Plague, rats, and ships The realisation of the infection routes of plague.

Three plague pandemics plus several epidemics have ravaged the world. The three pandemics were characterised by the role shipping played in spreading of the plague. The third pandemic, which began in southern China in the 1850s, was carried out of Hong Kong in 1894 to all continents by steamships.

[Canaries, germs, and poison gas. The physiologist J.S. Haldane's contributions to public health and hygiene].

The Scottish physiologist John Scott Haldane (1860-1936) spent most of his professional career in Oxford after graduating from the medical school in Edinburgh. He was deeply involved in applying basic science on problems in society but also making these problems guide his choice of projects in his experimental work. Thus, he has demonstrated that the increased contents of carbon dioxide in dwellings, schools, and factories was of less importance than the high contents of bacteria and fungal spores, and that even the foul air in the sewers was less harmful than that in crowded dwellings.

The relationship between immediate relevant basic science knowledge and clinical knowledge: physiology knowledge and transthoracic echocardiography image interpretation.

Two major views on the relationship between basic science knowledge and clinical knowledge stand out; the Two-world view seeing basic science and clinical science as two separate knowledge bases and the encapsulated knowledge view stating that basic science knowledge plays an overt role being encapsulated in the clinical knowledge. However, resent research has implied that a more complex relationship between the two knowledge bases exists. In this study, we explore the relationship between immediate relevant basic science (physiology) and clinical knowledge within a specific domain of medicine (echocardiography).

[Early clinical exposure--an instant success. The new medical curriculum at the University of Aarhus].

Introduction: In the new medical curriculum at the University of Aarhus, a third term, 20-week course focussing on early patient contact was launched.

Material And Methods: Nine prototypical and clinically important disease entities each formed the basis of one-week courses covering an introductory clinical lecture, presentation of "paper" cases, and formalised training of pertinent clinical skills. This was integrated with plenaries and group work in physiology pertaining to the disease and the patient cases.

Identification of the haemoglobin scavenger receptor.

Intravascular haemolysis is a physiological phenomenon as well as a severe pathological complication when accelerated in various autoimmune, infectious (such as malaria) and inherited (such as sickle cell disease) disorders. Haemoglobin released into plasma is captured by the acute phase protein haptoglobin, which is depleted from plasma during elevated haemolysis. Here we report the identification of the acute phase-regulated and signal-inducing macrophage protein, CD163, as a receptor that scavenges haemoglobin by mediating endocytosis of haptoglobin-haemoglobin complexes.

In vivo inflammatory stimulation induces a transient change in the binding of thrombin to rat peritoneal macrophages.

The binding of 125I-labeled thrombin to rat peritoneal macrophages isolated 20 h after the ip injection of thioglycollate broth or lipopolysaccharide decreased to 20% of the value found in resident macrophages due to a decrease in the number of receptors. The binding returned to normal values within a week after the injection. The decline parallelled more or less the Vmax for the 5'-nucleotidase activity.

A thrombin receptor in resident rat peritoneal macrophages.

Resident rat peritoneal macrophages possess 6 x 10(2) high-affinity binding sites per cell for bovine thrombin with a Kd of 11 pM, and 7.5 x 10(4) low-affinity sites with a Kd of 5.8 nM.

A rapid microtitration plate assay for non-specific esterase.

A simple and convenient colorimetric assay for the quantification of non-specific esterase is described. The assay takes advantage of the microtitration plate format, and the high capacity of repetitive dispensers and the microplate reader for this format. The assay is well suited for the quantification changes in the esterase activity in homogeneous cell populations like monocytes maturing into macrophages.

Isolation of rat peritoneal mononuclear and polymorphonuclear leucocytes on discontinuous gradients of Nycodenz.

Centrifugation of rat leucocytes from thioglycollate-induced inflammatory peritoneal exudate on a discontinuous gradient of Nycodenz with a density of 1106 g/l and an osmolarity of 400 mosmol/l separated the polymorphonuclear from the mononuclear leucocytes. The cells on the interphase between the buffer and the gradient medium contained 96% mononuclear leucocytes with a recovery of greater than 60%, and the bottom fraction consisted of 98% polymorphonuclear leucocytes with a yield of 91%, when an exudate isolated 20 h after the injection of thioglycollate was fractionated. Leucocytes isolated from non-inflamed rat peritoneum could be enriched in the fraction of nonspecific esterase-positive cells from 86% to 96% with a recovery of 82% on a gradient with a density of 1091 g/l and an osmolarity of 325 mosmol/l.

Cellular targets and receptors for interleukin-6. II. Characterization of IL-6 binding and receptors in peripheral blood cells and macrophages.

Within 15 min, approximately 2.5% of 125I-labelled interleukin-6 (IL-6) injected intravenously into rats was taken up by the spleen. As determined by light microscopic autoradiography, uptake was mainly (60%) accounted for by macrophages in the red pulp.

Cellular targets and receptors for interleukin-6. I. In vivo and in vitro uptake of IL-6 in liver and hepatocytes.

Interleukin-6 (IL-6) is a potent stimulator of the hepatic synthesis of acute-phase proteins. 125I-labelled IL-6 disappeared from the blood of rats with an overall half-time of about 1.5 min; 41% of the injected tracer dose was recovered in the liver by 15 min.

Characterization of the binding of bovine thrombin to isolated rat hepatocytes.

