27-Hydroxycholesterol induces macrophage gene expression via LXR-dependent and -independent mechanisms

27-Hydroxycholesterol (27OHChol) exhibits agonistic activity for liver X receptors (LXRs). To determine roles of the LXR agonistic activity in macrophage gene expression, we investigated the effects of LXR inhibition on the 27OHChol-induced genes. Treatment of human THP-1 cells with GSK 2033, a potent cell-active LXR antagonist, results in complete inhibition in the transcription of LXR target genes (such as LXRα and ABCA1) induced by 27OHChol or a synthetic LXR ligand TO 901317. Whereas expression of CCL2 and CCL4 remains unaffected by GSK 2033, TNF-α expression is further induced and 27OHChol-induced CCL3 and CXCL8 genes are suppressed at both the transcriptional and protein translation levels in the presence of GSK 2033. This LXR antagonist downregulates transcript levels and surface expression of CD163 and CD206 and suppresses the transcription of CD14, CD80, and CD86 genes without downregulating their surface levels. GSK 2033 alone had no effect on the basal expression levels of the aforementioned genes. Collectively, these results indicate that LXR inhibition leads to differential regulation of 27-hydroxycholesterolinduced genes in macrophages. We propose that 27OHChol induces gene expression and modulates macrophage functions via LXR-dependent and -independent mechanisms.

27-Hydroxycholesterol induces macrophage gene expression via LXR-dependent and -independent mechanisms

27-Hydroxycholesterol (27OHChol) exhibits agonistic activity for liver X receptors (LXRs). To determine roles of the LXR agonistic activity in macrophage gene expression, we investigated the effects of LXR inhibition on the 27OHChol-induced genes. Treatment of human THP-1 cells with GSK 2033, a potent cell-active LXR antagonist, results in complete inhibition in the transcription of LXR target genes (such as LXRα and ABCA1) induced by 27OHChol or a synthetic LXR ligand TO 901317. Whereas expression of CCL2 and CCL4 remains unaffected by GSK 2033, TNF-α expression is further induced and 27OHChol-induced CCL3 and CXCL8 genes are suppressed at both the transcriptional and protein translation levels in the presence of GSK 2033. This LXR antagonist downregulates transcript levels and surface expression of CD163 and CD206 and suppresses the transcription of CD14, CD80, and CD86 genes without downregulating their surface levels. GSK 2033 alone had no effect on the basal expression levels of the aforementioned genes. Collectively, these results indicate that LXR inhibition leads to differential regulation of 27-hydroxycholesterolinduced genes in macrophages. We propose that 27OHChol induces gene expression and modulates macrophage functions via LXR-dependent and -independent mechanisms.

Giant Sellar Xanthogranuloma after Surgical Treatment of Symptomatic Rathke's Cleft Cyst

Extremely massive sellar xanthogranuloma (XG) are rare, and the surgical outcome and prognosis are not well known. XG remain unknown whether they are derived from Rathke's cleft cysts (RCCs) or craniopharyngiomas (CPs) following extensive inflammation and metaplasia, to the point that no epithelium is readily identifiable. These lesions usually tend to occur in younger patients (mean 28.3 years), have a smaller diameter, and remain primarily intrasellar region with infrequent calcification. This 36-year-old man presented our hospital with visual deterioration. At the time of visit, there were no neurological problems other than visual field defect and hormonal disorder. He visited our hospital in 2007 due to headache and decreased vision, and underwent transphenoid surgery for pituitary RCC. Since then, he has received treatment at our hospital for postoperative hormonal disorders. Through preoperative imaging study, the author suspected CP and underwent surgery. During the operation, the adhesion of the tumor to the surrounding major neurovascular structures was severe in the naked eyes, but the tumor could be removed more easily than expected. The postoperative histological findings were confirmed as XG. The postoperative course was uneventful. Compared to the previous literature, this case is a case where the size of XG is very large in a sellar region and it can be proved that it originated from the RCC. And regular follow-up is necessary to confirm the prognosis after surgery.

