A case of spontaneous direct vertebral artery - External vertebral venous plexus fistula in the upper cervical portion.

Background: Spontaneous direct vertebral artery-external vertebral venous plexus (VA-EVVP) fistula is a rare disease that presents in patients with neurofibromatosis type 1 (NF-1) or trauma. Case Description: An 82-year-old female patient with no neurological deficits or trauma presented to our hospital with right hemianopsia. Head magnetic resonance imaging (MRI) revealed left occipital cerebral infarction and magnetic resonance angiography demonstrated high signal intensity in the left transverse sinus (TS). The attending doctor diagnosed an old infarction on the left occipital lobe and dural arteriovenous fistula (AVF) in the TS. After 3 years after the first diagnosis, her new attending doctor re-checked the MRI and performed digital subtraction angiography (DSA). The DSA examination revealed a single-hole AVF between the vertebral artery and external vertebral plexus at the C2 level, which was diagnosed as upper cervical VA-EVVP. The patient presented with tinnitus due to a high-flow VA-EVVP fistula, so we performed coil embolization of the fistula under general anesthesia using a double-catheter technique and achieved subtotal embolization, which diminished the intracranial reflux. The 6-month follow-up DSA image revealed complete obliteration of the AVF. Conclusion: We report a rare case of upper cervical VA-EVVP fistula in a patient with no history of trauma and relevant medical conditions. Coil embolization of the fistula was performed using a combination of balloon-assisted and double-catheter techniques. Although the patient showed residual shunt flow after the intervention, follow-up DSA revealed complete obliteration. These findings should provide novel insights for the treatment strategy against VA-EVVP fistula.

A case of primary aldosteronism with excessive secretion of renin that was unmasked by kidney transplantation.

A 42-year-old man showed marked hypokalemia after kidney transplantation. He was diagnosed with hypertension and suffered from acute myocardial infarction at 33 and 38 years of age. At 40 years of age, hemodialysis was introduced. A left adrenal tumor was noted and suspected as a non-functional adrenal adenoma at that time. Therefore, he received a living-donor kidney transplant at 42 years of age. After kidney transplantation, the serum creatinine level dropped. His blood pressure remained high, and the serum potassium level decreased. The PRA and PAC were elevated, and ARR was not elevated. Based on the results of various confirmatory tests and vein sampling, he was diagnosed with excessive secretion of renin from the native kidneys that was complicated by primary aldosteronism (PA), and left nephrectomy and adrenalectomy were performed. The overproduction of aldosterone in the resected adrenal adenoma and over secretion of renin in the kidney with arteriolosclerosis were immunohistologically confirmed. After surgery, the PAC decreased, but the PRA did not decrease. The postoperative serum potassium level improved, and the blood pressure was well controlled with a small dose of medication. This is the first reported case of PA with hyperreninemia after kidney transplantation. It should be noted that PA in dialysis patients and kidney transplant recipients may not fulfill the usual diagnostic criteria of an elevated ARR. In such patients, PA should be suspected based on the absolute value of the PAC and responsiveness to ACTH stimulation, and adrenal and renal vein sampling is required for a definitive diagnosis.

Seronegative Full-house Nephropathy with Crohn's Disease.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease. Lupus nephritis (LN) is a major risk factor for mortality in SLE, and glomerular "full-house" immunofluorescence staining is a well-known characteristic of LN. However, some cases of non-lupus glomerulonephritis can also present with a "full-house" immunofluorescence pattern. We recently encountered a patient with full-house nephropathy (FHN) during adalimumab administration for Crohn's disease. IgA nephropathy or idiopathic FHN was diagnosed, and treatment with steroids was started, after which there was improvement in proteinuria. The prognosis of FHN has been reported to be poor; therefore, aggressive treatment is required for such patients.

Comparison of comfortable and maximum walking speed in the 10-meter walk test during the cerebrospinal fluid tap test in iNPH patients: A retrospective study.

