Erythromycin-resistant group a streptococcal isolates collected between 2000 and 2005 in Oahu, Hawaii, and their emm types

We examined erythromycin and clindamycin susceptibilities with Etest methodology among 546 group A streptococcal isolates collected in Hawaii between February 2000 and November 2004. Erythromycin resistance was low (3.1%). No isolate was clindamycin resistant. The prevalence of erythromycin resistance in group A streptococci remains low in Hawaii.     

Treatment with granulocyte colony-stimulating factor prevents diabetes in NOD mice by recruiting plasmacytoid dendritic cells and functional CD4(+)CD25(+) regulatory T-cells

Accumulating evidence that granulocyte colony-stimulating factor (G-CSF), the key hematopoietic growth factor of the myeloid lineage, not only represents a major component of the endogenous response to infections, but also affects adaptive immune responses, prompted us to investigate the therapeutic potential of G-CSF in autoimmune type 1 diabetes. Treatment with G-CSF protected NOD mice from developing spontaneous diabetes. G-CSF triggered marked recruitment of dendritic cells (DCs), particularly immature CD11c(lo)B220(+) plasmacytoid DCs, with reduced costimulatory signal expression and higher interferon-alpha but lower interleukin-12p70 release capacity than DCs in excipient-treated mice. G-CSF recipients further displayed accumulation of functional CD4(+)CD25(+) regulatory T-cells that produce transforming growth factor-beta1 (TGF-beta1) and actively suppressed diabetes transfer by diabetogenic effector cells in secondary NOD-SCID recipients. G-CSF's ability to promote key tolerogenic interactions between DCs and regulatory T-cells was demonstrated by enhanced recruitment of TGF-beta1-expressing CD4(+)CD25(+) cells after adoptive transfer of DCs isolated from G-CSF- relative to vehicle-treated mice into naive NOD recipients. The present results suggest that G-CSF, a promoter of tolerogenic DCs, may be evaluated for the treatment of human type 1 diabetes, possibly in association with direct inhibitors of T-cell activation. They also provide a rationale for a protective role of the endogenous G-CSF produced during infections in early diabetes.     

Functionalized pyrrolidines inhibit alpha-mannosidase activity and growth of human glioblastoma and melanoma cells

New substituted pyrrolidine-3,4-diol derivatives were prepared from d-(-)- and l-(+)-phenyl glycinol. The influence of the configuration and the substitution of the lateral side chain of these derivatives on the inhibition of 25 commercial glycosidases were determined. (2R,3R,4S)-2-({[(1R)-2-Hydroxy-1-phenylethyl]amino}methyl)pyrrolidine-3,4-diol ((+)-7a) was a potent and selective inhibitor of jack bean alpha-mannosidase (K(i) = 135 nM). However, when evaluated on human tumor cells, 7a, and the reference compound swainsonine, did not efficiently inhibit the growth of glioblastoma cells. Further derivatization of the hydroxyl group with lipophilic groups to increase bioavailability improved their growth inhibitory properties for human glioblastoma and melanoma cells. In particular, the 4-bromobenzoyl derivative 26 demonstrated high efficacy for human tumor cells whereas primary human fibroblasts were less sensitive to 26. Therefore, functionalized pyrrolidines have the potential to inhibit the growth of tumor cells and display selectivity for tumor cells when compared to normal cells.     

Characterization of a community cluster of group a streptococcal invasive disease in Maui, Hawaii

A community cluster of severe group A streptococcal skin infections occurred in Maui, Hawaii with 3 fatal cases of necrotizing fasciitis in 2002. emm types 1, 12, 58, 74, 85 and 109 were identified from 8 patients. emm types 74 and 109 have not been previously described in the United States according to the Centers for Disease Control and Prevention database. The identification of uncommon emm types suggested that group A streptococcal sero-types in Hawaii are different from those in the continental United States and can result in serious disease.     

Importance de la mesure radioimmunologique de l'insuline dans l'étude de la pathogénèse du diabète

Resume Le développement d'une méthode radioimmunologique de détermination de l'insuline a permis de revoir toute la pathogénèse du diabète. Cette méthode apporte également des renseignements précieux sur l'évolution et le traitement des cas de diabète.

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Summary The setting-up of a radio-immunologic method for insulin assay enables us to put under discussion all the diabetes pathogenesis. This method supplies precious news about the course and the treatment of diabetes.

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Zusammenfassung Die Ueberarbeitung einer radioimmunologischen Methode fuer die Bestimmung des Insulins erlaubte die neue Durchsicht der gesamten Pathogenese des Diabetes. Diese Methode liefert ferner wertvolle Hinweise betr. die Entwicklung und Behandlung der Diabetesfaelle.

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Resumen El perfeccionamiento de un método radioinmunológico para la determinación de la insulina ha permitido reexaminar toda la patogénesis de la diabetes. Este método proporciona, además, valiosos datos sobre la evolución y el tratamiento de los casos de diabetes.

