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Biomedical subjects

R van Furth

Publications and source records attributed to R van Furth.

At least 361 records · Page 20Linked to original sources
PubMed1975

The effect of azathioprine (Imuran) on the cell cycle of promonocytes and the production of monocytes in the bone marrow.

The present communication concerns the effect of azathioprine on the mitotic activity of promonocytes and the production of monocytes. In vitro and in vivo labeling with [3H]thymidine showed that during azathioprine treatment the promonocytes synthesize DNA and that, contrary to expectation, the labeling index increases. Cytospectrophotometric determination of the Feulgen-DNA content of the promonocytes during azathioprine treatment showed an increase in the percentage of tetraploid promonocytes, and determination of the various phases of the cell cycle showed significantly increased DNA synthesis and cell cycle times as compared with the normal steady state. On the basis of these results it can be concluded that azathioprine arrests the cell cycle of the promonocytes late in the DNA synthesis phase or in the postsynthesis (G2) phase and mitosis does not occur. This timing of the effect of azathioprine had not been previously observed. The diminished mitotic activity of the promonocytes during azathioprine treatment depressed monocyte production. During treatment with 3 mg/kg azathioprine the cell cycle time of the promonocytes was on the average 5.5 h longer than in the normal steady state and the rate of monocyte production was reduced by 70%. During an acute inflammatory reaction too, monocyte production is affected by azathioprine. In animals not treated with azathioprine but with an acute inflammation the cell cycle time becomes shorter and the monocyte production increases, but animals treated with (3 mg/kg) azathioprine do not show this effect. The kinetics of the monocyte also changes under the low dosage of azathioprine. As consequence of the diminished production of monocytes, far fewer (about 50%) monocytes enter and leave the circulation than during the normal steady state. During an acute inflammatory reaction the numbers in transit through the circulation are slightly augmented but remain considerably lower than in nonazathioprine-trehat of animals not treated with azathioprine.

Acute Disease↗
PubMed1975

Infection in immunodepressed patients. The approach to diagnosis and treatment.

Infection is an important cause of death in patients receiving cytostatic drugs or with any other impairment of host resistance. Such infections are frequently due to opportunist micro-organisms usually belonging to the endogenous flora of the patient. It is often difficult to obtain an exact diagnosis of the cause and localization of the infection. The problems associated with the prevention of infection are manifold. Exogenous infections can be prevented by proper isolation and a sterile diet. Endogenous infections can only be prevented by eradication of the patient's endogeous flora, so-called decontamination. Special attention should be given to treatment of foci of chronic infection and of the carrier state of certain microorganisms. However, the prophylactic use of antibiotics should be avoided. The curative use of antibiotics should be based on the most probable micro-organism. We consider the inventory of the patient's microflora, repeated weekly, of great help in the choice of antibiotics in cases of septicaemia of unknown aetiology. The initial therapy usually consists of a broad-spectrum combination of antibiotics, which should be bactericidal. When the causative bacteria have been isolated and the sensitivity is known, antibiotic therapy should be adjusted to the narrowest spectrum possible.

Anti-Bacterial Agents↗
PubMed1975

In vitro synthesis of lysozyme by human and mouse tissues and leucocytes.

Previous studies have shown that lysozyme can be detected in many body fluids, in extracts of tissues, and also in granulocytes, monocytes and macrophages. However, the sites of synthesis of lysozyme have not been defined. In the present report, the synthesis of lysozyme by tissues, and by defined cell populations cultured in vitro has been studied by detecting the incorporation of 14-C-labelled amino acids into lysozyme. This method detects only lysozyme newly synthesized during the incubation of the specimen and therefore shows unequivocally which tissues and cell types are capable of lysozyme synthesis. The validity of the method has been shown by parallel studies using an independent method to detect lysozyme production in vitro. In studies in humans and mice, lysozyme synthesis has been demonstrated in the mucosa of the respiratory and gastrointestinal tracts, and in lymphoid organs. In studies of defined cell populations, monocytes and macrophages (mononuclear phagocytes) have been shown to synthesize lysozyme. Granulocytes from peripheral blood contain lysozyme but do not synthesize it, and lymphocytes neither contain nor synthesize lysozyme. The present findings provide further evidence that lysozyme has an important role in the defence of the host against micro-organisms, and the findings suggest that lysozyme may reach its target by several routes. At an intracellular level it is delivered from lysosomes into the phagocytic granules of granulocytes and macrophages. Local synthesis of the mucous membranes contributes lysozyme to secretions. Synthesis and secretion by mononuclear phagocytes which reach a tissue in response to an inflammatory stimulus contribute lysozyme to the exudate, and the release of lysozyme from breakdown of granulocytes has the same effect.

