Search PubMed⌕ Search

Biomedical subjects

C F Graham

Publications and source records attributed to C F Graham.

At least 19 recordsLinked to original sources
PubMed1991

Macrophages in haemopoietic and other tissues of the developing mouse detected by the monoclonal antibody F4/80.

Macrophages are widely distributed in lymphohaemopoietic and other tissues of the normal and diseased adult, where they play an important role in host defence and repair. Although the development of haemopoiesis has been well studied in several species, the ontogeny of the mononuclear phagocyte system remains poorly understood. We have used a highly specific mAb, F4/80, to examine the distribution of mature macrophages in the developing mouse, with special reference to their presence in the haemopoietic microenvironment. Monocytes and macrophages were first seen in embryos on day 10 in the yolk sac and liver as well as in mesenchyme. In liver, spleen and bone marrow, there was expansion of this population associated with the initiation of haemopoiesis on days 11, 15 and 17, respectively. Macrophages in these sites formed part of the haemopoietic stroma and their extensively spread plasma membrane processes could be seen making intimate contacts with clusters of differentiating haemopoietic cells. F4/80+ cells were widely dispersed in undifferentiated mesenchymal tissue in organs such as lung, kidney and gut. Numbers of F4/80-labelled cells increased concomitantly with organ growth and local mitoses were evident, as well as actively phagocytic macrophages. Our studies establish that macrophages are among the earliest haemopoietic cells to be produced during development and that they are relatively abundant in fetal tissues in the absence of overt inflammatory stimuli. Their distribution is correlated with the sequential migration of haemopoiesis and they constitute a prominent component of the stroma in fetal liver, spleen red pulp and bone marrow. Apart from a role in haemopoietic cellular interactions, their highly developed endocytic and biosynthetic activities suggest that macrophages contribute major undefined functions during growth, turnover and modelling of fetal tissues.

Animals↗
PubMed1989

Neonatal anuria with maternal angiotensin-converting enzyme inhibition.

The use of angiotensin-converting enzyme inhibitors as antihypertensives has increased rapidly since the introduction of captopril in 1981. Seven cases of neonatal renal failure have been reported in patients with exposure to angiotensin-converting enzyme inhibitors that continued to the time of delivery. Two cases resulted in death of the newborn; the other five patients recovered after peritoneal dialysis. Because the relative frequency of normal outcomes is unknown, these data are insufficient for incidence-rate estimates or risk/benefit analyses. However, given the potential neonatal morbidity and mortality associated with late-pregnancy exposure to angiotensin-converting enzyme inhibitors, alternative therapies in the third trimester should be given consideration. If these drugs must be used in this context, the clinician should be prepared to deal with renal failure and hypotension in the newborn. The Food and Drug Administration invites reports of adverse pregnancy outcomes associated with such exposure.

Acute Kidney Injury↗
PubMed1988

Insulin-like growth factors and the multiplication of Tera-2, a human teratoma-derived cell line.

A human teratoma cell line (Tera-2) was grown in serum-free medium, and the population multiplication was stimulated by the addition of somatomedins/insulin-like growth factors (IGFs). Both IGF-I and IGF-II gave maximal stimulation when added daily at 10 ng ml-1. The IGFs did not substantially change the labelling index of the cells, and the IGFs appeared to exert their effect on population multiplication by increasing cell survival. Membranes isolated from Tera-2 cells displayed both type 1 and type 2 IGF receptors.

Cell Division↗
PubMed1987

Identity of cells containing apolipoprotein B messenger RNA, in 6- to 12-week postfertilization human embryos.

Apolipoprotein B (Apo B) mRNA has been localized by in situ hybridization to various cell types in the liver, gut and yolk sack of the 6- to 12-week postfertilization human conceptus. In the fetal liver it is probable that the immature hepatocytes contain Apo B mRNA. In the yolk sack, the Apo B cDNA probe hybridizes mainly to the large endodermal cells and in the fetal gut the epithelium seems responsible for the majority of Apo B mRNA production. The fetal brain did not show any detectable hybridization to the Apo B probe. Unlike the situation seen in the adult, immunoprecipitation experiments demonstrated that only the B100 form of the protein was synthesized and secreted by the liver, gut and yolk sack at this early stage of human development.

Apolipoproteins B↗
PubMed1987

Expression of c-myc during differentiation of the human teratocarcinoma cell line Tera-2.

The quantity of c-myc mRNA was measured during the retinoic-acid-induced differentiation of the pluripotent human teratoma cell line, Tera-2 cl. 13. As the cells were exposed to retinoic acid for longer periods of time the duration of the cell cycle progressively increased (measured by the rate of S phase entry) until the cells were effectively quiescent and expressed characteristic differentiation markers. Under these circumstances steady-state levels of c-myc expression increased by up to 1.6-fold with respect to rapidly growing undifferentiated cells. Southern blot analysis of the c-myc genes in Tera-2 indicated no major rearrangement or amplification in the cell line.

Cell Differentiation↗
PubMed1986

Organ distribution of apolipoprotein gene transcripts in 6-12 week postfertilization human embryos.

In the liver and the yolk sack of 6-12 week postfertilization human embryos, we have detected RNA transcripts from the following apolipoprotein genes: AI, AII, B, CII, CIII and E. The mRNA from the apolipoprotein CIII gene was relatively more abundant in the total RNA from the yolk sack than in that from the liver. The gut and adrenals contained transcripts of all these apolipoprotein genes apart from apolipoprotein AII. The kidneys and heart contained some apolipoprotein transcripts. In conjunction with previous studies, these results suggest that in the human embryo apolipoprotein genes are transcribed in a much larger range of organs than is the case in the adult. Many of these organs lack endoderm tissues.

