Cerebrospinal Fluid Rhinorrhea and Seizure Caused by Temporo-Sphenoidal Encephalocele

This case report describes the symptoms and clinical course of a 35-year-old female patient who was diagnosed with a temporo-sphenoidal encephalocele. It is characterized by herniation of cerebral tissue of the temporal lobe through a defect of the skull base localized in the middle fossa. At the time of first presentation the patient complained about recurrent nasal discharge of clear fluid which had begun some weeks earlier. She also reported that three months earlier she had for the first time suffered from a generalized seizure. In a first therapeutic attempt an endoscopic endonasal approach to the sphenoid sinus was performed. An attempt to randomly seal the suspicious area failed. After frontotemporal craniotomy, it was possible to localize the encephalocele and the underlying bone defect. The herniated brain tissue was resected and the dural defect was closed with fascia of the temporalis muscle. In summary, the combination of recurrent rhinorrhea and a first-time seizure should alert specialists of otolaryngology, neurology and neurosurgery of a temporo-sphenoidal encephalocele as a possible cause. Treatment is likely to require a neurosurgical approach.     

Mesenteric B cells centrally inhibit CD4+ T cell colitis through interaction with regulatory T cell subsets

Inflammatory bowel disease reflects an aberrant mucosal CD4+ T cell response to commensal enteric bacteria. In addition to regulatory T cell subsets, recent studies have revealed a protective role of B cells in murine CD4+ T cell colitis, but the relationship of their action to T cell immunoregulation is unknown. Here we report that mesenteric lymph node (MLN) B cells protect mice from colitis induced by Galphai2-/- CD4+ T cells. Protection required the transfer of both B cells and CD8alpha+ T cells; neither cell type alone was sufficient to inhibit CD4+ T cell-mediated colitis. Similar results were also observed in colitis induced by CD4+CD45RBhi T cells. Immunoregulation was associated with localization of B cells and expansion of CD4-CD8- CD3+NK1.1+ T cells in the secondary lymphoid compartment, as well as expansion of CD4+CD8alpha+ T cells in the intestinal intraepithelial compartment. MLN B cells from Galphai2-/- mice were deficient in a phenotypic subset and failed to provide cotransfer colitis protection. These findings indicate that protective action of B cells is a selective trait of MLN B cells acquired through a Galphai2-dependent developmental process and link B cells with the formation of regulatory T cells associated with mucosal immune homeostasis.     

Hydroxyl radical-induced acute diastolic dysfunction is due to calcium overload via reverse-mode Na(+)-Ca(2+) exchange

Hydroxyl radicals (OH) are involved in the development of reperfusion injury and myocardial failure. In the acute phase of the OH-mediated diastolic dysfunction, increased intracellular Ca(2+) levels and alterations of myofilaments may play a role, but the relative contribution of these systems to myocardial dysfunction is unknown. Intact contracting cardiac trabeculae from rabbits were exposed to OH, resulting in an increase in diastolic force (F(dia)) by 540%. Skinned fiber experiments revealed that OH-exposed preparations were sensitized for Ca(2+) (EC(50): 3.27+/-0.24 x 10(-6) versus 2.69+/-0.15 x 10(-6) mol/L; P<0.05), whereas maximal force development was unaltered. Western blots showed a proteolytic degradation of troponin T (TnT) with intact troponin I (TnI). Blocking of calpain I by MDL-28.170 inhibited both TnT-proteolysis and Ca(2+) sensitization, but failed to prevent the acute diastolic dysfunction in the intact preparation. The OH-induced diastolic dysfunction was similar in preparations with intact (540+/-93%) and pharmacologically blocked sarcoplasmic reticulum (539+/-77%), and was also similar in presence of the L-type Ca(2+)-channel antagonist verapamil. In sharp contrast, inhibition of the reverse-mode sodium-calcium exchange by KB-R7943 preserved diastolic function completely. Additional experiments were performed in rat myocardium; the rise in diastolic force was comparable to rabbit myocardium, but Ca(2+) sensitivity was unchanged and maximal force development was reduced. This was associated with a degradation of TnI, but not TnT. Electron microscopic analysis revealed that OH did not cause irreversible membrane damage. We conclude that OH-induced acute diastolic dysfunction is caused by Ca(2+) influx via reverse mode of the sodium-calcium exchanger. Degradation of troponins appears to be species-dependent but does not contribute to the acute diastolic dysfunction.     

