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Biomedical subjects

C A Pearson

Publications and source records attributed to C A Pearson.

At least 37 records · Page 2Linked to original sources
PubMed1991

Mycobacterium avium-intracellulare induces interleukin-6 from human monocytes and large granular lymphocytes.

Mycobacterium avium-intracellulare (MAI) is an opportunistic pathogen commonly found in acquired immunodeficiency syndrome patients, whose immune systems are severely compromised. However, normal responses to this bacterium are apparently sufficient to prevent disseminated infection because disease is rarely found unless an immunocompromised state is present. Because interleukin-6 (IL-6) is an inflammatory cytokine with a multitude of activities, we investigated the potential of MAI to induce IL-6 from normal human leukocytes. Peripheral blood mononuclear cells were fractionated into monocytes (Mo), large granular lymphocytes (LGL), and T cells and stimulated with bacteria. Culture supernatants were collected and assayed for IL-6 activity by bioassay. Mo and LGL, but not T cells, were found to release IL-6 within 12 hours of stimulation, with optimal production occurring by 2 days of culture. Production of IL-6 from human leukocyte subsets was confirmed by Northern blot analysis and by neutralization of biologic function of the culture supernatants with specific antisera. Taken together, these results indicate that production of IL-6 is a key response of Mo and LGL to MAI. The role of IL-6 in MAI infection, therefore, needs to be further investigated.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by monocytes and large granular lymphocytes stimulated with Mycobacterium avium-M. intracellulare: activation of bactericidal activity by GM-CSF.

Treatment of monocytes with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) was shown to enhance their antimycobacterial activity in an in vitro assay. Furthermore, Mycobacterium avium-M. intracellulare was found to induce the production of this hemopoietic growth factor. Human peripheral blood mononuclear cells were fractionated by plastic adherence and Percoll density centrifugation, and each population of cells was stimulated with mycobacteria. GM-CSF was produced by both monocytes and large granular lymphocytes (LGL) but not T lymphocytes. The phenotype of the GM-CSF-producing LGL was found to be CD2+, CD16+, and HLA-DR+ but negative for T-cell and monocyte markers. Kinetic studies demonstrated that GM-CSF appeared in the supernatant fluids within 2 days of culture of either monocytes or LGL and continued to be produced up to 7 days of incubation. Northern (RNA) blot analysis of RNA from both cell types demonstrated the expression of GM-CSF message within 24 h of stimulation. From these studies, LGL and monocytes are capable of responding to M. avium-M. intracellulare by producing factors that augment normal immune functions, including the antibacterial capability of monocytes.

Antigens, CD↗
PubMed1990

Hypomelanosis in tuberculosis--unrelated to anaemia.

Previous work has shown that hypomelanosis is a useful sign to aid suspicion of tuberculosis in patients with dark skins. This study has confirmed that it is unrelated to haemoglobin levels. A simple colour card 'melanometer' for clinical use is described. As hypomelanosis has not been noted in HIV infection in African, and as tuberculosis is an important differential in case-definition where diagnostic facilities are limited, it is suggested that more clinical research on hypomelanosis in relation to disease is urgent.

Adolescent↗
PubMed1989

Participation of tenascin and transforming growth factor-beta in reciprocal epithelial-mesenchymal interactions of MCF7 cells and fibroblasts.

The tumor stroma is essential for the development of the tumor epithelium. Tenascin is an extracellular matrix protein highly expressed in the stroma of malignant mammary tumors. We therefore tested whether in vitro MCF7 cells were able to induce fibroblasts to synthesize tenascin. Indeed MCF7 cell-conditioned medium contained tenascin-inducing activity. This activity was shown to be transforming growth factor-beta. The morphology of the MCF7 cells was in turn affected by the addition of tenascin to the culture medium. The cells partially detached from the substratum and lost their cell-cell contracts.

Animals↗
PubMed1988

Tenascin interferes with fibronectin action.

Primary chick embryo fibroblasts attach to a tenascin substrate, but remain rounded and do not spread out. The proportion between tenascin and fibronectin in mixtures used to coat the substrate determines the shape of the cells. Tenascin inhibits integrin-mediated chick fibroblast attachment to fibronectin, laminin, and the GRGDS peptide. Rat fibroblast attachment to fibronectin, but not to laminin, is inhibited by tenascin. A monoclonal antibody against tenascin, as well as its Fab fragments, is able to neutralize the inhibitory activity on cell attachment and is therefore assumed to mask the cell-binding site of tenascin. On electron micrographs showing this monoclonal antibody bound to tenascin, its epitope can be localized to the terminal knob at the distal ends of the tenascin arms.

