Localization of IGF-I in adult rats. Immunohistochemical studies.
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Biomedical subjects
Publications and source records attributed to I Andersson.
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The structure of the complex between Cys-46-carboxymethylated horse liver alcohol dehydrogenase (CM-LADH) and reduced nicotinamide adenine dinucleotide (NADH) has been determined by X-ray analysis. The complex represents NADH binding to the orthorhombic, "open" conformation of the enzyme. Coenzyme binding here induces a local structural change in the peptide loop 293-297, but there is no domain rotation, as observed for the "closed" conformation of the protein. This local movement of a few residues in the loop is sufficient to trap the nicotinamide ring of NADH within the active-site area close to a productive binding position. The carboxymethyl group on the zinc ligand cysteine-46 is oriented between the pyrophosphate bridge of NADH and the guanidinium group of arginine-369 and can occupy this position because the coenzyme binding cleft remains open and unchanged upon coenzyme binding. The zinc coordination sphere is distorted, and the position of the metal atom is shifted 1 A compared to native unliganded LADH. The distance between the zinc ion and the sulfur of the alkylated cysteine residue is of the order of 3 A. Alkylation experiments were performed at 0.15 and 10 mM iodoacetate, and peptide maps were examined. Gentle treatment with reagent yields an enzyme product which is substituted at only one of the two zinc binding sites per subunit of LADH (Cys-46). This enzyme species maintains its structural integrity; it binds coenzyme which induces conformational changes resolved into two steps. Thus, in addition to the orthorhombic complex, a crystalline NADH complex in the closed conformation of CM-LADH was obtained. These crystals showed enzymic activity, and single crystals were analyzed with microspectrophotometric methods. Formation of the stable crystalline abortive complex between CM-LADH-NAD+ and 4-trans-(N,N-dimethylamino)cinnamaldehyde (DACA) could be observed upon addition of excess aldehyde to the closed complex of CM-LADH-NADH. The CM-LADH-NAD+-DACA complex is characterized by an intense absorption band with a lambda max at 456 nm which corresponds to a shift in the spectrum of free DACA of approximately 60 nm. At the higher concentration of iodoacetate, three of the cysteine ligands to the second zinc atom (Cys-100, -103, and -111) are alkylated in addition to Cys-46. This enzyme product rapidly denatures and cannot be crystallized under our conditions. This is an experimental indication that the intact noncatalytic zinc binding site contributes to the structural stability of the protein.
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A randomized trial is presented on the effect of repeated invitation to breast cancer screening with mammography on mortality from breast cancer. The invited group and the control group each consisted of approximately 21,000 women aged 45-69 yr at the start of the screening. The attendance rate was 74% at the first screening and 70% at the two subsequent screening rounds. The cancer detection rate was 7.5 per 1000 women examined in the first screening round and 2.2 and 2.0 per 1000 woman-years in the second and third screenings with an incidence of 0.9 in the intervals. The incidence in the control group was 2.7 per 1000 woman-years. The proportion of positive biopsies was 61% in the first screening round, 33% in the second, and 58% in the third. After the prevalence screening, the stage distribution was more favourable in the invited group (including non-attenders) than in the control group. In the two most recent periods of the programme, 62 out of 160 women with cancer (39%) in the invited group were in stage II-IV compared with 91 out of 159 (57%) in the control group. More than 60% of cancers detected at screening were either non-invasive or invasive with a diameter of 1 cm. The corresponding percentage in the control group was 27%. The importance of sampling bias is discussed. Although data on mortality still have to be awaited, the results so far clearly indicate a positive effect of screening.
The present study examines the influence of Freund's complete adjuvant (FCA) injections on sensitized PVG rats with respect to serum levels of IgE and IgG2 alpha antibodies and total IgE (all assessed by radioimmunoassays) and the capacity of serosal mast cells to release histamine on challenge in vitro with 'immunological' secretagogues (specific antigen, anti-IgE, concanavalin A) or with compound 48/80. The rats were immunized with 10 micrograms ovalbumin (OA); alum, Bordetella pertussis vaccine, or silica gel were employed as adjuvants. Treatment with FCA was performed by single intraperitoneal injections 3, 2, or 1 week(s) before or 1 or 2 weeks after sensitization. Tests were conducted 3 weeks after sensitization. The results show that the effect of FCA treatment varied reproducibly with the adjuvant employed for sensitization and with the timing of the FCA administration. FCA treatment could either increase, fail to affect, or decrease total serum IgE and OA-IgG2 alpha antibody levels as well as serosal mast cell responsiveness, whereas OA-IgE antibody responses were decreased or not affected. Moreover, serum levels of OA-IgE and OA-IgG2 alpha antibodies and total IgE were affected by FCA treatment independently of each other. Finally, serosal mast cell responsiveness to a given secretagogue could be influenced by the FCA treatment apparently independently of that to other secretagogues. A salient finding was that effects of FCA treatment on mast cell responsiveness did not necessarily conform to effects on antibody synthesis. Collectively, these data support the opinion that the mechanisms of action of the IgE-promoting adjuvants employed differ and suggest that the expression of serosal mast cell responsiveness to each examined secretagogue can be regulated separately. They also suggest that the serosal mast cell sensitizing capacity of homocytotropic antibodies may not be adequately quantified by immunochemical methods employing reagents prepared against IgE and IgG2 alpha protein.
