasia, indicating that the occurrence of apoptotic granules may be related to the "biological age" of the adenoma. Early studies suggest that these inclusions may be the remains of intraepithelial lymphocytes. A lymphoid follicle aggre-gate subjacent to flat adenomas was recorded in 38% of the cases. Whether the intraepithelial lymphocytes derive from the lymphocytes contained in these satellite lymphoid aggregates remains unclear. Conventional and immunohistochemical stains demonstrated that these inclusions represent apoptotic mate-rial. The possibility that tumor cells from flat neoplastic lesions of the colorectal mucosa inflict apoptosis upon non-epithelial (i.e. foreign) cells has been entertained.

Adenoma↗

Evaluation of the protracted stress in the esophageal mucosa of rats.

The effect of protracted stress upon the DNA synthesis of the esophageal mucosa of the rat was investigated at various time intervals ranging from one to 56 days. A total of 80 Sprague-Dawley rats were investigated. Lots of 25 rats each were either shock-plunged, subjected to swimming in large basins for two hours or were only transported to the swimming laboratory and used as controls. The remaining 5 rats were non-transported (resting) controls. At the end of the above described procedures, all 80 rats received an intraperitoneal injection of 1 microCi3H-thymidine/gr bodyweight. one hour later the rats were killed. Half of the esophagus was processed for DNA extraction and the other half for autoradiography. When compared to day 0 (resting control rats), the DNA values in experimental animals had increased significantly at day 1, decreased significantly at day 7 in swimming rats and risen once again in both experimental groups at day 14 and more notably at day 28. By 56 days, the values had reached those of day 0. When compared to transported controls at each time interval, both experimental groups had significantly higher DNA values at day 1, significantly lower at day 7 and once again, significantly higher at day 28. Autoradiographic studies of plunged rats showed similar fluctuations in the percentage of labelled basal-parabasal cells in the esophageal mucosa at the various time intervals. The results of this work are similar to those reported previously for the gastric mucosa, the duodenal mucosa and the colonic mucosa of rats subjected to the same stressors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Flat serrated adenomas of the colorectal mucosa in Japanese patients.

While reviewing the histological sections of 319 flat colorectal polyps at three different Hospitals in Tokyo, 7 cases of flat serrated adenomas were found. Flat serrated adenomas differ histologically from flat tubular adenomas. In the former the dysplastic cells are found initially at the lower part of the crypts of Lieberkuhn, and the epithelium of the sides of those crypts have serrated infoldings without dysplastic cells. In flat tubular adenomas, however, the dysplastic cells are initially found in the upper part of straight crypts (i.e. without epithelial infoldings). Six of the 7 serrated adenomas had low grade dysplasia (LGD) and the remaining one high grade dysplasia (HGD). Atypical mitosis were present in the dysplastic epithelium of serrated adenomas. Depending upon the topographic distribution of the dysplastic epithelium within the crypts flat serrated adenomas were divided into Type I, where the dysplastic epithelium was limited to the lower half of the serrated crypts, and Type II where the dysplastic epithelium was present even in the superficial half of the serrated crypts. Of the 7 serrated adenomas, 3 were Type I and the remaining 4 Type II lesions. The dysplastic epithelium seemed to have originated at the base of the crypts and progressed upwards, replacing the scalloped, serrated epithelium. Flat serrated adenomas appeared as benign lesions upon endoscopy (their pit pattern being identical to flat hyperplastic polyps), but in a previous survey of Swedish patients 3 of 47 flat serrated adenomas had invasive adenocarcinoma (i.e. with submucosal extension). Whether serrated adenomas evolved into invasive carcinoma in the Japanese should be assessed in a larger series of cases.

Adenoma↗

Differences in the distribution of acidic mucins between flat tubular adenomas and flat serrated adenomas of the colorectal mucosa.