Fluorochrome‐based definition of naturally occurring Foxp3+ regulatory T cells of intra‐ and extrathymic origin

Under physiological conditions, studies on the biology of naturally induced Foxp3⁺ Treg cells of intra‐ and extrathymic origin have been hampered by the lack of unambiguous markers to discriminate the mature progeny of such developmental Treg‐cell sublineages. Here, we report on experiments in double‐transgenic mice, in which red fluorescent protein (RFP) is expressed in all Foxp3⁺ Treg cells, whereas Foxp3‐dependent GFP expression is exclusively confined to intrathymically induced Foxp3⁺ Treg cells. This novel molecular genetic tool enabled us to faithfully track and characterize naturally induced Treg cells of intrathymic (RFP⁺GFP⁺) and extrathymic (RFP⁺GFP^?) origin in otherwise unmanipulated mice. These experiments directly demonstrate that extrathymically induced Treg cells substantially contribute to the overall pool of mature Foxp3⁺ Treg cells residing in peripheral lymphoid tissues of steady‐state mice. Furthermore, we provide evidence that intra‐ and extrathymically induced Foxp3⁺ Treg cells represent distinct phenotypic and functional sublineages.     

Different neural capacity limitations for articulatory and non-articulatory maintenance of verbal information

Many studies have demonstrated attenuated verbal working memory (WM) under articulatory suppression. However, performance is not completely abolished, suggesting a less efficient, non-articulatory mechanism for the maintenance of verbal information. The neural causes for the reduced efficiency of such a putative complementary maintenance system have not yet been addressed. The present study was conducted to fill this gap. Subjects performed a Sternberg task (a) under articulatory maintenance at low, high, and supracapacity set sizes and (b) under non-articulatory maintenance at low and high set sizes. With functional magnetic resonance imaging, set-size related increases in activity were compared between subvocal articulatory rehearsal and non-articulatory maintenance. First, the results replicate previous findings showing different networks underlying these two maintenance strategies. Second, activation of all key nodes of the articulatory maintenance network increased with the amount of memorized information, showing no plateau at high set sizes. In contrast, for non-articulatory maintenance, there was evidence for a plateau at high set sizes in all relevant areas of the network. Third, for articulatory maintenance, the non-articulatory maintenance network was additionally recruited at supracapacity set sizes, presumably to assist processing in this highly demanding condition. This is the first demonstration of differential neural bottlenecks for articulatory and non-articulatory maintenance. This study adds to our understanding of the performance differences between these two strategies supporting verbal WM.     

Variation and association to diabetes in 2000 full mtDNA sequences mined from an exome study in a Danish population

In this paper, we mine full mtDNA sequences from an exome capture data set of 2000 Danes, showing that it is possible to get high-quality full-genome sequences of the mitochondrion from this resource. The sample includes 1000 individuals with type 2 diabetes and 1000 controls. We characterise the variation found in the mtDNA sequence in Danes and relate the variation to diabetes risk as well as to several blood phenotypes of the controls but find no significant associations. We report 2025 polymorphisms, of which 393 have not been reported previously. These 393 mutations are both very rare and estimated to be caused by very recent mutations but individuals with type 2 diabetes do not possess more of these variants. Population genetics analysis using Bayesian skyline plot shows a recent history of rapid population growth in the Danish population in accordance with the fact that >40% of variable sites are observed as singletons.     

Identification and functional characterization of imatinib‐sensitive DTD1‐PDGFRB and CCDC88C‐PDGFRB fusion genes in eosinophilia‐associated myeloid/lymphoid neoplasms

Eosinophilia‐associated myeloid neoplasms with rearrangement of chromosome bands 5q31‐33 are frequently associated with PDGFRB fusion genes, which are exquisitely sensitive to treatment with imatinib. In search for novel fusion partners of PDGFRB, we analyzed three cases with translocation t(5;20)(q33;p11), t(5;14)(q33;q32), and t(5;17;14)(q33;q11;q32) by 5′‐rapid amplification of cDNA ends polymerase chain reaction (5′‐RACE‐PCR) and DNA‐based long‐distance inverse PCR (LDI‐PCR) with primers derived from PDGFRB. LDI‐PCR revealed a fusion between CCDC88C exon 25 and PDGFRB exon 11 in the case with t(5;17;14)(q33;q11;q32) while 5′‐RACE‐PCR identified fusions between CCDC88C exon 10 and PDGFRB exon 12 and between DTD1 exon 4 and PDGFRB exon 12 in the cases with t(5;14)(q33;q32) and t(5;20)(q33;p11), respectively. The PDGFRB tyrosine‐kinase domain is predicted to be retained in all three fusion proteins. The partner proteins contained coiled‐coil domains or other domains, which putatively lead to constitutive activation of the PDGFRB fusion protein. In vitro functional analyses confirmed transforming activity and imatinib‐sensitivity of the fusion proteins. All three patients achieved rapid and durable complete hematologic remissions on imatinib. © 2014 Wiley Periodicals, Inc.