Apolipoprotein A-I↗
PubMed1985

Synthesis of apolipoproteins, alphafoetoprotein, albumin, and transferrin by the human foetal yolk sack and other foetal organs.

Fragments of human foetal organs and blood at 5-11 weeks of postfertilization development were cultured in radioactive protein precursors. The secreted products were characterized by immunoprecipitation, and by measuring the mobility of the immunoprecipitates on polyacrylamide gels. It was found that secondary human yolk sacks secreted apolipoproteins A1 and B. The work of previous authors on the synthesis of other serum products by this organ and by the foetal liver and by the foetal intestines was confirmed. Within the yolk sack, the endoderm, the blood cells, and the outside epithelium reacted with antibodies against apolipoprotein A1 and transferrin. By metabolic labelling of umbilical cord blood, it was found that blood did not secrete apolipoproteins A1 and B. Blood cells could therefore not be a source of these secreted products.

Albumins↗
PubMed1984

Cloned human teratoma cells differentiate into neuron-like cells and other cell types in retinoic acid.

Single cell clones were isolated from the human teratoma line, Tera-2. The cells of three of these clones were studied. The progressively growing cells were shown to be tumorigenic, and they were characterized by the lack of expression of beta 2-microglobulin and HLA-A,B,C determinants on the cell surface. The majority of the cells expressed Thy-1 antigen and a 90 X 10(3) molecular weight protein recognized by the monoclonal antibody F10.44.2; between a third and half of the cells expressed the sugar specificities detected by the anti-SSEA-1 monoclonal antibody. In response to 5 X 10(-5) M-retinoic acid applied to cells in monolayer culture, the cells differentiated into a population of flat static cells arrested in the G1 phase of the cell cycle. A substantial proportion of these differentiated cells expressed beta 2-microglobulin and 43 X 10(3) molecular weight HLA-A,B,C polypeptides, Thy-1, SSEA-1 sugar determinants, and the 90 X 10(3) Mr protein recognized by F10.44.2. The apparent molecular weight of fibronectin secreted by the cells decreased by about 5 X 10(3) Mr to 235 X 10(3) Mr after differentiation. The progressively growing cells lacked reactivity with reagents that mark cells in the nervous system. Following aggregation and retinoic acid treatment, neuron-like cells were formed. These cells reacted with reagents that also react with human neurons in culture: they reacted with tetanus toxin, the anti-neurofilament antibodies BF10 and RT97, the anti-ganglioside, GQ1c antibody F12 A2B5, and anti-Thy-1. The progressively growing cells of these Tera-2 clones are therefore capable of forming at least two types of cell: the flat cells in monolayer cultures and the neuron-like cells. None of the cell populations reacted with the monoclonal antibody against SSEA-3 and these cloned cells are therefore distinct from previous isolates from Tera-2.

Animals↗
PubMed1979

Epidermal growth factor receptors increase during the differentiation of embryonal carcinoma cells.

Mouse teratocarcinoma stem cells (embryonal carcinoma, or EC cells) bind very small amounts of mouse epidermal growth factor (EGF) and the latter hormone seems to have no stimulatory effect on the growth of two cloned lines of EC cells. However, when EC cells are induced to differentiate into large flat endodern-like cells (END cells), EGF receptors increase in number reaching a plateau in 6 to 8 days. At 8 to 10 days after induction, END cells multiply very slowly, but when EGF is added (3 x 10(-10) M) to the medium, cell division is stimulated and a further change in morphology occurs. This letter describes the binding characteristics and numbers of the EGF receptors on EC and END cells and shows that exogenous retinoic acid increases the numbers of EGF receptors on END cells. We were unable to find endogenous competing factors produced by EC cells. Such factors could account for the lack of detectable binding of EGF on these cells. As EC cells differentiate to END cells, so the ability of the cells to form tumours is reduced. Since this change is accompanied by an increase in the number of EGF receptors there may be a relationship between these two events.

Animals↗
PubMed1979

Formation and consequences of cell patterns in preimplantation mouse development.

The behaviour of groups of cells was studied in culture during preimplantation mouse development. The following observations were made with intact embryos minus the zona pellucida and with embryos whose cells had been dissociated and recombined. The form of the 4-cell embryo was related to the behaviour of the first cell to divide to this stage. The form of the 8-cell embryo depended on contact between the groups of four cells each derived from a single cell at the 2-cell stage. The form of the 16-cell embryo depended on cell movement during and after division from the 8- to the 16-cell stage. These results suggest that the morphogenetic movements of these early embryonic cells are principally governed by continuous cell interactions after fertilization. The cell surfaces of the embryos were examined with scanning electron microscopy in an attempt to discriminate between the mechanisms which could account for these movements.

Animals↗
PubMed1979

Growth and differentiation of an embryonal carcinoma cell line (C145b).

Several cell and tumour lines were isolated from a single-embryo-derived teratocarcinoma and their karyotypes and differentiation in adult hosts recorded. The majority of cells contained normal karyotypes by banding. The cells were injected into blastocysts and although they sometimes colonized the yolk sac, they never colonized the embryo. Thus the possession of a normal karyotype is not a sufficient condition for embryo colonization. The loss of growth capacity was investigated by studying differentiation and tumourigenicity in a variety of circumstances. The change in appearance from an EC cell morphology to a big flat cell in culture leads to retardation of growth in adult hosts. When EC cells are injected into a blastocyst, the ability to grow progressively both in culture and in adult hosts is lost.

Animals↗