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Biomedical subjects

R van Furth

Publications and source records attributed to R van Furth.

At least 343 records · Page 19Linked to original sources

Properties of a factor increasing monocytopoiesis (FIM) occurring in serum during the early phase of an inflammatory reaction.

A factor increasing monocytopoiesis (FIM) has been demonstrated during the onset of an acute inflammatory reaction caused by an intraperitoneal injection of polystyrene latex particles. It is protein in nature, does not contain a carbohydrate moiety essential for its function, and is very probably not a glycoprotein. The molecular weight of FIM lies between 18,000 and 24,000 daltons (determined with both ultrafiltration membranes and gel filtration on Sephadex G100). The monocytosis induced by FIM is dose dependent. FIM is thermolabile, having a half-time of about 20 min at 37 degrees C in serum; temperature inactivation can be delayed by the addition of epsilon-aminocaproic acid, the half-time at 37 degrees C then being about 45 min. In vitro treatment of normal murine blood with the inducers of the inflammatory reaction does not result in FIM activity in the serum. FIM dose not have chemotactic activity toward macrophages, is not a clotting factor, is not a biologically active fragment of the complement system, and has no colony-stimulating or-enhancing activity in the vitro bone marrow colony assay. On the basis of these results, a mechanism is postulated for the humoral regulation of monocytopoiesis.

Aminocaproic Acid↗

An approach to the characterization of mononuclear phagocytes involved in pathological processes.

Cells participating in an inflammatory response are derived from the bone marrow (i.e. granulocytes and monocytes) or lymphoid organes (i.e. T and B lymphocytes), or of mesenchymal origin (i.e. fibroblast, reticulum cells). The identification of these different kinds of cell in the inflammatory exudate is often difficult, because the morphological characteristics are not specific enough. For example, in the morphological description of pathological processes often terms such as round-cell infiltration and mononuclear cells are used, which is confusing. For the clear understanding of the course of an inflammatory reaction and the effect of anti-inflammatory drugs it is necessary, however, to define exactly the participating cells. Such an identification can be performed on the basis of morphological, cytochemical and immunological characteristics of the cells, together with their kinetic parameters. These characteristics have been established for murine mononuclear phagocytes. Recently these characteristics have also been studied in human promonocytes, monocytes and skin macrophages. The results show that human mononuclear phagocytes are in many respects similar to those of mice. On this basis an outline for the participation of mononuclear phagocytes in pathological processes (i.e. inflammatory processes, neoplastic processes, and storage disorders) has been made.

Animals↗

Quantitative studies on the dispersal of skin bacteria into the air.

Dispersal of skin micro-organisms into the air during undressing was studied in 72 members of surgical and nursing staff. Few pathogens were found to be dispersed. Males dispersed more normal skin organisms than did females. Males were also more heavily colonised than females, and sex differences in dispersal diminished when allowance was made for the denser colonisation of males. Dispersal was correlated most strongly with the counts on the thighs and abdomen in males but on the shins in females.

Air Microbiology↗

Macrophage activity and clinical immunology. Origin and kinetics of mononuclear phagocytes.

The origin and kinetics of mononuclear phagocytes can only be studied after the cells have been properly characterized. The basis for such a characterization on morphological, cytochemical, functional, and immunological grounds has been discussed. The production and kinetics of mononuclear phagocytes during the normal steady state have been described and compared with the effect of an acute inflammatory stimulus on these parameters. The influence of hydrocortisone and azathioprine was also studied in this connection. The increased production and monocytosis seen during an acute inflammatory response have been shown to be regulated by a humoral factor. The concept of the mononuclear phagocyte system was also discussed and an outline of the participation of mononuclear phagocytes in pathological processes put forward.

Animals↗

Effect of warfarin on the induction and course of experimental endocarditis.

The effect of warfarin treatment on an experimental endocarditis was studied in rabbits. Warfarin had no effect on the induction of a Streptococcus sanguis infection in catheter-induced endocardial vegetations, and the course of this infection was also unaltered. However, warfarin treatment resulted in rapidly progressive bacteremia, probably due to impaired circulation in clearing organs such as the lungs, liver, and spleen. Warfarin also reduced the survival time of the infected rabbits, in which pulmonary edema and extensive lung hemorrhages may have been a contributory factor.

Animals↗

A serum facted by newborn calf serum.