Two consecutive sections from 72 endoscopically detected flat colorectal polyps (flat tubular adenomas n = 40, flat serrated adenomas n = 18, flat hyperplastic polyps n = 7 and normal colonic mucosa n = 7) were stained with Alcian blue pH 2.5 (AB) or with high iron diamine (HID) without counterstain, to evidence the most important attribute of the colorectal cells i.e. their capacity to produce acidic mucins (sialomucins and sulphomucins respectively). Intense AB and HID staining (++) was found in the upper part of the crypts of all (100%) sections with normal colonic mucosa or with flat hyperplastic polyps, in 13 of the 18 (72%) flat serrated adenomas (with low grade dysplasia = LGD, n = 16; or high grade dysplasia = HGD, n = 2) but in none (0%) of the 40 tubular adenomas. Slight (+) or negative staining of the upper part of the crypts were recorded in all 40 (100%) flat tubular adenomas (LGD n = 32; HGD, n = 8), but in only 5 of the 18 (27,7%) flat serrated adenomas (LGD n = 3; HGD n = 2) and in none (0%) of the sections with normal colonic mucosa or with flat hyperplastic polyps. Intense AB and HID staining (++) was found in the lower part of the crypts in all sections (100%) with normal mucosa or with flat hyperplastic polyps, in 36 of the 40 flat (90%) tubular adenomas (LGD n = 32; HGD n = 8), but in none (0%) of the flat serrated adenomas. Slight (+) or negative stainings in the lower part of the crypts were recorded in all 18 (100%) flat serrated adenomas, but in only 4 of the 40 (10%) flat tubular adenomas and in none of the sections (0%) with normal mucosa or with flat hyperplastic polyps. Thus, the mucosal localization of the depletion of mucin production differs in flat serrated adenomas and in flat tubular adenomas. The difference in topographic distribution of the depletion of acidic mucins in epithelial cells is a new argument in favour of the identity of flat serrated adenomas as an independent neoplastic phenotype in the colorectal mucosa.

Adenoma↗

Hyperplastic foveolar gastropathy and hyperplastic foveolar gastritis in baboons.

While reviewing gastric specimens from 215 baboons, we found diffuse giant mucosal folds in 2 specimens and multiple giant mucosal nodules in another 3. The increased mucosal thickness in those areas was due to giant hyperplasia of the foveolar epithelium. The former 2 specimens were classified as Menetrier's disease (MD) and the latter 3 as Varioliform Lymphocytic Gastritis (VLG), since they were histologically identical to those gastropathies in humans. Whereas MD had diffuse giant hyperplastic foveoli (without lymphocytic infiltration) and prominent glandular cysts, VLG had nodules due to giant hyperplastic foveoli with intraepithelial lymphocytosis. Since the causes leading to gastric MD and VLG in humans remain unknown, the spontaneous occurrence of these two conditions in the baboon may open new avenues for the investigation of possible etiologic factors in the laboratory.

Animals↗

Differences in angiogenesis and collagenesis between exophytic and flat adenomas of the colorectal mucosa.

A connective tissue core is present in exophytic colorectal adenomas but not in flat adenomas. In the present work, the occurrence of collagen (the principal and most abundant component of the connective tissue) and of microvessels was investigated in 68 colorectal adenomas (35 exophytic and 33 flat). Tissue sections were alternatively challenged with Sirius stain (to evidence collagen) and with von Willebrand Factor (to evidence endothel-lined microvessels). The reactions were semiquantitatively estimated and the number of microvessels quantitatively assessed. Both collagen and microvessels were moderately to markedly increased in 34 of the 35 exophytic adenomas, but only slightly increased or normal in all 33 flat adenomas. Since factors released from neoplastic cells evoke microangiogenesis and those released from mesodermal cells evoke collagenesis, it would appear that the molecular information aimed at generating both microvessels and collagen in the connective tissue core of exophytic adenomas emanates from two different cell systems. The reason(s) for the inability of neoplastic cells and mesodermal cells to induce microangiogenesis and collagenesis in flat adenomas remains unclear.

Adenoma↗

Atypical mitoses in colectomy specimens from patients with long standing ulcerative colitis.

About 1% of dividing epithelial cells in esophageal, gastric and duodenal mucosas with chronic inflammation have been found to be atypical. In the present work, the characteristics of the mitotic figures in the colorectal mucosa with ulcerative colitis (UC)--a disease characterized by chronic mucosal inflammation--were investigated. Feulgen-stained histologic sections (having > 30 mitoses in 3 large tissue sections) from 59 colectomy specimens with long standing total UC were scrutinized at high power microscopy (1000 x). A total of 2,104 mitoses were recorded in the 59 specimens with UC: 591 (28.1%) were atypical. Atypical mitoses were present in 19.2% (SE 4.7) of the 26 specimens having chronic active inflammation, in 16.9% (SE 5.6) of the 9 with UC in remission, in 34.6% (SE 7.7) in mucosas with dysplasia (n = 8) and in 49.1% (SE 10.2) in carcinoma (n = 16). Atypical mitoses were also found in 17.0% (SE 5.4) in the non-dysplastic mucosa from colitic patients having dysplasia or carcinoma elsewhere as well as in 0.96% (SE 0.3) in 14 "noncolitic" controls with chronic inflammation. The percentage of atypical mitoses was influenced-except in areas with dysplasia or carcinoma-by the duration of the disease (< 15 or > 16 years), but not by the age or the gender of the patients. Since the frequency of atypical mitoses in "noncolitic" controls with chronic inflammation was low, it is evident that factors other than chronic inflammation may be involved in the induction of atypical mitoses in colitics. Acquired nuclear aberrations detected during the mitotic phase, but not at interphase do occur in colorectal epithelial cells from long-standing UC patients, not only in areas with dysplasia or carcinoma but also in areas without those neoplastic changes.