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Riassunto La messa a punto di un metodo radioimmunologico per la determinazione dell'insulina ha permesso di rivedere tutta la patogenesi del diabete. Questa metodica inoltre fornisce dei preziosi ragguagli sull'evoluzione ed il trattamento dei casi di diabete.

     

Detection and localization of 14-3-2 protein in primary cultures of embryonic rat brain

The development of embryonic rat brain in cell cultures was studied by an immunocytochemical method based on the detection of 14-3-2 protein (neuron-specific enolase or NSE), a neuron-specific protein. This protein was already present in undifferentiated neurons (less than 5 days in culture), being dispersed throughout the cytoplasm, though seemingly concentrated in the vicinity of polyribosomal structures. It was not found in nuclei, in mitochondria or in the Golgi apparatus. During neuron differentiation, the location of 14-3-2 protein was related to neurite development insofar as it was detected along the axon and even in what could be taken to be the presynaptic region of numerous interneuron contacts. In contact areas, a thickening of the junction membrane was observed but the presence of 14-3-2 protein was always unilateral demonstrating the absence of a true synapse and reflecting the halt in neurite development observed after 15 days in culture. The presence of 14-3-2 protein in the cell cultures was confirmed by a microcomplement fixation assay. The protein detected in cell cultures had the same immunological properties as that found in the 17-day-old embryo, but was slightly different from that found in adult rat brain. This observation can be confronted with the lack of neuron maturation in the immunocytochemical studies.     

Patterns of genomic aberrations suggest that Burkitt lymphomas with complex karyotype are distinct from other aggressive B‐cell lymphomas with MYC rearrangement

We previously showed that complex karyotypes (CK) and chromosome 13q abnormalities have an adverse prognostic impact in childhood Burkitt lymphomas/leukemias (BL) and diffuse large B‐cell lymphomas (DLBCL). The aim of our study was to identify recurrent alterations associated with MYC rearrangements in aggressive B‐cell lymphomas with CK. Multicolor fluorescence in situ hybridization (M‐FISH) was performed in 84 patient samples (59 adults and 25 children), including 37 BL (13 lymphomas and 24 acute leukemias), 12 DLBCL, 28 B‐cell lymphomas with intermediate features (DLBCL/BL), 4 B‐cell precursor acute lymphoblastic leukemias (BCP‐ALL), and 3 unclassifiable B‐cell lymphomas. New (cytogenetically undetected) abnormalities were identified in 80% of patients. We also refined one‐third of the chromosomal aberrations detected by karyotyping. M‐FISH proved to be more useful in identifying chromosomal partners involved in unbalanced translocations and in revealing greater complexity of 13q rearrangements. Most of the newly identified or refined recurrent alterations involved 1q, 13q and 3q (gains/losses), 7q and 18q (gains), or 6q (losses), suggesting that these secondary aberrations may play a role in lymphomagenesis. Several patterns of genomic aberrations were identified: 1q gains in BL, trisomies 7 in DLBCL, and 18q‐translocations in adult non‐BL. BCP‐ALL usually displayed an 18q21 rearrangement. BL karyotypes were less complex and aneuploid than those of other MYC‐rearranged lymphomas. BCP‐ALL and DLBCL/BL were associated with a higher rate of early death than BL and DLBCL. These findings support the categorization of DLBCL/BL as a distinct entity and suggest that BL with CK are indeed different from other aggressive MYC‐rearranged lymphomas, which usually show greater genetic complexity. © 2012 Wiley Periodicals, Inc.     

A systematic review on the outcome of mandibular distraction osteogenesis in infants suffering Robin sequence

Objectives

Mandibular distraction osteogenesis (MDO) has been successfully applied in infants suffering Robin sequence (RS) with severe upper airway obstruction, but no comparative studies for the different types of MDO exist to date. The objective of the current study was to systematically review the published data considering this matter, providing a fundament for protocols and a more conscious treatment strategy for infants with RS in the near future.

Material and methods

For the period from January 1966 to January 2012, the Pubmed, EMBASE, and Cochrane Library databases were searched. Abstracts were screened based on predetermined selection criteria. Relevant full-text articles were retrieved. The articles were analyzed on the type of MDO used, preoperative workup, patient characteristics, postoperative outcome, and complications.

Results

The search yielded 109 articles. After checking abstracts and full texts on predetermined inclusion and exclusion criteria, 12 studies (four describing external MDO, five internal MDO, and three both types) were extracted for further analyses.

Conclusion

Internal MDO seems very feasible in infants suffering RS, minimizing side effects such as hypertrophic scarring, nerve damage, and extensive care needs, although the indications for usage are more limited compared to the external device. Corresponding protocols and long-term outcome studies are needed to make a better comparison and the use and indication of the different types of distraction even more distinct.

Clinical relevance

A base for a guideline to support the choice of a designated operative management for neonates with RS is provided, hereby obviating possible complications of the different types of MDO in the future.