Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Review of the coagulation laboratory records and medical records at Memorial Sloan-Kettering Cancer Center over a three year period (1971--1974) revealed 89 patients with disseminated intravascular coagulation (DIC). The diagnosis of DIC was made if laboratory studies showed evidence of quantitative and qualitative changes in fibrinogen and significant thrombocytopenia. The patients included 19 with leukemia (17 acute), 3 with multiple myeloma, 15 with lymphoma, 46 with metastatic solid tumors, (10 lung, 9 breast, 8 gastrointestinal, 12 genitourinary, 7 miscellaneous) 4 with vascular tumors, and 3 without tumor. Other conditions which might have precipitated or initiated DIC such as gram-negative sepsis, liver impairment, or mucin secreting tumors were present in the majority of patients. Bleeding occurred in 75% of the patients and was fatal in 36%. Thromboembolism occurred in 22.5%. Thirteen percent were asymptomatic. Serum lactic dehydrogenase was elevated in over 75% of the patients at the time of, or subsequent to the occurrence of DIC. Treatment with heparin was helpful in only three of twenty patients. Eighty percent of the patients died within one to over 30 days of the onset of DIC. Post mortem evidence of DIC was present in 18 of 43 autopsies. Results of this study indicate that DIC is a frequent complication of a wide variety of tumors and that its occurrence causes morbidity and mortality in a significant number of patients. Treatment with heparin is of little help unless remission is induced and the precipitating factor(s) are reversed.
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PMID:Disseminated intravascular coagulation: experience in a major cancer center. 17 94

An antigen immunologically related to a group-specific antigen (gp52, a 52,000-dalton glycoprotein) of the mouse mammary tumor virus has been identified in paraffin sections of human breast cancers by means of the indirect immunoperoxidase technique. The specificity of the reaction with antibody against mouse mammary tumor virus was examined by absorption of the IgG with the following: (a) purified gp52; (b) a number of virus preparations (mouse mammary tumor virus, Rauscher leukemia virus, simian sarcoma virus, baboon endogenous virus, and Mason-Pfizer monkey virus); (c) normal plasma, leukocytes, breast tissue, milk, actin, collagen, and hyaluronic acid, all of human origin; (d) sheep erythrocytes and mucin. Only mouse mammary tumor virus (from C(3)H or Paris RIII strains and grown in either murine or feline cells) and purified gp52 eliminated the immunohistochemical reaction in the human breast tumors. Positive reactions were seen in 51 of 131 (39%) breast carcinomas of various histologic types, a minimal estimate in view of the limited number of sections from each tumor that could be examined. Negative reactions were obtained in all 119 benign breast lesions (cystic disease, fibroadenoma, papilloma, gynecomastia) and in all 18 normal breast tissues. With one exception, 99 carcinomas from 13 organs other than breast and 8 cystosarcomas were all negative.
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PMID:Detection in human breast carcinomas of an antigen immunologically related to a group-specific antigen of mouse mammary tumor virus. 20 5

Peritoneal implants of mucin and columnar epithelium with variable amounts of free peritoneal mucin complicated 11 mucinous ovarian neoplasms. Slides of the primary ovarian tumors were reviewed in eight cases. Although all contained areas of mucinous cystadenomatous tumor of low malignant potential, the neoplasms displayed additional features not well recognized as manifestations of invasive disease in the ovary. Irregular pools of mucin were present in the ovarian stroma and contained at least rare fragments of columnar epithelium in most cases. The epithelium was often more plentiful in the peritoneal mucin. Cytologic atypia was minimal in all except one case. Goblet cells were present in both the ovarian tumor epithelium and the peritoneal implants in most cases and may have a role in dissemination of the tumor. We propose the term "ovarian carcinoma with extracellular mucin production" for this form of mucinous carcinoma; this term is both descriptive of its histologic appearance and indicative of its malignant behavior. Eight of the 11 patients died of their disease from 8 months to 13.5 years after diagnosis. One additional patient died of chemotherapy-related leukemia. The mean survival was 4.2 years. The short-term prognosis is better than that for mucinous carcinoma in general, but most patients eventually die of their disease.
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PMID:Ovarian carcinoma with extracellular mucin production: reassessment of "pseudomyxoma ovarii et peritonei". 282 52

