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Biomedical subjects

K Norrby

Publications and source records attributed to K Norrby.

At least 91 records · Page 5Linked to original sources

Immunological challenge causes mitogenic stimulation in normal connective tissue cells.

Because polyamine-induced mast-cell secretion causes mitogenesis in surrounding tissue cells in the rat mesentery, we studied whether an immunological challenge in guinea-pig and rat that normally involves mast-cell secretion caused mitogenesis in adjacent normal tissue cells. The appropriate antigen was injected intraperitoneally into pre-sensitized animals. Mast-cell secretion was assessed as histamine release and proliferation by estimating DNA synthesis and mitotic index in the mesentery of the intact animals. In both species the immunological challenge causing significant release of mast-cell histamine was followed by a marked mitogenic response in fibroblasts and mesothelial cells of the mesentery. Although the present study was not primarily designed to study the molecular mechanisms for stimulating cell proliferation, the results suggest that the role of primary mast-cell products on a quantitative basis is significantly different in the mitogenesis following immunological challenge than in polyamine-induced mast-cell mediated mitogenesis in the rat.

Animals↗

Intramural haemorrhage of the intestine as an indirect effect of missile trauma.

An experimental model for the study of intramural haemorrhages in the intestinal wall following indirect trauma by low-velocity missile is presented. Penetrating or non-penetrating abdominal gun-shot wounds were inflicted on pigs. The macro- and microscopical appearance and development of the haematoma-like lesions were studied. The commonest sites of early (ca. 0.5 h) microscopical lesions were the loose submucosal connective tissue and the mucosa. Mucosal ulcerations were seen in about half of the pigs after 1.5 h. They were probably caused by severe circulatory disturbance after bleeding in the submucosa and mucosa. Later perforating lesions also developed, but not until after ca. 24 h.

Animals↗

Changes in cyclic nucleotide levels and phosphodiesterase and protein kinase activities in mitogenically stimulated 3T3 fibroblasts.

Activities of cyclic-nucleotide-hydrolysing enzymes cAMP-, cCMP- and cGMP phosphodiesterase, the intracellular concentrations of cAMP, cCMP, and cGMP, and the activity of the cAMP-dependent protein kinase were studied in serum-starved 3T3 cells stimulated to proliferate by serum. Within 1 and 2 min after stimulation the activities of cAMP- and cGMP phosphodiesterase were unaffected while the concentration of cGMP was raised and that of cAMP lowered, suggesting increased synthesis of cGMP and simultaneously reduced synthesis of cAMP. 48 h after stimulation, when the cells multiplied rapidly, both the cAMP phosphodiesterase and the cCMP phosphodiesterase were reduced. Evidence was also obtained that cAMP-dependent protein kinase is important for expressing the cAMP effect in the 3T3 cells.

Animals↗

On the 48/80-induced secretion of tissue mast cells and its mitogenic effect on nearby cells in the intact rat.

Histamine release from tissue-bound mast cells and cell proliferation in the proper mesentery in the intact rat was quantitated following in intraperitoneal injection of graded doses of compound 48/80. The dose-response curves were sigmoid-like in linear-log plots. ED50 for histamine release was 0.035-0.040 and for increased cell proliferation 0.040-0.048 microgram per g BW. The proliferative response following mast-cell secretion ceased after a period of between 48-72 h, irrespective of whether a high or a low dose of 48/80 was used. Basal on the net rate of histamine synthesis (ca. 0.45 microgram/g mesentery wet weight/h) after an initial injection of 48/80, on the extent of histamine release and the proliferative response after a repeated injection of 48/80, it is concluded that there is a lag period of at least 3 days before proliferation can be re-stimulated by renewed 48/80-induced mast-cell secretion.

Animals↗

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↗

On the prevalence of adult coeliac disease in Sweden.

The occurrence of coeliac disease has been less recognized among adults than in children. We have examined the prevalence of adult coeliac disease in a defined population in Sweden, on the basis of results obtained during 7 years' gastroenterological routine practice. On 1 July 1979, the overall prevalence rate was found to be 58/100,000 (1:1700). The age-adjusted rates were unevenly distributed. The peak rate, 130/100,00 (1:750), appearing in the age interval of 45-54 years, indicates that unrecognized middle-aged coeliacs are not symptom-free and that they can be found in routine practice. Our peak rate of coeliac disease unaccompanied by dermatitis herpetiformis is in the same range as the rate found in Swedish children.

Adult↗

Gluten-free diet for dermatitis herpetiformis: the long-term effect on cutaneous, immunological and jejunal manifestations.

In 32 patients with dermatitis herpetiformis (DH) we studied the effect of gluten-free (22 patients) and gluten-reduced (10 patients) diet for periods ranging between 15 and 43 months. Variables such as cutaneous manifestations, dependence on dapsone, IgA deposits in the skin, small-bowel function, and jejunal mucosal morphology were studied. 59% of the patients on gluten-free diet could stop dapsone medication and remain symptom-free, compared with 10% on gluten-reduced diet. The time needed to achieve this therapeutic response varied from 5 to 31 months. IgA decreased in the skin to a degree which roughly paralleled the morphological normalization of the jejunal mucosa. In no patient, however, did the IgA completely disappear. It is suggested that IgA is not the main factor inducing DH symptoms, but rather a secondary phenomenon. Repeated jejunal biopsies revealed normalization of the mucosal histology in 52% of the patients on gluten-free diet, compared with none in the gluten-reduced diet group.

