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G W Stamp

Publications and source records attributed to G W Stamp.

At least 73 records · Page 4Linked to original sources
PubMed1992

Lysozyme gene expression in inflammatory bowel disease.

Riboprobe in situ hybridization (rISH) demonstrates active lysozyme synthesis in ulcerative colitis and Crohn's disease. Maximal labeling was seen in Paneth cells, macrophages, and granulomas. Diffuse infiltration of the mucosa by lysozyme-rich polymorphs characterizes ulcerative colitis but obscures reactivity in other cell lineages in immunohistochemical studies; lysozyme mRNA is not detected in polymorphs, rISH giving a clearer picture than immunohistochemical studies of the active synthesis of lysozyme within the gut in inflammatory bowel disease. In ulcerative colitis, strong signals localized to Paneth cell metaplasia were found in 11 of 20 cases and to a lesser degree in non-Paneth cell lineages in regenerative mucosa in 13 of 20 cases. In Crohn's disease, abundant labeling was seen in tuberculoid granulomas (5 of 20) and over macrophage aggregates in the lamina propria in another 7, characteristic patterns not encountered in ulcerative colitis. Low levels of lysozyme messenger RNA were found in the ulceration-associated cell lineage ("pseudopyloric metaplasia"). These results support the view that neutrophils are largely responsible for elevated fecal lysozyme levels in ulcerative colitis and macrophages for elevated serum lysozyme levels in Crohn's disease.

Colitis, Ulcerative↗
PubMed1992

Integrins and their accessory adhesion molecules in mammary carcinomas: loss of polarization in poorly differentiated tumors.

The integrins are alpha beta heterodimeric transmembrane proteins mediating cell-substratum as well as cell-cell interactions. To identify the pattern of expression of the beta 1, beta 3, and beta 4 integrins and their accessory adhesion molecules in relation to the malignant phenotype of invasive breast cancer, we performed an immunohistochemical study for the alpha 2 beta 1 (VLA-2), alpha 6 beta 1 (VLA-6), alpha v and alpha v beta 3 (vitronectin receptor), alpha 6 beta 4, carcinoembryonic antigen, and carcinoembryonic antigen-related molecules in a series of 37 invasive breast carcinomas. All integrin chains examined showed similar patterns in nonneoplastic breast tissue, with strong membrane staining of the myoepithelial cells and weak to moderate staining on the basolateral surfaces of the luminal cells. We found that downregulation of the alpha 2 chain of VLA-2 occurs more frequently in poorly differentiated grade III invasive ductal carcinomas (IDCs) (P = .048). Loss of alpha 6 beta 4 seems also to occur more frequently in grade III IDC (seven of 11 cases, 63.6%) than in grade I/II IDC (two of eight cases, 25%), although this did not reach statistical significance. Carcinoembryonic antigen and carcinoembryonic antigen-related antigens, which are known to function as accessory adhesion molecules, were found mainly in the cytoplasm of neoplastic cells and there was reduced membrane polarization in poorly organized tumors. In contrast the alpha v beta 3, vitronectin receptor heterodimer recognized by the 23C6 monoclonal antibody was weak or absent in normal breast epithelium, and was weakly expressed in two of 19 (10%) IDCs and in nine of 18 (50%) invasive lobular carcinomas (P = .008). However, the alpha v chain detected with the antibody 13C2 was weakly to moderately expressed on nonneoplastic epithelium and at a similar intensity in 13 of 19 IDCs and 15 of 17 invasive lobular carcinomas, suggesting that in IDC the alpha v chain may be associated with a different beta chain (possibly beta 1 or beta 5). No correlation between integrin expression and estrogen/progesterone receptor status was found. These data provide further evidence that in invasive breast carcinomas there is a widespread deregulated expression of integrins and their accessory adhesion molecules with loss of polarization. Changes in the expression and function of cell adhesion molecules, which control growth and differentiation, may have clinical relevance in the behavior of breast cancer.

Antigens, Surface↗
PubMed1992

Morphoregulatory activities of E-cadherin and beta-1 integrins in colorectal tumour cells.