BACKGROUND: The 10-meter walking test (10 MWT) is widely used during a cerebrospinal fluid tap test (CSFTT) for idiopathic normal-pressure hydrocephalus (iNPH). However, various previous studies and guidelines do not specify whether to adopt a comfortable walking speed or maximum walking speed when implementing the 10 MWT. In this study, we analyzed the values of comfortable and maximum walking speeds during the CSFTT in patients who underwent shunt surgery to determine which walking form is desirable for evaluation. METHODS: The patients were 29 consecutive cases in which a CSFTT was performed, followed by shunting, between October 2012 and April 2019. Data on the 10 MWT comfortable walking speed and maximum walking speed were collected, as were data on the timed up and go (TUG) test and Mini-Mental State Examination (MMSE). We analyzed the rate of change in comfortable walking speed and maximum walking speed before CSFTT and on the first day after CSFTT, and the amount of improvement compared to baseline ability. In addition, diagnostic performance was compared using a receiver operating characteristic (ROC) analysis. RESULTS: Twenty-eight patients who underwent shunt surgery improved their symptoms and were designated as shunt responders. The remaining patient who underwent surgery was considered a non-responder with no improvement in symptoms. The parameters of the shunt responders that changed were muscle strength, the 10 MWT, and the TUG test, and there was no significant change in cognitive function. The rate of change, amount of change, and sensitivity were large at a comfortable walking speed, but ROC analysis showed that the maximum walking speed had a large area under the curve and excellent specificity. The higher the preoperative gait function, the lower the improvement rate of gait function. DISCUSSION: The comfortable walking speed is easy to measure, but its specificity is inferior to the maximum walking speed. However, the maximum walking speed may be affected by the ceiling effect and measurement errors. Despite this, we concluded that the maximum walking speed had a better diagnostic performance. Because the causes of gait disturbance in iNPH include decreased muscle output, postural instability, and gait rhythm disorder, and maximum walking speed is strongly related to each of these factors, this accounts for the changes in maximum walking speed. CONCLUSION: In conclusion, although comfortable walking speed was easy to measure in terms of changes and had high sensitivity, the maximum walking speed had the highest specificity and comprehensive diagnostic performance. It is recommended that maximum walking speed be evaluated when making a definitive diagnosis of iNPH.

Duplicated Middle Cerebral Artery Aneurysms Treated by Coil Embolization; A Report of Two Cases and Literature Review.

BACKGROUND: Duplication of the middle cerebral artery (DMCA) is an anomalous vessel arising from the internal carotid artery (ICA). Aneurysms at the origin of a DMCA have been reported; however, most have been treated with clipping surgery. Here, we describe two cases of aneurysms at the origin of a DMCA treated with coil embolization. CASE PRESENTATION: Case 1: A seventy-three year-old man presented with severe headache and was diagnosed with subarachnoid hemorrhage (SAH). Digital subtraction angiography (DSA) and 3-dimensional (3-D) DSA showed an aneurysm arising from a DMCA. Coil embolization was performed with DMCA patency. The patient had an uneventful postoperative course. CASE 1: A 44-year-old woman presented with a history of clipping for an IC-anterior choroidal artery (AchA) aneurysm 8 years prior. Magnetic resonance imaging (MRI) showed regrowth of the aneurysm. 3-D DSA showed an IC-DMCA aneurysm located laterally and distal to the AchA. The DMCA arose from the bottom of the aneurysm. Coil embolization was performed without DMCA occlusion and showed no postoperative ischemic changes. CONCLUSION: An IC-DMCA aneurysm is rare and may be misdiagnosed as an AchA aneurysm. Clinicians should perform a 3D-DSA evaluation if the aneurysm arises from the lateral wall of the IC to obtain a precise diagnosis and to preserve the DMCA during coil embolization.

Thyroid hormone-induced expression of Foxl1 in subepithelial fibroblasts correlates with adult stem cell development during Xenopus intestinal remodeling.