Two patients developed graft versus host disease (GvHD) following allogeneic bone marrow transplantation for leukemia. One patient developed acute GvHD 12 days after transplantation, and the second developed chronic GvHD 100 days after transplantation. Tear analysis and conjunctival impression cytology were performed. The results were compared to a normal control and to another patient who was 18 months status post bone marrow transplantation with successfully treated GvHD. Tear sampling on the patient with chronic GvHD revealed greatly elevated IgG levels with an inverse IgG to IgA ratio, as compared with normals. In addition, two of three leukemia patients demonstrated decreased mucin levels in tears. Conjunctival impression cytology from the patient with chronic GvHD revealed an abundance of plasma cells.
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PMID:Elevated tear IgG and conjunctival plasma cell infiltrate in a graft versus host disease patient. 334 90

We have investigated the expression of the protooncogenes of the myc and ras family in HT29 cells and in three differentiated clonal cell lines derived from this colon carcinoma cell line. In contrast to the decrease in myc expression seen when leukemia cells are induced to differentiate, we have found no changes in expression of the myc gene family in differentiated colon carcinoma cells. However, a greater than 5-fold increase in expression of sequences which hybridize to Ha-ras was observed in cells which secrete mucin, with a smaller increase seen in expression of Ki-ras in the same cells. This increase was not seen in cells which exhibit vectorial transport of water and ions, and which are not mucus-secreting. All differentiated lines were less tumorigenic in nude mice than the parental HT29 cells, irrespective of the level of ras expression. These results are consistent with the reports that ras expression is highest in the most differentiated cells of the colon and is substantially decreased in metastatic human colon tumors as compared to primary colon tumors. The data also suggest that a high level of ras gene expression is a marker for a particular differentiated state in colon cells rather than being directly equated with transformation or tumorigenicity. Hence, the results may reflect on some of the discrepancies concerning ras gene expression in human colon and other tumors which appear in the literature.
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PMID:Overexpression of ras in mucus-secreting human colon carcinoma cells of low tumorigenicity. 359 36

The monoclonal antibody C215 (IgG2a) was obtained by the immunization of BALB/c mice with the human colon adenocarcinoma cell line COLO 205 and used in the targeting of colorectal carcinomas. The partial characterization and purification of the C215 target molecule from solubilized COLO 205 membranes indicated that it is an integral membrane glycoprotein of the non-mucin type. The denatured antigen appeared as a major 40-kDa form in Western blots after SDS-polyacrylamide gel electrophoresis and migrated as a monomeric 36-kDa species after the reductive cleavage of intramolecular disulfide bridges. Using a five-step procedure, the antigen was purified 4,300-fold from COLO 205 tumors raised in nude mice to a homogeneity of 95% when assessed by capillary electrophoresis. Removal of N-linked carbohydrate by peptide:N-glycosidase treatment did not affect the visualization of the purified antigen in immunoblots but resulted in a faster migration in the SDS gels. The amino acid sequence was partially determined. Seventeen contiguous NH2-terminal amino acids were identified and coincided exactly with residues 82-98 of the GA733-2 protein cloned by Szala et al. (Szala, S., Froehlich, M., Scollon, M., Kasai, Y., Steplewske, Z., Koprowski, H., and Linnenback, A. J. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 3542-3546). Therefore, the predicted amino acid sequence of this protein was used to prepare overlapping synthetic peptides that cover the entire extracellular domain in order to identify the C215 epitope. A likely epitope, close to the NH2 terminus and corresponding to the first distinct hydrophilic stretch after the putative signal sequence, was identified in a peptide enzyme-linked immunosorbent assay. Moreover, GA733-2 cDNA was used for the cloning of the C215 protein from COLO 205 cells and the subsequent transfection to K36.16 mouse T cell leukemia cells. The transfected cells were C215 reactive in fluorescence-activated cell sorter analysis, and a 42 kDa band was visualized in Western blots under both non-reducing and reducing conditions. Our findings indicate a close relationship between the C215 antigen and other members of the GA-733 family, some of which are currently being used as targets in clinical trials with monoclonal antibodies. The mammalian expression system described here will enable further studies into the biological role of this protein and the construction of animal models in order to develop optimal therapeutic strategies.
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PMID:Isolation, partial characterization, and molecular cloning of a human colon adenocarcinoma cell-surface glycoprotein recognized by the C215 mouse monoclonal antibody. 769 97

