PubMed Health⌕ Search

Biomedical subjects

H Turley

Publications and source records attributed to H Turley.

67 records · Page 4Linked to original sources

bcl-2 protein in non-small-cell lung carcinoma.

BACKGROUND: The proto-oncogene bcl-2 encodes a protein that inhibits programmed cell death (apoptosis). The protein is expressed in basal cells in normal human epithelium, but no data are available on the frequency or clinical importance of its expression in carcinoma. We studied bcl-2 expression in patients with non-small-cell lung carcinoma and correlated this phenomenon with survival. METHODS: Immunochemical analysis with a monoclonal antibody specific for bcl-2 was used to detect the protein in tumor samples from 122 patients undergoing surgery for squamous-cell carcinoma (80 patients) or adenocarcinoma (42 patients). The possibility that bcl-2 expression correlated with survival was investigated with use of the log-rank test, hazard ratios, and their confidence intervals. RESULTS: We detected bcl-2 protein in 25 percent of squamous-cell carcinomas (20 of 80) and 12 percent of adenocarcinomas (5 of 42). In adjacent normal respiratory epithelium, bcl-2 was expressed only in basal cells. Survival at five years was higher among patients with bcl-2-positive tumors, both in the group as a whole (P < 0.1) and in the group with squamous-cell carcinoma (P < 0.02). Patients 60 years of age or older who had bcl-2-positive tumors had the best prognoses, both in the group as a whole (P < 0.02) and in the group with squamous-cell carcinoma (P < 0.01). CONCLUSIONS: The proto-oncogene bcl-2 is abnormally expressed in some lung carcinomas, and its expression may have prognostic importance.

Adenocarcinoma↗

ICAM-3 expression on endothelium in lymphoid malignancy.

Intercellular adhesion molecule-3 (ICAM-3), the third receptor for lymphocyte function-associated antigen molecule-1 and a new member of the immunoglobulin superfamily has been recently characterized using specific monoclonal antibodies. In the present study, we show immunocytochemically that ICAM-3 is present on T and B cells in the mantle zones and on a subpopulation of follicular center cells in reactive lymph nodes and only occasionally in endothelium. In 52 cases of Hodgkin's disease, ICAM-3, although present on the majority of the reactive lymphoid cells, was absent from the Reed-Sternberg cells and their variants. However, in 28 cases (54%), there was prominent endothelial staining in small vessels. Similar findings were noted in 16 out of 49 cases (33%) of non-Hodgkin's lymphomas. This finding suggests that analogous to ICAM-1 and ICAM-2, ICAM-3 expression can be induced on endothelial cells in lymphoid neoplasms, probably by an as yet unidentified cytokine-mediated mechanism.

Antigens, CD↗

Molecular cloning of ICAM-3, a third ligand for LFA-1, constitutively expressed on resting leukocytes.

The co-ordinated function of effector and accessory cells in the immune system is assisted by adhesion molecules on the cell surface that stabilize interactions between different cell types. Leukocyte function-associated antigen 1 (LFA-1) is expressed on the surface of all white blood cells and is a receptor for intercellular adhesion molecules (ICAM) 1 and 2 (ref. 3) which are members of the immunoglobulin superfamily. The interaction of LFA-1 with ICAMs 1 and 2 provides essential accessory adhesion signals in many immune interactions, including those between T and B lymphocytes and cytotoxic T cells and their targets. In addition, both ICAMs are expressed at low levels on resting vascular endothelium; ICAM-1 is strongly upregulated by cytokine stimulation and plays a key role in the arrest of leukocytes in blood vessels at sites of inflammation and injury. Recent work has indicated that resting leukocytes express a third ligand, ICAM-3, for LFA-1 (refs 11, 12). ICAM-3 is potentially the most important ligand for LFA-1 in the initiation of the immune response because the expression of ICAM-1 on resting leukocytes is low. We report the expression cloning of a complementary DNA, pICAM-3, encoding a protein constitutively expressed on all leukocytes, which binds LFA-1. ICAM-3 is closely related to ICAM-1, consists of five immunoglobulin domains, and binds LFA-1 through its two N-terminal domains.

Amino Acid Sequence↗

Characterization of a 4.8kb transcript from the Duchenne muscular dystrophy locus expressed in Schwannoma cells.