In the Xenopus laevis intestine during metamorphosis, stem cells appear and generate the adult epithelium analogous to the mammalian one. We have previously shown that connective tissue cells surrounding the epithelium are essential for the stem cell development. To clarify whether such cells correspond to mammalian Foxl1-expressing mesenchymal cells, which have recently been shown to be a critical component of intestinal stem cell niche, we here examined the expression profile of Foxl1 in the X. laevis intestine by using RT-PCR and immunohistochemistry. Foxl1 expression was transiently upregulated only in connective tissue cells during the early period of metamorphic climax and was the highest just beneath the proliferating stem/progenitor cells. In addition, electron microscopic analysis showed that these subepithelial cells are ultrastructurally identified as telocytes like the mammalian Foxl1-expressing cells. Furthermore, we experimentally showed that Foxl1 expression is indirectly upregulated by thyroid hormone (TH) through Shh signaling and that TH organ-autonomously induces the Foxl1-expressing cells concomitantly with appearance of the stem cells in the tadpole intestine in vitro. The present results suggest that intestinal niche cells expressing Foxl1 are evolutionally conserved among terrestrial vertebrates and can be induced by TH/Shh signaling during amphibian metamorphosis for stem cell development.

Delayed Intracranial Parenchymal Changes After Aneurysmal Coil Embolization Procedures for Unruptured Intracranial Aneurysms.

BACKGROUND: With the recent advances in endovascular treatment devices, it has become standard in wide-neck or large intracranial aneurysms to perform coil embolization with adjunctive techniques. However, device-related perioperative complications have been reported because of the use of more complex systems. OBJECTIVE: To investigate patients who developed multiple parenchymal lesions after undergoing coil embolization for treating an unruptured intracranial aneurysm. METHODS: This study investigated 305 consecutive patients who underwent coil embolization of unruptured intracranial aneurysms between 2015 and 2017. Delayed inflammatory changes referred to the delayed observation of multiple cerebral white matter lesions on follow-up magnetic resonance imaging at an area corresponding to the perfused area of the treatment target vessel. The timing and pattern of onset, device used, the combined use of adjunctive techniques, and the clinical course after steroid treatment were retrospectively investigated. RESULTS: The 7 patients (2.3%) who showed delayed inflammatory changes were all women with a mean age of 59 yr. A mean duration from treatment to onset was 28 d. Symptoms were convulsions in 3 patients, hemiplegia in 2 patients, and homonymous hemianopia in 1 patient. All 7 patients were treated with adjunctive technique including stents, double catheter method, and balloon assist. Response to steroid treatment was satisfactory both clinically and on imaging in all 7 patients. Skin patch test was positive for nickel allergy in 2 patients. CONCLUSION: Clinicians must be fully aware of symptomatic delayed inflammatory changes may occur after endovascular aneurysmal treatment with the use of various devices.

Adenosine Attenuates Aortic Smooth Muscle Cell Calcification through A3 Adenosine Receptor.

Vascular calcification is a typical feature of atherosclerosis and is associated with adverse cardiovascular events such as myocardial infarction and stroke. Several studies have suggested that adenosine, an ATP metabolite may function as an endogenous regulator of arterial calcification. However, its effects on vascular smooth muscle cell calcification have not been clarified. In this study, we investigated the inhibitory effects of adenosine on vascular calcification in vitro by utilizing the culture of human aortic smooth muscle cells (HASMCs). Osteoblastic differentiation of HASMCs was induced by the treatment with oncostatin M and osteogenic differentiation medium. Adenosine and its metabolically stable analogue, 2-chloroadenosine (CADO) significantly reduced matrix mineralization and alkaline phosphatase (ALP) activities in HASMCs. The mRNA expression of tissue non-specific alkaline phosphatase (TNAP) was down-regulated by adenosine and CADO, but the mRNA expression of other osteoblastic differentiation markers, such as Runt-related transcription factor 2 (RUNX2) and bone sialoprotein (BSP)-II, was not significantly affected by these two reagents. Among the adenosine receptor (AR) subtype-selective agonists used, only IB-MECA (A3 AR-selective agonist) significantly decreased in vitro mineralization and ALP activities in HASMCs, but not with CCPA (A1 AR-selective agonist), CGS21680 (A2a AR-selective agonist), or BAY60-6583 (A2b AR-selective agonist). Importantly, IB-MECA also down-regulated expression of TNAP mRNA. Finally, knockdown of A3 AR, but not A1 AR, A2a AR, or A2b AR, significantly reversed the inhibitory actions of adenosine, CADO, or IB-MECA on in vitro calcification and ALP activities in HASMCs. These data suggest that adenosine attenuates HASMC calcification through A3 AR.

