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Biomedical subjects

C L Corless

Publications and source records attributed to C L Corless.

50 records · Page 3Linked to original sources

Papillary renal cell carcinoma. Histology and immunohistochemistry.

Papillary renal cell carcinoma (RCC) is an uncommon subtype of RCC that has distinctive gross, histologic, and cytogenetic features, but for which only limited immunohistochemistry data have been reported. We compared 36 papillary RCCs and five renal cell adenomas with 19 non-papillary (clear cell and granular) RCCs using a variety of antibodies to keratin and carcinoembryonic antigen (CEA). Papillary tumors were often multifocal and associated with coexistent adenomas, whereas nonpapillary tumors generally lacked these features. Low-grade papillary RCCs demonstrated three occasionally overlapping histologic patterns (typical, trabecular, and sclerotic), whereas high-grade tumors were characterized by an admixture of many patterns. Immunohistochemically, 100% (36 of 36 cases) of the papillary tumors were positive for AE1/AE3, and 92% (33 of 36 cases) were positive for callus keratins; only 3% (one of 36 cases) stained for 34BE12, and 11% (four of 36 cases) weakly stained for CEA. The five renal cell adenomas were likewise positive for AE1/AE3 (five of five cases) and callus (five of five cases) keratins. In contrast, 85% (16 of 19 cases) of the nonpapillary tumors stained for AE1/AE3, but only 5% (one of 19 cases) stained for callus; none (0/19) stained for 34BE12, and 10% (2/19) weakly stained for CEA. The consistent expression of callus keratins by papillary RCCs and renal cell adenomas underscores the close relation of these lesions, providing additional evidence for their oncological distinction from nonpapillary RCCs.

Adenoma↗

Biochemical and biologic characterization of murine monocyte chemoattractant protein-1. Identification of two functional domains.

Monocyte chemoattractant protein-1 (MCP-1) is a member of the chemokine-beta (or C-C) family of cytokines. Murine MCP-1, first identified as the JE gene, differs from human MCP-1 in molecular size and extent of glycosylation. We have used Chinese hamster ovary cells to express recombinant murine MCP-1 and find that its predominant form is a microheterogeneous protein of M(r) approximately 25,000. Most of MCP-1's microheterogeneity is due to variable amounts of sialic acid that are terminally attached to a constant number of O-linked oligosaccharide chains per molecule. This carbohydrate, along with a small amount of N-linked carbohydrate, accounts for 50% of the apparent molecular size of murine MCP-1 and is not required for in vitro monocyte chemoattractant activity. Mutational analysis shows that most of the carbohydrate is added to a 49-amino acid C-terminal domain that is not present in human MCP-1 and is not required for in vitro biologic activity, suggesting that murine MCP-1 consists of an N-terminal domain containing monocyte chemoattractant activity and a heavily glycosylated C-terminal domain of as yet unknown function. MCP-1 produced in COS cells contains a small amount of sulfate, but Chinese hamster ovary-produced MCP-1 does not. The absence of sulfate does not alter MCP-1's in vitro chemoattractant properties. In vitro, highly purified murine MCP-1 attracts monocytes, but not neutrophils, with a specific activity similar to human MCP-1 (EC50 approximately 0.5 nM). Equilibrium binding experiments with human monocytes reveal the presence of approximately 3000 binding sites per cell with a Kd of 0.77 nM. In vivo, injection of up to 1 micrograms murine MCP-1 in a variety of murine strains induces the appearance of a sparse mixed inflammatory infiltrate. The disparity between MCP-1's in vitro and in vivo effects suggests that other factors may be required to elicit a full-blown monocyte chemotactic response to MCP-1 in vivo.

Animals↗

Small (< or = 3 cm) renal masses: correlation of spiral CT features and pathologic findings.

OBJECTIVE: We describe our 3-year experience using spiral CT in the evaluation of small renal masses in order to determine the usefulness of this technique for classifying the lesions and to correlate specific CT features with pathologic findings. MATERIALS AND METHODS: We retrospectively analyzed spiral CT scans and results of pathologic examinations of surgically extirpated small (< or = 3 cm) renal masses in 35 patients. The masses included 27 renal cell carcinomas, two transitional cell carcinomas, one leiomyoma, one angiomyolipoma, and four benign cysts. Several imaging features, including attenuation, pattern of contrast enhancement, presence and type of calcification, cyst wall, and septation, were correlated with pathologic findings. RESULTS: Most renal cell carcinomas had a solid growth pattern (n = 19), had attenuation values on unenhanced scans of 20 H or greater (n = 26), and had attenuation values that increased by at least 10 H with contrast enhancement (n = 26). Only three renal cell carcinomas were mostly cystic on pathologic examination. Heterogeneous enhancement correlated with the presence of acellular regions (p = .02). Of 12 cystic masses, spiral CT showed the absence of a thick or nodular fibrous capsule in seven of nine masses (specificity, 0.78) and the absence of several (or nodular) septations in six of seven masses (specificity, 0.86) but was not as sensitive in detecting these features. CONCLUSION: Spiral CT can show many of the key imaging features of small renal masses used to distinguish between benign and malignant lesions. However, despite the theoretical benefits of volumetric CT, some lesions remain indeterminate and require surgical removal for diagnosis.

