Pancreatic cancer: from bench to 5-year survival.

Pancreatic ductal adenocarcinoma is one of the most aggressive human malignancies, with an overall 5-year survival rate of less than 4%. On the molecular level, an increasing number of genetic and epigenetic alterations have been discovered, with a particular focus on growth factors and related pathways. Small-molecule tyrosine kinase inhibitors, antibodies, and other approaches have been developed in recent years to target these signal transduction pathways, and first clinical trials show encouraging results.

Cyclooxygenase-2 inhibition induces apoptosis signaling via death receptors and mitochondria in hepatocellular carcinoma.

Inhibition of cyclooxygenase (COX)-2 elicits chemopreventive and therapeutic effects in solid tumors that are coupled with the induction of apoptosis in tumor cells. We investigated the mechanisms by which COX-2 inhibition induces apoptosis in hepatocellular carcinoma (HCC) cells. COX-2 inhibition triggered expression of the CD95, tumor necrosis factor (TNF)-R, and TNF-related apoptosis-inducing ligand (TRAIL)-R1 and TRAIL-R2 death receptors.

A naturally occurring mutation in the SLC21A6 gene causing impaired membrane localization of the hepatocyte uptake transporter.

The organic anion transporter SLC21A6 (also known as OATP2, OATP-C, or LST-1) is involved in the hepatocellular uptake of a variety of endogenous and xenobiotic substances and drugs. We analyzed 81 human liver samples by immunoblotting and found one with a strongly reduced amount of SLC21A6 protein suggesting mutations in the SLC21A6 gene. The SLC21A6 cDNA from this sample contained five base pair changes in one allele; three of the mutations resulted in amino acid substitutions designated SLC21A6-N130D, SLC21A6-P155T, and SLC21A6-L193R.

Use of capillary tubes and plate heat exchanger to validate U.S. Department of Agriculture pasteurization protocols for elimination of Listeria monocytogenes in liquid egg products.

D-values for a five-strain cocktail of Listeria monocytogenes in five different liquid egg products (whole egg, egg yolk, egg white, egg yolk + 5% sucrose + 5% NaCl, and egg yolk + 10% NaCl) were determined using 100-microl capillary tubes. The egg products were inoculated with approximately 1 x 10(10) organisms/ml and heated in capillary tubes to temperatures ranging from 53 to 69 degrees C for various time intervals. Using a pilot scale plate heat exchanger, the U.

Use of capillary tubes and plate heat exchanger to validate U.S. Department of Agriculture pasteurization protocols for elimination of Salmonella enteritidis from liquid egg products.

D values for a five-strain cocktail of Salmonella Enteritidis in five different liquid egg products (whole egg, egg yolk, egg white, egg yolk + 5% sucrose + 5% NaCl, and egg yolk + 10% NaCl) were determined using 100-microl capillary tubes. The egg products were inoculated with approximately 1 X 10(10) organisms/ml and heated in capillary tubes to temperatures ranging from 51 to 68 degrees C for various time intervals. Using a pilot scale plate heat exchanger, the U.

Human pre-alpha-inhibitor: isolation from a by-product of industrial scale plasma fractionation and structural analysis of its H3 heavy chain.

Pre-alpha-inhibitor (P alpha I) is a serine proteinase inhibitor from human plasma. It comprises bikunin (BK) responsible for antiprotease activity, covalently linked to a heavy chain H3. Here we describe its isolation from a side fraction of an industrial preparation of plasma clotting factors.

Development of an enzyme-linked immunosorbent assay for human plasma inter-alpha-trypsin inhibitor (ITI) using specific antibodies against each of the H1 and H2 heavy chains.

Inter-alpha-trypsin inhibitor (ITI) is a serine-proteinase inhibitor of human plasma enzymes. ITI is composed of three polypeptide chains covalently linked: bikunin, responsible for the antiprotease activity and two heavy chains H1 and H2. Human plasma also contains other components immunologically related to ITI such as pre-alpha-trypsin inhibitor (paI), inter-alpha-like inhibitor (IalphaLI) and free bikunin.

Chondroitin sulphate covalently cross-links the three polypeptide chains of inter-alpha-trypsin inhibitor.

Inter-alpha-trypsin inhibitor (ITI) is a tight complex of three different proteins: bikunin and two heavy chains H1 and H2. In order to demonstrate that the three chains are covalently linked by a chondroitin sulphate chain as previously proposed [Enghild, J. J.

Preparation and properties of a therapeutic inter-alpha-trypsin inhibitor concentrate from human plasma.

Inter-alpha-trypsin inhibitor (ITI) is a serine protease inhibitor found in human plasma. Its antiprotease activity is due to bikunin which is effective in various types of experimental shock and pancreatitis. Therefore ITI, which releases bikunin by proteolytic cleavage, could be of therapeutic interest.