Oncostatin M induces C2C12 myotube atrophy by modulating muscle differentiation and degradation.

Oncostatin M (OSM) is a cytokine of the interleukin-6 family and plays a role in various disorders such as cancer and inflammatory diseases, which are often accompanied by skeletal muscle atrophy, or sarcopenia. However, the role of OSM in the regulation of skeletal muscle mass remains to be identified. In this study, we investigated the effect of OSM on C2C12 myotube formation in vitro. C2C12 myoblasts were induced to differentiate into myotubes for 3 days and then treated with OSM for 24 or 48 h. The diameter of differentiated C2C12 myotubes were reduced by 18.7% and 23.3% compared to control cells after treatment with OSM for 24 and 48 h, respectively. The expression levels of MyoD and myogenin were decreased, while those of atrogin-1, CCAAT/enhancer binding protein δ, and OSM receptor were increased in C2C12 myotubes treated with OSM for 24 h compared to control cells. Furthermore, the inhibitory effect of OSM on myotube formation was significantly attenuated by pretreatment with an inhibitor of signal transducer and activator of transcription (STAT) 3 or by knockdown of Stat3. Finally, the OSM-induced changes in the expression levels of MyoD, myogenin, and atrogin-1 were reversed by pretreatment with an inhibitor of STAT3 or by Stat3 knockdown in C2C12 myotubes. In conclusion, OSM induces C2C12 myotube atrophy by inhibiting myogenic differentiation and activating muscle degradation in a STAT3-dependent manner.

Genetic Phagocyte NADPH Oxidase Deficiency Enhances Nonviable Candida albicans-Induced Inflammation in Mouse Lungs.

Patients with chronic granulomatous disease (CGD) have mutated phagocyte NADPH oxidase, resulting in reduced production of reactive oxygen species (ROS). While the mechanism underlying hyperinfection in CGD is well understood, the basis for inflammatory disorders that arise in the absence of evident infection has not been fully explained. This study aimed to evaluate the effect of phagocyte NADPH oxidase deficiency on lung inflammation induced by nonviable Candida albicans (nCA). Mice deficient in this enzyme (CGD mice) showed more severe neutrophilic pneumonia than nCA-treated wild-type mice, which exhibited significantly higher lung concentrations of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and keratinocyte-derived chemokine (KC). Neutralization of these proinflammatory mediators significantly reduced neutrophil infiltration. In vitro, production of IL-1ß and TNF-α from neutrophils and that of KC from macrophages was enhanced in nCA-stimulated neutrophils from CGD mice. Expression of IL-1ß mRNA was higher in the stimulated CGD neutrophils than in the stimulated wild-type cells, concomitant with upregulation of nuclear factor (NF)-κB and its upstream regulator extracellular-signal regulated kinase (ERK) 1/2. Pretreatment with an NADPH oxidase inhibitor significantly enhanced IL-1ß production in the wild-type neutrophils stimulated with nCA. These results suggest that lack of ROS production because of NADPH oxidase deficiency results in the production of higher levels of proinflammatory mediators from neutrophils and macrophages, which may at least partly contribute to the exacerbation of nCA-induced lung inflammation in CGD mice.

Thyroid hormone activates Wnt/ß-catenin signaling involved in adult epithelial development during intestinal remodeling in Xenopus laevis.