Carcinoma, Renal Cell↗

Colocalization of thrombospondin and syndecan during murine development.

Thrombospondin is an adhesive glycoprotein that is thought to play a role in tissue genesis and repair. We have used a monoclonal anti-thrombospondin antibody, designated 5G11, to localize thrombospondin in paraformaldehyde fixed, paraffin-embedded sections of developing mouse embryos. Thrombospondin expression is observed in uterine smooth muscle, endometrial glands, the decidua, and trophoblastic giant cells during the initial phase of post-implantation development in the embryo. Cardiac myocytes and neuroepithelial cells show positive staining for thrombospondin at day 8.5 of gestation, and this expression continues throughout the development of the myocardium and central nervous system. Strong staining for thrombospondin is seen in developing bone and in the liver. Thrombospondin is also observed in developing smooth muscle and skeletal muscle, as well as in a variety of epithelia, including the epidermis, small intestinal epithelium, lens epithelium, renal tubular epithelium, and the epithelium of the developing tooth. Comparison of thrombospondin staining with that of two known cell surface receptors for thrombospondin, syndecan and the vitronectin receptor, reveals remarkable colocalization of thrombospondin and syndecan in all tissues, but almost no coexpression with the vitronectin receptor. Coexpression of thrombospondin and syndecan may play an important role in cell-cell or cell-matrix interactions during development.

Animals↗

Gonadotropin alpha subunit. Differential processing of free and combined forms in human trophoblast and transfected mouse cells.

The gonadotropins luteinizing hormone, follicle-stimulating hormone, and human chorionic gonadotropin are composed of two noncovalently linked subunits, alpha and beta. The alpha subunit, identical in all three hormones, is produced in excess over the unique beta subunits by pituitary and placenta, and is secreted as uncombined, or free subunit. Free alpha subunit from both tissues has a larger molecular weight than the dimer form. In bovine pituitary an extra O-linked oligosaccharide is added to free alpha subunit, and this modification has recently been detected at an analogous position (threonine 39) on human alpha subunit secreted by choriocarcinoma cells. To assess the contribution of N-linked and O-linked oligosaccharides to the heterogeneity of human free alpha subunit, we have compared free alpha with human chorionic gonadotropin alpha secreted by explants and cultured cytotrophoblasts of human first trimester placenta. We have also examined the free and combined forms of human alpha subunit expressed in transfected C-127 mouse mammary tumor cells. Processing of the alpha subunit in placental and C-127 cells was similar. Tryptic mapping of placental-derived and transfected alpha subunits indicated that O-glycosylation at threonine 39 was not a major modification. In the presence of the oligosaccharide processing inhibitor swainsonine the difference in size between the free and combined forms of alpha was eliminated in both placental and C-127 cells, indicating that the two forms of alpha differed in their N-linked oligosaccharides. Furthermore, the oligosaccharides of free alpha subunits from placental and transfected cells were resistant to endoglycosidase H, but the combined forms of alpha were partially sensitive to the enzyme. Thus, in human first trimester placenta and mouse C-127 cells, combination of alpha with human chorionic gonadotropin beta alters the processing of N-linked oligosaccharides on alpha subunit.

Alkaloids↗

Effects of preventing O-glycosylation on the secretion of human chorionic gonadotropin in Chinese hamster ovary cells.

Human chorionic gonadotropin (hCG) is a member of a family of heterodimeric glycoprotein hormones that have a common alpha subunit but differ in their hormone-specific beta subunits. The beta subunit of hCG (hCG beta) is unique among the beta subunits in that it contains four mucin-like O-linked oligosaccharides attached to a carboxyl-terminal extension. To study the effects of O-glycosylation on the secretion and assembly of hCG, expression vectors containing either the hCG beta gene alone or together with the hCG alpha gene were transfected into a mutant Chinese hamster ovary cell line, IdID, which exhibits a reversible defect in O-glycosylation. Our results reveal that hCG beta can be secreted normally in the absence of its O-linked oligosaccharides. hCG beta devoid of O-linked carbohydrate can also combine efficiently with hCG alpha and be secreted as an intact dimer. We conclude that in Chinese hamster ovary cells, the hCG beta O-linked chains play no role in the assembly and secretion of hCG. The normal and O-linked oligosaccharide-deficient forms of hCG secreted by these cells should prove useful in examining the role of O-linked chains on the biological function of hCG.