Adult↗

Intraepithelial lymphocytes in flat colorectal adenomas.

The occurrence of intraepithelial lymphocytes (IELs) was investigated in 118 flat colorectal adenomas. IEL infiltration was recorded in 61.9% or in 73 of the 118 flat adenomas. Of the 58 flat adenomas with LGD, 30 (or 51.7%) had IELs, and of the 60 flat adenomas with HGD, 43 (71.7%) had IELs. The significance of IELs in flat colorectal adenomas remains obscure. The finding that the epithelium of flat adenomas with HGD had more IELs than the epithelium of flat adenomas with LGD suggests that the degree of IEL infiltration may increase with increasing degree of epithelial severity in adenomas. One possible implication from this work may be that immunologic mechanisms orchestrated by the host and directed towards the neoplastic cells, may be acting at the early stages of colorectal carcinogenesis.

Adenoma↗

Ethnic or environmental differences in disparate geographic regions may influence the histology of flat colorectal neoplasias.

Histologic sections of endoscopically flat colorectal polyps removed in Tokyo and Stockholm were reviewed. A total of 178 flat colorectal neoplasias (88 from the Tokyo Medical College Hospital, Tokyo and 90 from the Karolinska Hospital, Stockholm) were classified following strict histologic criteria by two different pathologists (one Swedish and the other Japanese). The number of polyps with high grade dysplasia, with intramucosal carcinoma and with invasive carcinoma were significantly higher (p < 0.001) in Tokyo (61.4% or 54/88) than in Stockholm (15.0% or 14/90). The present results suggest that flat colorectal neoplasic polyps may be histologically more "severe" and more "aggressive" in Japanese than in Swedish patients. The possibility that more "advanced" lesions had been inadvertently removed in Tokyo was discounted as Japanese endoscopists were also instrumental in excising many of the flat colorectal polyps in Stockholm. Ethnic and/or environmental differences seem to play a crucial role in the evolution of flat colorectal neoplasic polyps from LGD and HGD, to intramucosal and to invasive carcinoma.

Adult↗

Adenocarcinoma of the cecum with Crohn's-like features in baboons.

During the past 9.5 years, 51 baboons dying as a result of chronic diarrhea and poor health and having a chronic inflammatory process of the cecum (i.e. typhlitis) were recorded. The cecum was turgid, irregularly thickened the lumen reduced and the mesenteric lymph nodes enlarged. Of the 45 baboons with well preserved histologic material, 24 had shallow ulcerations and/or focal mucosal inflammation, 3 had crypt abcesses, 3 had mucosal fissures,l aphtoid ulcerations, and 1 pseudopyloric metaplasia (ulcer associated cell lineage-UACL-). The submucosa in all 45 animals was thick due to fibrosis, 35 had focal chronic inflammation with lymphoid aggregates, 12 submucosal abcesses, 6 epithelioid cell granulomas, 5 fissures reaching the submucosa, 3 neural hyperplasia of the myenteric plexus, and 2 lymphangiectasia. Focal chronic transmural inflammation with lymphoid aggregates was recorded in 44 animals. In addition, 2 animals showed deep fissure tracts. Ten of the 45 animals had in addition a cecal adenocarcinoma; one was overlayed by a villous adenoma with high grade dysplasia. Liver metastasis was found in another animal. The present study indicated that a) baboons may develop transmural chronic focal inflammation in the proximal colon (cecum), b) the inflammation in baboons closely mimic Crohn's disease of the cecum in humans c) adenocarcinomas in baboons with Crohn's-like inflammatory changes may originate in an adenomatous growth, and d) cecal adenocarcinomas in baboons with Crohn's-like inflammatory changes of the cecum, are able to metastasize.

Adenocarcinoma↗

The detection of bile ducts in liver biopsies by cytokeratin 7.

