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Leukemia. 2003 May;17(5):910-8.
Aberrant methylation and impaired expression of the p15(INK4b) cell cycle regulatory gene in chronic myelomonocytic leukemia (CMML).

Tessema M, Langer F, Dingemann J, Ganser A, Kreipe H, Lehmann U.

1Institute of Pathology, Medizinische Hochschule Hannover, Carl-Neuberg-Street 1, Hannover, Germany.

The important cell cycle regulatory gene p15(INK4b) has been shown to be inactivated in acute myeloid leukemia and myelodysplastic syndrome. Little is known about the expression and epigenetic modification of this gene in chronic myelomonocytic leukemia (CMML) that belongs to the myelodysplastic/myeloproliferative disorders (MDS/MPD) with a high proportion of blastic transformation. Analysis of bone marrow trephines in a series of 33 CMML cases showed an aberrant p15(INK4b) gene methylation in up to 58% of cases. Methylation was analyzed employing different methylation-specific PCR and genomic sequencing protocols. It turned out to be spread over a broad area of the 5' region and exhibited substantial heterogeneity between cases and even in individual patients. The degree of aberrant methylation was correlated with a reduced mRNA as well as reduced protein expression, and was associated with a higher expression of DNA methyltransferase DNMT 3A. We conclude that aberrant gene methylation is a frequent event in CMML that might contribute to the pathogenesis of this MDS/MPD.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12750705&dopt=Abstract

Leukemia. 2003 May;17(5):925-30.
Infectious complications in patients with acute promyelocytic leukaemia treated with the AIDA regimen.

Girmenia C, Lo Coco F, Breccia M, Latagliata R, Spadea A, D'Andrea M, Gentile G, Micozzi A, Alimena G, Martino P, Mandelli F.

Dipartimento di Biotecnologie Cellulari ed Ematologia, University La Sapienza, Rome, Italy.

Infections represent a frequent complication of chemotherapy used for acute myeloid leukaemia (AML) and are associated with important toxicity frequently leading to treatment discontinuation. Acute promyelocytic leukaemia (APL) is a unique AML subset requiring tailored therapy including all-trans retinoic acid and anthracycline-based chemotherapy. We analysed in this study the incidence and type of infections complicating the clinical course of 89 consecutive APL patients receiving the AIDA protocol at a single institution. A total of 179 febrile episodes were registered during induction and consolidation, 52% of which were of unknown origin. Infections were clinically and microbiologically documented in 10.6 and 37.4% of cases, respectively. Coagulase-negative staphylococci represented the major cause of septicaemia (28%) and were more frequently isolated during induction, whereas viridans group streptococci, the second pathogen most frequently isolated from blood (27%), represented the principal pathogen detected during consolidation and were significantly associated with mucositis. Gram-negative bacteria accounted for 33.3% of all blood isolates. Fungal infections were only occasionally observed. Bloodstream infections in APL patients were compared with those documented in 271 consecutive patients affected by other subtypes of AML. The incidence of total septicaemia episodes, of staphylococcal bacteraemias and of fungaemias was significantly higher in patients with other AMLs. Empirical antibiotic therapy with ceftriaxone plus amikacin was effective in 73% of APL cases, most of the remaining cases being successfully managed by the addition of teicoplanin. One single death apparently related to infectious complication was recorded. Overall, infections led to antileukaemic treatment withdrawal in six patients, five of whom currently remain in haematologic remission for 13-106 months. These results indicate that a particular pattern of infections is observed in APL patients receiving ATRA plus anthracycline-based chemotherapy and that these appear to be effectively counteracted by standard management.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12750707&dopt=Abstract

Rev Esp Quimioter. 2003 Mar;16(1):58-60.
[Susceptibility of Streptococcus pyogenes isolates from pharyngeal exudates in Cordoba (Spain)]

[Article in Spanish]

Gordillo RM, Lacasa MJ, Ibarra A, Rodriguez F, Casal M.