Acetylgalactosamine↗

Gonadotropin beta subunits determine the rate of assembly and the oligosaccharide processing of hormone dimer in transfected cells.

The glycoprotein hormones lutropin (LH) and chorionic gonadotropin (CG) share a common structure consisting of an identical alpha subunit noncovalently linked to a hormone-specific beta subunit. While LH is produced in the anterior pituitary, CG is synthesized in placenta. To compare the assembly, processing, and secretion of human LH and CG in the same cell type, we have expressed their subunits, individually and together, in mouse C-127 mammary tumor cells. Analysis of transfected clones revealed an unexpected difference in the secretion of individually expressed subunits. Whereas alpha and CG beta subunits were rapidly and quantitatively secreted, only 10% of newly synthesized LH beta subunit reached the medium. The remaining subunit was found in an intracellular, endoglycosidase H (endo H)-sensitive pool that had a turnover rate of approximately 8 h. Coexpression with alpha subunit resulted in "rescue" of LH beta subunit by formation of LH dimer, which was efficiently secreted. However, combination of LH beta with alpha was slow, with an overall efficiency of only 50% despite the presence of excess alpha. In contrast, CG beta was rapidly assembled with the alpha subunit after synthesis. The two beta subunits also differed in their influence on the N-linked oligosaccharide processing of combined alpha. The oligosaccharides of LH dimer were endo H resistant, while those of CG dimer remained partially endo H sensitive. Thus, despite a high degree of homology between LH beta and CG beta, the two subunits differ in their secretion as free subunits, their rate of assembly with alpha subunit, and in their effect on the N-linked oligosaccharide processing of combined alpha.

Animals↗

Differential secretion of O-glycosylated gonadotropin alpha-subunit and luteinizing hormone (LH) in the presence of LH-releasing hormone.

The pituitary hormones LH, FSH, and TSH are secreted as dimers of two subunits, alpha and beta. The alpha-subunit, identical in all three hormones, is produced by the pituitary in excess of beta and secreted as free subunit. Bovine free alpha does not combine with purified beta-subunit and contains an extra O-linked oligosaccharide not found on dimer alpha. We have developed an assay to quantitate this modified form of alpha in the medium of incubated steer pituitary slices. The assay, based on reverse phase HPLC analysis of radiolabeled alpha-subunit tryptic peptides, shows that under basal conditions, 75% of secreted free alpha is O-glycosylated. When the secretagogue LHRH is added to the slices, a 14-fold increase in LH dimer release is observed, but secretion of the modified alpha is increased by only 2-fold. Our results indicate that the majority of free alpha-subunit secreted by the pituitary contains O-linked oligosaccharide, and that secretion of this form of alpha differs from that of LH dimer.

Animals↗

Endoluminal treatment of ruptured abdominal aortic aneurysm with small intestinal submucosa sandwich endografts: a pilot study in sheep.

PURPOSE: To evaluate efficacy of small intestinal submucosa (SIS) Sandwich endografts for the treatment of acute rupture of abdominal aortic aneurysms (AAA) and to explore the short-term reaction of the aorta to this material. METHODS: In eight adult sheep, an infrarenal AAA was created transluminally by dilation of a short Palmaz stent. In six sheep, the aneurysm was then ruptured by overdilation of the stent with a large angioplasty balloon. Two sheep with AAAs that were not ruptured served as controls. A SIS Sandwich endograft, consisting of a Z stent frame with 5 bodies and covered inside and out with SIS, was used to exclude the ruptured and non-ruptured AAAs. Follow-up aortography was done immediately after the procedure and before sacrifice at 4, 8, or 12 weeks. Autopsy and histologic studies followed. RESULTS: Endograft placement was successful in all eight sheep. Both ruptured and non-ruptured AAAs were successfully excluded. Three animals with AAA rupture developed hind leg paralysis due to compromise of the arterial supply to the lower spinal cord and were sacrificed 1 day after the procedure. In five animals, three with rupture and two controls, follow-up aortograms revealed no aortic stenoses and no perigraft leaks. Gross and histologic studies revealed incorporation of the endografts into the aortic wall with replacement of SIS by dense neointima that was completely endothelialized in areas where the endograft was in direct contact with the aortic wall. In central portions of the endograft, in contact with the thrombosed aneurysm, endothelialization was incomplete even at 12 weeks. CONCLUSION: The SIS Sandwich endografts effectively excluded simple AAAs and ruptured AAAs. They were rapidly incorporated into the aortic wall. A detailed long-term study is warranted.

Angioplasty↗

Retrievable IVC square stent filter: experimental study.

