Convenient preparation of L-arabino-hexos-5-ulose derivatives from lactose

2,6-di-O-benzyl- (9), 2-O-benzyl-3,4-O-isopropylidene- (19), and 2-O-benzyl-6-O-m-chlorobenzoyl-L-arabino-hexos-5-ulose (20) have been prepared using 4'-deoxy-4'-eno- and 6'-deoxy-5'-eno lactose dimethyl acetal derivatives 7 and 14 as key intermediates. The synthesis of enol ethers 7 and 14 has been performed with good yields by base-promoted elimination of acetone or p-toluenesulfonic acid from 2',6'-di-O-benzyl-, and 6'-O-p-toluenesulfonyl-2,3:5,6:3',4'-tri-O-isopropylidenelactose dimethyl acetal, respectively. The epoxidation with MCPBA of 7 and 14 in methanol or dichloromethane furnishes C-5'-methoxy and C-5'-m-chlorobenzoyloxy derivatives, easily transformed with good yields into L-arabino 5-ketoaldohexoses 9, 19 and 20.     

Macrofollicular encapsulated variant of papillary thyroid carcinoma as a potential pitfall in histologic and cytologic diagnosis. A report of three cases

BACKGROUND: Macrofollicular encapsulated papillary carcinoma (MEPC) is a variant of papillary carcinoma with a favorable clinical course. Its characteristic histologic pattern could be mistaken for that of an adenoma or hyperplastic nodule. Fine needle aspiration of this neoplasm may not show the particular nuclear features of papillary carcinoma, so the cytologic diagnosis may be benign. CASE REPORTS: Three paradigmatic cases of MEPC with different histologic patterns, diagnosed as a follicular neoplasm using fine needle aspiration biopsy (FNAB) are described. Preoperative cytology showed scattered clusters of thyrocytes with prominent nuclear pleomorphism and irregularities and focal oxyphilic changes mixed with colloid and aggregates of typical thyrocytes. The histologic picture exhibits small, neoplastic foci showing a microfollicular structure within an encapsulated neoplasm with a macrofollicular pattern. In microfollicular areas obvious nuclear pseudoinclusions were seldom observed. CONCLUSION: MEPC represents a challenging tumor subtype that infrequently shows the pathognomonic cytologic characteristics of papillary carcinoma, and therefore it is much more difficult to diagnose with a FNAB. Nuclear pleomorphism and irregularity of the nuclear membrane of thyrocytes are clues to this variant, although in some cases a clear-cut preoperative diagnosis cannot be made.     

The expression of native and oxidized LDL receptors in brain microvessels is specifically enhanced by astrocytes-derived soluble factor(s)

Based on the functional characterization of sucrose biosynthesis related protiens[SBP: sucrose-phosphate synthase (SPS), sucrose-phosphate phosphatase (SPP), and sucrose synthase (SuS)] in Anabaena sp. PCC7120 and sequence analysis, we have shown that SBP are restricted to cyanobacterium species and plants, and that they are multidomain proteins with modular architecture. Anabaena SPS, a minimal catalytic SPS unit, defines a glucosyltransferase domain present in all SPSs and SuSs. Similarly, Anabaena SPP defines a phosphohydrolase domain characteristic of all SPPs and some SPSs. Phylogenetic analysis points towards the evolution of modern cyanobacterial and plant SBP from a bidomainal common ancestral SPS-like gene.     

Identification of a chemotactic,MCP-1-like protein from Mycobacterium avium

In the immunocompetent host, Mycobacterium avium is responsible for chronic localized pulmonary disease, which is characterized by the presence of increased numbers of activated T cells and macrophages in the lungs. M. avium organisms as well as sonic extracts of M. avium were found to act as chemoattractants for THP-1 cells as well as monocytes, monocyte-derived macrophages and alveolar macrophages obtained from normal human donors in an in vitro chemotaxis assay, where a significantly higher number of cells were found in wells containing M. avium compared to control wells. Proteolytic treatment of M. avium sonicate resulted in significant loss (50%) of chemotactic activity. Monoclonal antibodies against recombinant human monocyte chemoattractant protein-1 (MCP-1) were found to cross-react with a 34-kDa protein of M. avium sonicate on Western blot and inhibit M. avium sonicate-mediated chemotaxis of THP-1 cells (47%). These data suggest the presence of an 'MCP-1 like' molecule on M. avium. Recruitment of host immune regulatory cells to the site of infection by pathogens may be involved in generating a local immune response or may be a bacterial strategy for survival within the host by recruiting the cells that they infect, i.e. macrophages.     

Controllability of selection-mutation systems

The well-known Fisher type selection-mutation model is studied from the point of view of mathematical systems theory. Mutation rates are considered as control functions. Based on a general sufficient condition for local controllability of non-linear systems with invariant manifold, a method is proposed to guarantee the controllability of the considered population into a polymorphic equilibrium.     