The 14kb dystrophin transcript from the Duchenne muscular dystrophy (DMD) locus, which encodes a 427kDa protein, is differentially spliced at the amino terminal end giving rise to alternative transcripts expressed in muscle and brain. Here we present evidence for a 4.8kb transcript from the DMD locus which is ubiquitously expressed but is particularly abundant in Schwannoma cells where dystrophin could not be detected. The hybridisation of Western blots with dystrophin antibodies also identifies a protein of approximately 80kDa of variable abundance in different human and mdx tissues. Immunocytochemistry studies confirm the expression of this protein in nerve cells, a tissue in which full length dystrophin is not detected. Sequencing of the 5' end of a clone isolated from a rat Schwannoma cDNA library, shows that the 4.8kb transcript shares exons with the carboxy terminal end of dystrophin but the 5' untranslated region is not contained within the dystrophin transcript. We propose that the 4.8kb gene product be called apodystrophin-1 as its expression is distinct from the dystrophin 14kb mRNA but it is transcribed from the same locus.

Amino Acid Sequence↗

Immunocytochemical localization of the cystic fibrosis gene product CFTR.

Antisera against two peptides, corresponding to different domains of the cystic fibrosis gene product CFTR, have been raised and extensively characterized. Both antisera recognize CFTR as a 165-kDa polypeptide in Western analysis of cells transfected with CFTR cDNA as well as in epithelial cell lines. The cell and tissue distribution of CFTR has been studied by immunocytochemistry. CFTR is abundant in epithelial cells, including those lining sweat ducts, small pancreatic ducts, and intestinal crypts. Unexpectedly, the level of CFTR in lung epithelia is relatively low, while it is abundant in the epithelia of kidney tubules. The protein appears to be restricted to the apical, rather than basolateral, regions of epithelial cells and at least a proportion is associated with the plasma membrane. The cell and tissue distributions of CFTR are consistent with a function for this protein as a chloride channel or as a regulator of channel activity.

Animals↗

Interleukin 4 receptor expression on human lung tumors and normal lung.

Interleukin 4 (IL-4) receptors were detected by a monoclonal antibody on tumor cells of 10 of 29 squamous cell carcinomas and 6 of 17 adenocarcinomas of the lung. None of the small cell carcinomas or carcinoid tumors stained. Parallel sections stained for epidermal growth factor receptors showed that all but 2 of the IL-4 receptor-positive tumors also expressed epidermal growth factor receptors. Positive labeling for IL-4 receptors was also obtained on nonneoplastic bronchial epithelium and on lymphocytes and macrophages infiltrating the tumor stroma. The role of IL-4 and its receptor in normal human lung is unknown, but the expression of IL-4 receptors on particular subtypes of lung tumors suggests that they may have a role in differentiation or proliferation of squamous and adenocarcinomas.

Adenocarcinoma↗

NB84: a new monoclonal antibody for the recognition of neuroblastoma in routinely processed material.

A new monoclonal antibody NB84 recognizing an uncharacterized molecule of 57 kD was produced using human neuroblastoma tumour tissue as a source of antigen. The antibody was selected for its ability to give reliable staining on conventional formalin-fixed, paraffin-embedded material. In the present study, NB84 was assessed for its usefulness in the differential diagnosis of paediatric small cell tumours. It gave reliable staining of 17/19 (90 per cent) neuroblastomas and was negative on all other tumours apart from Ewing's sarcomas, of which 9/14 (64 per cent) showed mainly focal positivity. It is concluded that in association with a panel of markers against leucocyte, muscle, epithelial, and neural markers NB84 provides considerable assistance in the recognition of neuroblastoma and thus is important in enabling the most appropriate therapy to be given.

Antibodies, Monoclonal↗

A human macrophage-associated antigen (CD68) detected by six different monoclonal antibodies.