Animals↗
PubMed1988

Tenascin: cDNA cloning and induction by TGF-beta.

cDNA clones coding for tenascin, an extracellular matrix glycoprotein with a restricted tissue distribution, were isolated from a chicken fibroblast cDNA expression library using a specific tenascin antiserum. Antibodies eluted from the cDNA-encoded fusion proteins reacted exclusively with tenascin. Limited trypsin treatment of purified tenascin resulted in a peptide which confirmed the deduced protein sequences. The largest clone encoding 632 amino acids showed a cysteine-rich region containing 13 consecutive epidermal growth factor-like repeats of unusual uniformity. Northern blot analysis revealed 8- to 9-kb messages. Tenascin is shown to be induced in vitro by fetal calf serum as well as by transforming growth factor beta (TGF-beta). A 4-fold increase in tenascin secretion by chick embryo fibroblasts was seen after TGF-beta treatment. The induction of tenascin protein synthesis was preceded by an increase of tenascin mRNA as determined by Northern blot analysis. The induction of tenascin was compared with fibronectin. The accumulation of the two extracellular matrix proteins in the medium was differentially affected by fetal calf serum and TGF-beta and the increase was in both cases higher for tenascin.

Amino Acid Sequence↗
PubMed1988

Epithelial induction of stromal tenascin in the mouse mammary gland: from embryogenesis to carcinogenesis.

The distribution of the extracellular matrix glycoprotein tenascin was studied by immunofluorescence in the developmental history of the mouse mammary gland from embryogenesis to carcinogenesis. Tenascin appeared only in the mesenchyme immediately surrounding the epithelia just starting morphogenesis, that is, in embryonic mammary glands from 13th to 16th day of gestation, in mammary endbuds which are a characteristic structure starting development during maturation of the mammary gland, and in the stroma of malignant mammary tumors. However, tenascin was absent in the elongating ducts of embryonic, adult, proliferating, and involuting mammary glands and preneoplastic hyperplastic alveolar nodules. The transplantation of embryonic submandibular mesenchyme into adult mammary glands induces the development of duct-alveolus nodules, which morphologically resemble developing endbuds. Tenascin reappeared around those nodules during the initial stages of their development. Tenascin expression could be induced experimentally in several ways. First, tenascin was detected at the site where the first mammary tumor cells GMT-L metastasized. Second, tenascin was detected in the connective tissue in the tumors derived from the injected C3H mammary tumor cell line CMT315 into Balb/c nude mouse. Cross-strain marker anti-CSA antiserum clearly showed that the tenascin-positive fibroblasts were of Balb/c origin. Third, when embryonic mammary epithelium was explanted on to embryonic mammary fat pad cultures, the mesenchymal cells condensed immediately surrounding the epithelium. Tenascin was detected in these condensed cells. From these three observations we conclude that both embryonic and neoplastic epithelium induced tenascin synthesis in their surrounding mesenchyme.

Animals↗
PubMed1987

Tenascin is a stromal marker for epithelial malignancy in the mammary gland.

Tenascin is an extracellular matrix glycoprotein that is not present in the normal mature rat mammary gland. The distribution of tenascin was examined by immunohistochemistry in mammary tumors from carcinogen-treated and untreated rats, in virus-induced mammary tumors from mice, and in a variety of mammary gland lesions from humans. Tenascin was detectable in the stroma of the malignant but not of the benign tumors from all species. An inhibition ELISA, testing homogenates of rat tumors, confirmed that tenascin was present in malignant but not in benign tumors. Thus, tenascin was consistently found to be a stromal marker for epithelial malignancy in the mammary gland. It is concluded that tenascin may be involved in the interactions between the epithelial and mesenchyme-derived (stromal) components of the mammary gland, which are known to influence epithelial carcinogenesis in this organ.

Adenocarcinoma↗
PubMed1986

Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis.

The extracellular matrix protein tenascin (previously described as myotendinous antigen) is selectively present in the mesenchyme surrounding fetal rat mammary glands, hair follicles, and teeth, three organ anlagen where the mesenchyme is essential for development. No tenascin is detectable in the normal adult mammary gland. Carcinogen-induced mammary tumors contained tenascin in their fibrous tissue. As reported for the molecule described as a "hexabrachion," tenascin contaminates so-called "cell-surface fibronectin," where it accounts for most of the detectable hemagglutinating activity. Of the extracellular matrix proteins compared, tenascin is the least effective substrate for attachment of primary mammary tumor cells, but the most effective in promoting cell growth after serum is removed from the culture medium.

Adenocarcinoma↗