The cadherin family of adhesion molecules are prime mediators of cell-cell interactions while the integrins predominantly mediate cell-matrix and to a lesser extent cell-cell binding specificity. We have recently shown that a human colon carcinoma cell line (SW1222) organizes into glandular structures, with well defined polarity when cultured in three-dimensional type I collagen gel. The current study indicates that SW1222 cells display high levels of E-cadherin (E-cd, epithelial cadherin) by western blotting and immunohistochemical staining. A monoclonal antibody (HECD-1) specific for human E-cd blocks cell-cell adhesion (100%) and inhibits (up to 75%) the glandular differentiation of SW1222 cells growing in collagen gel. Furthermore the anti-beta 1 integrin monoclonal antibody (mAb13) inhibits the glandular differentiation of SW1222 cells (61%) and their cellular binding to type I collagen (60%). However, no significant inhibition of cell-cell adhesion was demonstrated using mAb13 nor the anti-carcinoembryonic antigen monoclonal antibody (PR3B10). These results are consistent with E-cd being a cell-cell adhesion molecule expressed by SW1222 cells. These data indicate that E-cd and beta 1 integrins mediate cell-cell and cell-collagen interactions required for the induction and maintenance of the glandular differentiation of colorectal tumour cells. Thus the down-regulation or loss of E-cd and beta 1 integrins seen in poorly differentiated colorectal tumours may represent one of the abnormalities underlying their progression towards an undifferentiated phenotype in vivo.

Blotting, Western↗
PubMed1992

Beta actin expression and organization of actin filaments in colorectal neoplasia.

Several studies have linked abnormal actin cytoskeletal organization and mutant actin genes with neoplastic transformation. Using in situ hybridization techniques we looked at expression of beta actin mRNA at a cellular level in normal, benign and neoplastic human colorectal tissues and correlated the level of expression with the extent of actin cytoskeletal organization in sequential sections. Normal tissues showed light labelling with the actin riboprobe, but non-neoplastic crypts, with evidence of regeneration and repair, showed greater levels. Higher levels of actin mRNA expression were found in adenomas and metaplastic polyps, but the highest levels were found in carcinomas, particularly those that were poorly differentiated. Cytoskeletal actin organization was, however, reduced in colorectal neoplasia. Normal mucosa showed the highest level of cytoskeletal actin organization, as assessed by phalloidin binding, and adenomas and metaplastic polyps also stained strongly. In contrast, phalloidin binding to poorly differentiated carcinomas was absent or very weak. The inverse relationship between actin mRNA expression and actin filament organization was confined to the carcinomas studied and may indicate defects in actin binding proteins or in post-transcriptional or translational events.

Actins↗
PubMed1992

Stromal expression of 72 kda type IV collagenase (MMP-2) and TIMP-2 mRNAs in colorectal neoplasia.

We undertook an in situ hybridization study to localize the mRNAs for the 72 kda type IV collagenase (MMP-2) and its specific inhibitor (TIMP-2) in 12 colorectal carcinomas, 3 adenomas, and 4 uninvolved resection margins to see how their distributions correlated with that of the reported distribution of MMP-2 protein. Labeling for MMP-2 and TIMP-2 mRNAs was detectable in 10 of 12 carcinomas and in 2 of 3 adenomas. Unexpectedly, we found much stronger signals for MMP-2 and TIMP-2 mRNAs within the mesenchymal cells in the desmoplastic stroma, of endothelial and/or (myo)fibroblastic nature, rather than in tumor epithelial cells in which localization of MMP-2 was anticipated. Our data indicate that stromal cells may have the ability to synthesize a metalloproteinase that degrades basement membrane, and may together with the neoplastic epithelial cells participate actively in the tissue remodeling and disruption of the basement membrane integrity which is characteristic of invasive tumors.

Actins↗
PubMed1991

Distribution of beta 1, alpha 1, alpha 2 and alpha 3 integrin chains in basal cell carcinomas.

The integrins are alpha beta heterodimeric transmembrane proteins mediating cell-substratum as well as cell-cell interactions. Changes in their expression and/or function seem to occur in a number of malignant epithelial neoplasms and may in part explain their abnormal patterns of growth and differentiation. Using monoclonal antibodies to the beta 1 (DH12), alpha 1 (TS2/7), alpha 2 (B1.515), and alpha 3 (E1.56) integrin chains, the alpha 1 beta 1 (VLA-1), alpha 2 beta 1 (VLA-2), and alpha 3 beta 1 (VLA-3) integrin receptors were studied on cryostat sections of 22 basal cell carcinomas (BCCs) and adjacent normal tissues by a standard peroxidase-antiperoxidase technique. In non-neoplastic skin, VLA-2 and VLA-3 were found in the basal layer, eccrine glands, and cells of the outer root sheath in which VLA-1 was detected. In BCCs, there was a considerably higher expression of VLA-2 and VLA-3 compared with epidermal basal cells but similar to that seen in hair bulb and outer root sheath. In two cases of nodular BCC showing evidence of regression, both VLA-2 and VLA-3 were completely negative, in contrast to non-regressing foci which were strongly positive. The high level of expression of two adhesion molecules (VLA-2 and VLA-3) involved in cell-substratum as well as cell-cell interactions may account for the more indolent pattern of growth characteristic of BCC and perhaps reflect its high degree of differentiation towards the hair follicle.