Animals↗
PubMed1975

The effect of azathioprine (Imuran) on the kinetics of monocytes and macrophages during the normal steady state and an acute inflammatory reaction.

The effect of azathioprine on the kinetics of peripheral blood monocytes and peritoneal macrophages was studied in normal mice and in mice in which an inflammatory reaction was provoked. Two dosage levels were used: a high dose of 200mg/kg which is the maximum tolerated daily dose in mice, and low dose of 3 mg/kg which is about equivalent to a nontoxic, immunosuppressive, anti-inflammatory dose in man. The number of peripheral blood monocytes decreases gradually during azathioprine treatment of normal mice, the extent and duration being dependent on the dose and duration of administered over a period of 9 days gives an almost complete reduction, and a low dose (3 mg/kg) given for the same period results in a reduction of about 50%. This effect seems to be reversible, because when treatment is stopped the number of monocytes starts to increase 24-48 hr later. The number of peritoneal macrophages is only affected when a high dose (200 mg/kg) is given over a long period; a low dose has virtually no effect. In mice in which an inflammatory reaction was prevoked in the peritoneal cavity, the normally occurring increase in the numbers of both peripheral blood monocytes and peritoneal macrophages was suppressed, the extent being dependent on the dose of azathioprine administered. Labeling studies with 3H-thymidine indicated that the reduction of peripheral blood monocytes and peritoneal macrophages in the inflammatory exudate is due to a diminished monocyte production.

Animals↗
PubMed1975

In vitro synthesis of some complement components (C1q, C3 and C4) by lymphoid tissues and circulating leucocytes in man.

Human lymphoid tissues and peripheral blood leucocytes and monocytes were studies with respect to the synthesis of complement components (C1q, C3 and C4) using an in vitro culture technique. All of the lymphoid tissues investigated (bone marrow, thymus, lymph node, spleen, tonsil, adenoid) synthesize complement components in different patterns. C3 was produced by all lymphoid tissues except the spleen, which was the only lymphoid tissue in which C4 production was regularly found. C1q synthesis was demonstrated in the spleen and adenoid cultures, and occasionally also in those of lymph node tissue. Lymphocytes in peripheral blood from normal individuals and in thoracic duct lymph, and also from patients suffering from chronic lymphatic leukaemia, do not synthesize any of these complement components. Peripheral blood leucocyte samples from normal individuals, containing 60 per cent lymphocytes and 40 per cent monocytes, do synthesize C3, however. Separation of the monocytes from these samples showed that it was in these cells that the synthesis of C3 occurred. Production of C3 by mononuclear phagocytes is also supported by the finding that peripheral blood leucocytes from patients suffering from acute monocytic leukaemia synthesize C3. C1q and C4 synthesis could not be demonstrated in any of the cultures of circulating leucocytes.

Adenoids↗
PubMed1973

The effect of glucocorticosteroids on the proliferation and kinetics of promonocytes and monocytes of the bone marrow.

To elucidate mechanisms underlying the prolonged monocytopenia induced in the peripheral blood of mice by injection of a subcutaneous depot of hydrocortisone acetate, the effect of this compound on the production of monocytes and their release from the bone marrow was studied. Hydrocortisone was found to cause a rapid reduction of the bone marrow promonocytes to about 65% of their initial number. The number of monocytes in the bone marrow decreased gradually, over a period of 96 h, to 75% of the initial value. The mitotic activity of the promonocytes was not diminished, as judged from the labeling in vitro with [(3)H]thymidine and the DNA-synthesis and cell-cycle times of these cells. The production of monocytes was only moderately diminished, i.e., to about 80% of the normal amount. The release of monocytes from the bone marrow was found to be influenced by hydrocortisone. After in vivo labeling with [(3)H]thymidine the monocyte-labeling indices were initially significantly higher in hydrocortisone-treated than in normal mice. It is concluded that a decreased production of monocytes in the bone marrow cannot account for the prolonged monocytopenia in the peripheral blood after hydrocortisone administration. However, hydrocortisone interferes with the release of newly formed monocytes from the bone marrow, resulting in a prolonged sojourn of these cells in this compartment.

Animals↗