Sarcoidosis of the liver, complicated by bleeding oesophageal varices.

Case report of a 57-year-old woman with pulmonary and hepatic sarcoidosis. As a rare complication, portal hypertension developed and first became manifest as bleeding from oesophageal varices. A portocaval shunt was successfully performed and the patient remained in stable condition after a follow-up of two years.

Comparison of the in vivo and in vitro proliferation of monoblasts, promonocytes, and the macrophage cell line J774.

Mononuclear phagocytes are localized in the bone marrow compartment (monoblasts, promonocytes and macrophages), the circulation (monocytes), and the tissues and serous cavities (macrophages). In vivo and in vitro studies done in murine bone marrow have shown that monoblasts and promonocytes are the most immature, dividing cells of the mononuclear phagocyte cell line; monocytes and resident macrophages do not divide. A very small percentage of the mononuclear phagocytes in the tissues, which are bone-marrow derived and have already the morphology of macrophages, divide once in vivo. The progeny of these dividing cells contribute to the maintenance of the tissue population of macrophages under steady-state conditions. In vitro an appreciable percentage of (young) macrophages divide, in all probability due to the influence of colony-stimulating factor. The cells of macrophage cell lines are transformed cells that proliferate continuously. The morphological, cytochemical and functional characteristics of all these kinds of cells, as well as their proliferative behavior in vivo and in vitro, show great similarity, although there are also distinct differences.

Corticosteroids and liver amoebiasis.

Patients with amoebiasis who receive steroid treatment may suffer adverse affects including acute amoebic dysentery and exacerbation of the amoebiasis. In some cases the presenting symptoms are initially misdiagnosed and steroids prescribed, which provokes fulminating progression of hepatic amoebiasis. Repeated stool examinations often yield negative results. Any patient being considered for treatment with corticosteroids who has lived in the tropics should be investigated for amoebiasis serologically and by repeated stool examination. Even after negative results the possibility of amoebiasis should be reconsidered if diarrhoea or fever develops during or after steroid treatment.

Proliferative characteristics of monoblasts grown in vitro.

In a previous study also done with a liquid culture technique, the monoblast was identified and characterized as the most immature cell of the mononuclear phagocyte cell line recognized so far. The present study concerned the proliferative behavior of the monoblast and promonocyte in colonies. The cell-cycle times of both cell types were determined on the basis of four independent methods. The resulting values all show excellent agreement: for the monoblast 11.0-11.9 h, and for the promonocyte 11.4-12.8 h. The DNA-synthesis time found for the two cell types amounted to 5.7 h for the monoblast and 5.5 h for the promonocyte. The duration of the other phages of the cell cycle of the proliferating mononuclear phagocytes proved to be: G2 phase, 0.6 h; mitosis phage, 1.8 h; and G1 phase, 3.5-3.8 h. The individual colonies showed a biphasic pattern of colony growth, an initial phase of rapid proliferation being followed by a stage wtih a markedly decreased growth rate. In the initial stage only monoblasts are present in the colony; when the growth rate slows down promonocytes and macrophages appear. These observations support the earlier conclusion that the monoblast is without doubt the precursor of the promonycyte. Colony size was found to vary widely. The main factor underlying this variation proved to be the lag time between the start of the culture and the time point at which the colony-forming cells begin to divide. Mathematical analysis showed that the variation in colony size probably does not arise from heterogeneity of the population of colony-forming cells. A mathematical approach was used to determine the proportion of self-replicating and differentiating cells among the dividing monoblasts and promonocytes in the colony. The results indicate that initially in vitro the majority of the cells of both types are self-replicating cells, but later an increasing proportion of the dividing cells give rise to another, more mature type of cell. On the basis of the conclusion that the monoblast initiates the mononuclear phagocyte colony, the number of monoblasts (2.5 X 10(5)) present in vivo was estimated to be half the number of the promonocytes. In view of this ratio the mostly likely pattern for the proliferation of mononuclear phagocytes in the bone marrow is that a monoblast divides once, giving rise to two promonocytes which in their turn divide once and form two nonproliferating monocytes.

Identification and characterization of the monoblast in mononuclear phagocyte colonies grown in vitro.

A liquid culture technique for growing mononuclear phagocyte colonies on a glass surface is described. This useful and reliable technique made it possible to study immature mononuclear phagocytes. In the mononuclear phagocyte colonies the cells grow separate from each other in a single layer. Three types of cells are recognized in these colonies, namely nondividing macrophages, and proliferating promonocytes and monoblasts. The macrophage and the promonocyte exhibit the typical characteristics previously demonstrated by the other methods, whereas the monoblast could only be fully characterized by the present liquid culture method. This proliferating cell (labeling index with [3H]thymidine, 92-96%) is almost round (diameters, 10 X 10 mum), has only a small rim of strongly basophilic cytoplasm, almost devoid of granules, and shows a certain degree of ruffling of the cell surface. The monoblast is positive for esterase with alpha-naphthyl butyrate as substrate (91%), for peroxidase (78% in the peroxidase-positive colonies), and lysozyme (43%). The monoblast is able to pinocytize dextran sulphate (15-20%) and to phagocytize opsonized bacteria (20-30%), latex particles (47%), and IgG-coated red cells (96%). IgG receptors (94%) and complement receptors (16%) are present at the cell surface. In these respects the monoblast has the typical characteristics of the mononuclear phagocytes, but its properties show it to be a more immature cell type than the promonocyte. On the basis of these criteria and the sequence of appearance of the different cell types during incubation and during the development of the individual mononuclear phagocyte colony, monoblasts being present before promonocytes appear in the colony, it is concluded that the monoblast is the precursor of the promonocyte. In these cultures granulocyte colonies are also formed, consisting of myeloblasts, (pro)myelocytes, stabs, and polymorphonuclear neutrophils. Besides the typically tight structure of this kind of colony, the granulocytic cells themselves are quite distinct from the mononuclear phagocytes by their morphology, cytochemical characteristics (e.g. all negative for esterase with alpha-naphthyl butyrate, but 96% positive with N-acetyl DL-alanyl 1-naphthylester), functional characteristics (pinocytic index 13-21%; phagocytic index; for opsonized bacteria 15-36%, for latex particles 10%, and for IgG-coated red cells 0%), and their very small number of IgG receptors and lack of complement receptors. On the basis of these criteria, these granulocytic cells are easily distinguished from the immature cells of the mononuclear phagocyte colonies. The present study confirms the conclusion that the mononuclear phagocytes are a separate cell line, quite distinct from the granulocytic series, since even the most immature cells so far identified--the monoblast and the myeloblast--have quite different characteristics.