Basal Cell Carcinoma↗
PubMed1991

Low expression of beta 1, alpha 2 and alpha 3 subunits of VLA integrins in malignant mammary tumours.

The Very Late Antigens (VLAs) are alpha beta heterodimeric transmembrane proteins mediating cell-substratum as well as cell-cell interactions. Changes in their expression and/or function seem to occur in a number of invasive carcinomas and may at least in part explain their abnormal patterns of growth and differentiation. Using monoclonal antibodies to the beta 1 (DH12, A1A-5), alpha 2 (B1.515) and alpha 3 (E1.56) chains, VLA-2 (alpha 2 beta 1) and VLA-3 (alpha 3 beta 1) were studied on cryostat sections of three fibroadenomas and 43 invasive breast carcinomas (29 ductal, 14 lobular) by the avidin-biotin complex immunoperoxidase technique. In non-neoplastic breast tissue and in fibroadenomas VLA-2 and VLA-3 were expressed by myoepithelial cells and on the basolateral surface of the luminal cells. There was weak or absent expression of alpha 2, alpha 3 and the common beta 1 chain in the majority of invasive carcinomas compared to the adjacent normal breast epithelium and preinvasive (in-situ) carcinomas. In addition, the expression of the alpha 2 chain of VLA-2 was reduced significantly (P less than 0.005) in the poorly differentiated ductal breast carcinomas (Grade III) compared to the well (Grade I) and moderately (Grade II) differentiated ductal tumours. These data give further evidence that loss or down-regulation of VLA-2 and VLA-3 occur relatively frequently in invasive cancers, and, at least in the invasive ductal breast carcinomas. Loss of an extracellular matrix receptor controlling growth and differentiation seems to be one of the abnormalities underlying the progression towards an undifferentiated morphology.

Adenofibroma↗
PubMed1991

Achlorhydria-induced hypergastrinaemia: the role of bacteria.

1. Studies of Helicobacter pylori show that microbes can alter gastrin release. Lack of gastric acid (achlorhydria) causes hypergastrinaemia and allows bacteria to grow within the stomach. We speculated that the bacteria contribute to the rise in gastrin seen after acid inhibition, and tested the idea by comparing plasma gastrin levels during inhibition of acid secretion between germ-free and conventional rats. 2. Matched germ-free and conventional rats (n = 8 per group) received either vehicle (saline) or one of two doses of the histamine-H2-receptor antagonist loxtidine for 1 week. Gastrin was measured in cardiac blood by a specific r.i.a. 3. Plasma gastrin concentrations in germ-free and conventional rats were 59 +/- 11 pmol/l (mean +/- SEM) and 36 +/- 8 pmol/l, respectively, after vehicle, and 153 +/- 30 pmol/l and 181 +/- 27 pmol/l, respectively, after loxtidine at a dose of 10 mg day -1 kg -1, which partially inhibits acid secretion. Administration of loxtidine at a dose of 70 mg day -1 kg-1, which completely inhibits acid secretion, did not produce a significant extra rise in plasma gastrin concentration in germ-free rats (178 +/- 11 pmol/l), but further elevated plasma gastrin concentrations to 278 +/- 26 pmol/l in conventional rats (P less than 0.005 compared with germ-free rats). 4. Loxtidine produced a dose-dependent rise in the number of eosinophils in the gastric mucosa of conventional rats. 5. We conclude that partial inhibition of gastric acid secretion increases gastrin release independently of bacteria, but that bacteria are involved in the further rise in gastrin which occurs on more profound inhibition of gastric acid secretion.

Achlorhydria↗
PubMed1990

Investigation of cytokine gene expression in human colorectal cancer.