During amphibian intestinal remodeling, thyroid hormone (TH) induces some larval epithelial cells to dedifferentiate into adult stem cells, which newly generate the absorptive epithelium analogous to the mammalian epithelium. To clarify molecular mechanisms underlying adult epithelial development, we here focus on TH response genes that are associated with the canonical Wnt pathway. Our quantitative reverse transcription plus polymerase chain reaction and immunohistochemical analyses indicate that all of the genes examined, including ß-catenin, c-Myc and secreted frizzle-related protein 2 (SFRP2), are up-regulated in Xenopus laevis intestine during both natural and TH-induced metamorphosis. Moreover, immunoreactivity for nuclear ß-catenin becomes detectable in adult stem cells from the start of their appearance and then increases in intensity in adult epithelial primordia derived from the stem cells, which actively proliferate and coexpress Wnt target genes c-Myc and LGR5. These expression profiles strongly suggest the involvement of the canonical Wnt pathway in the maintenance and/or proliferation of adult stem/progenitor cells. More importantly, by using organ cultures of the tadpole intestine, we have experimentally shown that the addition of exogenous SFRP2 protein to the culture medium promotes cell proliferation of the adult epithelial primordia, whereas inhibition of endogenous SFRP2 by its antibody suppresses their proliferation. The inhibition of SFRP2 suppresses larval epithelial changes in shape from simple columnar to stem-cell-like roundish cells, resulting in the failure of epithelial dedifferentiation. Thus, TH-up-regulated SFRP2 in the postembryonic intestine promotes adult stem cell development, possibly by acting as an agonist of both canonical and non-canonical Wnt signaling.

[Relationship of Distal Anterior Cerebral Artery Aneurysm Arising from the Supracallosal Portion and Accessory Anterior Cerebral Artery].

Median artery of the corpus callosum(MACC)refers to the median artery of the triplicate anterior cerebral artery(ACA). When MACC distributes to one or to both hemispheres, it is known as the accessory ACA. We performed detailed angiographic analysis of 32 consecutive patients operated upon for distal ACA(DACA)aneurysms, and noted that all DACA aneurysms occurring in the supracallosal portion were accompanied by an accessory ACA as vascular malformation. Such relationship between accessory ACA and DACA aneurysm in the supracallosal portion has not been previously reported.

Histone Methylation and STAT-3 Differentially Regulate Interleukin-6-Induced Matrix Metalloproteinase Gene Activation in Rheumatoid Arthritis Synovial Fibroblasts.

OBJECTIVE: Synovial fibroblasts (SFs) produce matrix-degrading enzymes that cause joint destruction in rheumatoid arthritis (RA). Epigenetic mechanisms play a pivotal role in autoimmune diseases. This study was undertaken to elucidate the epigenetic mechanism that regulates the transcription of matrix metalloproteinases (MMPs) in RASFs. METHODS: MMP gene expression and histone methylation profiles in the MMP promoters were examined in RASFs. The effect of WD repeat domain 5 (WDR5) silencing on histone methylation and MMP gene expression in RASFs was analyzed. MMP gene expression, surface expression of the interleukin-6 (IL-6) receptor, phosphorylation of STAT-3, and binding of STAT-3 in the MMP promoters were investigated in RASFs stimulated with IL-6. RESULTS: The MMP-1, MMP-3, MMP-9, and MMP-13 genes were actively transcribed in RASFs. Correspondingly, the level of histone H3 trimethylated at lysine 4 (H3K4me3) was elevated, whereas that of H3K27me3 was suppressed in the MMP promoters in RASFs. The decrease in H3K4me3 via WDR5 small interfering RNA reduced the levels of messenger RNA for MMP-1, MMP-3, MMP-9, and MMP-13 in RASFs. Interestingly, IL-6 signaling significantly increased the expression of MMP-1, MMP-3, and MMP-13, but not MMP-9, in RASFs. Although the IL-6 signaling pathway was similarly active in RASFs and osteoarthritis SFs, STAT-3 bound to the MMP-1, MMP-3, and MMP-13 promoters, but not the MMP-9 promoter, after IL-6 stimulation in RASFs. CONCLUSION: Our findings indicate that histone methylation and STAT-3 regulate spontaneous and IL-6-induced MMP gene activation in RASFs. The combination of chromatin structure and transcription factors may regulate distinct arthritogenic properties of RASFs.