Oxidative damage of the gastric mucosa in Helicobacter pylori positive chronic atrophic and nonatrophic gastritis, before and after eradication

Background. Helicobacter pylori is the main cause of gastritis and a primary carcinogen. The aim of this study was to assess oxidative damage in mucosal compartments of gastric mucosa in H. pylori positive and negative atrophic and nonatrophic gastritis. Materials and methods. Five groups of 10 patients each were identified according to H. pylori positive or negative chronic atrophic (Hp‐CAG and CAG, respectively) and nonatrophic gastritis (Hp‐CG and CG, respectively), and H. pylori negative normal mucosa (controls). Oxidative damage was evaluated by nitrotyrosine immunohistochemistry in the whole mucosa and in each compartment at baseline and at 2 and 12 months after eradication. Types of intestinal metaplasia were classified by histochemistry. Results. Total nitrotyrosine levels appeared significantly higher in H. pylori positive than in negative patients, and in Hp‐CAG than in Hp‐CG (p < .001); no differences were found between H. pylori negative gastritis and normal mucosa. Nitrotyrosine were found in foveolae and intestinal metaplasia only in Hp‐CAG. At 12 months after H. pylori eradication, total nitrotyrosine levels showed a trend toward a decrease in Hp‐CG and decreased significantly in Hp‐CAG (p = .002), disappearing from the foveolae (p = .002), but remaining unchanged in intestinal metaplasia. Type I and II of intestinal metaplasia were present with the same prevalence in Hp‐CAG and CAG, and did not change after H. pylori eradication. Conclusions. Oxidative damage of the gastric mucosa increases from Hp‐CG to Hp‐CAG, involving the foveolae and intestinal metaplasia. H. pylori eradication induces a complete healing of foveolae but not of intestinal metaplasia, reducing the overall oxidative damage in the mucosa.     

Synthesis,characterization and immunochemical evaluation of cephalosporin antigenic determinants

Lack of knowledge of the exact chemical structure of cephalosporin antigenic determinants has hindered clinical interpretation of adverse reactions to these drugs and delayed understanding of the mechanisms involved in the specific recognition and binding of IgE molecules to these antigenic determinants. We further resolve the relationship between structure and activity of proposed antigenic chemicals, including the rational design and synthesis of these haptenic structures. Comparative RAST inhibition studies of the synthesized molecules revealed that they were recognized by IgE antibodies induced by cephalosporin antibiotics. Thus, these data indicate that recognition is mainly directed to the acyl side chain and to the beta-lactam fragment that remains linked to the carrier protein in the cephalosporin conjugation course.     

Effect of High-Fidelity Simulation on Medical Students’ Knowledge about Advanced Life Support: A Randomized Study

High-fidelity simulation (HFS) is a learning method which has proven effective in medical education for technical and non-technical skills. However, its effectiveness for knowledge acquisition is less validated. We performed a randomized study with the primary aim of investigating whether HFS, in association with frontal lessons, would improve knowledge about advanced life support (ALS), in comparison to frontal lessons only among medical students. The secondary aims were to evaluate the effect of HFS on knowledge acquisition of different sections of ALS and personal knowledge perception. Participants answered a pre-test questionnaire consisting of a subjective (evaluating personal perception of knowledge) and an objective section (measuring level of knowledge) containing 100 questions about algorithms, technical skills, team working/early warning scores/communication strategies according to ALS guidelines. All students participated in 3 frontal lessons before being randomized in group S, undergoing a HFS session, and group C, receiving no further interventions. After 10 days from the end of each intervention, both groups answered a questionnaire (post-test) with the same subjective section but a different objective one. The overall number of correct answers of the post-test was significantly higher in group S (mean 74.1, SD 11.2) than in group C (mean 65.5, SD 14.3), p = 0.0017, 95% C.I. 3.34 – 13.9. A significantly higher number of correct answers was reported in group S than in group C for questions investigating knowledge of algorithms (p = 0.0001; 95% C.I 2.22–5.99) and team working/early warning scores/communication strategies (p = 0.0060; 95% C.I 1.13–6.53). Students in group S showed a significantly higher score in the post-test subjective section (p = 0.0074). A lower proportion of students in group S confirmed their perception of knowledge compared to group C (p = 0.0079). HFS showed a beneficial effect on knowledge of ALS among medical students, especially for notions of algorithms and team working/early warning scores/communication.     

A Highlights from MBoC Selection: Golgi Partitioning Controls Mitotic Entry through Aurora-A Kinase

At the onset of mitosis, the Golgi complex undergoes a multistep fragmentation process that is required for its correct partitioning into the daughter cells. Inhibition of this Golgi fragmentation results in cell cycle arrest at the G2 stage, suggesting that correct inheritance of the Golgi complex is monitored by a “Golgi mitotic checkpoint.” However, the molecular basis of this G2 block is not known. Here, we show that the G2-specific Golgi fragmentation stage is concomitant with centrosome recruitment and activation of the mitotic kinase Aurora-A, an essential regulator for entry into mitosis. We show that a block of Golgi partitioning impairs centrosome recruitment and activation of Aurora-A, which results in the G2 block of cell cycle progression. Overexpression of Aurora-A overrides this cell cycle block, indicating that Aurora-A is a major effector of the Golgi checkpoint. Our findings provide the basis for further understanding of the signaling pathways that coordinate organelle inheritance and cell duplication.