Servicio de Microbiologia y Parasitologia, Hospital Universitario Reina Sofia, Cordoba, Espana. mi1caroco.es

Streptococcus pyogenes is an important human pathogen. Betalactams are still the drug of choice for the treatment of infections caused by this microorganism. In recent years an increase in the use of macrolides for initial treatment in respiratory infections has been observed; consequently, the number of macrolide-resistant isolates has also increased. We investigated the susceptibility of S. pyogenes to penicillin, erythromycin, clarithromycin and clindamycin in Cordoba during 2000, 2001 and the first 6 months of 2002. We obtained 100 isolates of S. pyogenes from 1232 pharyngeal exudates, all of which were susceptible to penicillin and 39 of which were resistant to erythromycin and clarithromycin. Twenty-six of these 39 isolates were susceptible to clindamycin.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12750758&dopt=Abstract

Drugs Today (Barc). 2001 Jul;37(7):477-484.
The role of chemokines and adhesion molecules in the pathogenesis of rheumatoid arthritis.

Tanaka Y.

The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. tanaked.uoeh-u.ac.jp

Rheumatoid arthritis (RA) is characterized by marked infiltration of the synovium by T-cells. The mediator of joint inflammation has been shown to be both cellular and soluble and the concept of cross-talk between adhesion molecules and cytokines, and its relevance to inflammation, is emerging. The expression and function of adhesion molecules are tightly regulated via intracellular signaling induced by cytokine or chemokine stimulation, a process which is designated "inside-to-out signaling". Such regulation is particularly important in inflammatory processes in which T-cells migrate from the circulation into the tissue. Adhesion molecules not only function as glue, but also transduce extracellular information into cytoplasmic organelles via the "outside-to-in signal", resulting in cell activation and cytokine production. For instance, the abundant intracellular adhesion molecule ICAM-1 and CD44 on RA synoviocytes not only potentially facilitate the interaction with T-cells or extracellular matrix, but also induce cytokine gene transcription in synovial cells. Thus, the two-directional cross-talk among adhesion molecules and cytokines appears to be significant for the initiation and prolongation of inflammatory processes through T-cell migration into RA synovial tissues and activation of both T-cells and synovial cells in this region. The concept proposed would greatly help in clarifying the pathological processes in rheumatoid synovitis, as well as in discovering new pharmacological approaches to more specifically control synovial inflammation. (c) 2001 Prous Science. All rights reserved.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12750765&dopt=Abstract [PubMed - as supplied by publisher]

Theor Appl Genet. 2003 May;106(8):1438-46. Epub 2003 Feb 19.
Identification of non-TIR-NBS-LRR markers linked to the Pl5/ Pl8 locus for resistance to downy mildew in sunflower.

Radwan O, Bouzidi MF, Vear F, Philippon J, De Labrouhe DT, Nicolas P, Mouzeyar S.

UMR 1095 INRA-UBP "Amelioration et Sante des Plantes", Universite Blaise Pascal, 24, Avenue des Landais 63177 Aubiere Cedex, France.

The resistance of sunflower, Helianthus annuus L., to downy mildew, caused by Plasmopara halstedii, is conferred by major genes denoted by Pl. Using degenerate and specific primers, 16 different resistance gene analogs (RGAs) have been cloned and sequenced. Sequence comparison and Southern-blot analysis distinguished six classes of RGA. Two of these classes correspond to TIR-NBS-LRR sequences while the remaining four classes correspond to the non-TIR-NBS-LRR type of resistance genes. The genetic mapping of these RGAs on two segregating F2 populations showed that the non-TIR-NBS-LRR RGAs are clustered and linked to the Pl5/ Pl8 locus for resistance to downy mildew in sunflower. These and other results indicate that different Pl loci conferring resistance to the same pathogen races may contain different sequences.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12750787&dopt=Abstract [PubMed - in process]

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