Neuropsychiatric Presentation in Indirect Carotid-Cavernous Fistula: A Case Report.

Carotid-cavernous fistula (CCF) is a rare sight and potentially life-threatening disorder arising from an abnormal connection between the carotid artery and the cavernous sinus. It can be classified into direct or indirect according to different arteriovenous shunts. Direct CCF usually has dramatic ocular presentations, whereas indirect CCF has a more insidious course and may be associated with neurologic symptoms in posteriorly draining fistulas. A 61-year-old gentleman presented with five days history of altered behavior and double vision preceding a bulging left eye. Ocular examination showed left eye proptosis, generalized chemosis, total ophthalmoplegia, and raised intra-ocular pressure. Computed tomography angiography (CTA) brain and orbit demonstrated dilated superior ophthalmic vein (SOV) with communication to a tortuous cavernous sinus suggestive of carotid-cavernous fistula (CCF). Digital subtraction angiography (DSA) eventually confirmed the presence of indirect communication between branches of the bilateral external carotid artery (ECA) and left cavernous sinus, which is a type C indirect CCF according to the Barrow classification. Total embolization of left CCF was successfully achieved via transvenous access. A marked reduction of proptosis and intra-ocular pressure was noted following the procedure. Although rare, neuropsychiatric presentation could be a possible presentation of CCF, and treating physicians should be aware of it. A high index of suspicion and prompt diagnosis is crucial in managing this sight and life-threatening condition. Early intervention can improve the prognosis of patients.

A subpopulation of high IL-21-producing CD4(+) T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers.

The production of IL-21 by T follicular helper (Tfh) cells is vital in driving the germinal centre reaction and high affinity antibody formation. However, the degree of Tfh cell heterogeneity and function is not fully understood. We used a novel IL-21eGFP reporter mouse strain to analyze the diversity and role of Tfh cells. Through the analysis of GFP expression in lymphoid organs of IL-21eGFP mice, we identified a subpopulation of GFP(+), high IL-21 producing Tfh cells present only in Peyer's Patches. GFP(+)Tfh cells were found to be polyclonal and related to GFP(-)Tfh cells of Peyer's Patches in TCR repertoire composition and overall gene expression. Studies on the mechanisms of induction of GFP(+)Tfh cells demonstrated that they required the intestinal microbiota and a diverse repertoire of CD4(+) T cells and B cells. Importantly, ablation of GFP(+) cells resulted in a reduced frequency of Peyer's Patches IgG1 and germinal center B cells in addition to small but significant shifts in gut microbiome composition. Our work highlights the diversity among IL-21 producing CD4(+) Tfh cells, and the interrelationship between the intestinal bacteria and Tfh cell responses in the gut.

Regulation of Tcf7 by Runx2 in chondrocyte maturation and proliferation.

Runx2 plays important roles in the regulation of chondrocyte differentiation and proliferation; however, the Runx2 target molecules still remain to be investigated. We searched the genes upregulated by the introduction of Runx2 into Runx2(-/-) chondrocytes using microarray and found that Tcf7 is upregulated by Runx2. Thus, we examined the functions of Runx2 in the regulation of the Tcf/Lef family of transcription factors. Runx2 induced Tcf7 and Lef1 strongly, but Tcf7l1 and Tcf7l2 only slightly in Runx2(-/-) chondrocytes; the expressions of Tcf7 and Tcf7l2 were reduced in Runx2(-/-) cartilaginous skeletons and calvaria, and Tcf7 showed a similar expression pattern to Runx2. In reporter assays, Runx2 mildly activated the 8.6 and 1.8 kb Tcf7 promoter constructs. The reporter assays using the deletion constructs of the 1.8-kb fragment showed that the 0.3-kb promoter region is responsible for the Runx2-dependent transcriptional activation. To investigate the function of Tcf7 in skeletal development, we generated dominant-negative (dn) Tcf7 transgenic mice using the Col2a1 promoter. Dn-Tcf7 transgenic embryos showed dwarfism, and mineralization was retarded in limbs, ribs, and vertebrae in a manner dependent on the expression levels of the transgene. In situ hybridization analysis showed that endochondral ossification is retarded in dn-Tcf7 transgenic embryos due to the decelerated chondrocyte maturation. Further, BrdU labeling showed a reduction in chondrocyte proliferation in the proliferating layer of the growth plate in dn-Tcf7 transgenic embryos. These findings indicate that Runx2 regulates chondrocyte maturation and proliferation at least partly through the induction of Tcf7.