Human leucocyte elastase (HLE) preferentially cleaves the heavy chain H2 of inter-alpha-trypsin inhibitor (ITI).

Inter-alpha-trypsin inhibitor (ITI) is a complex protein containing two heavy polypeptide chains (H1 and H2) and a light chain, which in the free state is known as bikunin. In vitro cleavage of ITI with different proteases releases bikunin, but does not abolish the antitryptic activity. To study the mechanism of bikunin release, ITI was incubated with human leucocyte elastase (HLE).

Interlaboratory evaluation of methods for the assay of Protein C in purified concentrates.

Determination of the quantity and activity of the Protein C molecule is of the utmost importance in highly purified concentrates prepared for replacement therapy. A multicenter study was undertaken to evaluate the comparability and accuracy of Protein C assays from commercial sources. Significant between-assay and interlaboratory differences were found for both functional and immunological assays.

Breast augmentation mammoplasty. Preoperative and postoperative nursing care.

Breast augmentation mammoplasty is a vital part of reconstructive breast surgery. More than 2 million women over the past 30 years have undergone this type of surgery either for reconstruction or augmentation. There continues to be a need for further investigation of the human biological response to these devices.

The future of breast implants: alternatives to silicone gel-filled implants.

1. Women undergoing breast implant surgery run the risk of possible complications including infection, bleeding or hematoma, scarring, changes in breast sensation, displacement, capsular contraction, or fracture rupture in a small percentage of cases; this is still under investigation. 2.

[Multicenter study on purified protein C concentrates and defined plasma levels].

A variety of protein C assays are available as commercial kits. A collaborative study was undertaken to evaluate the performance of protein C assays. Various samples including calibrated plasmas and high purity concentrates destined to therapy were distributed among five laboratories.

Properties of a highly purified human plasma factor IX:c therapeutic concentrate prepared by conventional chromatography.

We have characterized a highly purified (HP) factor IX concentrate intended for therapy of hemophilia B. The product has been prepared from pooled human plasma using a large-scale procedure combining three conventional chromatographic steps based on DEAE ion exchange and affinity on immobilized heparin. The specific activity of the product was 119 +/- 10 IU factor IX:c/mg protein (n = 15), corresponding to a purification factor of about 9,000.

Large-scale production and properties of a solvent-detergent-treated factor IX concentrate from human plasma.

A human solvent-detergent (SD)-treated factor IX concentrate has been produced from cryoprecipitate-poor plasma using DEAE-Sepharose CL-6B and heparin-Sepharose CL-6B chromatography. The DEAE eluate was incubated with an SD mixture [0.3% tri(n-butyl) phosphate-1% Tween 80, 6-h at 24 degrees C] which was found to inactivate, in less than 1 h, more than 3.

Reconstitution of the ubiquinol: cytochrome c reductase from a bc1 subcomplex and the 'Rieske' iron-sulfur protein isolated by a new method.

1. A method for preparing the 'Rieske' iron-sulfur protein and the bc1 subcomplex of complex III was developed. The new method is advantageous over the published ones in that: (a) the final yield and amount exceeds by far those obtained when employing the hitherto published methods; (b) the iron-sulfur protein as well as the bc1 subcomplex are obtained by one and the same preparation procedure from a common source; and (c) the preparation method is easier than the published ones.

Influence of magnesium and polyamines on the reactivity of individual ribosomal subunit proteins to lactoperoxidase-catalyzed iodination.

30S and 50S subunits, in the presence of either 20 mM Mg2+ or 6 mM Mg2+ and 5mM spermidine plus 25 mM putrescine, were observed to completely associate to form 70S monosomes as monitored by sucrose gradient sedimentation. Subunits maintained under the above ionic conditions were compared with 30S and 50S particles at low (6 mM) magnesium concentration with respect to the reactivity of individual ribosomal proteins to lactoperoxidase-catalyzed iodination. Altered reactivity to enzymatic iodination of ribosomal proteins S4, S9, S10, S14, S17, S19, and S20 in the small subunit of ribosomal proteins, L2, L9, L11, L27, and L30 in the large subunit following incubation with high magnesium or magnesium and polyamines suggests that a conformation change in both subunits accompanies the formation of 70S monosomes.

Molecular morphology of ribosomes. Iodination of Escherichia coli ribosomal proteins with solid-state lactoperoxidase.

Using either soluble or solid-state lactoperoxidase, a comparison was made between the enzymic iodination of ribosomal proteins iodinated as 30-S and 50-S subunits or as 70-S monosomes. Proteins S7, S11 and S12 of the 30-S subunit and proteins L2, L11, L26 and L28 of the 50-S subunit were labelled to a greater extent in isolated particles than in the 70-S ribosome. In contrast, proteins S4, S19 and S20 were labelled to a lesser extent in the isolated subunit.