Antibodies grouped together by the Third Workshop on Leucocyte Differentiation Antigens on the basis of pan-macrophage reactivity on tissue sections were analysed in immunoprecipitation experiments. Antibodies Y2/131, EBM11, Ki-M6 and Ki-M7 all precipitated antigens of Mr 110,000 which were shown to be identical by preclearing experiments. In addition a recently produced antibody, KP1, which identifies macrophages in paraffin-embedded tissue, was shown to recognize the same antigen. The antibodies were tested on murine cells transfected with two clones, which had been isolated by screening a cDNA library with antibodies Y1/82A and EBM11. Cells transfected with the longer cDNA clone, coding for a molecule of Mr 110,000, reacted with antibodies Y2/131, EBM11, Y1/82A and Ki-M6, whilst the shorter clone, encoding a molecule of Mr 70,000 gave the same result except that it did not induce expression of the Ki-M6 epitope. KP1 antibody did not recognize any transfectants, possibly because of differences in glycosylation by the transfected cell line compared with human tissue. Five of the six antibodies appear to recognize different epitopes (the sixth, Ki-M7, not having been evaluated in this way). It was concluded that these six antibodies react with a macrophage-associated antigen for which the gene has been cloned. This group of antibodies has recently been designated CD68 by the Fourth Workshop on Human Leucocyte Differentiation Antigens.

Antibodies, Monoclonal↗

The immunohistological detection of platelets, megakaryocytes and thrombi in routinely processed specimens.

The production and characterization of a new monoclonal antibody, Y2/51, against platelet glycoprotein IIIa is described. A useful feature of this antibody is its ability to recognize platelets and megakaryocytes in formalin-fixed routinely processed material. It could also be used to reveal platelets both in thrombi in large vessels and in microthrombi too small to be readily apparent on conventional microscopic examination. For this purpose it was helpful to use the antibody in conjunction with a new monoclonal reagent (Ret40f) against red cell sialoglycoprotein beta which detects red cells and their precursors in routinely processed tissue. The use of these antibodies should be valuable for the detection of thrombi in a variety of situations such as renal transplant rejection, coronary artery disease and vasculitis.

Animals↗

Biochemical evidence that cytokeratins are present in smooth muscle.

Recent immunocytochemical studies have revealed that cytokeratin intermediate filaments, previously thought to be restricted to epithelial tissues, are present in muscle. In view of the implications of these reports for diagnostic pathology it is important to investigate by biochemical means whether these findings represent the presence of true cytokeratin proteins or an unexpected antigenic cross-reaction. In the present study intermediate filament proteins have been extracted from samples of human myometrium and identified by immunoblotting techniques using well characterized monoclonal antibodies, two against cytokeratins and two against desmin. The results show that the proteins of the appropriate molecular weight for cytokeratin were labelled by anti-cytokeratin antibodies and were quite distinct from those recognized by anti-desmin antibodies. This study therefore confirms previous immunocytochemical findings and emphasizes the need for caution when using anti-intermediate filament antibodies for diagnostic purposes.

Antibodies, Monoclonal↗

Reuse of disposable insulin syringes.

Seventeen insulin-dependent diabetics reused 111 disposable plastic syringes (Terumo 40/80-U; detachable needle) a total of 2363 times. Each syringe was used for an average of 12.2 days (range, one to 80 days), making an average of 21.3 injections each (range, two to 126 injections). There were no injection-related infections or local reactions. Six syringes from four patients were contaminated by non-pathogenic skin organisms (Staphylococcus albus and Bacillus spp.) without any detrimental effects. Contamination was independent of duration of syringe use or skin preparation technique. The reuse of plastic disposable insulin syringes appears to be a safe, cost-saving practice.

Adolescent↗

Evidence for the synthesis and secretion of a CBG-like serpin by human cumulus oophorus and fallopian tubes.

The acrosome reaction (AR)-inducing effect of follicular cells, like that of the cumulus oophorus and granulosa cells, has been described previously. In addition to the well known steroid secreting activity of cumulus cells, the results obtained here demonstrate the secretion of a corticosteroid-binding globulin (CBG)-like protein. An AR-inducing effect was shown with the culture medium of human cumulus oophorus. This effect could be eliminated by treating the sample with monoclonal antibodies against CBG. Moreover, Western blotting after SDS-PAGE of the culture medium strongly indicates that human cumulus cells actively express and secrete a CBG-like protein. This might give an indication as to the origin of the acrosome reaction-inducing substance found in follicular fluid. Furthermore, AR-inducing activity and the elimination of this activity by antibodies against CBG was shown for oviductal fluid. With immunohistochemical techniques the CBG-like protein was localized in the epithelial lining of the fallopian tubes, giving possible evidence for the involvement of this molecule in fallopian tube function.

Fallopian Tubes↗