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Biomedical subjects

K Stanley

Publications and source records attributed to K Stanley.

At least 55 records · Page 3Linked to original sources
PubMed1989

Membrane-anchored and soluble forms of betaglycan, a polymorphic proteoglycan that binds transforming growth factor-beta.

Transforming growth factors beta 1 and beta 2 bind with high affinity to the core protein of a 250-350-kD cell surface proteoglycan. This proteoglycan (formerly referred to as the type III TGF-beta receptor) coexists in many cells with the receptor implicated in TGF-beta signal transduction (type I TGF-beta receptor), but its function is not known. We report here that soluble TGF-beta-binding proteoglycans are released by several cell types into the culture media, and can be found in serum and extracellular matrices. As has been shown for the membrane-bound form, the soluble proteoglycans have a heterogeneous core protein of 100-120 kD that carries chondroitin sulfate and/or heparan sulfate glycosaminoglycan chains and a small amount of N-linked carbohydrate. The membrane-bound form of this proteoglycan is hydrophobic and associates with liposomes, whereas the soluble forms lack a membrane anchor and do not associate with liposomes. Differences in the electrophoretic migration of the soluble and membrane forms of this proteoglycan suggest additional structural differences in their core proteins and glycosaminoglycan chains. These soluble and membrane-bound proteoglycans, for which we propose the name "betaglycans," might play distinct roles in pericellular retention, delivery, or clearance of activated TGF-beta.

Animals↗
PubMed1988

Heterodimeric transforming growth factor beta. Biological properties and interaction with three types of cell surface receptors.

Type beta transforming growth factors (TGF) are disulfide-linked homo- and heterodimers of two related polypeptide chains, beta 1 and beta 2. The homodimers TGF-beta 1 and TGF-beta 2 are widely distributed, but the heterodimer TGF-beta 1.2 has been found only in porcine platelets (Cheifetz, S., Weatherbee, J.A., Tsang, M.L.-S., Anderson, J.K., Mole, J.E., Lucas, R., and Massagué, J. (1987) Cell 48, 409-415). Here we characterize the receptor binding and biological properties of TGF-beta 1.2 and compare them with those of TGF-beta 1 and TGF-beta 2. Three types of cell surface receptors previously identified by affinity labeling with 125I-TGF-beta 1 are available for binding to TGF-beta 1.2. These three types of receptors are detected as 65-kDa (type I), 85-95-kDa (type II), and 250-350-kDa (type III) affinity-labeled receptor complexes on electrophoresis gels. They co-exist in many cell types, have high affinity for TGF-beta 1, and varying degrees of affinity for TGF-beta 2. Of the 11 cell lines screened in the present study none showed evidence for additional receptor types that would bind TGF-beta 2 but not TGF-beta 1. In receptor competition studies, TGF-beta 1, TGF-beta 1.2, and TGF-beta 2 competed for binding to type I and type II receptors with a relative order of potencies of 16:5:1 and 12:3:1, respectively, whereas all three forms of TGF-beta were equipotent as ligands for the type III receptors. The three forms of TGF-beta were equally potent at stimulating the biosynthesis of extracellular sulfated proteoglycan in BRL-3A rat liver epithelial cells, a response that presumably involves the type III receptor present in these cells. In contrast, the ability of the three ligands to inhibit the growth of B6SUt-A multipotential hematopoietic progenitor cells which display only type I receptors decreased in the order TGF-beta 1, TGF-beta 1.2, and TGF-beta 2 with a relative potency of 100:30:1. The results indicate that the presence of one beta 1 chain in TGF-beta 1.2 increases (with respect to TGF-beta 2) the biological potency and binding affinity toward receptor types I and II, but the presence of a second beta 1 chain in the dimer is required for full potency.

Binding, Competitive↗
PubMed1988

Cancers of the stomach, lung and breast: mortality trends and control strategies.

Mortality trends for the three most common tumours--stomach, lung and breast cancer--were evaluated for nine countries. Stomach cancer is decreasing sharply and consistently in the countries studied. However, virtually all of this decline can be attributed to improvements in food preservation techniques and the resulting change in diet, rather than any action of the medical community. Lung cancer is rapidly increasing in most countries, especially in women, and is likely to become the dominant cancer worldwide by the end of this century. So far, only comprehensive tobacco-control programmes in the United Kingdom and Finland have succeeded in reversing the upward trend in lung-cancer mortality. Breast-cancer death rates are generally rising, although some recent, but probably short-term, declines have been seen. Effectiveness of the currently available approaches for each of the common cancers is summarized in Table 1. Because about half of worldwide mortality from cancer occurs in developing countries and resources in these countries are severely limited, care needs to be taken in the selection of proper priorities (18). The most effective tool we have at this time to deal with these tumours is the control of tobacco for the prevention of lung cancer. Comprehensive national programmes, consisting of legislative and education measures, are needed. The greatest decrease in breast-cancer mortality is likely to be the result of early detection and prompt treatment of the disease; public awareness of the value of early detection is an important factor here. Fortunately, mortality from stomach cancer is decreasing on its own, as little can be done to control this disease otherwise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Bladder cancer: approaches to prevention and control.