An intraperitoneal injection of newborn calf serum (NBCS) into CRF Swiss mice causes an inflammatory reaction characterized by an increase in the number of macrophages in the peritoneal cavity and a concomitant monocytosis. The serum of such mice contains a monocytosis-inducing factor, as demonstrated by the intravenous injection of serum collected 18 (CalS18) and 24 hr (CalS24) after the intraperitoneal injection of NBCS. Serum from normal untreated mice, from mice given an intraperitoneal injection of sterile pyrogen-free saline, which does not cause an inflammatory reaction, or from mice 72 hr after an intraperitoneal injection of NBCS, when the inflammatory reaction has subsided, does not cause a monocytosis in test mice. Intravenous injection of CalS18 causes not only a monocytosis but also an increase in the number of promonocytes and bone marrow monocytes, suggesting an increased in the number of promonocytes and bone marrow monocytes, suggesting an increased production of monocytes. The effect of CalS18, CalS24 and CalS18 filtrate is specific for the mononuclear phagocytes, since only non-significant increases in the numbers of lymphocytes and granulocytes were observed. The active factor in CalS18 was shown to be different from the monocytosis-inducing factor present in NBCS. The monocytosis-inducing factor in CalS18 passes through an ultrafiltration membrane with an exclusion limit of 50,000 Daltons, so that the molecular weight must be below this value.

Animals↗

In vitro synthesis of immunoglobulins, secretory component, complement and lysozyme by human gastrointestinal tissues. II. Pathological tissues.

An in vitro culture technique has been used to study synthesis of proteins by biopsies of human gastrointestinal mucosa which were obtained at endoscopy or surgery from patients with biliary gastritis, atrophic gastritis, peptic ulcer, gastric cancer, coeliac disease, Crohn's disease and ulcerative colitis. As in normal mucosa, immunoglobulin synthesis was found in all sites, but marked increases, especially in IgG, were seen in biliary gastritis and ulcerative colitis. In untreated coeliac disease, synthesis of IgG and IgM was increased. Synthesis of complement components did not differ from that found in normal mucosa. Increased lysozyme synthesis was seen in Crohn's disease. This study shows that useful information may be acquired from short-term culture studies of the small biopsies obtained with fibre optic endoscopes.

Complement C3↗

In vitro synthesis of immunoglobulins, secretory component, complement and lysozyme by human gastrointestinal tissues. I. Normal tissues.

An in vitro culture technique has been used to demonstrate synthesis of proteins by human gastrointestinal tissues cultured in vitro. Histologically normal tissues were obtained endoscopically and surgically. IgA and secretory component (SC) were produced in all sites, but the relative intensity of IgA synthesis and SC synthesis varied. In stomach and small intestine the intensity of IgA synthesis was greater than that of SC, but in large bowel mucosa, there appeared to be an excess of SC synthesis. Synthesis of IgG and IgM was also found in all sites. Complement proteins were produced by some of the intestinal biopsies, and by parotid gland. Lysozyme was synthesized by parotid gland and by gastric mucosa, and to a lesser extent in small intestine, and rarely in large intestine. The results suggest that in addition to the local mucosal IgA system the local production of other immunoglobulins, as well as non-immunoglobulin humoral defence factors, may be important host defences of the normal gastrointestinal tract.

Complement C3↗

Ultrastructure of mouse mononuclear phagocytes in bone marrow colonies grown in vitro.

Recently a new method was developed to culture bone marrow cells in a liquid medium on a glass surface. Two kinds of colonies develop in these cultures, namely mononuclear phagocyte and granulocyte colonies. The study of the ultrastructure of the cells in the mononuclear phagocyte colonies was the primary aim of the present study. The architecture of the mononuclear phagocyte colonies appeared to be quite different from that of the granulocyte colonies, since in the latter, the cells lie close together in dense clusters, whereas in mononuclear phagocyte colonies the cells are more loosely dispersed with the highest cell density at the center and stellate orientation of the cells at the periphery. However, both kind of colonies grow entirely separate from each other and mixed colonies are not observed. Electron microscopy showed that there are three types of cell in the mononuclear phagocyte colonies, i.e., monoblasts, promonocytes, and macrophages. The ultrastructure of the promonocytes and macrophages of the colonies is similar to that of the same types of cell isolated directly from the mouse. The monoblast, the most immature cell of mononuclear phagocyte colonies has not been characterized before. The ultrastructure of this cell is clearly distinct from that of the promonocyte in having a round contour without pseudopods, a nuclear to cytoplasmic ratio greater than one, a cytoplasm that contains many polyribosomes, a few small granules, and a small Golgi complex surrounded by a few short strips of rough endoplasmic reticulum.

Bone Marrow↗

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.

Acid Phosphatase↗

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.

Animals↗

New familial defect in microbicidal function of polymorphonuclear leucocytes.

A family is described in which a defect in intracellular killing affected two, and probably three, siblings of both sexes. From an early age they have had recurrent severe infections. During these episodes their white-blood-cell count became very high. This familial disorder seems to differ from previously reported syndromes of abnormal leucocyte function.

Adolescent↗