[Percutaneous transluminal angioplasty using a stent for an aberrant left subclavian artery stenosis with a right-sided aortic arch: a case report].

An aberrant left subclavian artery is a rare variant that has been reported to coexist with the right-sided aortic arch in many cases. We encountered a case in which percutaneous transluminal angioplasty using a stent was performed for an aberrant left subclavian artery and left carotid artery. The patient was a 63-year-old man in whom left carotid artery stenosis and abnormal flow pattern of the left vertebral artery was accidently found during an ultrasound screening of his carotid artery. The right-sided aortic arch with the aberrant left subclavian artery was revealed by a cerebral angiogram via the right femoral artery. Despite difficulty in inserting a catheter at the origin of the aberrant left artery, the treatment was completed successfully. To our knowledge, endovascular treatment for an aberrant left subclavian artery has not been reported until date.

[Successful surgical treatment of an extrasinusal dural arteriovenous fistula located in the lateral wall of the cavernous sinus: a case report].

We report the successful surgical treatment of a dural arteriovenous fistula(AVF)located in the lateral wall of the cavernous sinus. A 44-year-old woman presented with facial numbness in the left V3 area. Magnetic resonance imaging showed a flow void sign around the sphenoid ridge on a T2-weighted image. Digital subtraction angiography(DSA)demonstrated a dural AVF that was supplied by feeding arteries from the C4 portion of the left internal carotid artery. Without sinus enhancement, the draining vein flowed directly through the superficial sylvian vein into the vein of Labbé. Following treatment of the dural AVF located in the anterior cranial fossa, we ligated the draining vein at the penetrating point in the intradural region using surgical management. Intraoperative findings showed that the shunt point was located in the left lateral wall of the cavernous sinus. The postoperative course was uneventful and DSA showed no evidence of the AVF. The patient was discharged with no neurological deficits. Few studies have reported the use of direct surgery alone for the treatment of dural AVFs located in the cavernous sinus with a perfusion pattern as in this case.

Development of a mouse monoclonal antibody for the detection of asymmetric dimethylarginine of Translocated in LipoSarcoma/FUsed in Sarcoma and its application in analyzing methylated TLS.

BACKGROUND: RNA-binding protein Translocated in LipoSarcoma/FUsed Sarcoma (TLS/FUS) is one of causative genes for familial amyotrophic lateral sclerosis (ALS). We previously identified that TLS was associated with protein arginine methyltransferase 1 (PRMT1), and four arginine residues within TLS (R216, R218, R242 and R394) were consistently dimethylated. Protein arginine methylation is involved in various cellular events such as signal transduction, transcriptional regulation and protein-protein interactions. RESULTS: To understand the biological role of arginine methylation of RNA-binding protein, we prepared and characterized a mouse monoclonal antibody against asymmetric dimethylarginine of TLS. By cloning and screening, one stable hybridoma cell clone (2B12) producing anti-asymmetric dimethylated TLS on R216 and R218 antibody was established. The monoclonal antibody 2B12 is specific for the asymmetrically dimethylated arginine peptide and does not react with the same peptide sequence containing unmodified and symmetrically dimethylated arginine residues by dot-blot analysis. 2B12 was also validated GST tagged TLS with PRMT1 by in vitro arginine methylation assays. Since methylated TLS in HeLa cells and mouse and human brain protein extracts was immunoprecipitated with 2B12, we performed RNA-binding protein immunoprecipitation assays using HeLa cell lysate and this antibody. We demonstrated that the long noncoding RNA (lncRNA) transcribed from cyclin D1 promoter binds methylated TLS. CONCLUSIONS: A monoclonal antibody that is capable of detecting the methylarginine status of TLS will facilitate the molecular and cellular analysis of transcriptional regulation by lncRNA through methylated TLS, and can be used as a favorable tool for clinical diagnosis of ALS caused by TLS dysregulation.