Bladder cancer is the twelfth most common cancer globally, with approximately 170 000 new cases each year; a third of these cases are in the developing countries. There are two major etiological types. The first is more common in the industrialized countries and is associated with exposure to certain occupational and environmental carcinogens, but most importantly with tobacco smoking. The second type is associated with Schistosoma haematobium infection of the urinary tract and is one of the most frequent tumours in eastern Mediterranean and African countries. Both types of bladder cancer are largely preventable. Comprehensive education and legislative approaches are recommended to reduce tobacco consumption and exposure to industrial carcinogens. Safe and effective drugs are available to treat schistosomiasis within integrated control programmes in endemic areas.

Humans↗
PubMed1987

Women and cancer.

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Cross-Cultural Comparison↗
PubMed1986

Cancer control: introduction to a series of reports on strategies and approaches.

No search for new treatments of cancer or new preventive measures can realistically hope to offer benefits anywhere near as large as those that can be gained by the wider application of current knowledge. A series of papers on strategies in cancer control, to be published in the Bulletin of the World Health Organization, will describe the foundations and approaches that can significantly reduce morbidity and mortality from cancer.

Adult↗
PubMed1986

National cancer control programs and setting priorities.

Although considerable resources are being allocated globally to cancer research, efforts to implement these findings efficiently are lagging behind. Enough is known about the cause of common tumors such as lung, oral, and liver cancer to allow active measures to be taken for their prevention. Effective early detection programs have been developed for cervical, breast, and oral cancer, and treatment methods exist whereby at least one-third of all cancer patients can be cured if their disease is detected early. Unfortunately, however, most cancer activities currently in place were developed haphazardly and lack overall coordination. National cancer control efforts can be more effectively planned and implemented if they follow a systematic stepwise approach of assessing the current situation, setting health objectives, evaluating the possible strategies, and setting priorities using quantitative assessments. Cancer affects both developed and developing countries of the world, and well planned national efforts emphasizing prevention and early detection can significantly reduce the cancer problem.

Adolescent↗
PubMed1985

Chromosome mapping of cell membrane antigens expressed on activated B cells.

Hybrids formed by fusion of either human acute lymphoblastic or chronic lymphocytic leukemia cells and the mouse myeloma P3.X63.Ag8/653 have been used to show that the expression of two cell surface antigens, Bp37 and p76, associated with B cell activation and detected by the monoclonal antibodies BB1 and BB2, respectively, segregate with human chromosomes 12 and 19, respectively. Another antigen expressed on activated B cells (p24) also maps to chromosome 12 (Katz et al., Eur. J. Immunol. 1984. 13: 1008) which is of interest in the light of the frequent involvement of this chromosome in certain B cell leukemias and lymphomas.

Animals↗
PubMed1985

A human cell-surface antigen defined by a monoclonal antibody and controlled by a gene on human chromosome 1.

An antigen expressed by most human cells, but not erythrocytes, has been defined by a murine monoclonal antibody, TRA-2-10. This antigen is expressed on the surface of human-mouse somatic cell hybrids, and segregation analysis indicates that it is controlled by a gene located on human chromosome 1. From lysates of most human cells, surface-labelled with 125I, TRA-2-10 immunoprecipitates two polypeptides with molecular weights in the range of about 55 000 to 73 000 depending upon the cell line. Since the TRA-2-10 polypeptides from a fibroblast cell strain and a hepatoma cell line from one individual differ, we conclude that the observed difference in molecular weight has an epigenetic origin.

Animals↗
PubMed1983

Chromosome assignment of monoclonal antibody-defined determinants on human leukemic cells.

Hybrids formed between human acute lymphoblastic leukemia (ALL) cells and mouse myeloma have been used to determine the chromosomal location of genes required for the expression of several monoclonal antibody (mAb)-defined cell surface antigens on ALL cells. Cloned hybrids were tested for antibody binding, immunoprecipitation of the relevant protein, chromosome isoenzyme markers and karyotype. Two antigens of those studies could be definitively mapped, OKT10/p45 to chromosome 4 and BA-2/p24 to chromosome 12. mAb BA-2 reacts with the same protein as another mAb designated 609-29 (anti-teratocarcinoma). Reactivity with the latter mAb has been previously shown to segregate with chromosome 12.

Animals↗
PubMed1983

Integration of Ecogpt and SV40 early region sequences into human chromosome 17: a dominant selection system in whole cell and microcell human-mouse hybrids.

The dominant selectable gene, Ecogpt, has been introduced, by the calcium phosphate precipitation technique, into normal human fibroblasts, along with the SV40 early region genes. In one transfectant clone, integration of these sequences into human chromosome 17 was demonstrated by the construction of human-mouse somatic cell hybrids, selected for by growth in medium containing mycophenolic acid and xanthine. A whole cell hybrid, made between the human transfectant and a mouse L cell, was used as donor of the Ecogpt-carrying human chromosome 17 to 'tribrids' growing in suspension, made by whole cell fusion between a mouse thymoma cell line, and to microcell hybrids made with a mouse teratocarcinoma cell line. Two tribrids contained karyotypically normal human chromosomes 17 and a small number of other human chromosomes, while a third tribrid had a portion of the long arm of chromosome 17 translocated to mouse as its only human genetic material. Two independent microcell hybrids contained a normal chromosome 17 and no other human chromosome on a mouse teratocarcinoma background. These experiments demonstrate the ability to construct human-mouse somatic cell hybrids using a dominant selection system. By applying this approach it should be possible to select for a wide range of different human chromosomes in whole cell and microcell hybrids. In particular, transfer of single human chromosomes to mouse teratocarcinoma cells will allow examination of developmentally regulated human gene sequences after differentiation of such hybrids.

Animals↗