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Biomedical subjects

A Shaw

Publications and source records attributed to A Shaw.

At least 145 records · Page 8Linked to original sources

Evidence that high mannose glycopeptides are able to functionally interact with recombinant tumor necrosis factor and recombinant interleukin 1.

Both recombinant tumor necrosis factor (rTNF) and recombinant interleukin 1 (rIL-1) are able to mediate vascular collapse and death in a previously described murine model, using galactosamine to enhance the toxicity of these cytokines. Unexpectedly, both acid-treated tumor necrosis factor (TNF) and a site-specifically mutagenized form of interleukin 1 (IL-1) (His-30----Arg-30), which fails to bind to the IL-1 receptor, retain full in vivo toxicity in this model of TNF- and IL-1-mediated shock. Previous studies have shown that rTNF and rIL-1 exhibit two functionally distinct binding regions. Both cytokines bind to their respective cell surface receptors and they also express lectin like binding specificity (Muchmore and Decker, J. Biol. Chem., 261: 13404-13407, 1986; Muchmore and Decker, J. Immunol., 138: 2541-2546, 1987) for defined oligosaccharides. The specificity of these two types of interactions is quite different. Cell surface receptors for IL-1 and TNF demonstrate essentially no cross-reactivity, whereas, in the case of carbohydrate binding, competition studies reveal an almost identical carbohydrate specificity for the structure Man5(6)GlcNAc2-Asn. Man5(6)GlcNAc2-Asn binding is either unaffected or actually enhanced by either acid treatment of rTNF or mutation at His-30 for rIL-1. Both deoxymannojirimycin and swainsonine, inhibitors of glycoprotein processing, raise intracellular levels of Man5-9GlcNAc2 and enhance the in vitro biological activity of both rTNF and rIL-1. Conversely, castanosperimine, a glucosidase I inhibitor which blocks the synthesis of mature high mannose structures, inhibits the biological activity of IL-1. These observations support the hypothesis that some effects of IL-1 and TNF may involve interaction with high mannose-substituted glycoproteins.

Animals↗

Congenital muscular torticollis. A spectrum of disease.

Sternocleidomastoid muscle fibrosis has been recognized for centuries, but its pathogenesis and treatment remains controversial. Pseudotumor of infancy is a firm fibrous mass in the sternocleidomastoid muscle appearing at 2 to 3 weeks of age. Congenital muscular torticollis is less common and appears later in life. Pseudotumor and congenital muscular torticollis probably represent different manifestations of sternocleidomastoid muscle fibrosis. Pseudotumor will usually resolve with conservative therapy; however, some patients will subsequently develop torticollis. Congenital muscular torticollis usually requires surgical release of the sternocleidomastoid muscle to achieve a good cosmetic result and to prevent plagiocephaly, facial asymmetry, and scoliosis. This report provides guidelines for the management of congenital muscular torticollis and pseudotumor of infancy based on the authors' experience and review of the medical literature. Representative case histories from the neonate through the adult are presented, and the pathogenesis, diagnosis, treatment, and prognosis are discussed.

Adult↗

Monoclonal antibodies reacting with the interleukin 1 receptor define a multi-molecular complex.

By sequential immunization with a variety of different interleukin (IL) 1 receptor (IL 1R)-bearing cells and by generating a large number of clones from a single fusion experiment, we have managed to produce two monoclonal antibodies which react with the lymphocyte IL 1R. The antibodies also react with the mouse fibroblast line, 3T3, but we have not yet defined their reactivity with cells carrying low-affinity receptors. Immunoprecipitation allows the IL 1R to be isolated from EL4 6.1 cell membrane preparations and shows that the IL 1R exists as a complex. The antibodies clearly interfere with IL 1 responses both in vitro and in vivo. These are the first anti-mouse IL 1R antibodies to be described which clearly and profoundly affect the immune response.

Animals↗

Induction of interleukin 6 by human and murine recombinant interleukin 1 in mice.