PURPOSE: In vitro and in vivo evaluation of a new retrievable, home-made, inferior vena cava (IVC) Square stent filter (SSF) with two trapping levels. METHODS: In vitro, the SSF was compared in a flow model with the stainless steel Greenfield filter (SGF) for emboli-trapping efficiency by serially passing 300 emboli of 3 and 6 mm in diameter and 15-30 mm in length in each type of filter. Nine swine were used for the in vivo testing of the SSF for deployment and retrievability, emboli-trapping efficiency, stability, and self-centering ability and two were used (total of 11 swine) for testing repositioning and retrievability of the SSF at 2 weeks and for gross and histologic IVC changes at 2 months. RESULTS: In vitro, the SSF and SGF had similar efficiency in trapping large emboli but the SSF had significantly better efficiency than the SGF for trapping all sizes of emboli (91.7% vs 81%), medium size emboli (93% vs 80%), and small emboli (86% vs 69%). Efficiency decreased in both filters from the first to the fifth embolus in each series but was still significantly better for the SSF. With the SSF, 89% of emboli were caught at the primary and 11% at the secondary filtration level. In the nine animals used for acute studies, the SSF was easily placed in all 27 attempts, assumed a central position 26 times, and was easily retrieved in 21 of 22 attempts. One tilted filter needed additional manipulation for retrieval. During emboli injection in five swine, the SSF had 97.2% emboli-trapping efficiency and demonstrated good stability. In the two animals used for longer-term evaluation, the filters were easily retrieved 2 weeks after implantation. Histologic evaluation at 2 months showed neointimal proliferation around the SSF wires in contact with the IVC wall, which was otherwise normal. CONCLUSION: The SSF is a promising filter. It is easy to place and retrieve, is stable after placement, and has high efficiency for trapping emboli. Promising results justify further experimental and eventual clinical studies with a commercially manufactured SSF.

Animals↗

Small intestinal submucosa covered expandable Z stents for treatment of tracheal injury: an experimental pilot study in swine.

PURPOSE: To evaluate efficacy of small intestinal submucosa (SIS) as a stent covering in healing experimentally created tracheal defects and to explore the trachea's reaction to placement of SIS-covered stents. MATERIAL AND METHODS: A tracheal defect with a diameter of approximately 10 mm was created in six swine with use of a blade or electrocauterization. A double-body, self-expandable SIS-covered Gianturco Rösch Z stent was placed into the trachea to cover the defect. The animals were observed, and were killed when they developed respiratory problems. Autopsy and histologic studies were performed. RESULTS: The SIS-covered stents were accurately placed without immediate complications related to placement. All animals developed respiratory problems on follow-up. One animal died 9 days after procedure because of pneumonia, the others five were killed at 12, 17, 18, 28, and 56 days because of stridor, wheezing, and cough. At autopsy and histology, the tracheal defects were found to be completely healed, with epithelial lining and regeneration of submucosal glands. Animals whose defects were created with a blade demonstrated cartilage remodeling between 9 and 18 days, and apparent deposition of new cartilage at 28 days after SIS placement. The defects made by electrocauterization showed only fibrous tissue with no cartilage regeneration. The tracheal lumen was narrowed by overgrowth of granulation tissue, particularly at the end wires of the stents. In three animals, polypoid masses caused 60%, 70%, and 80% tracheal obstruction, respectively. CONCLUSION: Placement of SIS-covered stents contributed to rapid and effective healing of large tracheal defects. Rigidity and oversizing of Gianturco Rösch Z stents led to secondary changes of the tracheal wall, causing significant airway obstructions. Smaller size and flexible stents should be selected for future work.

Animals↗

Bile duct injury as a major cause of stenosis and occlusion in transjugular intrahepatic portosystemic shunts: comparative histopathologic analysis in humans and swine.

PURPOSE: A comparative histologic analysis of human and swine transjugular intrahepatic portosystemic shunts (TIPS) was performed to investigate factors limiting TIPS patency and to further develop an animal model for TIPS. MATERIALS AND METHODS: Twenty-one human and 13 porcine shunts were evaluated by means of gross inspection, histologic evaluation, and electron microscopy. RESULTS: Severe stenosis (> 75% narrowing) or occlusion was detected with portal venography in nine of the 21 human shunts (48%) and in 10 of 13 porcine shunts (77%). Gross or histologic evidence of a substantial biliary fistula was observed in seven of nine porcine shunts and in seven of eight human shunts with severe parenchymal tract stenosis or occlusion. No evidence of substantial bile duct injury was identified in the 13 human shunts or two swine shunts with patent, nonstenotic parenchymal tracts (P < .01, Fisher exact). Histologic findings in porcine shunts mimicked human tissue responses, including a metaplastic proliferation of bile duct epithelium at sites of bile duct transection. CONCLUSION: Bile duct transection and bile leak are significantly associated with TIPS parenchymal tract abnormalities in patients and swine. TIPS in swine created with the Wallstent faithfully reproduce gross morphologic and histologic changes observed in patients.

Animals↗