We report the synthesis and characterization of a novel secondary structural motif, the poly-proline beta-turn helix. This motif is found in the proline-rich immunogenic domains of feline retroviruses, mucins and many proline-rich tandem repeat-containing surface proteins. We describe the synthetic methodology to directly synthesize natural and engineered immunogens of up to 100+ amino acids. Using manual solid-phase peptide synthesis modified for optimal efficiency, we directly synthesized 1, 2, 3, 4 and 5.25 tandem repeats corresponding to 20, 40, 60, 80, 105 amino acids of the human mucin muc-1, the complete 60 amino acid proline-rich neutralization domain of feline leukemia virus, and 70 and 72 amino acids of two very hydrophobic engineered tandem repeat proteins. High pressure liquid chromatography and mass spectrometry results indicate that the desired peptide can be synthesized up to 92% pure. The secondary structures of these peptides were studied using circular dichroism (CD) spectroscopy. The CD spectra revealed a characteristic intense negative band at 198 nm. A melting of structure could be demonstrated with increasing temperature as measured by decreasing molar ellipticity at 198 nm. The intensity of the molar ellipticity at 198 nm, as compared to the molar ellipticity of random coil, non-proline-containing peptides, led to the conclusion that the large, intense negative band at 198 nm is diagnostic of the poly-proline beta-turn helix.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Synthesis of large multideterminant peptide immunogens using a poly-proline beta-turn helix motif. 829 50

To elucidate control mechanisms of O-glycan biosynthesis in leukemia and to develop biosynthetic inhibitors we have characterized core 2 UDP-GlcNAc:Gal beta 1-3GalNAc-R(GlcNAc to GalNAc) beta 6-N-acetylglucosaminyltransferase (EC 2.4.1.102; core 2 beta 6-GlcNAc-T) and CMP-sialic acid: Gal beta 1-3GalNAc-R alpha 3-sialyltransferase (EC 2.4.99.4; alpha 3-SA-T), two enzymes that are significantly increased in patients with chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML). We observed distinct tissue-specific kinetic differences for the core 2 beta 6-GlcNAc-T activity; core 2 beta 6-GlcNAc-T from mucin secreting tissue (named core 2 beta 6-GlcNAc-T M) is accompanied by activities that synthesize core 4 [GlcNAc beta 1-6(GlcNAc beta 1-3)GalNAc-R] and blood group I [GlcNAc beta 1-6(GlcNAc beta 1-3)Gal beta-R] branches; core 2 beta 6-GlcNAc-T in leukemic cells (named core 2 beta-GlcNAc-T L) is not accompanied by these two activities and has a more restricted specificity. Core 2 beta 6-GlcNAc-T M and L both have an absolute requirement for the 4- and 6-hydroxyls of N-acetylgalactosamine and the 6-hydroxyl of galactose of the Gal beta 1-3GalNAc alpha-benzyl substrate but the recognition of other substituents of the sugar rings varies, depending on the tissue. alpha 3-sialyltransferase from human placenta and from AML cells also showed distinct specificity differences, although the enzymes from both tissues have an absolute requirement for the 3-hydroxyl of the galactose residue of Gal beta 1-3GalNAc alpha-Bn. Gal beta 1-3(6-deoxy)GalNAc alpha-Bn and 3-deoxy-Gal beta 1-3GalNAc alpha-Bn competitively inhibited core 2 beta 6-GlcNAc-T and alpha 3-sialyltransferase activities, respectively.
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PMID:Processing O-glycan core 1, Gal beta 1-3GalNAc alpha-R. Specificities of core 2, UDP-GlcNAc: Gal beta 1-3 GalNAc-R(GlcNAc to GalNAc) beta 6-N-acetylglucosaminyltransferase and CMP-sialic acid: Gal beta 1-3GalNAc-R alpha 3-sialyltransferase. 829 5