Interleukin (IL) 6 is a pleistropic cytokine with activities, among others, on immune cells, hematopoietic precursor cells and hepatocytes. We have investigated the kinetics and amplitude of its in vivo induction in mice after injection of four different IL 1 species as well as murine (m) and human (h) tumor necrosis factor (TNF) and bacterial lipopolysaccharide (LPS) using a sensitive bioassay on 7TD1 cells to measure the IL 6 concentrations. Recombinant mIL 1 beta, administered as a single i.v. injection in mice, induced the appearance of IL 6 in the plasma with peak levels observed after 2 h. A dose-response correlation was found between serum IL 6 levels and injected IL 1 alpha concentrations at 3 and 8 h after the injection. We then compared the ability of h/mIL 1 alpha, h/mIL 1 beta, h/mTNF and LPS to induce IL 6 in mice. We found: (a) LPS is the most potent inducer of IL 6; (b) 3 h after injection, the four IL 1 preparations had induced IL 6 levels comparable with the IL 6 levels observed after TNF injection; (c) high doses of mIL 1, alpha or beta, but not hIL 1, resulted in a high IL 6 level persisting for over 8 h. We conclude that IL 1 is a potent inducer of IL 6 in vivo and that no major differences are observed between the four IL 1 preparations, as evaluated at 3 h after the injection. However, mIL 1 alpha and mIL 1 beta, in contrast to hIL 1 alpha and hIL 1 beta, induced a sustained IL 6 level over a longer time period. This pattern of prolonged IL 6 induction is even much more pronounced after mTNF injection, but not after hTNF injection.

Animals↗

Stimulation of human interleukin 1 production and specific mRNA expression by microtubule-disrupting drugs.

The production of interleukin 1 (IL1), a pleiotropic monocyte-derived interleukin, can be induced in vitro by various stimuli. The present study shows that cytochalasins which inhibit actin filament polymerization in various cell types have no significant effect on IL1 production from human monocytic cells. On the contrary, microtubule disrupters such as colchicine, vinblastine, and vincristine dramatically potentiate (15- to 35-fold), in a dose-dependent fashion, cell-associated IL1 and to a lesser extent (2.5- to 7-fold) released IL1 in the myelomonocytic THP1 cell line and in adherent peripheral blood mononuclear cells. The enhancing effect of the drugs was blocked by actinomycin D and by cycloheximide and was accompanied by an increase of specific IL1 beta mRNA expression as measured by Northern blot analysis, thus indicating that these drugs act at a transcriptional or post-transcriptional IL1 gene expression level.

Actin Cytoskeleton↗

Some factors influencing the efficiency of a jet nebuliser system.

The operation of a commercially available nebuliser system (Medic-Aid Ltd) is reviewed and the efficiency with which it produces an aerosol assessed. Defining the efficiency of nebulisation E as the fraction of the original mass of solution released as an aerosol it is found that the internal surface area, mass of solution used, the surface tension of the solution and the angle of tilt are important factors in determining E. Reducing the internal surface area of the nebuliser by means of Perspex inserts significantly increases E for 3 g of water from 49% for the unmodified system to 67% for the modified nebuliser (P less than 0.01). E increases with the mass of solution used but only exceeds 60% when 4.5 g water are used. Decreasing the surface tension of the solution from 7.2 x 10(-3) N m-1 (water) to 3.7 x 10(-3) N m-1 and 3.1 x 10(-3) N m-1 (using two different concentrations of a detergent in water) significantly increases E for 3 g solution from 49% to 65% and 69% respectively (P less than 0.05). Operating the nebuliser at a tilt also increases E. The measurements emphasise the importance of reducing the internal surface area of this type of nebuliser, using an adequate volume of drug solution (at least 4 ml is suggested) and operating the nebuliser at an angle to the vertical (20 degrees suggested) in order to maximise E. The surface tension of the drug solution is a further important determinant of E.

Evaluation Studies as Topic↗

Nutrient intakes during pregnancy: observations on the influence of smoking and social class.

