Association of chromosome 12p genetic polymorphisms with lung adenocarcinoma risk and prognosis

The mapping near Kras2 of pulmonary adenoma susceptibility 1 (Pas1), a major locus affecting inherited predisposition to lung cancer in mice prompted us to test the homologous human region (12p12) for association with lung adenocarcinoma, by a population-based study. We genotyped 213 lung adenocarcinoma patients and 219 healthy blood donor subjects for five polymorphic markers mapping in the putative region of interest. Three marker polymorphisms, located in a region spanning approximately 700 kb, were significantly associated with lung adenocarcinoma risk. Furthermore, polymorphisms in KRAS2 and PTHLH loci were also associated with tumor prognosis. These results suggest the existence of a human Pas1 homologous locus on chromosome 12p12.     

Intraoperative arthrography and the Ilizarov technique. Role in the correction of paediatric deformity and leg lengthening

We performed intraoperative arthrography of the knee in 12 children with congenital short femur, Blount's disease or Ollier's disease in whom the Ilizarov technique was used for correction of deformity, leg lengthening or both. In each case, arthrography revealed a joint surface considerably different from that assumed from plain radiographs, and resulted in a change in the placement of our reference wires before application of the frame. This gave significant improvement in the mechanical axis obtained at the time of removal of the frame. The technique is safe, cheap and easy to perform. It is a useful adjunct to the application of the Ilizarov frame when used for complex lengthening and correction of deformity in the leg.     

Efficient autoproteolytic processing of the MHV-A59 3C-like proteinase from the flanking hydrophobic domains requires membranes

The replicase gene of the coronavirus MHV-A59 encodes a serine-like proteinase similar to the 3C proteinases of picornaviruses. This proteinase domain is flanked on both sides by hydrophobic, potentially membrane-spanning, regions. Cell-free expression of a plasmid encoding only the 3C-like proteinase (3CLpro) resulted in the synthesis of a 29-kDa protein that was specifically recognized by an antibody directed against the carboxy-terminal region of the proteinase. A protein of identical mobility was detected in MHV-A59-infected cell lysates. In vitro expression of a plasmid encoding the 3CLpro and portions of the two flanking hydrophobic regions resulted in inefficient processing of the 29-kDa protein. However, the efficiency of this processing event was enhanced by the addition of canine pancreatic microsomes to the translation reaction, or removal of one of the flanking hydrophobic domains. Proteolysis was inhibited in the presence of N-ethylmaleimide (NEM) or by mutagenesis of the catalytic cysteine residue of the proteinase, indicating that the 3CLpro is responsible for its autoproteolytic cleavage from the flanking domains. Microsomal membranes were unable to enhance the trans processing of a precursor containing the inactive proteinase domain and both hydrophobic regions by a recombinant 3CLpro expressed from Escherichia coli. Membrane association assays demonstrated that the 29-kDa 3CLpro was present in the soluble fraction of the reticulocyte lysates, while polypeptides containing the hydrophobic domains associated with the membrane pelletes. With the help of a viral epitope tag, we identified a 22-kDa membrane-associated polypeptide as the proteolytic product containing the amino-terminal hydrophobic domain.     

Placental pathology and antiphospholipid antibodies: a descriptive study

We described placental pathology in antiphospholipid antibody (APL) syndrome, APL and no history of recurrent pregnancy loss, and in treated and untreated pregnancies of APL syndrome. Thirty-nine pregnancies of 28 patients were studied: 23 placentas delivered from 23 women with APL (13 with APL syndrome and 10 with serological APL); 8 untreated miscarriages before APL diagnosis from 6 of the 13 patients with APL syndrome and 1 of 10 with serological APL; and 8 miscarriages by 5 additional women before APL syndrome diagnosis. Histopathology was reviewed by a pathologist blinded except to gestational age. Contingency tables and analysis of variance (ANOVA) considered p < 0.05 significant. Comparing the placentas delivered at > 18 weeks' gestation, excessive perivillous coagulation, avascular terminal villi, and chronic villitis/uteroplacental vasculitis tended to be more common in treated APL syndrome than serological APL cases (p = 0.07). Of the 16 miscarriages before diagnosis of APL, 11 were lost at < 18 weeks' gestation. None had pathology typical of APL, but 4 of 11 (36%) had chronic intervillositis. Five of 16 miscarriages before the diagnosis of APL were miscarried between 18-22 weeks. Three of 5 (60%) miscarried after 18 weeks had multifocal uteroplacental thromboses, compared to 6 of 13 (46%) treated pregnancies with APL syndrome and 0 of 10 cases with serological APL.     