Uterine epithelial cells (UEC) isolated from 6-week-old CF-1 mice were immortalized using retroviral-mediated transfection of SV40 large T-antigen. One line, WEG-1, retained epithelial morphology and reacted with antibodies to cytokeratins 18, 19, laminin, fibronectin, and beta-catenin. In addition, WEG-1 cells displayed strong nuclear immunoreactivity to SV40 large T-antigen, confirming integration of the retrovirus vector and expression of this gene. WEG-1 cells were negative for nonepithelial markers such as desmin and factor 8. WEG-1 cells did not proliferate in serum-free medium; however, addition of 0.5% FBS supported proliferation to the same extent as 10% FBS. Addition of 50 ng/ml epidermal growth factor to medium containing 0.5% charcoal-stripped FBS restored proliferation comparable with 0.5% whole FBS. Epidermal growth factor or transforming growth factor-alpha (50 ng/ml), but not transforming growth factor-beta, leukemia-inhibiting factor, or fibroblast growth factor, induced the secretion of three proteins (M(r) approximately to 158K, 148K, and 36K). Comparison of protein secretions of WEG-1 cells and UEC showed shared as well as distinct bands. Like UEC, WEG-1 cells secreted PGF2a and PGE2 and expressed PG GH synthase-2. Unlike UEC, WEG-1 cells showed no apical/basal preference for either uptake of methionine or secretion of proteins. The absence of immunoreactive E-cadherin or zona occludens-1 was consistent with the absence of cell polarity in WEG-1 cells. Primary UEC, which polarize in vitro, do not support blastocyst attachment. WEG-1 cells, although not polarized in vitro, also exhibited delayed blastocyst attachment compared with nonuterine cell lines, suggesting that WEG-1 cells partially retained some aspects of UEC function relevant to embryo attachment. WEG-1 cells expressed messenger RNA for Muc-1, an UEC mucin suggested to have antiadhesive properties. Furthermore, WEG-1 cells did not display high affinity heparin binding sites, an activity associated with embryo attachment. WEG-1 cells may provide a model for studying various aspects of UEC function and murine embryo attachment.
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PMID:Production and characterization of WEG-1, an epidermal growth factor/transforming growth factor-alpha-responsive mouse uterine epithelial cell line. 853 10

Embryonic hematopoiesis is initiated in part in the blood islands of the yolk sac. Previous confocal microscopic analysis has shown that the CD34 antigen, a mucin-like cell surface glycoprotein that is expressed by hematopoietic progenitors and all endothelial cells of the adult and embryo, is also found on a subset of luminal hematopoietic-like cells in the yolk sac blood islands as well as on the vascular endothelium lining these early hematopoietic locations. We show here that, as in all other hematopoietic sites thus far examined, immunoaffinity-purified CD34+ nonadherent cells from murine yolk sacs contain the vast majority of erythroid and myeloid progenitor cell colony forming activity. To examine the developmental interactions between these CD34+ hematopoietic progenitor cells of the yolk sac and the CD34+ yolk sac endothelium, we have immunaffinity-purified adherent endothelial cells from day 10.5 yolk sacs using CD34 antiserum and produced cell lines by transformation with a retrovirus expressing the polyoma middle T antigen. Analysis of these cell lines for CD34, von Willebrand's factor, FLK 1 and FLT 1 expression, and capillary growth in Matrigel indicates that they appear to be endothelial cells, consistent with their original phenotype in vivo. Coculture of yolk sac CD34+ hematopoietic cells on these endothelial cell lines results in up to a 60-fold increase in total hematopoietic cell number after approximately 8 days. Analysis of these expanded hematopoietic cells showed that the majority were of the monocyte/macrophage lineage. In addition, examination of the cultures showed the rapid formation of numerous cobblestone areas, a previously described morphologic entity thought to be representative of early pluripotential stem cells. Scrutiny of the ability of these endothelial cell lines to expand committed progenitor cells showed up to a sixfold increase in erythroid and myeloid colony-forming cells after 3 to 6 days in culture, consistent with the notion that these embryonic endothelial cells mediate the expansion of these precursor cells. Polymerase chain reaction analyses showed that most of the cell lines produce FLK-2/FLT-3 ligand, stem cell factor, macrophage colony-stimulating factor, leukemia-inhibitory factor, and interleukin-6 (IL-6), whereas there is a generally low or not measurable production of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, IL-1, IL-3, transforming growth factor beta-1, erythropoietin, or thrombopoietin. The output of mature hematopoietic cells from these cocultures can be modified to include an erythroid population by the addition of exogenous erythropoietin. These data suggest that endothelial cell lines derived form the yolk sac provide an appropriate hematopoietic environment for the expansion and differentiation of yolk sac progenitor cells into at least the myeloid and erythroid lineages.
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PMID:CD34+ endothelial cell lines derived from murine yolk sac induce the proliferation and differentiation of yolk sac CD34+ hematopoietic progenitors. 854 34


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