Thyroid hormone activates protein arginine methyltransferase 1 expression by directly inducing c-Myc transcription during Xenopus intestinal stem cell development.

Adult organ-specific stem cells are essential for organ homeostasis and tissue repair and regeneration. The formation of such stem cells during vertebrate development is poorly understood. Intestinal remodeling during thyroid hormone (T3)-dependent Xenopus metamorphosis resembles postembryonic intestinal maturation in mammals. During metamorphosis, the intestine is remodeled de novo via a yet unknown mechanism. Protein arginine methyltransferase 1 (PRMT1) is up-regulated in and required for adult intestinal stem cells during metamorphosis. PRMT1 up-regulation is the earliest known molecular event for the developing stem cells and is also conserved during zebrafish and mouse intestinal development. To analyze how PRMT1 is specifically up-regulated during the formation of the adult intestinal stem cells, we cloned the Xenopus PRMT1 promoter and characterized it in CaCo-2 cells, a human cell line with intestinal stem cell characteristics. Through a series deletion and mutational analyses, we showed that the stem cell-associated transcription factor c-Myc could bind to a conserved site in the first intron to activate the promoter. Furthermore, we demonstrated that during metamorphosis, both c-Myc and PRMT1 were highly up-regulated, specifically in the remodeling intestine but not the resorbing tail, and that c-Myc was induced by T3 prior to PRMT1 up-regulation. In addition, we showed that T3 directly activated the c-Myc gene during metamorphosis in the intestine via binding of the T3 receptor to the c-Myc promoter. These results suggest that T3 induces c-Myc transcription directly in the intestine, that c-Myc, in turn, activates PRMT1 expression, and that this is an important gene regulation cascade controlling intestinal stem cell development.

Liganded thyroid hormone receptor induces nucleosome removal and histone modifications to activate transcription during larval intestinal cell death and adult stem cell development.

Thyroid hormone (T(3)) plays an important role in regulating multiple cellular and metabolic processes, including cell proliferation, cell death, and energy metabolism, in vertebrates. Dysregulation of T(3) signaling results in developmental abnormalities, metabolic defects, and even cancer. We used T(3)-dependent Xenopus metamorphosis as a model to study how T(3) regulates transcription during vertebrate development. T(3) exerts its metamorphic effects through T(3) receptors (TR). TR recruits, in a T(3)-dependent manner, cofactor complexes that can carry out chromatin remodeling/histone modifications. Whether and how histone modifications change upon gene regulation by TR during vertebrate development is largely unknown. Here we analyzed histone modifications at T(3) target genes during intestinal metamorphosis, a process that involves essentially total apoptotic degeneration of the simple larval epithelium and de novo development of the adult epithelial stem cells, followed by their proliferation and differentiation into the complex adult epithelium. We demonstrated for the first time in vivo during vertebrate development that TR induces the removal of core histones at the promoter region and the recruitment of RNA polymerase. Furthermore, a number of histone activation and repression marks have been defined based on correlations with mRNA levels in cell cultures. Most but not all correlate with gene expression induced by liganded TR during development, suggesting that tissue and developmental context influences the roles of histone modifications in gene regulation. Our findings provide important mechanistic insights on how chromatin remodeling affects developmental gene regulation in vivo.

Early appearance of high grade glioma on magnetic resonance imaging.

The early appearance of high grade glioma on magnetic resonance (MR) imaging was retrospectively reviewed in the clinical records and MR images of 52 patients with intracerebral glioma treated in Osaka General Medical Center between 1997 and 2006. Three patients had no abnormal findings, and four patients had only hyperintense areas on T(2)-weighted imaging at initial MR examination. Five of the seven patients presented with generalized seizures. Six of the seven patients developed tumor progression within only 5 months. All patients underwent surgical tumor resection and the histological diagnoses were all high grade gliomas, glioblastomas in five, gliosarcoma in one, and anaplastic astrocytoma in one. Surveillance MR imaging should be performed at short intervals in adult patients presenting with seizures but with no or minimal abnormalities on initial MR imaging to identify progression of high grade glioma at the earliest opportunity.