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P Druvefors

Publications and source records attributed to P Druvefors.

7 recordsLinked to original sources
PubMed1989

Evidence of an acquired increase in mitogenesis in streptozotocin-diabetic rats, apparently relating to some tissue factor.

We have previously reported that rats which have been suffering from streptozotocin-diabetes for 4 weeks show a supranormal mast cell mediated mitogenesis in mesenteric windows and in the skin; this late emerging, augmented mitogenic responsiveness appears, to be unaffected by insulin per se. To test whether this increased proliferogenic response is effected by some acquired quality within the tissue rather than a systemic factor in the blood, we studied mast cell mediated mitogenesis in organ-cultured intact mesenteric windows from rats with diabetes of 4 weeks' duration, using a biochemically-defined serum-free growth medium. Mast cells were activated by Compound 48/80 and their secretion was quantified biochemically in terms of histamine release. The mast cell-dependent mitogenic reaction in the predominant, morphologically discrete fibroblasts and mesothelial cells was quantified photometrically using Feulgen-absorption analysis of individual cell nuclei, and by determination of the mitotic index. Both types of target cell responded to a significantly greater degree mitogenically in diabetic compared with control tissue. This finding suggests that a considerable part of the increased mitogenic responsiveness previously observed in diabetic animals in vivo is causally related to some tissue-bound, i.e., cellular and/or extracellular factor(s) acquired during the course of the disease.

Animals↗
PubMed1988

Molecular aspects of mast-cell-mediated mitogenesis in fibroblasts and mesothelial cells in situ.

Mast-cell-mediated mitogenesis in intact tissues is a paracrine reaction the molecular mechanisms of which still have to be elucidated. One strategy worth exploring is to study the mitogenic reaction under as defined conditions as possible. The present study demonstrates that in the virtually avascular rat mesentery, organ-cultured in a biochemically-defined medium, activation of mast cells induced a mitogenic reaction in fibroblasts and mesothelial cells, the two predominant, morphologically distinct neighboring cell types. Thus the system provides a means of studying the influence of defined molecules in the growth medium on the outcome of a mitogenic response in these two cell types in situ. It was further observed that exogenous platelet-derived growth factor (PDGF) was not essential for this mast-cell-mediated mitogenic reaction to occur in the tissue-bound fibroblasts and mesothelial cells.

Animals↗
PubMed1984

On disturbance of homeostasis in organ-cultured tissue.

The intact membranous rat mesentery was cultured in Eagle's minimum essential medium containing no serum or only low concentrations of serum. The procedure is in some important respects superior to previous organ culture techniques. To estimate the extent of disturbance of homeostasis of the tissue in culture, the spontaneous mast-cell histamine release was quantitated after preculture preparation of the specimens and after different intervals in culture. Also, the proliferation of fibroblasts and mesothelial cells that predominate in the mesentery was assessed at 48 h by cytofluorometric quantitation of DNA in single-tissue cells. Spontaneous histamine release was time dependent during cultivation, amounting to ca. 50% at 48 h, and was affected by the medium used for moistening the tissue before cultivation. Culturing also brought about great spontaneous increase in the proliferation of fibroblasts and mesothelial cells, the rate being related to the concentration of serum. Addition of the mast-cell secretagogues 48/80 or polymyxin B at 1 h caused rapid release of 50 to 60% of the histamine and was followed by augmented proliferation in the serum-containing media. The spontaneous increase of cell proliferation in tissue culture may be causally related to mast-cell secretion. Further studies are needed to define factors influencing the spontaneous mast-cell secretion and the mast-cell-dependent mitogenesis in normal tissue cells.

Animals↗
PubMed1983

The effect of insulin on delayed augmented mast-cell mediated mitogenesis in diabetic rats.

Delayed augmented mitogenic reactivity follows mast-cell secretion in mesentery and skin in streptozotocin-diabetic rats with 4-week insulin-deficiency (Norrby 1982; Norrby et al. 1982; Norrby 1983). In such rats the basal proliferation is essentially unchanged in the mesentery and skin, whereas it is significantly increased in the small gut and significantly decreased in the kidney. On treating rats with 4-week-old diabetes with very-long-acting insulin for over 3 days (16 U/kg X 2 daily) the basal proliferation of the small gut and the kidney apparently became normal, the body weight increased, and the blood glucose concentration dropped substantially and progressively. However, insulin-treatment did not affect the mast-cell-dependent mitogenesis in the mesentery following intraperitoneal injection of the mast-cell secretagogue compound 48/80, as judged by specific DNA activity and mitosis counting. We conclude that some metabolic or cellular feature of diabetes which is not restored by 3-day insulin treatment, and not insulin deficiency itself, is the cause of the delayed increased mitogenic reactivity that follows mast-cell secretion in diabetic rat.

Animals↗
PubMed1983

Hyperplasia and growth of the true mesentery in the diabetic rat.

The true mesentery was studied in rats 4 weeks after they had been rendered diabetic with streptozotocin. The diabetic animals showed elongation and enlargement of the small intestine despite reduced body growth compared with controls of the same age. The mesentery in diabetic animals showed increased total area and contained an increased number of "windows", but the increment of total protein, DNA, and histamine (a marker of mast cells) was non-uniform and less than the increase in area. There appeared to be a close relationship between hyperplasia of the small intestine and its mesentery. The number of mast cells yielded by peritoneal lavage was increased in the diabetics. We suggest that our observation of the hyperplastic mesenteric reaction in diabetic rats may make a useful model for the study of growth, profiferation, and function of the mesentery available.

Animals↗
PubMed1981

Age-dependent mitogenesis in normal connective tissue cells.

We have previously described ways to use the mesentery for studies of proliferation in intact tissue. Here we have studied a weak and a strong mitogenic response in the mesentery of rats aged 6--42 weeks, induced by a single intraperitoneal injection of saline or the mast-cell-degranulating drug 48/80. Proliferation was measured by the specific DNA activity, the fraction of fibroblast- and mesothelial-like cells in the S+G2 cell-cycle-phases, and the mitotic index. We also counted the relative number of mast cells in the tissue (normalized to 5,000 fibroblast-like and mesothelial-like cells), since this might influence 48/80-induced mast-cell-mediated proliferation. In old animals there was a decline in the proliferative response and the time required to initiate DNA synthesis was prolonged. This appears to be the first report of such an age-dependent proliferation characteristic in the mesentery, and probably in any connective tissue. The normalized number of mast cells in the mesentery also declined with increasing age.

Age Factors↗