RNA was extracted from 28 samples of colorectal cancer and 26 samples of adjacent normal bowel. Northern blotting analysis showed the presence of mRNA for tumor necrosis factor (TNF) in 15 of 28 cancer samples and 6 of 26 matched normal areas. In 10 patients, TNF mRNA was found only in the tumor; in 5, TNF mRNA was seen in tumor and normal areas; and in only 1 was TNF mRNA seen in the normal, but not the malignant, area. The expression of TNF mRNA was not related to the stage of disease, degree of lymphocyte infiltration, or necrosis in the tumor. Blots were reprobed for gamma-interferon, interleukin (IL) 1 alpha and beta, IL-6, and transforming growth factor beta 1 mRNA. One tumor sample was positive for IL-1 beta, and one normal sample expressed interferon gamma mRNA. All samples had transforming growth factor beta 1 mRNA, and there was no obvious difference between levels in tumor tissues or adjacent normal areas. In situ hybridization studies with a TNF riboprobe showed that TNF mRNA was only detectable in a small minority of mononuclear and predominantly stromal cells. Immunohistochemistry on sequential sections showed that CD4- and CD8-positive lymphocytes, and macrophages, were present in the stroma. An antibody to the macrophage C3b receptor identified a minority population whose distribution corresponded closely to the cells labeled with the TNF riboprobe.

Biological Factors↗
PubMed1990

Epidermal growth factor (EGF/URO) induces expression of regulatory peptides in damaged human gastrointestinal tissues.

The pS2 gene encodes for a small cysteine-rich protein, and was originally found by differential screening of a cDNA library from the human breast carcinoma cell line, MCF-7. The presence of pS2 is closely correlated with oestrogen dependence in breast carcinomas. While the function of pS2 is unknown, pS2 protein has been shown to be homologous with the gastrointestinal peptide hormone pancreatic spasmolytic polypeptide (PSP) and its human counterpart hSP, in which a 5-cysteine domain is tandemly repeated. The 5' flanking region of the pS2 gene contains an enhancer region responsive to oestrogens and to epidermal growth factor (EGF/URO). We now report that pS2 and hSP expression occurs in a wide range of endodermally-derived tissues, including the duodenum, the pancreas, and in a recently defined cell lineage associated with chronic gastrointestinal ulceration. In each case, this expression was associated with secretion of immunoreactive EGF/URO. We further show that the co-expression of pS2 and hSP in gastric surface epithelial cells is also associated with the secretion of EGF/URO in the subjacent mucous neck cells. Our results indicate that local EGF/URO secretion induces pS2 and hSP in adjacent cells, and that these molecules are then available to participate in pathophysiological responses. The finding of similar patterns of EGF/URO, hSP and pS2 expression in association with chronic damage suggests that this is a fundamental response in the healing of these tissues.

Cell Line↗
PubMed1990

In situ detection of tumour necrosis factor in human ovarian cancer specimens.

In situ hybridisation was used to study the local expression of tumour necrosis factor (TNF) mRNA in human ovarian tumours. In 8 of 14 ovarian cancers studied, a minority of cells in the epithelial areas of the tumour contained TNF mRNA. In individual high-power fields as many as 8% of cells were positive for TNF mRNA. Immunohistochemical studies on sequential sections and the morphology of the positive cells led to the conclusion that the ovarian tumour cells were transcribing the TNF gene. There was immunohistochemical evidence of the production of TNF protein by the tumour cells and TNF protein in a tumour lysate. The production of TNF by human ovarian cancer cells may influence the biology of the tumour, contribute to neoplastic progression and alter the response to therapy.

Antibodies, Monoclonal↗
PubMed1990

The rational use of monoclonal antibodies in tumour diagnosis.

Immunohistochemistry is now an established technique in larger diagnostic histopathology units, but its full potential is not always achieved due to irrational application and incorrect interpretation. This review attempts to place the use of monoclonal antibodies in relation to the wider aspects of morphological diagnosis. The necessity of obtaining familiarity with the techniques and reagents in order to recognise artefacts is emphasized, and the practical benefit of this technique in difficult diagnostic problems is discussed.

Antibodies, Monoclonal↗
PubMed1989

Expression of tachykinins by ileal and lung carcinoid tumors assessed by combined in situ hybridization, immunocytochemistry, and radioimmunoassay.