The influence of smoking and social class on dietary intake in pregnancy was investigated in a random sample of smokers (greater than or equal to 15 cigarettes/d) and nonsmokers. A total of 206 subjects (94 smokers and 112 nonsmokers) completed a 7-d weighed dietary intake at 28 wk gestation and 178 completed a second assessment at 36 wk. Nonsmokers had higher intakes of almost all nutrients than did smokers and the nutrient density of their diet was greater. Energy intake was nonsignificantly higher in nonsmokers. Women in higher social classes had the highest nutrient intakes. Smokers were shorter than nonsmokers and tended to be of lower social class. After maternal height and social class were controlled for, smoking had a significant effect on intake of many micronutrients. Dietary intake was reduced in late pregnancy, particularly in smokers. These data suggest that smokers in all social classes have a poorer quality of diet.

Adult↗

Dual tracer technique to measure salvaged red cell survival following autotransfusion in aortic surgery.

The survival of autotransfused red cells was measured for two salvage devices used in 12 elective aortic reconstructions. Six patients underwent cell salvage with the Solco-trans device and six with the Haemonetics cell saver. A double tracer technique was used to take account of post-operative blood loss and fluid replacement. Comparison was made with the results of a group of normal volunteers. A comparison was made of the labelling efficiency of damaged and undamaged red cells using chromium to check that red cells damaged during autotransfusion can be labelled. No significant difference was seen. There was no significant difference in red cell survival between the volunteer group and either of the two salvage device groups. These results suggest that red cell survival is not compromised by the autotransfusion process using these two devices.

Aortic Diseases↗

Cyclooxygenase inhibition enhances rat interleukin 1 beta-induced growth of rat mesangial cells in culture.

The cytokine interleukin 1 (IL-1) has growth-promoting activities on mesangial cells (MC) and enhances MC prostanoid formation. A possible role of endogenous cyclooxygenase products on IL-1-mediated growth of MC is, however, unknown. Therefore we evaluated the effect of cyclooxygenase inhibition on growth of mesangial cells in culture, which were exposed to DNA recombinant rat interleukin 1 beta (rIL-1 beta). rIL-1 beta increased [3H]thymidine uptake in MC by approximately 70% after 48 h. This growth-promoting activity of the cytokine was observed at 1 ng/ml and was not further enhanced by the increase of the IL-1 beta concentration less than or equal to 100-fold. IL-1 beta, however, dose dependently stimulated prostaglandin E2 (PGE2) formation by MC. When prostaglandin synthesis was inhibited by indomethacin (Indo, 1 microgram/ml), rIL-1 beta (10 ng/ml)-induced cell proliferation was sevenfold greater compared with rIL-1 beta alone. In the presence of Indo (1 microgram/ml), rIL-1 beta (1, 10, 50, and 100 ng/ml) dose dependently stimulated MC proliferation. The addition of exogenous PGE2 (10(-7) and 10(-8) M) to Indo-treated MC blocked the mitogenic response of IL-1 beta. We conclude that endogenous PGE2 formation, which is stimulated by IL-1 beta, antagonizes the growth-promoting activity of the cytokine. PGE2 may thus exert antiproliferative effects in glomerular diseases, whereas IL-1 might mediate cell growth.

Animals↗

Four different interleukin-1 species sensitize to the lethal action of tumour necrosis factor.

We studied the induction of lethal shock by Tumour Necrosis Factor (TNF) in mice and observed a remarkable difference between the effect of human and murine TNF, which could be eliminated by co-administration of sensitizing agents. We identified interleukin-1 (IL1) as a natural sensitizer, rendering mice as susceptible to human TNF as to murine TNF. This IL1 activity was found to be exerted to the same extent both by human and murine IL1-alpha or IL1-beta, and was also different from the sensitization obtained with galactosamine, since these agents had an additive effect. Pretreatment of the animals with indomethacin, a cyclooxygenase inhibitor, provided partial protection against TNF lethality in IL1-sensitized but not in galactosamine-sensitized mice.

Animals↗