Oral mucositis with features of psoriasis: report of a case and review of the literature

There complete 18S ribosomal RNA gene sequences from the rumen ciliates, Entodinium caudatum (1,639 bp), Epidinium caudatum (1,638 bp), and Polyplastron multivesiculatum (1,640 bp) were determined and confirmed in the opposite direction. Trees produced using maximum parsimony and distance-matrix methods (least squares and neighbour-joining), with strong bootstrap support, depict the rumen ciliates as a monophyletic group. Entodinium caudatum is the earliest branching rumen ciliate. However, Entodinium simplex does not pair with En. caudatum, but rather with Polyplastron multivesiculatum. Signature sequences for these rumen ciliates reveal that the published SSrRNA gene sequence from En. simplex is in fact a Polyplastron species. The free-living haptorian ciliates, The Loxophyllum, Homalozoon and Spathidium (Subclass Haptoria), are monophyletic and are the sister group to the rumen ciliates. The litostomes (Class Litostomatea), consisting of the haptorians and the rumen ciliates, are also a monophyletic group.     

Gastrin and its role in the development of ulcer disease

Helicobacter pylori infected patients have increased gastrin release which shows a marked fall after cure of the infection. Recent studies indicate that inflammatory cells and cytokines play an important role in the pathogenesis of Helicobacter-associated hypergastrinemia. Views differ regarding the impact of gastrin on acid secretion. Current evidence suggests that gastrin is responsible for at least some of the increased acid secretion seen in duodenal ulcer patients.     

Surface chemistry of wood‐based phosphoric acid‐activated carbons and its effects on adsorptivity

The surface oxygen content of selected wood‐based phosphoric acid‐activated carbons was quantified using X‐ray photoelectron spectroscopy (XPS) and correlated with the residual bulk phosphate levels of the carbons and their adsorptivity in solution. The adsorption of Al³⁺, Cu²⁺, and para‐chlorophenol, respectively, from water decreased as a function of increasing surface oxygen content of the carbons. When the carbon of lowest surface oxygen content was oxidized with ozone to impart a surface oxygen content comparable to that of a carbon with a much higher phosphate level, adsorption of Al³⁺, Cu²⁺, and para‐chlorophenol from water decreased proportionally. The increase in polarity of the carbon surface was accompanied by a decrease in pH and appeared to be the dominant factor with respect to the adsorption of the target species from water. Copyright © 2005 Society of Chemical Industry     

Genomic characterization of the coding region of the human type II 5''-deiodinase gene

The conserved residue Asp477 in yeast transketolase is located in the substrate channel of the enzyme and forms a hydrogen bond with the C2-hydroxyl group of the acceptor substrate. The significance of this interaction for the recognition of the preferred acceptor substrates, D-alpha-hydroxyaldehydes was investigated by site-directed mutagenesis. In the wild-type enzyme the kcat/KM values are by three to four orders of magnitude lower for 2-deoxyaldoses or substrates with L-configuration at the C2-atom. In the Asp477 Ala mutant, the kcat/KM values for D-alpha-hydroxyaldehydes are decreased by a thousandfold, while the kcat/KM values for substrates with L-configuration or 2-deoxyaldoses are similar to wild-type enzyme. These results indicate that Asp477 is involved in determining the enantioselectivity of transketolase.     

Primary gamma delta cell clones can be defined phenotypically and functionally as Th1/Th2 cells and illustrate the association of CD4 with Th2 differentiation

The division of CD4+ alpha beta T cells into Th1 and Th2 subsets has become an established and important paradigm. The respective activities of these subsets appear to have profound effects on the course of infectious and autoimmune diseases. It is believed that specific programs of differentiation induce the commitment of an uncommitted Th0 precursor cell to Th1 or Th2. A component of these programs is hypothesized to be the nature of MHC-peptide antigen presentation to the alpha beta T cell. It has heretofore remained uncertain whether a Th1/Th2 classification likewise defines, at the clonal level, gamma delta T cells. Such cells do not, as a general rule, express either CD4 or CD8 alpha beta, and they do not commonly recognize peptide-MHC. In this report, gamma delta cell clones are described that conform strikingly to the Th1/Th2 classification, both by cytokine expression and by functional activities of the clones in vitro and in vivo. Provocatively, both the gamma delta cell clones and primary gamma delta cells in vivo showed a strong association of the Th2 phenotype with CD4 expression. These results are discussed with regard to the immunoregulatory role that is increasingly emerging for gamma delta cells.