Mixed chimerism after bone marrow transplantation for thalassemia major

Thirty-four thalassemia patients were studied for chimerism by fluorescent in situ hybridization or variable number tandem repeats after bone marrow transplantation. Mixed chimerism was detected in 9 patients with host cells ranging from 4 to 56%. One had graft rejection and the others were transfusion independent. Mixed chimerism was common but mostly without deleterious effect.     

Genetic imbalances in benign bone tumors revealed by comparative genomic hybridization

There have been no reports on choromosomal aberrations of benign bone tumors revealed by comparative genomic hybridization (CGH). CGH analysis of benign tumors may be useful in understanding the mechanism of tumorigenesis with comparisons to malignant tumors. There were 4 tumors (2 enchondromas, one chondromyxoid fibroma, and one osteoid osteoma) and 8 tumor-like conditions (4 aneurysmal bone cysts (ABCs), one eosinophilic granuloma, one fibrous dysplasia, one solitary bone cyst, and one Rosai-Dorfman disease) available for analysis. One of 2 enchondromas and one of 4 ABCs exhibited rapid growth. Six lesions showed chromosomal aberrations, while 6 others did not. The most frequent aberrations were the loss of a whole chromosome-19 in 6 cases, the loss of chromosome-arm 22q in 4 cases, and the loss of chromosome-arm 17p in 3 cases. Gains were seen in 13q21 in 2 cartilaginous tumors and at 12q15-q21 in eosinophilic granulomas. Therefore, in benign bone tumors or tumor-like lesions, chromosomal aberrations are not frequent; however, some clear tendencies of clustering of aberrations can be observed.     

Recurrent deep neck abscess and piriform sinus tract: A 15-year review on the diagnosis and management

Background

Piriform sinus tract (PST) is a rare congenital condition. A delay in diagnosis is common leading to recurrent inflammation.

Method

A retrospective review was performed on all cases of PST treated at a tertiary referral centre between May 1997 and May 2012.

Results

Eighteen patients were reviewed with a mean age of 5.4 years at presentation (ranged from 0 day to 14 years). Most patients presented as acute inflammation (88.9%) and 16 had a left sided lesion. 72.2% of the PST are identified by contrast swallow study. The diagnostic yield was significantly higher if the study was done after the initial acute inflammation settled. Ultrasonography and computer tomography are less sensitive. The median duration from presentation to diagnosis was 17.6 months (ranged 0–120 months). Ten patients (55.6%) experienced recurrent inflammation before confirming the diagnosis. Fistulectomy alone was performed in 15 patients while an additional en-bloc hemithyroidectomy was done in 2 patients.

Conclusion

PST should be suspected in children presenting with a left deep neck abscess. Contrast swallow study is very effective in making diagnosis but has to be postponed after the acute inflammation settles. The condition can be effectively treated by fistulectomy without hemithyroidectomy in majority of our cases.     

PIKE is essential for oligodendroglia development and CNS myelination

Oligodendrocyte (OL) differentiation and myelin development are complex events regulated by numerous signal transduction factors. Here, we report that phosphoinositide-3 kinase enhancer L (PIKE-L) is required for OL development and myelination. PIKE-L expression is up-regulated when oligodendrocyte progenitor cells commit to differentiation. Conversely, depleting phosphoinositide-3 kinase enhancer (PIKE) expression by shRNA prevents oligodendrocyte progenitor cell differentiation. In both conventional PIKE knockout (PIKE^−/−) and OL-specific PIKE knockout mice, the number of OLs is reduced in the corpus callosum. PIKE^−/− OLs also display defects when forming myelin sheath on neuronal axons during neonatal development, which is partially rescued when PTEN is ablated. In addition, Akt/mTOR signaling is impaired in OL-enriched tissues of the PIKE^−/− mutant, leading to reduced expression of critical proteins for myelin development and hypomyelination. Moreover, myelin repair of lysolecithin-induced lesions is delayed in PIKE^−/− brain. Thus, PIKE plays pivotal roles to advance OL development and myelinogenesis through Akt/mTOR activation.Efficient propagation of action potentials depends on the presence of myelin sheath that spirals around the axon. As a membrane extension from oligodendrocytes (OLs), the myelin sheath has a unique lipid-rich composition that allows electrical insulation for high-speed conduction and fidelity of signal transfer (1). Generation of OLs is a developmentally regulated process, which involves the proliferation of oligodendrocyte progenitor cells (OPCs) at the germinal subventricular zones (SVZ), migration throughout the CNS, differentiation into mature OLs, and adhesion to the axon to form myelin (2). Although most OPCs first appear in early neonatal brain, maturation and myelination of OLs in rodents occur largely in postnatal life between P10 and P60 (1). The timing of s differentiation and myelin formation requires highly localized signaling mechanisms, which involves the coordinated activation/inactivation of Wnt/β-catenin, Hedgehog/Gli1, Jagged1/Notch, and PI3K/Akt/mTOR cascades (3). Disruption of these pathways via gene manipulation or modulation of their regulators results in defective OL development. For example, PI3K depletion causes reduced myelin expression in the cerebral cortex and striatum (4). On the other hand, mutation of PTEN, the negative regulator of PI3K/Akt cascade, causes thickening and unraveling of the myelin sheath surrounding hypertrophic axons in the corpus callosum (CC) (5).Phosphoinositide 3-kinase enhancer L (PIKE-L) is a CNS-specific GTPase that belongs to the centaurin family (6, 7). It participates in numerous cellular events to regulate neuronal activity and survival. Our previous studies show that PIKE-L interacts with both netrin receptor (UNC5H) and metabotropic glutamate receptor I (mGlu₁) to prevent apoptotic cell death (8, 9). In addition, PIKE-L controls cell-surface trafficking of 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid receptor and the formation of long-term potentiation in the postsynaptic neurons (10). Moreover, PIKE controls the neuronal dendritogenesis and survival through maintaining the integrity of the PI3K/Akt pathway (11). Indeed, PIKE is an important molecular switch to control the cellular PI3K/Akt activation as it links extracellular stimuli including netrin, glutamate, and neurotrophins to the intrinsic PI3K/Akt activities (12–14). Nevertheless, the functions of PIKE-L in nonneuronal cells such as OLs and astrocytes still remain unexplored. In this paper, we report that PIKE-L signals through the PI3K/Akt pathway to advance CNS myelinogenesis.     

Sealed primary molars are less likely to develop caries

BackgroundThe authors examined the association between light-polymerized resin-based fluoride-releasing sealants and the development of pit-and-fissure caries on primary molars.MethodsIn this 3-year retrospective study, the authors reviewed the dental records of 297 children (1,352 teeth) younger than 6 years who were at high caries risk. Sealant placement or nonplacement on primary molars in the outpatient clinic and operating room setting was recorded, and random-effects logistic regression analysis accounting for the effect of data clustering was performed to measure caries incidence over time.ResultsThe odds of developing pit-and-fissure carious lesions on sealed primary molars were 0.055 times (95% confidence interval [CI], 0.011 to 0.285; P = .001) and 0.013 times (95% CI, 0.001 to 0.159; P = .001) the odds of that on nonsealed primary molars in the outpatient clinic and in the operating room, respectively. In molars that became carious, those sealed were associated with longer time to caries development in both the outpatient clinic (2.69 years, 95% CI, 2.08 to 3.29) and operating room (1.97 years, 95% CI, 1.45 to 2.48).ConclusionsSealed primary molars were less likely to develop pit-and-fissure caries when placed in both the clinic and operating room settings.Practical ImplicationsDental sealants on primary molars should be considered for children at high caries risk.