The bladder capacities of 75 patients with superficial bladder tumors were measured prior to and during monthly intravesical instillation therapy with adriamycin. When taken off therapy, a decrease in bladder capacity of more than 20% was observed in 18 of the patients. In 14 of the treated patients an increase in bladder capacity of more than 20% was observed. In patients with reduced bladder capacity when taken off therapy, there were no correlations between the degree of decreased bladder capacity and the number of instillations or the total instilled amount of adriamycin, indicating that the observed decrease in bladder capacity was caused by the underlying disease and not by the treatment per se.
Large single crystals of a quaternary complex of spinach ribulose bisphosphate carboxylase, Mg2+, CO2 and the transition state analogue 2-C-carboxy-D-arabinitol-1,5-bisphosphate have been obtained from ammonium sulfate solutions. These crystals belong to space group C222 with cell dimensions a = 157.2 A, b = 157.2 A and c = 201.3 A. The crystals are pseudo F-centered with a pseudo 4-fold axis parallel to c. The space group of local symmetry F422 contains one large and one small subunit in the asymmetric unit. The crystals diffract beyond 2 A resolution.
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Responsiveness was compared for cell populations harvested from the peritoneal and pleural cavities of rats with respect to histamine release induced by specific antigen, anti-IgE, and Con A. Cell populations were obtained from Fischer, PVG or Sprague-Dawley (SD) rats, which were either untreated or immunized with 10 micrograms ovalbumin together with 100 mg alum intraperitoneally. Mast cell histamine release was examined with crude cell populations. The results show that differences in response capacity to the various secretagogues employed do exist between pleural and peritoneal cells in Fischer and PVG strains but under the present circumstances apparently not in SD rats. These differences vary in magnitude with the secretagogue employed and (for cells from immunized animals) with the time elapsed between immunization and test. In PVG rats, neither pleural nor peritoneal mast cell histamine release induced by antigen paralleled serum OA-IgE antibody levels. Furthermore, an increase in anti-IgE induced release of histamine from serosal mast cells occurred in parallel with a decrease in total serum IgE levels. These data indicate that the functional differences observed with respect to release properties of the two cell populations are due not only to intrinsic differences in mast cell populations but also to differences in reaginic antibodies sensitizing the cells.
Six middle-aged lactovegetarians (three men and three women) collected copies of four 24-h diets using the duplicate portion sampling technique. By chemical analyses, the nutrient composition of the lactovegetarian diet was determined in detail and compared with that of a mixed Swedish diet (normal) and a vegan diet (vegan) studied previously. The nutrient composition of the lactovegetarian diet expressed per 1000 kcal represented an average between normal and vegan diets. It was in closer agreement with Swedish recommended dietary allowances than the normal Swedish diet. Thus, the lactovegetarian diet contained 35% of the energy as fat and was rich in polyunsaturated fatty acids, especially linoleic acid, which resulted in a polyunsaturated/saturated fat ratio of 0.6. The lactovegetarian diet had a cholesterol concentration only half of that of a normal diet. Protein content and amino acid composition were well above recommendations. The lactovegetarian diets contained less sucrose than normal and vegan diets, but the sum of the intake of low molecular weight carbohydrates was comparable to normal and vegan diets. Dietary fiber was three times higher than in a normal diet. Essential minerals and trace elements, ie, Ca, Mg, Na, K, Fe, Zn, Cu, Se, satisfied current requirements. The intake of vitamin B12 by the lactovegetarians was around 1.4 micrograms daily, which is below the recommendations. The intake of folates was high, 300 to 400 micrograms daily. The clinical and biochemical investigation of the subjects revealed no signs of nutritional deficiency. Their plasma lipoproteins and the blood pressures were low for their age, in agreement with observations made earlier in a group of vegans.
A new barium sulphate suspension, E-Z-CAT, for use as an oral contrast medium at computed tomography of the abdomen has been compared with the commonly used water-soluble iodinated contrast medium Gastrografin as regards patient tolerance and diagnostic information. The investigation was conducted as an unpaired randomized single-blind study in 100 consecutive patients. E-Z-CAT seems to be preferred because of its better taste, its lesser tendency to cause diarrhoea, and for usage in patients who are known to be hypersensitive to iodinated contrast media. The diagnostic information was the same for both contrast media.
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Ribulose 1,5-bisphosphate carboxylase/oxygenase has been purified from spinach and crystallized by equilibrium vapor diffusion with polyethylene glycol 6000 as a precipitant. Crystals suitable for x-ray studies were obtained from a binary complex with a transition state analogue, 2-C-carboxy-D-arabinitol 1,5-bisphosphate, and a quaternary complex with 2-C-carboxy-D-arabinitol 1,5-bisphosphate, Mg2+, and HCO-3. Two forms of crystals were obtained in the presence of 2-C-carboxy-D-arabinitol 1,5-bisphosphate. Form B crystals are plates which have orthorhombic space group P2(1)2(1)2 with unit cell dimensions a = 184 A, b = 218 A, and c = 119 A. Form C crystals are tetragonal needles with space group I422 and with cell dimensions a = b = 275 A and c = 178 A. In both forms, the asymmetric unit contains half a molecule.
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