Adolescent↗

Influence of diabetes on oxidation of exogenous substrates in rat aorta.

The influence of diabetes on the oxidation of exogenous glucose, pyruvate, beta-hydroxybutyrate and palmitate was studied in rat aorta. Diabetes was induced by streptozotocin (65 mg/kg). The metabolic processes were measured during incubation in vitro for 90-180 min. After a diabetes duration of two weeks the oxidation of glucose, pyruvate and beta-hydroxybutyrate was lowered while the oxidation of palmitate was unaffected. The effect of diabetes on glucose oxidation appeared after 24 h and was more pronounced after 48 and 96 h. The lowered glucose oxidation in diabetic aorta was still present after incubation of rat aorta in organ culture for 48 h. Insulin treatment increased the glucose oxidation in diabetic aorta after 24 h and after 48 h the glucose oxidation in diabetic aorta was markedly increased. Incubation of diabetic aorta in organ culture for 48 h with insulin added to the incubation medium did not increase its glucose oxidation. Pretreatment of rats with diazepam and phentolamine before sacrifice, did not influence glucose oxidation or lactate production in vitro. Addition of albumin to the incubation medium slightly increased glucose oxidation but did not affect lactate production. The alternations in substrate oxidation in diabetic rat aorta found in this study are qualitatively similar to those found in diabetic striated muscle.

3-Hydroxybutyric Acid↗

Thyroid morphology and function after subtotal resection for hyperthyroidism.

Two main patterns of hyperplasia of the thyroid epithelium are seen in hyperthyroidism--toxic diffuse hyperplasia and toxic nodular hyperplasia. Toxic diffuse hyperplasia may affect the entire gland or it may arise in the extranodular tissue in a gland with nodular lesions. A series of patients treated by subtotal thyroidectomy for hyperthyroidism were classified into three morphological groups of goitre: 98 had a toxic diffuse goitre (TDG), 58 toxic nodular goiter with diffuse hyperplasia (TNGDH), and 105 toxic nodular goitre with nodular hyperplasia (TNGNH). The type of goitre was correlated to the development of disturbed thyroid function 1-6 years after surgery. Twenty-two patients with TDG and 18 (31 per cent) with TNGDH developed hypothyroidism; only 3 (3 per cent) with TNGNH showed hypofunction. Six patients with recurrent hyperthyroidism were found; all showed diffuse hyperplasia of the gland. It is concluded that the development of disturbed thyroid function after surgery is closely related to the histopathological type of goitre.

Adult↗

A tissue model for the study of cell proliferation in vitro.

A procedure for the cultivation of mesentery is described, in which the culture is fully representative of the tissue of origin. The intact mesenteric membrane -- exposed to a minimum of trauma -- was spread out over a hole in a filter paper strip in fluid medium and was cultivated free-hanging. Specimens from rats and guinea pigs were used. The organ culture model appears especially apt for cytochemical and proliferation studies. Proliferation variables based on Feulgen DNA analysis in individual, morphologically defined cells and on mitotic counting and radiochemical analysis were estimated. The tissue was fully viable in chemically defined growth medium and showed an almost unaltered light microscopical appearance after up to 52 hr in culture.

Animals↗

Mast cell histamine, a local mitogen acting via H2-receptors in nearby tissue cells.

The tissue mast cell is the major storage site of histamine in the body. The present study is concerned with the effect of one histamine H1- and one histamine H2-receptor antagonist on proliferation in the rat mesentery following drug-induced mast-cell secretion. The H2-receptor antagonist, but not the H1-receptor antagonist, significantly suppressed mast-cell-mediated proliferation in vivo and in organ-cultured mesentery. This finding indicates that mast-cell-histamine is a mitogen acting directly on histamine H2-receptors in surrounding tissue cells.

Animals↗

Local mitogenic effect of tissue mast cell secretion.

The effect of drug-induced mast cell secretion on proliferation was studied in fibroblast-like and mesothelial-like cells in organ-cultured rat mesentery. Mast cell degranulation achieved by Compound 48/80 was followed by a marked mitogenic reaciton in the surrounding tissue cells. The drug itself lacked mitogenic effect on cultured guinea-pig mesentery, the mast cells of which are unresponsive to the drug, and on a human normal fibroblast-like cell line. In contrast, histamine at about 10-(10) M, a major mast cell component, induced marked mitogenesis in guinea-pig mesentery without causing degranulation of mast cells. It is concluded that secreting rat-tissue mast cells release a mitogenic factor or factors acting locally on nearby tissue cells.

Animals↗

Subcellular fractionation of human intestinal mucosa by large-scale zonal centrifugation. I. Characterization of subcellular organelles in the distal part of the ileum.

The subcellular organelles in human ileal mucosa have been characterized by large-scale rate zonal and isopycnic density-gradient centrifugation. Mucosal scrapings were obtained from surgical specimens and the cells disrupted by extrusion under controlled pressure. The homogenized cells were then centrifuged to prepare a cell extract and the extract fractionated in a single-step procedure by zonal centrifugation on a continuous sucrose gradient. The subcellular organelles (brush borders, basal-lateral membranes, lysosomes, mitochondria, and endoplasmic reticulum) were located in the density gradient by assay of marker enzymes. Since a large number of analyses can be done on each fraction of interest, this fractionation technique may be used to study a variety of compounds and concepts involved in the subcellular physiology and pathology of human ileal mucosa.

Adult↗