PI3K and ERK signaling pathways are involved in differentiation of monocytic cells induced by 27-hydroxycholesterol

27-Hydroxycholesterol induces differentiation of monocytic cells into mature dendritic cells, mDCs. In the current study we sought to determine roles of the PI3K and the ERK pathways in the 27OHChol-induced differentiation. Up-regulation of mDC-specific markers like CD80, CD83 and CD88 induced by stimulation with 27OHChol was significantly reduced in the presence of LY294002, an inhibitor of PI3K, and U0126, an inhibitor of ERK. Surface expression of MHC class I and II molecules elevated by 27OHChol was decreased to basal levels in the presence of the inhibitors. Treatment with LY294002 or U0126 resulted in recovery of endocytic activity which was reduced by 27OHChol. CD197 expression and cell adherence enhanced by 27OHChol were attenuated in the presence of the inhibitors. Transcription and surface expression of CD molecules involved in atherosclerosis such as CD105, CD137 and CD166 were also significantly decreased by treatment with LY294002 and U0126. These results mean that the PI3K and the ERK signaling pathways are necessary for differentiation of monocytic cells into mDCs and involved in over-expression of atherosclerosis-associated molecules in response to 27OHChol.

The Pterional-Transsylvian Approach for Tumor in the Temporal Horn: A Case Report

A variety of surgical approaches to temporal horn tumors of the lateral ventricle have been described. Magnetic resonance imaging (MRI) and angiography are the preferred modalities for preoperative evaluation and provide important information for the choice of surgical approach. A 59-year-old man was referred to our hospital due to confusion and gait disturbance. On enhanced MRI, a homogeneous enhanced solitary mass was observed within the temporal horn of the left lateral ventricle with transependymal extension. The lesion was accompanied by increased hypervascular tumor blush on preoperative cerebral angiography. Subtotal removal of the temporal horn tumor was performed because the lesion was identified as lymphoma during surgery. The postoperative course was un-eventful. The patient was referred to the oncology department for conventional chemotherapy. Adjuvant chemotherapy improved the clinical outcome. The pterional-transsylvian approach was beneficial for partial removal of the tumor and tissue diagnosis in this case.

An Unusual Cervical Spinal Meningioma in a Child

The incidence of spinal meningioma is very rare in children. A 14-year-old girl presented with right arm weakness, gait disturbance, and urinary incontinence. Cervical magnetic resonance imaging revealed an intradural extramedullary tumor dorsal to the spinal cord in the level of C1. The tumor was totally removed despite the severe cord compression. Meningotheliomatous meningioma was diagnosed after histological examination.

An Organized Chronic Subdural Hematoma with Partial Calcification in a Child

The authors present a case in which an organized chronic subdural hematoma(CSDH) was incidentally found in a 9-year-old boy with no significant medical history after a pedestrian traffic accident. Preoperative magnetic resonance(MR) imaging showed calcification on the inner membrane and an irregular heterogeneous structure in the hematoma cavity. The findings from the preoperative brain computed tomogram(CT) and MR image were very useful for making the preoperative diagnosis and surgical decision. In choosing the proper surgical strategy for removing the organized CSDH, it was thought that burr hole trephination would present unnecessary difficulties. Thus, craniotomy was selected and the organized CSDH was successfully removed with no complications.

Nontraumatic Spontaneous Cervical Epidural Hematoma

Nontraumatic spontaneous spinal epidural hematoma is a rare entity, which can be associated with a severe neurologic deficit. The presenting symptoms are usually back or neck pain, either local or radicular, followed by progressive bilateral weakness, and sensory loss hours and even days later. In the absence of precipitating factors such as severe trauma or known coagulopathy, the diagnosis may be delayed. Imaging, including cervical CT or MRI, may play an essential role for the prompt diagnosis and differentiation from other cervical pathologies. With a full review of the literature, we report and discuss a case of nontraumatic cervical epidural hematoma in which a 67-year-old female visited the emergency center for neck and right shoulder pain. She experienced a complete recovery after conservative treatment only.