Isolated rat hepatocytes possess per cell 4,500 high-affinity binding sites for thrombin with a Kd of 30-40 pM, and 2.8 X 10(5) low-affinity sites with a Kd of 30 nM. These binding sites are highly specific for thrombin.

The specific binding of thrombin to human polymorphonuclear leucocytes.

Thrombin is a chemotaxin for polymorphonuclear leucocytes. In this paper the binding kinetics of 125I-labelled thrombin to purified polymorphonuclear leucocytes is characterized. At 4 degrees C, the 125I-labelled thrombin bound to the cells with a half-time of about 3 min.

The cellular dynamics of hepatic receptors for alpha 2-macroglobulin.protease complex and for insulin are different.

Making freshly isolated rat hepatocytes permeable by 0.4 g/liter digitonin doubled the number of binding sites for alpha 2-macroglobulin.trypsin complex without changing the affinity.

Receptor-mediated degradation of insulin in isolated rat adipocytes. Formation of a degradation product slightly smaller than insulin.

More than 90% of the radioactivity associated with isolated rat adipocytes incubated with [TyrA14-125I]monoiodoinsulin represented at steady state iodoinsulin possessing full binding affinity. In contrast, about half of the radioactivity dissociating from the cells was [125I]monoiodotyrosine. The other half was of a molecular size similar to that of iodoinsulin as judged from gel-filtration chromatography.

Preparative reversed-phase high-performance liquid chromatography of iodinated insulin retaining full biological activity.

Insulin monoiodinated in Tyr A14, A19, B16 and B26 can be separated from insulin and diiodoinsulins using reversed-phase high-performance liquid chromatography on LiChrosorb RP-18 columns. Monoiodoinsulins with high and low specific activities were isolated from a number of buffer systems without any reduction in binding affinity and biological activity in isolated rat fat cells. The reason for the previously observed reduction in the binding affinity was probably column bleeding, i.

Evidence for binding of human pregnancy zone protein-proteinase complex to alpha 2-macroglobulin receptors.

125I-labelled human pregnancy zone protein complexed with chymotrypsin was removed from the circulation with a half-time of 2.3 min after intravenous injection in rats. After 6 min about 67% of the label was present in the liver and about 3% was in the spleen, both in male and in female pregnant rats.

Luminal uptake and intracellular transport of insulin in renal proximal tubules.

It is generally accepted that proteins taken up from the renal tubular fluid are transported into lysosomes in proximal tubule cells. Recently, however, it has been postulated that insulin in isolated perfused rat kidneys did not accumulate in lysosomes but to a certain degree in the Golgi region. The present study was undertaken to investigate the intracellular handling of biologically unaltered insulin in rat renal proximal tubule cells.

The reversible receptor binding of insulin in isolated rat adipocytes measured at 37 degrees C. The binding is not rate limiting for cellular uptake.

The bimolecular binding reaction between mono[TyrA14-125I]iodoinsulin and the insulin receptor was investigated at 37 degrees C in intact isolated rat adipocytes in which membrane traffic was inhibited by 1 mM KCN. This treatment decreased the fraction of cell-associated radioactivity resistant to treatment at pH 3 (usually regarded as internalized ligand) from 70% to 17%. The total amount of tracer being cell-associated at steady state was reduced to about half of the control value partly because of a decreased apparent binding affinity.

Increased inhibitory potency of free fatty acid-poor albumin on the released and activity of insulin-degrading enzymes from isolated rat adipocytes and hepatocytes.

Isolated rat adipocytes and hepatocytes release protease(s) into the medium which degrade insulin and glucagon. This can be partially inhibited by high concentrations of bovine serum albumin. Free fatty acid-poor albumin prepared by charcoal treatment at pH 3 is a more potent inhibitor than untreated albumin.

Uptake of rat and human alpha 2-macroglobulin-trypsin complexes into rat and human cells.

Uptake of rat and human alpha 2-macroglobulin-trypsin complexes was measured in rat hepatocytes, rat and human adipocytes and human fibroblasts. Uptake and degradation of 125I-labelled rat complex were about one-third of that of the human complex in the various isolated cell types. In rat hepatocytes, the apparent Km for cell association of the rat complex was about 16 nM as compared to about 6 nM for the human complex.

Receptor-mediated degradation of human growth hormone in rat adipocytes and cultured human lymphocytes (IM-9).

In cultured human lymphocytes (IM-9) and in isolated rat adipocytes human growth hormone is substrate for a receptor-mediated degradation. When the cells are incubated with monoiodinated human growth hormone half of the radioactivity dissociating from the cells is in the form of [125I]monoiodotyrosine. Since IM-9 lymphocytes have no receptor-mediated degradation of insulin, obviously insulin and human growth hormone follow different pathways in this cell type.

Uptake and degradation of insulin and alpha 2-macroglobulin-trypsin complex in rat adipocytes. Evidence for different pathways.

The cell association and degradation of insulin and alpha 2-macroglobulin-trypsin complex were measured in rat adipocytes with or without various inhibitors in the attempt to clarify whether the two ligands were taken up by the same or by different pathways. Several inhibitors, and particularly those of membrane traffic, lysosomal function and transglutaminase activity, affected the two ligands differently. Thus, chloroquine (100 microM) reduced both the uptake of alpha 2-macroglobulin X trypsin and its receptor-mediated degradation by about 70%.