In hematoxylin and eosin (H and E) stained sections from liver biopsies, the destruction of bile ducts in the portal triads is regarded as an important histologic parameter in the diagnosis of primary biliary cirrhosis (PBC). In contrast, the bile ducts are not destroyed by chronic inflammation in chronic active hepatitis (CAH). Nevertheless, the differential histologic diagnosis between PBC and virus or autoinmune-induced chronic active hepatitis (CAH), is very difficult in 15% of cases. That difficulty is mainly due to the impossibility of identifying bile ducts in the portal triads with marked lymphocytic infiltration. In this investigation we report that bile ducts may be specifically stained by anti-human cytokeratin 7 (CK7). Sections from 16 liver biopsies (PBC = 6, CAH = 6 and fatty liver (FL) = 4) were stained with H and E and CK7. The results in H and E stained sections indicated that the mean number of bile ducts found in PBC was was 0.56 (range 0-2), in CAH 0.67 (range 1-3), and in FL 0.56 (range 1-3). In parallel CK7 stained sections, the mean number of bile ducts in PBC was 5.33 (range 2-35), in CAH 3.44 (range 4-18), and in FL 1.39 (range 2-6). The difference between H and E and CK7 stained sections was significant (p < 0.001) in all 3 groups. In the light of these preliminary results, it would appear that Cytokeratin 7 may be the stain of choice to detect bile ducts, an important parameter to histologically differentiate between PBC and CAH, as well as to classify PBC into its different stages.

Bile Ducts, Intrahepatic↗

A comparative study between the gastric mucosa of west Canadians and other dwellers of the Pacific Basin.

The presence of non-neoplastic changes in the gastric mucosa--such as intramucosal glandular cysts, pyloric cells with ciliated metaplasia, with large or small mucus negative vacuoles, and with glassy cytoplasm, as well as extensive intestinal metaplasia (IM)--was investigated in 241 consecutive gastrectomy specimens from the archival files of the Vancouver Hospital situated on the Pacific coast of Canada. A total of 2,938 sections were reviewed (mean number of sections per gastrectomy: 12.24 (range 5-56 sections). Of the specimens with intestinal type carcinoma (known to be promoted by environmental factors), 68.9% contained intramucosal cysts, 35.6% pyloric cells with ciliated metaplasia, 35.6% pyloric cells with large vacuoles, 20.0% pyloric cells with small vacuoles, 4.4% pyloric cells with glassy cytoplasm and 40.0% high IM values. Those percentages were significantly higher than for specimens having diffuse type carcinomas, peptic ulcers, benign gastric tumors or non-neoplastic gastric diseases. The present findings substantiate early results obtained in other populations dwelling along the Pacific Basin. In contrast, dwellers of the Atlantic Basin with gastric carcinoma of intestinal type or other gastric diseases, seldom have similar gastric non-neoplastic changes. It is suggested that the gastric mucosa of Pacific coast Canadians may develop, similarly with inhabitants of other regions of the Pacific Basin, non-neoplastic changes, most notably when harbouring an adenocarcinoma of intestinal type. Environmental factors acting in that basin may account for the results obtained.

Adenocarcinoma↗

Histologic phenotypes of colonic carcinoma in Sweden and in Japan.

The occurrence of predominant histologic phenotypes in overt colonic carcinomas from two disparate geographical regions were analyzed. A total of 424 overt colonic carcinomas (223 in Swedish and 201 in Japanese patients) were classified into predominant phenotypes (i.e. comprising > 50% of the tumor). Six predominant phenotypes were found: tubular, serrated-microcystic, villous, fenestrated, signet ring cell and undifferentiated. A predominant phenotype was present in 57.3% (n = 243) of the 424 tumors (in 55.2% of the 223 tumors from Swedish patients and in 61.7% of the 201 tumors from Japanese patients). The serrated-microglandular phenotype was significantly more frequent in Japanese than in Swedish patients. Environmental and/or ethnic factors may be the possible cause(s) for that difference. The frequency of regional lymph node tumor spread (Dukes C) was significantly lower in serrated-microglandular and in villous phenotypes than in undifferentiated-signet ring cell types, despite that patients harbouring either one of the two former phenotypes were among the oldest in the whole series. Serrated-microglandular and villous colonic cancer phenotypes may carry a better prognosis (independently of their degree of histologic differentiation or age) since they are less prone to metastasize to regional lymph nodes than undifferentiated-signet ring cell phenotypes.

Adult↗

A new phenotype of gastric pyloric cells. A study in baboons.

The histology of the stomach of 215 baboons having chronic gastritis (n = 7), hyperplastic foveolar gastropathy (resembling Menetrier's gastropathy in humans) (n = 2), hyperplastic foveolar lymphocytic gastritis (n = 3), adenocarcinoma (n = 1) or normal mucosa (n = 202), were reviewed. Pyloric glands having cells with a ground glass cytoplasm were found in two of the 7 animals with chronic gastritis. Those cells are characterised by an homogeneous, eosinophylic cytoplasm with "glassy" appearance. We previously found pyloric cells with ground-glass cytoplasm in gastrectomy specimens from patients dwelling in disparate geographic regions, suggesting that those cells occur independently of the race of the individuals or of different environmental conditions. The same cells are now found in the gastric antrum of baboons. "Glassy" pyloric cells showed a moderate positivity with PAS stain but they were negative after diastase treatment, suggesting that the glassy material may be a glycoprotein.

Animals↗