Mid-gut carcinoid tumors have been shown to produce substance P, a tachykinin. A recent addition to this family of peptides is neurokinin A which is cleaved from the same precursor as substance P; beta-pre-pro-tachykinin. The authors have examined mid-gut and pulmonary carcinoid tumors for the presence of the two tachykinins, using immunocytochemical study and radioimmunoassay, and have applied the techniques of in situ hybridization and Northern blot analysis to investigate the expression of mRNA for beta-pre-pro-tachykinin. All gut tumors (n = 8) and three of the six lung tumors examined were found by immunocytochemical study to contain both tachykinins or neurokinin A alone. Chromatographic analysis of tumor extracts suggests that this peptide is being detected as a separate molecule and/or as the C-terminal portion of a larger, uncleaved form. Three of the cases positive for tachykinins showed no detectable serotonin immunoreactivity. Strong hybridization signals for beta-pre-pro-tachykinin mRNA were seen in all but one of the cases studied which contained tachykinin immunoreactivity. Intact mRNA and positive hybridization was found by Northern blot analysis in two mid-gut tumors. Concentrations of tachykinins were found by radioimmunoassay to be higher in mid-gut tumors (substance P 27.2 +/- 19.7 pmol/g; neurokinin A 31.8 +/- 24.2 pmol/g; mean +/- SEM, n = 5) than in lung cases (substance P mean 0.8, range 0.5-1.0 pmol/g; neurokinin A mean 11.0, range 10.0-12.0 pmol/g; n = 3). These results show that mid-gut and pulmonary carcinoid tumors produce tachykinins, which are detected, in some cases, where no serotonin immunoreactivity can be found, possibly because of a high rate of amine secretion. Screening for tachykinins may prove to be a useful diagnostic adjunct for these tumors.

Blotting, Northern↗
PubMed1989

Tenascin distribution in basal cell carcinomas.

The distribution of tenascin, an extracellular matrix protein highly expressed in the stroma around sites of epithelial-mesenchymal interaction during morphogenesis and in malignant neoplasms, was assessed in cryostat sections of 17 basal cell carcinomas using a polyclonal antibody. There was marked staining of the vascularized stroma around neoplastic islands, usually as an intense, well-defined band, but being more widespread and diffuse in sclerosing, infiltrative areas. Apparently enhanced staining was seen in tumours showing retraction artefact, which may be related to the observation that tenascin interferes with the cell binding function of fibronectin. Reduced staining was seen in areas showing evidence of tumour regression. Tenascin is an important component of the epithelial-mesenchymal interactive process and further studies on its distribution in benign and malignant skin tumours are required.

Basal Cell Carcinoma↗
PubMed1988

Basal cell carcinoma xenografts in nude mice: studies on epithelial differentiation and stromal relationships.

Thirty-three basal cell carcinomas (BCC) were transplanted into athymic mice, and foci of tumour were identified in 17 grafts recovered after intervals of 2-5 months. Fifteen of these xenografts contained apparently normal differentiated epithelia, considered to derive from elements within the original tumours. The level of differentiation was very close in original and corresponding xenograft BCC. Morphologically recognizable 'specialized' stroma was present in some but not all xenografted BCC, and was also present in some grafts containing only differentiated elements. A monoclonal antibody specific to human type IV collagen showed intact epithelial and also vascular basement membranes within the graft. Surprisingly, mouse cells were found to line these vessels, and the stroma around normal and neoplastic epithelial islands was a mixture of mouse and human cells, with no consistent composition. These observations question the proposed dependence of BCC on its 'specialized' stroma.

Animals↗
PubMed1987

Accumulation of ceroid in smooth muscle indicates severe malabsorption and vitamin E deficiency.

Four patients had accumulation of ceroid in smooth muscle (lipofuscinosis), which indicated severe or uncontrolled malabsorption, with confirmed vitamin E deficiency in three cases. The distribution of the pigment was systematic, and there seemed to be an association between malabsorption syndrome and vitamin E deficiency. Vitamin E supplementation seems to be indicated in such patients, and it is suggested that studies of smooth muscle function should be made in cases of heavy accumulation of ceroid.

Adult↗
PubMed1987

Mice transgenic for a vasopressin-SV40 hybrid oncogene develop tumors of the endocrine pancreas and the anterior pituitary. A possible model for human multiple endocrine neoplasia type 1.

The authors have used transgenic mice to study the activity of a hybrid oncogene made up of 1.25 kb of 5' upstream sequences, derived from the bovine vasopressin gene, promoting the expression of the large T-antigen coding sequences of the early region of simian virus 40. Rather than promoting tumorigenesis in vasopressinergic cells of the hypothalamus, expression and activity of the hybrid oncogene, and consequent tumor formation, were confined to insulin-producing beta cells of the endocrine pancreas and to cells in the anterior pituitary. These observations suggest that the specificity of vasopressin gene expression normally results from an interaction between several regulatory elements, some of which are absent from the hybrid oncogene. The possible relationship between the endocrine tumor syndrome found in the vasopressin-SV40 transgenic mice and familial human multiple endocrine neoplasia is discussed.

Adenoma, Islet Cell↗