The significance of colour velocity and spectral Doppler ultrasound in the differentiation of liver tumours

BACKGROUND: The distinction between malignant mesothelioma (MM) and adenocarcinoma (ACA) in cytologic specimens frequently is difficult, often requiring immunocytochemistry to support the diagnosis. Recent reports have proposed the utilization of antibodies to mesothelial cell clone HBME-1 and thrombomodulin (TM), because they are immunoreactive in MM and less commonly reactive in ACA. Immunoreactivity for the monoclonal antibody CA 19-9 has been observed in many ACAs and reportedly is absent in MM. METHODS: In this study, immunostaining was performed on formalin fixed, paraffin embedded cell blocks from effusions or fine-needle aspirations using the avidin-biotin-peroxidase method. Thirty-eight MMs and 49 ACAs were tested using antibodies to CA 19-9, HBME-1, and TM. RESULTS: Anti-CA 19-9 stained only 1 of the 37 cases of MM tested (3%), but stained 24 of the 49 cases of ACA (49%). Anti-HBME-1 stained 34 of 38 cases of MM (89%), and 28 of 43 cases of ACA tested (65%). Anti-TM stained 24 of 36 cases of MM (67%), and 21 of 40 cases of ACA tested (53%). CONCLUSIONS: CA 19-9 has utility as part of an immunocytochemical panel for distinguishing ACA from MM, because a positive staining reaction would make the diagnosis of MM unlikely. Although HBME-1 and TM can identify MM positively, each frequently is detected in ACA, thus limiting the utility of these antibodies in cytologic specimens.     

A strain of the yeast Saccharomyces cerevisiae for testing environmental mutagens based on interaction of the mutations rad2 and him1

The interaction between mutations at the RAD2 and HIM1 genes was studied. The RAD2 gene encodes endonuclease involved in nucleotide excision repair. Mutants at this gene are highly sensitive to the lethal effect of a variety of mutagens. The product of the HIM1 gene is needed for correction of mismatched bases and repair of premutational DNA damage. Mutations in this gene lead to the formation of the mutator phenotype and high sensitivity to induced mutagenesis. The double rad2 him1 mutant manifested the synergic type of interaction. The level of UV-induced mutagenesis in the double mutant was five times higher than in single mutants, and the absolute yield of forward mutations in five genes controlling adenine biosynthesis was 1 to 2%. UV-induced mutagenesis was increased, at low doses, by several orders of magnitude in the double mutant, compared to the wild-type strain. The high level of mutagenesis in this mutant was caused by ethyl and methyl methanesulfonate. These properties of the stock with the double rad2 him1 mutation makes it promising as a tester in analysis of the gene toxicity of different substances.     

Oxidant mechanisms in toxic acute renal failure

Setting up a puppy training program is one of the most important services veterinarians can offer. Puppy socialization classes aim not only to socialize the puppies so that they learn to interact well with children, adults, and other dogs, but also to teach basic obedience exercises. The classes build a strong bond between puppy, owner, and veterinary clinic. This article covers the techniques used, the structure of the classes, and outlines benefits for the dog, owner, veterinarian, and community.     

The binding of receptor-recognized alpha2-macroglobulin to the low density lipoprotein receptor-related protein and the alpha2M signaling receptor is decoupled by oxidation

Receptor-recognized forms of alpha2-macroglobulin (alpha2M*) bind to two classes of cellular receptors, a high affinity site comprising approximately 1500 sites/cell and a lower affinity site comprising about 60,000 sites/cell. The latter class has been identified as the so-called low density lipoprotein receptor-related protein (LRP). Ligation of receptors distinct from LRP activates cell signaling pathways. Strong circumstantial evidence suggests that the high affinity binding sites are responsible for cell signaling induced by alpha2M*. Using sodium hypochlorite, a powerful oxidant produced by the H2O2-myeloperoxidase-Cl- system, we now demonstrate that binding to the high affinity sites correlates directly with activation of the signaling cascade. Oxidation of alpha2M* using 200 microM hypochlorite completely abolishes its binding to LRP without affecting its ability to activate the macrophage signaling cascade. Scatchard analysis shows binding to a single class of high affinity sites (Kd - 71 +/- 12 pM). Surprisingly, oxidation of native alpha2-macroglobulin (alpha2M) with 125 microM hypochlorite results in the exposure of its receptor-binding site to LRP, but the ligand is unable to induce cell signaling. Scatchard analysis shows binding to a single class of lower affinity sites (Kd - 0.7 +/- 0.15 nM). Oxidation of a cloned and expressed carboxyl-terminal 20-kDa fragment of alpha2M (RBF), which is capable of binding to both LRP and the signaling receptor, results in no significant change in its binding Kd, supporting our earlier finding that the oxidation-sensitive site is predominantly outside of RBF. Attempts to understand the mechanism responsible for the selective exposure of LRP-binding sites in oxidized native alpha2M suggest that partial protein unfolding may be the most likely mechanism. These studies provide strong evidence that the high affinity sites (Kd - 71 pM) are the alpha2M* signaling receptor.